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["Retinoic and skeletal/dental reviews",null,null,null,null,null,"This query was used to pull in the articles:  (retinoid OR retinoic) AND (skeletal OR bone OR Musculoskeletal System[mh] OR teeth OR Dentition[mh] OR Musculoskeletal Diseases[mh]) AND (review[pt] OR review[tiab])"]
[null,"Your search terms"]
["PMID","retin","denta","cleft palate","Total","Pub Yr","Title","Fauthor","LinkPMID","tiab"]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I4,I4)","v":27671426},{"$f":"(LEN($J4) - LEN(SUBSTITUTE(LOWER($J4),LOWER(B$3),\"\")))/LEN(B$3)","v":8},{"$f":"(LEN($J4) - LEN(SUBSTITUTE(LOWER($J4),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J4) - LEN(SUBSTITUTE(LOWER($J4),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B4:D4)","v":8},2016,"Apoptosis May Explain the Pharmacological Mode of Action and Adverse Effects of Isotretinoin, Including Teratogenicity.","Melnik",27671426,"Apoptosis May Explain the Pharmacological Mode of Action and Adverse Effects of Isotretinoin, Including Teratogenicity.    Abstract:    NlmCategory=UNASSIGNEDIsotretinoin (13-cis retinoic acid) is the most effective sebum-suppressive drug for the treatment of severe acne. Its effect depends on sebocyte apoptosis, which results from isotretinoin-induced expression of the apoptotic protein tumour necrosis factor-related apoptosis-inducing ligand, insulin-like growth factor-binding protein-3 and neutrophil gelatinase-associated lipocalin. This review proposes that the pharmacological mode of action of isotretinoin in the treatment of severe acne, acute promyelocytic leukaemia, and neuroblastoma results from apoptosis. Furthermore, apoptosis may be the underlying and unifying mechanism of the adverse effects of isotretinoin on neural crest cells (teratogenicity), hippocampal neurones (depression), epidermal keratinocytes and mucosa cells (mucocutaneous side-effects), hair follicle cells (telogen effluvium), intestinal epithelial cells (inflammatory bowel disease), skeletal muscle cells (myalgia and release of creatine kinase), and hepatocytes (release of transaminases and very low-density lipoproteins). Genetic variants of components of the apoptotic signalling cascade, such as RARA polymorphisms, might explain variations in the magnitude of isotretinoin-induced apoptotic signalling and apparently identify subgroups of patients who experience either stronger adverse effects with isotretinoin therapy or resistance to treatment."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I5,I5)","v":27621572},{"$f":"(LEN($J5) - LEN(SUBSTITUTE(LOWER($J5),LOWER(B$3),\"\")))/LEN(B$3)","v":4},0,0,{"$f":"SUM(B5:D5)","v":4},2016,"Supportive therapies for prevention of hepatocellular carcinoma recurrence and preservation of liver function.","Takami",27621572,"Supportive therapies for prevention of hepatocellular carcinoma recurrence and preservation of liver function.    Abstract:   Hepatocellular carcinoma (HCC) is one of the deadliest cancers in the world and is associated with a high risk of recurrence. The development of a wide range of new therapies is therefore essential. In this study, from the perspective of supportive therapy for the prevention of HCC recurrence and preservation of liver function in HCC patients, we surveyed a variety of different therapeutic agents. We show that branched chain amino acids (BCAA) supplementation and late evening snack with BCAA, strategies that address issues of protein-energy malnutrition, are important for liver cirrhotic patients with HCC. For chemoprevention of HCC recurrence, we show that viral control after radical treatment is important. We also reviewed the therapeutic potential of antiviral drugs, sorafenib, peretinoin, iron chelators. Sorafenib is a kinase inhibitor and a standard therapy in the treatment of advanced HCC. Peretinoin is a vitamin A-like molecule that targets the retinoid nuclear receptor to induce apoptosis and inhibit tumor growth in HCC cells. Iron chelators, such as deferoxamine and deferasirox, act to prevent cancer cell growth. These chelators may have potential as combination therapies in conjunction with peretinoin. Finally, we review the potential inhibitory effect of bone marrow cells on hepatocarcinogenesis."]
[27589347,7,2,0,9,2016,"Accelerated Skeletal Maturation in Disorders of Retinoic Acid Metabolism: A Case Report and Focused Review of the Literature.","Nilsson",27589347,"Accelerated Skeletal Maturation in Disorders of Retinoic Acid Metabolism: A Case Report and Focused Review of the Literature.    Abstract:    NlmCategory=UNASSIGNEDNutritional excess of vitamin A, a precursor for retinoic acid (RA), causes premature epiphyseal fusion, craniosynostosis, and light-dependent retinopathy. Similarly, homozygous loss-of-function mutations in CYP26B1, one of the major RA-metabolizing enzymes, cause advanced bone age, premature epiphyseal fusion, and craniosynostosis. In this paper, a patient with markedly accelerated skeletal and dental development, retinal scarring, and autism-spectrum disease is presented and the role of retinoic acid in longitudinal bone growth and skeletal maturation is reviewed. Genetic studies were carried out using SNP array and exome sequencing. RA isomers were measured in the patient, family members, and in 18 age-matched healthy children using high-performance liquid chromatography coupled to tandem mass spectrometry. A genomic SNP array identified a novel 8.3 megabase microdeletion on chromosome 10q23.2-23.33. The 79 deleted genes included CYP26A1 and C1, both major RA-metabolizing enzymes. Exome sequencing did not detect any variants that were predicted to be deleterious in the remaining alleles of these genes or other known retinoic acid-metabolizing enzymes. The patient exhibited elevated plasma total RA (16.5 vs. 12.6±1.5 nM, mean±SD, subject vs. controls) and 13-cisRA (10.7 nM vs. 6.1±1.1). The findings support the hypothesis that elevated RA concentrations accelerate bone and dental maturation in humans. CYP26A1 and C1 haploinsufficiency may contribute to the elevated retinoic acid concentrations and clinical findings of the patient, although this phenotype has not been reported in other patients with similar deletions, suggesting that other unknown genetic or environmental factors may also contribute."]
[27238416,2,0,0,2,2016,"Retinoic acid signalling in the development of the epidermis, the limbs and the secondary palate.","Mammadova",27238416,"Retinoic acid signalling in the development of the epidermis, the limbs and the secondary palate.    Abstract:    NlmCategory=UNASSIGNEDRetinoic acid (RA), the active derivative of vitamin A, is one of the major regulators of embryonic development, including the development of the epidermis, the limbs and the secondary palate. In the embryo, RA levels are tightly regulated by the activity of RA synthesizing and degrading enzymes. Aberrant RA levels due to genetic variations in RA metabolism pathways contribute to congenital malformations in these structures. In vitro and in vivo studies provide considerable evidence on the effects of RA and its possible role in the development of the epidermis, the limbs and the secondary palate. In conjunction with other regulatory factors, RA seems to stimulate the development of the epidermis by inducing proliferation and differentiation of ectodermal cells into epidermal cells. In the limbs, the exact timing of RA location and level is crucial to initiate limb bud formation and to allow chondrogenesis and subsequent osteogenesis. In the secondary palate, the correct RA concentration is a key factor for mesenchymal cell proliferation during palatal shelf outgrowth, elevation and adhesion, and finally to allow bone formation in the hard palate. These findings are highly relevant to understanding the mechanism of RA signalling in development and in the aetiology of specific congenital diseases."]
[27011226,5,0,0,5,2016,"Retinoic Acid for High-risk Neuroblastoma Patients after Autologous Stem Cell Transplantation - Cochrane Review.","Peinemann",27011226,"Retinoic Acid for High-risk Neuroblastoma Patients after Autologous Stem Cell Transplantation - Cochrane Review.    Abstract:    BACKGROUND : Neuroblastoma is a rare malignant disease and patients with high-risk neuroblastoma have a poor prognosis. Retinoic acid has been shown to inhibit growth of human neuroblastoma cells and has been considered as a potential candidate for improving the outcome.  METHODS : The objective was to evaluate effects of retinoic acid after consolidation with high-dose chemotherapy and bone marrow transplantation as compared to placebo or no further treatment in patients with high-risk neuroblastoma. We searched the databases CENTRAL, MEDLINE, and EMBASE from inception to 01 October 2014 and included randomized controlled trials.  RESULTS : We identified one relevant randomized controlled trial with 50 participants receiving retinoic acid and 48 participants receiving no further therapy. There was no statistically significant difference between the treatment groups in overall survival (hazard ratio 0.87, 95% confidence interval 0.46-1.63, P=0.66) and event-free survival (hazard ratio 0.86, 95% confidence interval 0.50-1.49, P=0.59). We did not identify results for other outcomes, including toxicity.  CONCLUSION : The difference in overall and event-free survival between treatment alternatives was not statistically significantly different. Based on the currently available evidence, we are uncertain about the effects of retinoic acid after bone marrow transplantation in patients with high-risk neuroblastoma."]
[26952139,1,0,0,1,2016,"The molecular basis of craniofacial placode development.","Singh",26952139,"The molecular basis of craniofacial placode development.    Abstract:   The sensory organs of the vertebrate head originate from simple ectodermal structures known as cranial placodes. All cranial placodes derive from a common domain adjacent to the neural plate, the preplacodal region, which is induced at the border of neural and non-neural ectoderm during gastrulation. Induction and specification of the preplacodal region is regulated by the fibroblast growth factor, bone morphogenetic protein, WNT, and retinoic acid signaling pathways, and characterized by expression of the EYA and SIX family of transcriptional regulators. Once the preplacodal region is specified, different combinations of local signaling molecules and placode-specific transcription factors, including competence factors, promote the induction of individual cranial placodes along the neural axis of the head region. In this review, we summarize the steps of cranial placode development and discuss the roles of the main signaling molecules and transcription factors that regulate these steps during placode induction, specification, and development. For further resources related to this article, please visit the WIREs website."]
[26823883,1,0,0,1,2015,"Acute promyelocytic leukemia with cryptic t(15;17) on isochromosome 17: a case report and review of literature.","Tang",26823883,"Acute promyelocytic leukemia with cryptic t(15;17) on isochromosome 17: a case report and review of literature.    Abstract:   Acute Promyelocytic Leukemia (APL) is one of the most curable leukemia which shows great sensitivity to all-trans retinoic acid (ATRA) although a small number of the patients present poor prognosis and short survival. Isochromosome 17 in APL which usually bears an additional copy of RARA/PML fusion gene is considered to be a negative factor on its prognosis. Cryptic t(15;17) on i(17q) leads to an extra copy of PML/RARA rather than RARA/PML which may confer a worse prognosis. We describe here a rare APL case with complex chromosomal abnormality including isochromosome 17 bearing cryptic t(15;17) showing poor outcome. The patient lacks a classic t(15;17) and fluorescence in situ hybridization (FISH) presents 2 PML/RARA fusion signals on both long arms of the isochromosome. The patient also acquired a secondary mutation at relapse when the initial karyotype was already a complex karyotype involving chromosome 13, 17 and 22 at the same time. The poor response of this patient to traditional chemotherapy like ATRA and novel therapy like arsenic trioxide (ATO) suggests that early auto-hematological stem cell transplantation may be the choice of APL with isochromosome 17 especially with cryptic t(15;17) on i(17q). We are the first to show a clear history and evidence of FISH of these kind of cases. A small summary of cases with cryptic t(15;17) on isochromosome 17 is also made."]
[26747887,1,0,0,1,2016,"Absorption, metabolism, and functions of β-cryptoxanthin.","Burri",26747887,"Absorption, metabolism, and functions of β-cryptoxanthin.    Abstract:   β-Cryptoxanthin, a carotenoid found in fruits and vegetables such as tangerines, red peppers, and pumpkin, has several functions important for human health. Most evidence from observational, in vitro, animal model, and human studies suggests that β-cryptoxanthin has relatively high bioavailability from its common food sources, to the extent that some β-cryptoxanthin-rich foods might be equivalent to β-carotene-rich foods as sources of retinol. β-Cryptoxanthin is an antioxidant in vitro and appears to be associated with decreased risk of some cancers and degenerative diseases. In addition, many in vitro, animal model, and human studies suggest that β-cryptoxanthin-rich foods may have an anabolic effect on bone and, thus, may help delay osteoporosis."]
[26715014,1,0,0,1,2015,"From pluripotency to myogenesis: a multistep process in the dish.","Świerczek",26715014,"From pluripotency to myogenesis: a multistep process in the dish.    Abstract:   Pluripotent stem cells (PSCs), such as embryonic stem cells or induced pluripotent stem cells are a promising source of cells for regenerative medicine as they can differentiate into all cell types building a mammalian body. However, protocols leading to efficient and safe in vitro generation of desired cell types must be perfected before PSCs can be used in cell therapies or tissue engineering. In vivo, i.e. in developing mouse embryo or teratoma, PSCs can differentiate into skeletal muscle, but in vitro their spontaneous differentiation into myogenic cells is inefficient. Numerous attempts have been undertaken to enhance this process. Many of them involved mimicking the interactions occurring during embryonic myogenesis. The key regulators of embryonic myogenesis, such as Wnts proteins, fibroblast growth factor 2, and retinoic acid, have been tested to improve the frequency of in vitro myogenic differentiation of PSCs. This review summarizes the current state of the art, comparing spontaneous and directed myogenic differentiation of PSCs as well as the protocols developed this far to facilitate this process."]
[26622430,1,0,0,1,2015,"Microgranular variant of acute promyelocytic leukemia with der(17) ins(17;15): A case report and review of the literature.","Guan",26622430,"Microgranular variant of acute promyelocytic leukemia with der(17) ins(17;15): A case report and review of the literature.    Abstract:    NlmCategory=UNASSIGNEDAcute promyelocytic leukemia (APL) with variant translocations is rare. The patient of the present case report, a 2-year-old male with a microgranular variant of APL carrying der(17) ins(17;15) translocation, exhibited fever and epistaxis. The complete blood count showed marked leukocytosis with 72% atypical promyelocytes, anemia and thrombocytopenia. Conventional cytogenetic analysis of the bone marrow cells revealed a karyotype of 47, XY, add(3)(q29), -7, ins(17;15)(q12;q14q22),+21,+mar. The promyelocytic leukemia/retinoic acid receptor α (PML/RARα) rearrangement and insertion were confirmed by fluorescence in situ hybridization. The PML/RARα transcripts were not detected by the reverse transcription polymerase chain reaction, and the patient was diagnosed with microgranular variant M3 APL. The patient achieved remission after a 30-day treatment and was still in remission during a recent follow-up. The present findings suggest that the ins(17;15) variant in APL may not be associated with an unfavorable prognosis. In summary, we reported an extremely rare case of APL with der(17) ins(17;15) abnormality in a pediatric patient and reviewed the literature."]
[26596315,1,0,0,1,2016,"Hypercalcemia. Pathophysiological aspects.","Žofková",26596315,"Hypercalcemia. Pathophysiological aspects.    Abstract:   The metabolic pathways that contribute to maintain serum calcium concentration in narrow physiological range include the bone remodeling process, intestinal absorption and renal tubule resorption. Dysbalance in these regulations may lead to hyper- or hypocalcemia. Hypercalcemia is a potentionally life-threatening and relatively common clinical problem, which is mostly associated with hyperparathyroidism and/or malignant diseases (90 %). Scarce causes of hypercalcemia involve renal failure, kidney transplantation, endocrinopathies, granulomatous diseases, and the long-term treatment with some pharmaceuticals (vitamin D, retinoic acid, lithium). Genetic causes of hypercalcemia involve familial hypocalciuric hypercalcemia associated with an inactivation mutation in the calcium sensing receptor gene and/or a mutation in the CYP24A1 gene. Furthermore, hypercalcemia accompanying primary hyperparathyroidism, which develops as part of multiple endocrine neoplasia (MEN1 and MEN2), is also genetically determined. In this review mechanisms of hypercalcemia are discussed. The objective of this article is a review of hypercalcemia obtained from a Medline bibliographic search."]
[26576076,1,6,0,7,2015,"An Overview of Pathogen Recognition Receptors for Innate Immunity in Dental Pulp.","Jang",26576076,"An Overview of Pathogen Recognition Receptors for Innate Immunity in Dental Pulp.    Abstract:   Pathogen recognition receptors (PRRs) are a class of germ line-encoded receptors that recognize pathogen-associated molecular patterns (PAMPs). The activation of PRRs is crucial for the initiation of innate immunity, which plays a key role in first-line defense until more specific adaptive immunity is developed. PRRs differ in the signaling cascades and host responses activated by their engagement and in their tissue distribution. Currently identified PRR families are the Toll-like receptors (TLRs), the C-type lectin receptors (CLRs), the nucleotide-binding oligomerization domain-like receptors (NLRs), the retinoic acid-inducible gene-I-like receptors (RLRs), and the AIM2-like receptor (ALR). The environment of the dental pulp is substantially different from that of other tissues of the body. Dental pulp resides in a low compliance root canal system that limits the expansion of pulpal tissues during inflammatory processes. An understanding of the PRRs in dental pulp is important for immunomodulation and hence for developing therapeutic targets in the field of endodontics. Here we comprehensively review recent finding on the PRRs and the mechanisms by which innate immunity is activated. We focus on the PRRs expressed on dental pulp and periapical tissues and their role in dental pulp inflammation."]
[26544673,1,0,0,1,2016,"Specification of anteroposterior axis by combinatorial signaling during Xenopus development.","Carron",26544673,"Specification of anteroposterior axis by combinatorial signaling during Xenopus development.    Abstract:   The specification of anteroposterior (AP) axis is a fundamental and complex patterning process that sets up the embryonic polarity and shapes a multicellular organism. This process involves the integration of distinct signaling pathways to coordinate temporal-spatial gene expression and morphogenetic movements. In the frog Xenopus, extensive embryological and molecular studies have provided major advance in understanding the mechanism implicated in AP patterning. Following fertilization, cortical rotation leads to the transport of maternal determinants to the dorsal region and creates the primary dorsoventral (DV) asymmetry. The activation of maternal Wnt/ß-catenin signaling and a high Nodal signal induces the formation of the Nieuwkoop center in the dorsal-vegetal cells, which then triggers the formation of the Spemann organizer in the overlying dorsal marginal zone. It is now well established that the Spemann organizer plays a central role in building the vertebrate body axes because it provides patterning information for both DV and AP polarities. The antagonistic interactions between signals secreted in the Spemann organizer and the opposite ventral region pattern the mesoderm along the DV axis, and this DV information is translated into AP positional values during gastrulation. The formation of anterior neural tissue requires simultaneous inhibition of zygotic Wnt and bone morphogenetic protein (BMP) signals, while an endogenous gradient of Wnt, fibroblast growth factors (FGFs), retinoic acid (RA) signaling, and collinearly expressed Hox genes patterns the trunk and posterior regions. Collectively, DV asymmetry is mostly coupled to AP polarity, and cell-cell interactions mediated essentially by the same regulatory networks operate in DV and AP patterning. For further resources related to this article, please visit the WIREs website."]
[26435449,8,0,0,8,2016,"The role of vitamin A and retinoic acid receptor signaling in post-natal maintenance of bone.","Green",26435449,"The role of vitamin A and retinoic acid receptor signaling in post-natal maintenance of bone.    Abstract:   Vitamin A and retinoid derivatives are recognized as morphogens that govern body patterning and skeletogenesis, producing profound defects when in excess. In post-natal bone, both high and low levels of vitamin A are associated with poor bone heath and elevated risk of fractures. Despite this, the precise mechanism of how retinoids induce post-natal bone changes remains elusive. Numerous studies have been performed to discover how retinoids induce these changes, revealing a complex morphogenic regulation of bone through interplay of different cell types. This review will discuss the direct and indirect effects of retinoids on mediators of bone turnover focusing on differentiation and activity of osteoblasts and osteoclasts and explains why some discrepancies in this field have arisen. Importantly, the overall effect of retinoids on the skeleton is highly site-specific, likely due to differential regulation of osteoblasts and osteoclasts at trabecular vs. cortical periosteal and endosteal bone surfaces. Further investigation is required to discover the direct gene targets of retinoic acid receptors (RARs) and molecular mechanisms through which these changes occur. A clear role for RARs in regulating bone is now accepted and the therapeutic potential of retinoids in treating bone diseases has been established."]
[26416507,1,0,0,1,2015,"Mitochondrial regulation of macrophage cholesterol homeostasis.","Graham",26416507,"Mitochondrial regulation of macrophage cholesterol homeostasis.    Abstract:   This review explores the relationship between mitochondrial structure and function in the regulation of macrophage cholesterol metabolism and proposes that mitochondrial dysfunction contributes to loss of the elegant homeostatic mechanisms which normally maintain cellular sterol levels within defined limits. Mitochondrial sterol 27-hydroxylase (CYP27A1) can generate oxysterol activators of liver X receptors which heterodimerise with retinoid X receptors, enhancing the transcription of ATP binding cassette transporters (ABCA1, ABCG1, and ABCG4), that can remove excess cholesterol via efflux to apolipoproteins A-1, E, and high density lipoprotein, and inhibit inflammation. The activity of CYP27A1 is regulated by the rate of supply of cholesterol substrate to the inner mitochondrial membrane, mediated by a complex of proteins. The precise identity of this dynamic complex remains controversial, even in steroidogenic tissues, but may include steroidogenic acute regulatory protein and the 18 kDa translocator protein, together with voltage-dependent anion channels, ATPase AAA domain containing protein 3A, and optic atrophy type 1 proteins. Certainly, overexpression of StAR and TSPO proteins can enhance macrophage cholesterol efflux to apoA-I and/or HDL, while perturbations in mitochondrial function, or changes in the expression of mitochondrial fusion proteins, alter the efficiency of cholesterol efflux. Molecules which can sustain or improve mitochondrial function or increase the activity of the protein complex involved in cholesterol transfer may have utility in resolving the problem of dysregulated macrophage cholesterol homeostasis, a condition which may contribute to inflammation, atherosclerosis, nonalcoholic steatohepatitis, osteoblastic bone resorption, and some disorders of the central nervous system."]
[26373900,1,0,0,1,2016,"A novel mutation in two Hmong families broadens the range of STRA6-related malformations to include contractures and camptodactyly.","Marcadier",26373900,"A novel mutation in two Hmong families broadens the range of STRA6-related malformations to include contractures and camptodactyly.    Abstract:   PDAC (also termed Matthew Wood) syndrome is a rare, autosomal recessive disorder characterized by pulmonary hypoplasia/aplasia, diaphragmatic defects, bilateral anophthalmia, and cardiac malformations. The disorder is caused by mutations in STRA6, an important regulator of vitamin A and retinoic acid metabolism. We describe six cases from four families of Hmong ancestry, seen over a 30 years period in California. These include: (i) consanguineous siblings with a combination of bilateral anophthalmia, diaphragmatic abnormalities, truncus arteriosus, and/or pulmonary agenesis/hypoplasia; (ii) a singleton fetus with bilateral anophthalmia, pulmonary agenesis, cardiac malformation, and renal hypoplasia; (iii) a sibling pair with a combination of antenatal contractures, camptodactyly, fused palpebral fissures, pulmonary agenesis, and/or truncus arteriosus; (iv) a fetus with bilateral anophthalmia, bushy eyebrows, pulmonary agenesis, heart malformation, and abnormal hand positioning. The phenotypic spectrum of PDAC syndrome has until now not included contractures or camptodactyly. Sequencing of STRA6 in unrelated members of families three and four identified a novel, shared homozygous splice site alteration (c.113 + 3_4delAA) that is predicted to be pathogenic. We hypothesize this may represent a unique disease allele in the Hmong. We also provide a focused review of all published PDAC syndrome cases with confirmed or inferred STRA6 mutations, illustrating the phenotypic and molecular variability that characterizes this disorder."]
[26342691,1,0,0,1,2015,"A new transcriptional variant and small azurophilic granules in an acute promyelocytic leukemia case with NPM1/RARA fusion gene.","Kikuma",26342691,"A new transcriptional variant and small azurophilic granules in an acute promyelocytic leukemia case with NPM1/RARA fusion gene.    Abstract:   We report here the first case of NPM1/RARA-positive acute promyelocytic leukemia (APL) preceded by myeloid sarcoma (MS) in the vertebra. A 52-year-old man was diagnosed with MS, as the tumor cells were positive for myeloperoxidase and CD68 but negative for CD163. After treatment with steroids and radiation, the size of the tumor was markedly reduced and peripheral blood count was normal. Bone marrow examination showed 89.2% consisted of unclassified promyelocytes characterized by round nuclei and abundant small azurophilic granules but no Auer rods. The results of chromosome analysis showed 46,XY,t(5;17)(q35;q12). Reverse-transcription polymerase chain reaction amplified the NPM1/RARA fusion transcripts derived from a combination of NPM1 exon 4 and RARA exon 5, or of NPM1 exon 1 and RARA exon 5; the latter of these has not been reported previously. Electron microscopic examination of the promyelocyte nuclei showed they were oval with mild nuclear chromatin condensation and small- to medium-sized nucleoli. Hematological and molecular complete remission was attained after induction therapy including all-trans retinoic acid. As MS was also diagnosed in two of the seven other reported cases of APL with NPM1/RARA, MS may occur more frequently in APL with NPM1/RARA than APL with PML/RARA."]
[26249743,2,0,0,2,2015,"How the embryo makes a limb: determination, polarity and identity.","Tickle",26249743,"How the embryo makes a limb: determination, polarity and identity.    Abstract:   The vertebrate limb with its complex anatomy develops from a small bud of undifferentiated mesoderm cells encased in ectoderm. The bud has its own intrinsic polarity and can develop autonomously into a limb without reference to the rest of the embryo. In this review, recent advances are integrated with classical embryology, carried out mainly in chick embryos, to present an overview of how the embryo makes a limb bud. We will focus on how mesoderm cells in precise locations in the embryo become determined to form a limb and express the key transcription factors Tbx4 (leg/hindlimb) or Tbx5 (wing/forelimb). These Tbx transcription factors have equivalent functions in the control of bud formation by initiating a signalling cascade involving Wnts and fibroblast growth factors (FGFs) and by regulating recruitment of mesenchymal cells from the coelomic epithelium into the bud. The mesoderm that will form limb buds and the polarity of the buds is determined with respect to both antero-posterior and dorso-ventral axes of the body. The position in which a bud develops along the antero-posterior axis of the body will also determine its identity - wing/forelimb or leg/hindlimb. Hox gene activity, under the influence of retinoic acid signalling, is directly linked with the initiation of Tbx5 gene expression in the region along the antero-posterior axis of the body that will form wings/forelimbs and determines antero-posterior polarity of the buds. In contrast, Tbx4 expression in the regions that will form legs/hindlimbs is regulated by the homeoprotein Pitx1 and there is no evidence that Hox genes determine antero-posterior polarity of the buds. Bone morphogenetic protein (BMP) signalling determines the region along the dorso-ventral axis of the body in which both wings/forelimbs and legs/hindlimbs develop and dorso-ventral polarity of the buds. The polarity of the buds leads to the establishment of signalling regions - the dorsal and ventral ectoderm, producing Wnts and BMPs, respectively, the apical ectodermal ridge producing fibroblast growth factors and the polarizing region, Sonic hedgehog (Shh). These signals are the same in both wings/forelimbs and legs/hindlimbs and control growth and pattern formation by providing the mesoderm cells of the limb bud as it develops with positional information. The precise anatomy of the limb depends on the mesoderm cells in the developing bud interpreting positional information according to their identity - determined by Pitx1 in hindlimbs - and genotype. The competence to form a limb extends along the entire antero-posterior axis of the trunk - with Hox gene activity inhibiting the formation of forelimbs in the interlimb region - and also along the dorso-ventral axis."]
[26123688,1,0,0,1,2015,"Temporally coordinated signals progressively pattern the anteroposterior and dorsoventral body axes.","Tuazon",26123688,"Temporally coordinated signals progressively pattern the anteroposterior and dorsoventral body axes.    Abstract:   The vertebrate body plan is established through the precise spatiotemporal coordination of morphogen signaling pathways that pattern the anteroposterior (AP) and dorsoventral (DV) axes. Patterning along the AP axis is directed by posteriorizing signals Wnt, fibroblast growth factor (FGF), Nodal, and retinoic acid (RA), while patterning along the DV axis is directed by bone morphogenetic proteins (BMP) ventralizing signals. This review addresses the current understanding of how Wnt, FGF, RA and BMP pattern distinct AP and DV cell fates during early development and how their signaling mechanisms are coordinated to concomitantly pattern AP and DV tissues."]
[26042120,1,0,0,1,2015,"Revisiting mouse peritoneal macrophages: heterogeneity, development, and function.","Cassado",26042120,"Revisiting mouse peritoneal macrophages: heterogeneity, development, and function.    Abstract:   Tissue macrophages play a crucial role in the maintenance of tissue homeostasis and also contribute to inflammatory and reparatory responses during pathogenic infection and tissue injury. The high heterogeneity of these macrophages is consistent with their adaptation to distinct tissue environments and specialization to develop niche-specific functions. Although peritoneal macrophages are one of the best-studied macrophage populations, recently it was demonstrated the co-existence of two subsets in mouse peritoneal cavity (PerC), which exhibit distinct phenotypes, functions, and origins. These macrophage subsets have been classified, according to their morphology, as large peritoneal macrophages (LPMs) and small peritoneal macrophages (SPMs). LPMs, the most abundant subset under steady state conditions, express high levels of F4/80 and low levels of class II molecules of the major histocompatibility complex (MHC). LPMs appear to be originated from embryogenic precursors, and their maintenance in PerC is regulated by expression of specific transcription factors and tissue-derived signals. Conversely, SPMs, a minor subset in unstimulated PerC, have a F4/80(low)MHC-II(high) phenotype and are generated from bone-marrow-derived myeloid precursors. In response to infectious or inflammatory stimuli, the cellular composition of PerC is dramatically altered, where LPMs disappear and SPMs become the prevalent population together with their precursor, the inflammatory monocyte. SPMs appear to be the major source of inflammatory mediators in PerC during infection, whereas LPMs contribute for gut-associated lymphoid tissue-independent and retinoic acid-dependent IgA production by peritoneal B-1 cells. In the previous years, considerable efforts have been made to broaden our understanding of LPM and SPM origin, transcriptional regulation, and functional profile. This review addresses these issues, focusing on the impact of tissue-derived signals and external stimulation in the complex dynamics of peritoneal macrophage populations."]
[25929900,1,0,0,1,2015,"Congenital scoliosis in Smith-Magenis syndrome: a case report and review of the literature.","Li",25929900,"Congenital scoliosis in Smith-Magenis syndrome: a case report and review of the literature.    Abstract:   The Smith-Magenis syndrome (SMS) is a complex and rare congenital condition that is characterized by minor craniofacial anomalies, short stature, sleep disturbances, behavioral, and neurocognitive abnormalities, as well as variable multisystemic manifestations. Little is reported about spinal deformity associated with this syndrome.This study is to present a case of scoliosis occurring in the setting of SMS and explore the possible mechanisms between the 2 diseases.The patient is a 13-year-old Chinese female with congenital scoliosis and Tetralogy of Fallot, mental retardation, obstructive sleep apnea, hypertrophy of tonsil, conductive hearing loss, and agenesis of the epiglottis. An interphase fluorescent in situ hybridization at chromosome 17p11.2 revealed a heterozygous deletion, confirming a molecular diagnosis of SMS. She underwent a posterior correction at thoracic 1-lumbar 1 (T1-L1) levels, using the Moss-SI spinal system. At 6-month follow-up, the patient was clinically pain free and well balanced. Plain radiographs showed solid spine fusion with no loss of correction.Congenital cardiac disease, immunodeficiency, and severe behavioral problems can affect the surgical outcome following spine fusion and need to be taken into consideration for the surgeon and anesthesiologist. Scoliosis is not uncommon among patients with SMS, and there is a potential association between congenital scoliosis and SMS. The potential mechanisms in the pathogenesis of congenital scoliosis of SMS included retinoic acid-induced 1 (RAI1) microdeletion and RAI1 gene point mutation."]
[25929514,1,0,0,1,2015,"Signaling networks organizing regenerative growth of the zebrafish fin.","Wehner",25929514,"Signaling networks organizing regenerative growth of the zebrafish fin.    Abstract:   In contrast to mammals, adult salamanders and fish can completely regenerate their appendages after amputation. The cellular and molecular mechanisms underlying this fascinating phenomenon are beginning to emerge, including substantial progress in the identification of signals that control regenerative growth of the zebrafish caudal fin. Despite the fairly simple architecture of the fin, the regulation of its regeneration is complex. Many signals, including fibroblast growth factor (FGF), Wnt, Hedgehog (Hh), retinoic acid (RA), Notch, bone morphogenic protein (BMP), activin, and insulin-like growth factor (IGF), are required for regeneration. Much work needs to be done to dissect tissue-specific functions of these pathways and how they interact, but Wnt/β-catenin signaling is already emerging as a central player. Surprisingly, Wnt/β-catenin signaling appears to largely indirectly control epidermal patterning, progenitor cell proliferation, and osteoblast maturation via regulation of a multitude of secondary signals."]
[25879031,13,0,0,13,2015,"Vitamin A, cancer treatment and prevention: the new role of cellular retinol binding proteins.","Doldo",25879031,"Vitamin A, cancer treatment and prevention: the new role of cellular retinol binding proteins.    Abstract:   Retinol and vitamin A derivatives influence cell differentiation, proliferation, and apoptosis and play an important physiologic role in a wide range of biological processes. Retinol is obtained from foods of animal origin. Retinol derivatives are fundamental for vision, while retinoic acid is essential for skin and bone growth. Intracellular retinoid bioavailability is regulated by the presence of specific cytoplasmic retinol and retinoic acid binding proteins (CRBPs and CRABPs). CRBP-1, the most diffuse CRBP isoform, is a small 15 KDa cytosolic protein widely expressed and evolutionarily conserved in many tissues. CRBP-1 acts as chaperone and regulates the uptake, subsequent esterification, and bioavailability of retinol. CRBP-1 plays a major role in wound healing and arterial tissue remodelling processes. In the last years, the role of CRBP-1-related retinoid signalling during cancer progression became object of several studies. CRBP-1 downregulation associates with a more malignant phenotype in breast, ovarian, and nasopharyngeal cancers. Reexpression of CRBP-1 increased retinol sensitivity and reduced viability of ovarian cancer cells in vitro. Further studies are needed to explore new therapeutic strategies aimed at restoring CRBP-1-mediated intracellular retinol trafficking and the meaning of CRBP-1 expression in cancer patients screening for a more personalized and efficacy retinoid therapy."]
[25860246,0,0,0,0,2015,"Outcomes of acute myeloid leukemia with t(15;17) not associated with acute promyelocytic leukemia.","Soni",25860246,"Outcomes of acute myeloid leukemia with t(15;17) not associated with acute promyelocytic leukemia.    Abstract:  "]
[25816151,2,0,0,2,2015,"Retinoic acid-related orphan receptor RORβ, circadian rhythm abnormalities and tumorigenesis (Review).","Feng",25816151,"Retinoic acid-related orphan receptor RORβ, circadian rhythm abnormalities and tumorigenesis (Review).    Abstract:   Nuclear receptors are a superfamily of transcription factors including the steroid hormone receptors, non-steroid hormone receptors and the orphan nuclear receptor family. Retinoic acid-related orphan receptor (ROR)β, as a member of the orphan nuclear receptor family, plays an important regulatory role in the maintenance of a variety of physiological and pathological processes. RORβ has been determined to act as an osteogenic repressor in regulating bone formation, and is involved in regulating circadian rhythm. The findings of recent studies concerning the association between tumorigenesis and circadian rhythm have shown that an aberrant circadian rhythm may promote tumorigenesis and tumor progression. The mechanisms discussed in this review demonstrate how aberrant RORβ-induced circadian rhythm may become a new direction for future studies on tumorigenesis and strategy design for cancer prevention."]
[25815127,1,0,0,1,2015,"Neural differentiation from embryonic stem cells in vitro: An overview of the signaling pathways.","Chuang",25815127,"Neural differentiation from embryonic stem cells in vitro: An overview of the signaling pathways.    Abstract:   Neurons derived from embryonic stem cells (ESCs) have gained great merit in both basic research and regenerative medicine. Here we review and summarize the signaling pathways that have been reported to be involved in the neuronal differentiation of ESCs, particularly those associated with in vitro differentiation. The inducers and pathways explored include retinoic acid, Wnt/β-catenin, transforming growth factor/bone morphogenetic protein, Notch, fibroblast growth factor, cytokine, Hedgehog, c-Jun N-terminal kinase/mitogen-activated protein kinase and others. Some other miscellaneous molecular factors that have been reported in the literature are also summarized and discussed. These include calcium, calcium receptor, calcineurin, estrogen receptor, Hox protein, ceramide, glycosaminioglycan, ginsenoside Rg1, opioids, two pore channel 2, nitric oxide, chemically defined medium, cell-cell interactions, and physical stimuli. The interaction or crosstalk between these signaling pathways and factors will be explored. Elucidating these signals in detail should make a significant contribution to future progress in stem cell biology and allow, for example, better comparisons to be made between differentiation in vivo and in vitro. Of equal importance, a comprehensive understanding of the pathways that are involved in the development of neurons from ESCs in vitro will also accelerate their application as part of translational medicine."]
[25814978,7,0,0,7,2015,"Retinoid receptors in bone and their role in bone remodeling.","Henning",25814978,"Retinoid receptors in bone and their role in bone remodeling.    Abstract:   Vitamin A (retinol) is a necessary and important constituent of the body which is provided by food intake of retinyl esters and carotenoids. Vitamin A is known best for being important for vision, but in addition to the eye, vitamin A is necessary in numerous other organs in the body, including the skeleton. Vitamin A is converted to an active compound, all-trans-retinoic acid (ATRA), which is responsible for most of its biological actions. ATRA binds to intracellular nuclear receptors called retinoic acid receptors (RARα, RARβ, RARγ). RARs and closely related retinoid X receptors (RXRα, RXRβ, RXRγ) form heterodimers which bind to DNA and function as ligand-activated transcription factors. It has been known for many years that hypervitaminosis A promotes skeleton fragility by increasing osteoclast formation and decreasing cortical bone mass. Some epidemiological studies have suggested that increased intake of vitamin A and increased serum levels of retinoids may decrease bone mineral density and increase fracture rate, but the literature on this is not conclusive. The current review summarizes how vitamin A is taken up by the intestine, metabolized, stored in the liver, and processed to ATRA. ATRAs effects on formation and activity of osteoclasts and osteoblasts are outlined, and a summary of clinical data pertaining to vitamin A and bone is presented."]
[25742431,0,0,0,0,2015,"Nutritional status in children with Shwachman-diamond syndrome.","Pichler",25742431,"Nutritional status in children with Shwachman-diamond syndrome.    Abstract:    OBJECTIVE : In Shwachman-Diamond syndrome (SDS), pancreatic insufficiency can lead to malabsorption of fat-soluble vitamins and trace elements. The aim of this study was to assess the serum concentrations of vitamins A and E, zinc, copper, and selenium and their deficiencies.  METHODS : This retrospective review was performed in 21 children (12 were male; median age, 7.8 years) with genetically confirmed SDS at a tertiary pediatric hospital. Pancreatic enzyme replacement therapy (PERT) and vitamin or trace elements supplements were documented.  RESULTS : Twenty patients (95%) had pancreatic insufficiency receiving PERT, 10 (47%) had a combined vitamin and trace element deficiency, 6 (29%) had an isolated vitamin deficiency, and 4 (19%) had an isolated trace element deficiency. Vitamins A and E deficiency occurred in 16 (76%) and 4 (19%) of 21, respectively. Low serum selenium was found in 10 (47%), zinc deficiency in 7 (33%), and copper deficiency in 5 (24%). Eleven patients (52%) were on multivitamin supplementation, and 2 (10%) on zinc and selenium supplements. No statistical differences were found between repeated measurements for all micronutrients.  CONCLUSIONS : More than 50% of the children had vitamin A and selenium deficiencies despite adequate supplementation of PERT and supplements. Micronutrients should be routinely measured in SDS patients to prevent significant complications."]
[25643123,1,0,0,1,2016,"Mesenchymal Stem Cells and C-type Natriuretic Peptide Signaling: A Proposal for a New Treatment Approach for Skeletal Dysplasias.","Serkant Unal",25643123,"Mesenchymal Stem Cells and C-type Natriuretic Peptide Signaling: A Proposal for a New Treatment Approach for Skeletal Dysplasias.    Abstract:    NlmCategory=UNASSIGNEDEndochondral ossification is under the regulation of endocrine, paracrine and otocrine factors including transforming growth factor-amp;amp;#946; superfamily members, fibroblast growth factors, retinoids, products of hedgehog gene, parathyroid hormone-related peptide, molecules involved in cell adhesion, and extracellular matrix components. Natriuretic peptide receptor-B, and its ligand C-type natriuretic peptide have also been implicated in the regulation of limb bone development. Results of recent studies are promising in terms of systemic elevation of C-type natriuretic peptide level inducing growth. In addition, same strategy also overcomes the dwarf phenotype of achondroplasia, the most frequently seen skeletal dysplasia in human, in a mouse model. Based on this literature and a series of recent experiments discussed here, this perspective underlines the abundant C-type natriuretic peptide expression in trabecular bone derived mesenchymal stem cells of human, chicken, and rat origin, and proposes the potential use of mesenchymal stem cells as a part of growth inducing treatment strategy in osteochondrodisyplasias in the future."]
[25641139,0,0,0,0,2015,"[Acute promyelocytic leukaemia with translocations of t(15;17)(q22;q21) and rob(13;21): a case report and literatures review].","Zheng",25641139,"[Acute promyelocytic leukaemia with translocations of t(15;17)(q22;q21) and rob(13;21): a case report and literatures review].    Abstract:    OBJECTIVE : To report an acute promyelocytic leukaemia (APL) case with translocation of rob (13;21) t(15;17) (q22;q21) and review its clinical and laboratory characteristics.  METHODS : Based on routine karyotype analysis and bone marrow morphology, we further used double color double fluorescent in situ hybridization (DCDF-FISH) and reverse transcriptase PCR (RT-PCR) to examine the patients abnormities on cytogenetic and molecular biology, and reveal the clinical characteristics of this rare translocation also from the related literatures.  RESULTS : The clinical manifestation and bone marrow morphology examination of this patient were in accordance with pathologic feature of APL. On first visit, immunophenotyping analysis showed positive myeloid markers. Through R-banding, the patients karyotype was confirmed as 45, XX, rob(13;21) t(15;17) (q22;q21) [6]/45, XX, rob(13;21) [14]. FISH results showed that 68.9% cells were typical t(15;17) pattern. The positive rates of fusion gene of PML-RARα detected by RT-PCR was 25.8%. Patient was treated by induction and consolidation therapy, the karyotype was 45, XX, rob(13;21 )[20] after complete remission. The positive rate of fusion gene of PML-RARα by FISH and its level were 2.5% and 0.003% respectively.  CONCLUSION : APL with rob (13;21) t(15;17) (q22;q21) was very rare, which was accorded with clinical and laboratory characteristics of APL. The value of chromosome abnormality as a prognostic marker in APL needs to be further observed.."]
[25634649,9,0,0,9,2015,"Retinoic acid post consolidation therapy for high-risk neuroblastoma patients treated with autologous hematopoietic stem cell transplantation.","Peinemann",25634649,"Retinoic acid post consolidation therapy for high-risk neuroblastoma patients treated with autologous hematopoietic stem cell transplantation.    Abstract:    BACKGROUND : Neuroblastoma is a rare malignant disease and mainly affects infants and very young children. The tumors mainly develop in the adrenal medullary tissue and an abdominal mass is the most common presentation. About 50% of patients have metastatic disease at diagnosis. The high-risk group is characterized by metastasis and other characteristics that increase the risk for an adverse outcome. High-risk patients have a five-year event-free survival of less than 50%. Retinoic acid has been shown to inhibit growth of human neuroblastoma cells and has been considered as a potential candidate for improving the outcome of patients with high-risk neuroblastoma.  OBJECTIVES : To evaluate efficacy and adverse events of retinoic acid after consolidation with high-dose chemotherapy followed by bone marrow transplantation as compared to placebo or no therapy in patients with high-risk neuroblastoma (as defined by the International Neuroblastoma Risk Group (INRG) classification system). Our outcomes of interest were overall survival and treatment-related mortality as primary outcomes; and progression- and event-free survival, early and late toxicity, and health-related quality of life as secondary outcomes.  SEARCH METHODS : We searched the electronic databases CENTRAL (2014, Issue 8) on The Cochrane Library, MEDLINE (1946 to October 2014), and EMBASE (1947 to October 2014). Further searches included trial registries, conference proceedings, and reference lists of recent reviews and relevant articles. We did not apply limits on publication year or languages.  SELECTION CRITERIA : Randomized controlled trials (RCTs) evaluating retinoic acid post consolidation therapy for high-risk neuroblastoma patients treated with autologous hematopoietic stem cell transplantation (HSCT) compared to placebo or no further treatment.  DATA COLLECTION AND ANALYSIS : Two review authors performed the study selection, extracted the data on study and patient characteristics and assessed the risk of bias independently. We resolved differences by discussion or by appeal to a third review author. We performed analyses according to the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions. The authors of the included study did not report the results specifically for the treatment groups relevant to this Cochrane Review. Therefore, we deduced the appropriate survival data from the published survival curves and calculated a hazard ratio (HR) based on the deduced data.  MAIN RESULTS : We identified one RCT (CCG-3891) that included patients with high-risk neuroblastoma who received high-dose chemotherapy followed by autologous HSCT (N = 98) after a first random allocation and who received retinoic acid (13-cis-retinoic acid; N = 50) or no further therapy (N = 48) after a subsequent second random allocation. These patients had no progressive disease after consolidation therapy. There was no clear evidence of difference between the treatment groups in both overall survival (HR 0.87, 95% CI 0.46 to 1.63; one trial; P = 0.66, low quality of evidence) and event-free survival (HR 0.86, 95% CI 0.50 to 1.49; one trial; P = 0.59, low quality of evidence). We calculated these HR values using the complete follow-up period of the trial. The study also reported five-year overall survival rates: 59% for the retinoic acid group and 41% for the no further therapy group (P value not reported). We did not identify results for treatment-related mortality, progression-free survival, early or late toxicity, or health-related quality of life. Also, we could not rule out the possible presence of selection bias, performance bias, attrition bias, and other bias.  AUTHORS CONCLUSIONS : We identified one RCT that evaluated retinoic acid as a consolidation therapy versus no further therapy after high-dose chemotherapy followed by bone-marrow transplantation in patients with high-risk neuroblastoma. The difference in overall survival and event-free survival between both treatment alternatives was not statistically significantly different. This could be the result of low power. Information on other outcomes was not available. This trial was performed in the 1990s, since then many changes in for example treatment and risk classification have occurred. Therefore, based on the currently available evidence, we are uncertain about the effects of retinoic acid in patients with high-risk neuroblastoma. More research is needed for a definitive conclusion."]
[25625930,0,0,0,0,2014,"Mechanisms and pathways of innate immune activation and regulation in health and cancer.","Cui",25625930,"Mechanisms and pathways of innate immune activation and regulation in health and cancer.    Abstract:   Research on innate immune signaling and regulation has recently focused on pathogen recognition receptors (PRRs) and their signaling pathways. Members of PRRs sense diverse microbial invasions or danger signals, and initiate innate immune signaling pathways, leading to proinflammatory cytokines production, which, in turn, instructs adaptive immune response development. Despite the diverse functions employed by innate immune signaling to respond to a variety of different pathogens, the innate immune response must be tightly regulated. Otherwise, aberrant, uncontrolled immune responses will lead to harmful, or even fatal, consequences. Therefore, it is essential to better discern innate immune signaling and many regulators, controlling various signaling pathways, have been identified. In this review, we focus on the recent advances in our understanding of the activation and regulation of innate immune signaling in the host response to pathogens and cancer."]
[25618772,1,0,0,1,2016,"Interactions of vitamin D and the proximal tubule.","Chesney",25618772,"Interactions of vitamin D and the proximal tubule.    Abstract:   Severe vitamin D deficiency (reduction in serum 25(OH)D concentration) in infants and children can cause features of the Fanconi syndrome, including phosphaturia, glycosuria, aminoaciduria, and renal tubular acidosis. This indicates that vitamin D and its metabolites influence proximal tubule function. Filtered 25(OH)D bound to vitamin D binding protein (DBP) is endocytosed by megalin-cubilin in the apical membrane. Intracellular 25(OH)D is metabolized to 1,25(OH)2D or calcitroic acid by 1-α-hydroxylase or 24-hydroxylase in tubule cell mitochondria. Bone-produced fibroblast growth factor 23 (FGF23) bound to Klotho in tubule cells and intracellular phosphate concentrations are regulators of 1-α-hydroxylase activity and cause proximal tubule phosphaturia. Aminoaciduria occurs when amino acid transporter synthesis is deficient, and 1,25(OH)2D along with retinoic acid up-regulate transporter synthesis by a vitamin D response element in the promoter region of the transporter gene. This review discusses evidence gained from studies in animals or cell lines, as well as from human disorders, that provide insight into vitamin D-proximal tubule interactions."]
[25548520,0,0,0,0,2014,"The clinical use of regenerative therapy in COPD.","Lipsi",25548520,"The clinical use of regenerative therapy in COPD.    Abstract:   Regenerative or stem cell therapy is an emerging field of treatment based on stimulation of endogenous resident stem cells or administration of exogenous stem cells to treat diseases or injury and to replace malfunctioning or damaged tissues. Current evidence suggests that in the lung, these cells may participate in tissue homeostasis and regeneration after injury. Animal and human studies have demonstrated that tissue-specific stem cells and bone marrow-derived cells contribute to lung tissue regeneration and protection, and thus administration of exogenous stem/progenitor cells or humoral factors responsible for the activation of endogenous stem/progenitor cells may be a potent next-generation therapy for chronic obstructive pulmonary disease. The use of bone marrow-derived stem cells could allow repairing and regenerate the damaged tissue present in chronic obstructive pulmonary disease by means of their engraftment into the lung. Another approach could be the stimulation of resident stem cells by means of humoral factors or photobiostimulation."]
[25546246,3,0,0,3,2015,"Treatment of keratitis-ichthyosis- deafness (KID) syndrome in children: a case report and review of the literature.","Patel",25546246,"Treatment of keratitis-ichthyosis- deafness (KID) syndrome in children: a case report and review of the literature.    Abstract:   Keratitis-ichthyosis-deafness (KID) syndrome is a rare hereditary cornification disorder resulting from mutations in connexin 26, a protein important for intercellular communication. In addition to the characteristic clinical triad of congenital bilateral sensorineural hearing loss, keratitis, and erythrokeratoderma, affected individuals also suffer from chronic bacterial and fungal infections and have an increased risk of benign and malignant cutaneous tumors. Treatments with antibiotics, antifungals, and systemic retinoids have been reported with variable response. Ocular and skeletal toxicity from prolonged exposure to systemic retinoids is a major concern especially in children. We report a case of a 7-year-old boy with KID syndrome complicated by frequent infections who responded well to acitretin 0.5-1.0 mg/kg/day. The patient had significant improvement of the hyperkeratosis on the scalp, trunk, and extremities within 4 weeks after initiating treatment. The patient has been on treatment for over a year without notable ocular, skeletal, or laboratory side effects. A review of the literature focusing on therapeutic options for KID syndrome and concerns about safety and tolerability is presented."]
[25546083,1,0,0,1,2015,"Cisplatin resistance in germ cell tumours: models and mechanisms.","Jacobsen",25546083,"Cisplatin resistance in germ cell tumours: models and mechanisms.    Abstract:   Recent years have led to a better understanding of the mechanisms underlying cisplatin response and resistance in germ cell tumours (GCT), and several promising targets have been identified. Two main mechanisms of the responsiveness to DNA damaging agents have been postulated. Firstly, GCT readily activate a DNA damage response, but show deficits in several damage repair pathways. In particular, they have been found to have defects in interstrand crosslink repair and in homologous recombination (HR). Secondly, GCT, especially embryonal carcinoma (EC) cells, show a hypersensitive apoptotic response to DNA damage, which activates p53, and leads to up-regulation of the pro-apoptotic factors Noxa, Puma and Fas in non-resistant EC. These cells fail to activate p21 which induces a G1/S arrest, but accumulate in G2/M phase. In the absence of functional p53, family members like p73 and GTAp63 might be important in initiating this response. Mechanisms involved in cisplatin resistance are as follows: down-regulation of Oct4 (e.g. as a result of hypoxia, treatment with retinoic acid or exposure to cisplatin) and failure to induce Puma and Noxa; changes in the expression levels of micro-RNAs such as miR-17/-106b, miR-302a, or miR-371 to -373; elevated levels of MDM2 and cytoplasmic translocation of p21 by phosphorylation; and activation of the PDGFRβ/PI3K/pAKT pathway. Several approaches to overcome resistance have been successfully examined in vitro and in vivo, including PARP inhibitors, especially in cells showing deficient HR-repair; stabilization of p53 using nutlin-3; inhibition of several components of the PI3K/pAKT pathway using small molecules; and DNA demethylation by 5-azacytidine or 5-aza-deoxy-cytidine, among others. Many of these substances deserve further exploration, alone or in combination with DNA damaging agents, and the most promising approaches should be taken forward to clinical testing. Targeted therapy based on mechanistic insights holds the promise to turn cisplatin-resistant GCT into a curable disease."]
[25526563,1,0,0,1,2014,"Recent developments in β-cell differentiation of pluripotent stem cells induced by small and large molecules.","Kumar",25526563,"Recent developments in β-cell differentiation of pluripotent stem cells induced by small and large molecules.    Abstract:   Human pluripotent stem cells, including human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), hold promise as novel therapeutic tools for diabetes treatment because of their self-renewal capacity and ability to differentiate into beta (β)-cells. Small and large molecules play important roles in each stage of β-cell differentiation from both hESCs and hiPSCs. The small and large molecules that are described in this review have significantly advanced efforts to cure diabetic disease. Lately, effective protocols have been implemented to induce hESCs and human mesenchymal stem cells (hMSCs) to differentiate into functional β-cells. Several small molecules, proteins, and growth factors promote pancreatic differentiation from hESCs and hMSCs. These small molecules (e.g., cyclopamine, wortmannin, retinoic acid, and sodium butyrate) and large molecules (e.g. activin A, betacellulin, bone morphogentic protein (BMP4), epidermal growth factor (EGF), fibroblast growth factor (FGF), keratinocyte growth factor (KGF), hepatocyte growth factor (HGF), noggin, transforming growth factor (TGF-α), and WNT3A) are thought to contribute from the initial stages of definitive endoderm formation to the final stages of maturation of functional endocrine cells. We discuss the importance of such small and large molecules in uniquely optimized protocols of β-cell differentiation from stem cells. A global understanding of various small and large molecules and their functions will help to establish an efficient protocol for β-cell differentiation."]
[25483334,1,0,0,1,2014,"Re-thinking the functions of IgA(+) plasma cells.","Gommerman",25483334,"Re-thinking the functions of IgA(+) plasma cells.    Abstract:   The intestinal mucosa harbors the largest population of antibody (Ab)-secreting plasma cells (PC) in the human body, producing daily several grams of immunoglobulin A (IgA). IgA has many functions, serving as a first-line barrier that protects the mucosal epithelium from pathogens, toxins and food antigens (Ag), shaping the intestinal microbiota, and regulating host-commensal homeostasis. Signals induced by commensal colonization are central for regulating IgA induction, maintenance, positioning and function and the number of IgA(+) PC is dramatically reduced in neonates and germ-free (GF) animals. Recent evidence demonstrates that the innate immune effector molecules tumor necrosis factor α (TNFα) and inducible nitric oxide synthase (iNOS) are required for IgA(+) PC homeostasis during the steady state and infection. Moreover, new functions ascribed to PC independent of Ab secretion continue to emerge, suggesting that PC, including IgA(+) PC, should be re-examined in the context of inflammation and infection. Here, we outline mechanisms of IgA(+) PC generation and survival, reviewing their functions in health and disease."]
[25241337,2,0,0,2,2015,"Essential role for CD103+ cells in the pathogenesis of spondyloarthritides.","Berthelot",25241337,"Essential role for CD103+ cells in the pathogenesis of spondyloarthritides.    Abstract:   The clinical features of spondyloarthritides include extraarticular manifestations involving the skin, eyes, and gastrointestinal tract. At these sites, a membrane integrin can be acquired by virtue of the presence of CD4+ T cells and specific dendritic cells and correlates with a regulatory behavior of these cells. This membrane integrin conjugates the beta7 subunit and the alphaE subunit, also known as CD103. CD103 expression requires high levels of TGF-beta and retinoic acid; in addition, expression of CD103 by T cells requires antigen recognition. Whether CD103 is found in the entheses has not yet been investigated. CD103 is expressed at high levels in the skin, eyes, and bowel but it is found in only very low levels in the bloodstream. CD8+ CD103+ T cells differ markedly from other CD103+ cells in that they are resident cells with no tendency to migrate and usually exert predominantly cytotoxic functions as opposed to regulatory functions. Several bacteria, such as Salmonella, can become dormant within the mucous membranes and/or their lymph nodes, where they use CD103+ dendritic cells and CD4+ CD103+ regulatory T cells (Tregs) to evade the immune response. This phenomenon could be studied in other tissues targeted by spondyloarthritides, where dormant microorganisms can migrate by using M2 macrophages as Trojan horses, since M2 macrophages express the CD103 ligand E-cadherin. Microorganism peptide recognition by CD8+ CD103+ T cells (which are overrepresented in psoriasis and joint fluid in some forms of spondyloarthritis) induces an inflammatory response that may be sufficient to transiently reverse the regulatory function of the CD103+ dendritic cells and CD4+ CD103+ T cells during disease flares. The sensitivity of these diseases to retinoids further supports a pathogenic role for transient CD103+ cell failure."]
[25040109,1,0,0,1,2015,"Signaling regulating inner ear development: cell fate determination, patterning, morphogenesis, and defects.","Nakajima",25040109,"Signaling regulating inner ear development: cell fate determination, patterning, morphogenesis, and defects.    Abstract:   The membranous labyrinth of the inner ear is a highly complex organ that detects sound and balance. Developmental defects in the inner ear cause congenital hearing loss and balance disorders. The membranous labyrinth consists of three semicircular ducts, the utricle, saccule, and endolymphatic ducts, and the cochlear duct. These complex structures develop from the simple otic placode, which is established in the cranial ectoderm adjacent to the neural crest at the level of the hindbrain at the early neurula stage. During development, the otic placode invaginates to form the otic vesicle, which subsequently gives rise to neurons for the vestibulocochlear ganglion, the non-sensory and sensory epithelia of the membranous labyrinth that includes three ampullary crests, two maculae, and the organ of Corti. Combined paracrine and autocrine signals including fibroblast growth factor, Wnt, retinoic acid, hedgehog, and bone morphogenetic protein regulate fate determination, axis formation, and morphogenesis in the developing inner ear. Juxtacrine signals mediated by Notch pathways play a role in establishing the sensory epithelium, which consists of mechanosensory hair cells and supporting cells. The highly differentiated organ of Corti, which consists of uniformly oriented inner/outer hair cells and specific supporting cells, develops during fetal development. Developmental alterations/arrest causes congenital malformations in the inner ear in a spatiotemporal-restricted manner. A clearer understanding of the mechanisms underlying inner ear development is important not only for the management of patients with congenital inner ear malformations, but also for the development of regenerative therapy for impaired function."]
[24975339,1,0,0,1,2014,"[T315I positive promyelocytic crisis of chronic myeloid leukemia].","Yamamoto",24975339,"[T315I positive promyelocytic crisis of chronic myeloid leukemia].    Abstract:   Promyelocytic crisis (PMC) of chronic myelogenous leukemia (CML) is relatively rare. We report a patient who progressed to PMC with a T315I mutation during the initial treatment with dasatinib for CML. He obtained hematological remission after combination therapy with all-trans retinoic acid and chemotherapy for PMC, and PML-RARA was not detected by FISH analysis. Arsenic trioxide (ATO) and imatinib therapy induced a second complete cytogenetic response, and PML-RARA mRNA detected by real-time quantitative RT-PCR dropped below the detection limit. Finally, allogeneic stem cell transplantation was performed. This case suggests that combination therapy with imatinib and ATO achieves favorable outcomes for PMC."]
[24959581,1,0,0,1,2014,"The ECM-cell interaction of cartilage extracellular matrix on chondrocytes.","Gao",24959581,"The ECM-cell interaction of cartilage extracellular matrix on chondrocytes.    Abstract:   Cartilage extracellular matrix (ECM) is composed primarily of the network type II collagen (COLII) and an interlocking mesh of fibrous proteins and proteoglycans (PGs), hyaluronic acid (HA), and chondroitin sulfate (CS). Articular cartilage ECM plays a crucial role in regulating chondrocyte metabolism and functions, such as organized cytoskeleton through integrin-mediated signaling via cell-matrix interaction. Cell signaling through integrins regulates several chondrocyte functions, including differentiation, metabolism, matrix remodeling, responses to mechanical stimulation, and cell survival. The major signaling pathways that regulate chondrogenesis have been identified as wnt signal, nitric oxide (NO) signal, protein kinase C (PKC), and retinoic acid (RA) signal. Integrins are a large family of molecules that are central regulators in multicellular biology. They orchestrate cell-cell and cell-matrix adhesive interactions from embryonic development to mature tissue function. In this review, we emphasize the signaling molecule effect and the biomechanics effect of cartilage ECM on chondrogenesis."]
[24939557,10,0,0,10,2015,"Could retinoids be a potential treatment for rheumatic diseases?","Miyabe",24939557,"Could retinoids be a potential treatment for rheumatic diseases?    Abstract:   Retinoid, a derivative of vitamin A, is a general term used to describe compounds that bind to and activate retinoic acid receptors [RARs (RARα, RARβ, and RARγ)] and/or retinoid X receptors [RXRs (RXRα, RXRβ, and RXRγ)]. They have been shown to surpress the differentiation of Th1/Th17 cells and induce the development of Th1/regulatory T cells. They also affect the proliferation of B cells as both an inducer and suppressor. Furthermore, retinoids may induce the maturation of dendritic cells and production of interleukin-10 from monocytes/macrophages. We recently demonstrated that retinoids suppressed the production of reactive oxygen species, the release of elastase from neutrophils by inhibiting mitogen-activated protein kinase signals, and both the migration speed and chemotaxis directionality of neutrophils. Retinoids, such as all-trans retinoic acid and tamibarotene, were previously shown to have positive effects on animal models of several rheumatic diseases, including arthritis, myositis, and vasculitis in vivo. Moreover, retinoids have been used in a pilot study to effectively treat patients with lupus nephritis and systemic sclerosis. We herein reviewed the effects of retinoids on immune cells, animal models of rheumatic diseases, and rheumatic patients."]
[24935219,1,0,0,1,2014,"Embryological signaling pathways in Barretts metaplasia development and malignant transformation; mechanisms and therapeutic opportunities.","Pavlov",24935219,"Embryological signaling pathways in Barretts metaplasia development and malignant transformation; mechanisms and therapeutic opportunities.    Abstract:   Barretts metaplasia of the esophagus (BE) is the precursor lesion of esophageal adenocarcinoma (EAC), a deadly disease with a 5-year overall survival of less than 20%. The molecular mechanisms of BE development and its transformation to EAC are poorly understood and current surveillance and treatment strategies are of limited efficacy. Increasing evidence suggests that aberrant signaling through pathways active in the embryological development of the esophagus contributes to BE development and progression to EAC. We discuss the role that the Bone morphogenetic protein, Hedgehog, Wingless-Type MMTV Integration Site Family (WNT) and Retinoic acid signaling pathways play during embryological development of the esophagus and their contribution to BE development and malignant transformation. Modulation of these pathways provides new therapeutic opportunities. By integrating findings in developmental biology with those from translational research and clinical trials, this review provides a platform for future studies aimed at improving current management of BE and EAC."]
[24933850,0,0,0,0,2014,"Palmoplantar papules and hyperkeratosis in a deaf man.","Taylor",24933850,"Palmoplantar papules and hyperkeratosis in a deaf man.    Abstract:   A 31-year-old man presented with a history of extensive thickened skin of the palms and soles since the age of 7. The patient reported difficulty in ambulating and in using his hands secondary to his skin condition and associated pain. He also reported being seen by numerous specialists in the past for his hands, feet, and fingernails. He tried various topical medications, none of which were successful in minimizing the lesions on the hands and feet. Pertinent review of systems was positive for complete deafness diagnosed at 9 months of age. The patient did not speak and used sign language to communicate. His family history was significant for two brothers, both of whom are deaf and who have a similar skin condition of their hands and feet, but with lesser severity than the patient. The patient had no other medical issues."]
[24928143,3,0,0,3,2015,"ZebRA: An overview of retinoic acid signaling during zebrafish development.","Samarut",24928143,"ZebRA: An overview of retinoic acid signaling during zebrafish development.    Abstract:   Retinoic acid (RA), the main active vitamin A derivative, is crucial for embryo development, regulating cellular processes, embryo patterning and organogenesis. Many studies performed in mammalian or avian models have successfully undertaken the investigation of the role played by RA during embryogenesis. Since the early 1980s, the zebraﬁsh (Danio rerio) has emerged as a powerful developmental model to study the in vivo role of RA during embryogenesis. Unlike mammalian models, zebraﬁsh embryogenesis is external, not only allowing the observation of the translucent embryo from the earliest steps but also providing an easily accessible system for pharmacological treatment or genetic approaches. Therefore, zebraﬁsh research largely participates in deciphering the role of RA during development. This review aims at illustrating different concepts of RA signaling based on the research performed on zebraﬁsh. Indeed, RA action relies on a multitude of cross-talk with other signaling pathways and requires a coordinated, dynamic and ﬁne-regulation of its level and activity in both temporal and spatial dimensions. This review also highlights major advances that have been discovered using zebraﬁsh such as the observation of the RA gradient in vivo for the ﬁrst time, the effects of RA signaling in brain patterning, its role in establishing left-right asymmetry and its effects on the development of a variety of organs and tissues including the heart, blood, bone and fat. This review demonstrates that the zebraﬁsh is a convenient and powerful model to study retinoic acid signaling during vertebrate embryogenesis. This article is part of a Special Issue entitled: Nuclear receptors in animal development."]
[24907019,0,0,0,0,2014,"Treatment of paediatric APL: how does the therapeutic approach differ from adults?","Kutny",24907019,"Treatment of paediatric APL: how does the therapeutic approach differ from adults?    Abstract:   Acute promyelocytic leukaemia (APL) in children and adolescents shares many features with APL in adults. There are important distinctions, however, between these age groups in the presentation, complications and treatment outcomes. Paediatric patients are more likely to present with high risk features including elevated WBC count or microgranular variant (M3v). Yet the early death rate is lower in paediatric patients compared to adult patients. Overall outcomes such as CR, OS and EFS appear similar in paediatric and adult patients treated on similar regimens except that very young children may have a higher risk of relapse. While contemporary studies have clearly demonstrated improved survival in adults receiving ATO therapy, currently there is more limited data on the role of ATO in paediatric patients. Here we highlight the similarities and important distinctions between paediatric and adult APL while reviewing available data on treatment of paediatric APL."]
[24823814,0,0,0,0,2014,"Vitamin A supplementation for cystic fibrosis.","Bonifant",24823814,"Vitamin A supplementation for cystic fibrosis.    Abstract:    BACKGROUND : People with cystic fibrosis and pancreatic insufficiency are at risk of fat soluble vitamin deficiency as these vitamins (A, D, E and K) are co-absorbed with fat. Thus, some cystic fibrosis centres routinely administer these vitamins as supplements but the centres vary in their approach of addressing the possible development of deficiencies in these vitamins. Vitamin A deficiency causes predominantly eye and skin problems while supplementation of vitamin A to excessive levels may cause harm to the respiratory and skeletal systems in children. Thus a systematic review on vitamin A supplementation in people with cystic fibrosis would help guide clinical practice.  OBJECTIVES : To determine if vitamin A supplementation in children and adults with cystic fibrosis:1. reduces the frequency of vitamin A deficiency disorders;2. improves general and respiratory health;3. increases the frequency of vitamin A toxicity.  SEARCH METHODS : We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of the most recent search of the Groups Cystic Fibrosis Trials Register: 07 April 2014.  SELECTION CRITERIA : All randomised or quasi-randomised controlled trials comparing all preparations of oral vitamin A used as a supplement compared to either no supplementation (or placebo) at any dose and for any duration, in children or adults with cystic fibrosis (defined by sweat tests or genetic testing) with and without pancreatic insufficiency.  DATA COLLECTION AND ANALYSIS : No relevant studies for inclusion were identified in the search.  MAIN RESULTS : No studies were included in this review.  AUTHORS CONCLUSIONS : As there were no randomised or quasi-randomised controlled trials identified, we cannot draw any conclusions on the benefits (or otherwise) of regular administration of vitamin A in people with cystic fibrosis. Until further data are available, country or region specific guidelines on the use of vitamin A in people with cystic fibrosis should be followed."]
[24726464,1,0,0,1,2014,"SAPHO syndrome in an adolescent: a clinical case with unusual severe systemic impact.","Freira",24726464,"SAPHO syndrome in an adolescent: a clinical case with unusual severe systemic impact.    Abstract:   SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome includes both dermatological and rheumatologic symptoms. Being a rare condition, the diagnosis is frequently late. The authors report a case of a 13-year-old boy diagnosed with synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome with unusual severe systemic repercussions. The patient presented with acne conglobata, inability to walk due to pain and weakness and weight loss. Bone scintigraphy was suggestive of sacroiliitis, and lumbar spine x-ray showed signs of hyperostosis. His clinical state improved after treatment with nonsteroidal anti-inflammatory drugs, methotrexate, clindamycin, and isotretinoin. A review of the clinical aspects of this syndrome is presented, emphasizing how this underdiagnosed syndrome can lead to severe weight loss and significant functional and psychological impairment at an early age."]
[24716429,8,0,0,8,2014,"[Isotretinoin and exercise: can the two walk together?].","Dalal",24716429,"[Isotretinoin and exercise: can the two walk together?].    Abstract:   Since its introduction in 1982, isotretinoin has revolutionized acne treatment, targeting the underlying mechanism of the disease, with effective and long-lasting results. During the first decade of its marketing, several cases of hyperCKemia and rhabdomyolysis were linked to isotretinon therapy. A special concern was given to the possible triggering of muscle toxicity by vigorous exercise. These potential effects discouraged the prescription of isotretinoin to physically active patients or required them to abstain from exercise during treatment. Common musculoskeletal adverse effects of isotretinoin include muscle or joint pains. HyperCKemia is frequently found in patients receiving treatment for rare cases of rhabdomyolysis. Isotretinoin-associated muscle toxicity is usually detected in asymptomatic patients, even though symptoms can appear without hyperCKemia. A possible synergistic effect of isotretinoin and exercise is plausible, although supported by weak evidence and mediated by an unknown mechanism. There are only two reports of myoglobinuria and no reports of decreased renal function in exercising patient under treatment. In conclusion, we believe that current data should not deter physicians from offering isotretinoin to physically active patients nor require them to abstain from exercise. Physicians must explain to patients the possible side effects of treatment, ask them to refrain from an unusual change in their exercise regimen and advise them to avoid other triggers of rhabdomyolysis. Patients should be aware of possible signs of muscle toxicity and inform their doctors about any relevant symptoms."]
[24666225,4,0,3,7,2014,"Roles of retinoic acid signaling in normal and abnormal development of the palate and tongue.","Okano",24666225,"Roles of retinoic acid signaling in normal and abnormal development of the palate and tongue.    Abstract:   Palatogenesis involves various developmental events such as growth, elevation, elongation and fusion of opposing palatal shelves. Extrinsic factors such as mouth opening and subsequent tongue withdrawal are also needed for the horizontal elevation of palate shelves. Failure of any of these steps can lead to cleft palate, one of the most common birth defects in humans. It has been shown that retinoic acid (RA) plays important roles during palate development, but excess RA causes cleft palate in fetuses of both rodents and humans. Thus, the coordinated regulation of retinoid metabolism is essential for normal palatogenesis. The endogenous RA level is determined by the balance of RA-synthesizing (retinaldehyde dehydrogenases: RALDHs) and RA-degrading enzymes (CYP26s). Cyp26b1 is a key player in normal palatogenesis. In this review, we discuss recent progress in the study of the pathogenesis of RA-induced cleft palate, with special reference to the regulation of endogenous RA levels by RA-degrading enzymes."]
[24619249,0,0,0,0,2014,"Limb regeneration in salamanders and digital tip regeneration in experimental mice: implications for the hand surgeon.","Al-Qattan",24619249,"Limb regeneration in salamanders and digital tip regeneration in experimental mice: implications for the hand surgeon.    Abstract:    UNLABELLEDSeveral lessons and observations from limb regeneration in animals could open new insights to direct related research in the field of hand surgery. This article briefly reviews the biology of limb regeneration in salamanders and experimental mice, with special emphasis on implications for hand surgery.  LEVEL OF EVIDENCE : 5."]
[24598685,1,0,0,1,2014,"[Research advance on the role of ubiquitin proteasome pathway in acute promyelocytic leukemia].","Liu",24598685,"[Research advance on the role of ubiquitin proteasome pathway in acute promyelocytic leukemia].    Abstract:   Acute promyelocytic leukemia (APL) is characterized by PML-RARa expression. Ubiquitin proteasome-pathway (UPP) plays a key role in all-trans retinoid acid (ATRA) and arsenic trioxide (ATO)-induced degradation. In addition, the regulations of cell cycle and transcription are also related to this pathway. Deeply studying the role of ubiquitin-proteasome pathway in APL contributes to elucidate the mechanisms of some drugs and explode the clinical therapeutical insight for APL. In this article, the constitution of UPP, the role of UPP-mediated protein modification in APL, the application of ubiquitination-associated drugs in APL are reviewed."]
[24547720,1,0,0,1,2014,"Should isotretinoin be stopped prior to surgery? A critically appraised topic.","Wootton",24547720,"Should isotretinoin be stopped prior to surgery? A critically appraised topic.    Abstract:  "]
[24524207,0,0,0,0,2014,"Peroxisome proliferator-activated receptors and their ligands: nutritional and clinical implications--a review.","Grygiel-Górniak",24524207,"Peroxisome proliferator-activated receptors and their ligands: nutritional and clinical implications--a review.    Abstract:   Peroxisome proliferator-activated receptors are expressed in many tissues, including adipocytes, hepatocytes, muscles and endothelial cells; however, the affinity depends on the isoform of PPAR, and different distribution and expression profiles, which ultimately lead to different clinical outcomes. Because they play an important role in lipid and glucose homeostasis, they are called lipid and insulin sensors. Their actions are limited to specific tissue types and thus, reveal a characteristic influence on target cells. PPARα mainly influences fatty acid metabolism and its activation lowers lipid levels, while PPARγ is mostly involved in the regulation of the adipogenesis, energy balance, and lipid biosynthesis. PPARβ/δ participates in fatty acid oxidation, mostly in skeletal and cardiac muscles, but it also regulates blood glucose and cholesterol levels. Many natural and synthetic ligands influence the expression of these receptors. Synthetic ligands are widely used in the treatment of dyslipidemia (e.g. fibrates--PPARα activators) or in diabetes mellitus (e.g. thiazolidinediones--PPARγ agonists). New generation drugs--PPARα/γ dual agonists--reveal hypolipemic, hypotensive, antiatherogenic, anti-inflammatory and anticoagulant action while the overexpression of PPARβ/δ prevents the development of obesity and reduces lipid accumulation in cardiac cells, even during a high-fat diet. Precise data on the expression and function of natural PPAR agonists on glucose and lipid metabolism are still missing, mostly because the same ligand influences several receptors and a number of reports have provided conflicting results. To date, we know that PPARs have the capability to accommodate and bind a variety of natural and synthetic lipophilic acids, such as essential fatty acids, eicosanoids, phytanic acid and palmitoylethanolamide. A current understanding of the effects of PPARs, their molecular mechanisms and the role of these receptors in nutrition and therapeutic treatment are delineated in this paper."]
[24396459,1,0,0,1,2014,"Hyperthyroidism with concurrent FMS-like tyrosine kinase 3-internal tandem duplication-positive acute promyelocytic leukemia: A case report and review of the literature.","Jiang",24396459,"Hyperthyroidism with concurrent FMS-like tyrosine kinase 3-internal tandem duplication-positive acute promyelocytic leukemia: A case report and review of the literature.    Abstract:   Neutropenia is a common side-effect in hyperthyroid patients with long-term use of antithyroid drugs. This may be caused by drug-induced immune dysfunction or increased thyroxine hematologic toxicity, which usually returns to normal after medication is discontinued or the hyperthyroidism becomes well controlled. However, hyperthyroidism with pancytopenia is extremely rare. The current case report presents a hyperthyroid patient complicated with pancytopenia who had taken antithyroid drugs for 14 years. Bone marrow analysis revealed primary leuokocytes, indicating M3 acute leukemia. Genetic analysis revealed promyelocytic leukemia-retinoic acid receptor α fusion and FMS-like tyrosine kinase 3-internal tandem duplication. The genetic abnormality was also associated with thyroid hormonal functions. After a standard anti-M3 regimen was administed, the patient achieved complete remission and maintained stable thyroid functions. To the best of our knowledge, this is the first reported case of a patient with hyperthyroidism acquiring M3 leukemia harboring the FMS-like tyrosine kinase 3-internal tandem duplication."]
[24385831,2,0,0,2,2013,"Co-expression of t(15;17) and t(8;21) in a Case of Acute Promyelocytic Leukemia: Review of the Literature.","Uz",24385831,"Co-expression of t(15;17) and t(8;21) in a Case of Acute Promyelocytic Leukemia: Review of the Literature.    Abstract:    UNLABELLEDAdditional chromosomal abnormalities in acute myelogenous leukemia have been identified as one of the most important prognostic factors. Favorable chromosomal changes such as t(8;21), inv(16), and t(15;17) are associated with higher rates of complete remission and event-free survival. Translocation (15;17) characterizes acute promyelocytic leukemia (APL) (French-American-British class M3) in almost all patients. Secondary chromosomal abnormalities are also present in approximately 23%-29% of patients with newly diagnosed APL. The prognostic implications of t(8;21) and other secondary cytogenetic aberrations in APL are reviewed here. We present a 47-year-old woman diagnosed with APL whose initial cytogenetic analysis included both t(8;21) and t(15;17). The initial induction chemotherapy included 3 days of idarubicin (12 mg/m2/day) and daily all-trans retinoic acid (ATRA; 45 mg/m2/day). At the sixth week of treatment, a control bone marrow biopsy was found to be normocellular, t(15;17) bcr3 and t(8;21) were negative, and t(15;17) bcr1 fusion transcripts were reduced from 5007 (1.78525699%) copies per 1 µg RNA to 40 (0.00062020%) with real-time quantitative polymerase chain reaction. Consolidation with 4 days of idarubicin (5 mg/m2/day), ATRA (45 mg/m2/day for 15 days), and cytarabine (1 g/m2/day for 4 days) was then started. However, the patient became pancytopenic and had neutropenic fever after consolidation treatment. Unfortunately, she died 3 months after the time of APL diagnosis, due to acute respiratory distress syndrome-like respiratory problems and multiorgan dysfunction requiring respiratory support and hemodialysis.  CONFLICT OF INTEREST : None declared. Akut miyeloid lösemide ek kromozomal anomaliler en önemli prognostik faktörlerden biri olarak belirlenmiştir. Translokasyon t(8;21), inv(16), ve t(15;17) gibi olumlu kromozomal değişiklikler daha yüksek tam remisyon ve olaysız sağkalım ile ilişkilidir. Translokasyon (15;17) neredeyse tüm hastalarda akut promiyelositik lösemiyi (APL) tanımlamaktadır (Fransız-Amerikan-İngiliz [FAB] sınıf M3). Yeni tanı alan APL hastalarının yaklaşık %23-29’unda ikincil kromozomal anomaliler de bulunmaktadır. Bu olgu vesilesiyle APL’de t(8;21) ve diğer ikincil sitogenetik aberasyonların prognostik etkileri gözden geçirilmiştir. APL tanısı konan 47 yaşındaki kadın hastanın tanı anındaki sitogenetik analizinde t(8;21) ve t(15;17) birlikteliği saptandı. Başlangıç indüksiyon kemoterapisi 3 gün idarubisin (12 mg/m2/gün), ve günlük all-trans retinoik asit (ATRA) (45 mg/m2/gün) içermekteydi. Tedavinin 6. haftasında yapılan kontrol kemik iliği biyopsisi normoselülerdi. t(15;17) bcr3 ve t(8;21) negatifti, ve gerçek zamanlı kantitatif polimeraz zincir reaksiyonu (RQ-PCR) ile tespit edilen t(15;17) bcr1 füzyon transkriptleri 5007 (1,78525699 %) kopya/1 µg RNA’dan 40 (0,00062020 %)’a düşmüştü. Bunun üzerine 4 gün idarubisin (5 mg/m2/gün), 15 gün ATRA (45 mg/m2/gün), ve 4 gün sitarabin (1 g/m2/gün) içeren konsolidasyon tedavisi başlandı. Konsolidasyon tedavisi sonrasında hastada pansitopeni ve nötropenik ateş tablosu gelişti. APL tanısından 3 ay sonra, solunum desteği ve hemodiyaliz gerektiren çoklu organ fonksiyon bozukluğu ve ARDS-benzeri solunum problemleri nedeniyle hasta kaybedildi."]
[24362249,0,0,0,0,2014,"Regulation of energy metabolism by long-chain fatty acids.","Nakamura",24362249,"Regulation of energy metabolism by long-chain fatty acids.    Abstract:   In mammals, excess energy is stored primarily as triglycerides, which are mobilized when energy demands arise. This review mainly focuses on the role of long chain fatty acids (LCFAs) in regulating energy metabolism as ligands of peroxisome proliferator-activated receptors (PPARs). PPAR-alpha expressed primarily in liver is essential for metabolic adaptation to starvation by inducing genes for beta-oxidation and ketogenesis and by downregulating energy expenditure through fibroblast growth factor 21. PPAR-delta is highly expressed in skeletal muscle and induces genes for LCFA oxidation during fasting and endurance exercise. PPAR-delta also regulates glucose metabolism and mitochondrial biogenesis by inducing FOXO1 and PGC1-alpha. Genes targeted by PPAR-gamma in adipocytes suggest that PPAR-gamma senses incoming non-esterified LCFAs and induces the pathways to store LCFAs as triglycerides. Adiponectin, another important target of PPAR-gamma may act as a spacer between adipocytes to maintain their metabolic activity and insulin sensitivity. Another topic of this review is effects of skin LCFAs on energy metabolism. Specific LCFAs are required for the synthesis of skin lipids, which are essential for water barrier and thermal insulation functions of the skin. Disturbance of skin lipid metabolism often causes apparent resistance to developing obesity at the expense of normal skin function."]
[24315941,1,0,0,1,2014,"Active signals, gradient formation and regional specificity in neural induction.","Pera",24315941,"Active signals, gradient formation and regional specificity in neural induction.    Abstract:   The question of how the vertebrate embryo gives rise to a nervous system is of paramount interest in developmental biology. Neural induction constitutes the earliest step in this process and is tightly connected with development of the embryonic body axes. In the Xenopus embryo, perpendicular gradients of BMP and Wnt signals pattern the dorsoventral and anteroposterior body axes. Both pathways need to be inhibited to allow anterior neural induction to occur. FGF8 and IGF are active neural inducers that together with BMP and Wnt signals are integrated at the level of Smad 1/5/8 phosphorylation. Hedgehog (Hh) also contributes to anterior neural induction. Suppressor-of-fused plays an important role in intertwining the Hh and Wnt pathways. Distinct mechanisms are discussed that establish morphogen gradients and integrate retinoic acid and FGF signals during posterior development. These findings not only improve our understanding of regional specification in neural induction, but have profound implications for mammalian stem cell research and regenerative medicine."]
[24291063,11,0,0,11,2014,"Consequences of metal exposure on retinoid metabolism in vertebrates: a review.","Defo",24291063,"Consequences of metal exposure on retinoid metabolism in vertebrates: a review.    Abstract:   What we generally refer to as vitamin A is a group of naturally-occurring molecules structurally similar to retinol that are capable of exerting biological activity. These retinoids are essential to diverse physiological functions including vision, immune response, bone mineralization, reproduction, cell differentiation, and growth. As well, some retinoids have antioxidant properties. Independent studies published over the last few decades have revealed that many fish and wildlife populations living in highly polluted environments have altered retinoid status possibly associated with retinoid metabolic or homeostatic mechanisms. Substantial evidence links organic contaminant exposure with changes in retinoid status in animal populations, but only a few detailed studies have been published implicating inorganic contaminants such as metals. This mini-review selectively deals with field and laboratory studies reporting associations between environmental contaminants, especially trace metals, and alterations in retinoid status. Both essential and non-essential trace metals have been reported to affect retinoid status. This review focuses on metabolic imbalances of retinoids in relation to metal contamination and illustrates possible modes of action. The role of retinoids as antioxidants and their potential as biomarkers of metal contamination are discussed."]
[24183637,0,0,0,0,2013,"Vitamin A and bone health: the balancing act.","Tanumihardjo",24183637,"Vitamin A and bone health: the balancing act.    Abstract:   The role of vitamin A status as it relates to bone health is historical yet controversial. Population-based studies have linked high dietary intake of preformed vitamin A, which is obtained from animal-source foods, fortified foods, and some supplements, to greater risk of osteoporosis and hip fracture. In contrast, carotenoids, some of which are vitamin A precursors from plants, are associated with improved bone health. Carotenoids may be a biomarker that reflects a generally healthy lifestyle, which includes fruit and vegetable consumption. Current dietary recommendations to increase fruit and vegetable intake in the Dietary Guidelines for Americans will result in greater intakes of provitamin A carotenoids if consumers comply. This could lead to artificially high intakes of vitamin A in dietary analyses. However, multiple factors affect the bioconversion of provitamin A carotenoids to the active form of vitamin A. The human body will strive to maintain vitamin A balance by down-regulating provitamin A carotenoid bioconversion. If high preformed vitamin A intake is associated with poor bone health and provitamin A carotenoids are protective, future studies are needed to clarify the associations between total body stores of vitamin A, dietary intake of the pre- and pro-forms, and bone health throughout the life cycle."]
[24139874,0,0,0,0,2014,"Multifunctional and potent roles of the 3-hydroxypropoxy group provide eldecalcitols benefit in osteoporosis treatment.","Ono",24139874,"Multifunctional and potent roles of the 3-hydroxypropoxy group provide eldecalcitols benefit in osteoporosis treatment.    Abstract:   Eldecalcitol (1α,25-dihydroxy-2β-(3-hydroxypropoxy)vitamin D3, [developing code: ED-71]), a new osteoporosis treatment drug that was recently approved in Japan, is a best-in-class drug in the class of calcitriol (1α,25-dihydroxyvitamin D3) and its prodrug alfacalcidol (1α-hydroxyvitamin D3), which have been used to treat osteoporosis for 30 years. In a comparative Phase III clinical study with alfacalcidol in osteoporosis patients, eldecalcitol demonstrated superior efficacy in the endpoints of increment of bone mineral density and reduction of bone fracture with equivalent safety to alfacalcidol. Eldecalcitol was discovered by searching synthetic analogs of calcitriol and alfacalcidol, and its main structural characteristic is having the 3-hydroxypropoxy group at the 2β-position. This review discusses why introducing the group leads to excellent efficacy and safety in osteoporosis treatment and elucidates the functional roles of the 3-hydroxypropoxy group. Briefly, the functional roles of the group are, first, realizing the metabolism switching in which eldecalcitol shows resistance to CYP24A1 and is metabolized in the liver; second, increasing the affinity to the serum carrier protein and prolonging the half-life to 53h; and third, stabilizing the eldecalcitol-receptor complex. Taken together, these functional roles of the 3-hydroxypropoxy group are beneficial in osteoporosis treatment. This review attempts to give a detailed account of the mode of action of eldecalcitol by clarifying these multifunctional roles of the 3-hydroxypropoxy group from the medicinal chemists perspective."]
[24088538,1,0,0,1,2013,"[Morphological and molecular bases of cardiac development].","Kobylińska",24088538,"[Morphological and molecular bases of cardiac development].    Abstract:   The heart is a mesoderm-derived organ, whose formation is regulated by various genes. Initially, the most important is expression of Nkx2.5, CR1, pitx2, anf and mhc2a, which are responsible for differentiation of cardiomyocytes. In a later phase activation of mhc2b, pitx2c, mesp1, pcmf1, vmhc, xin, mcl2v, mlc2a, mlc2a, mef2, hand1 and hand2 was revealed. Their expression is regulated by various molecules, including transcription (XIN, GATA, MEF, Tbx5, Baf60c, PECAM, tie-2, MEF2) and growth (VEGF, FGF, PDGF) factors, as well as proteins (i.e., dickkopf-1, cerberus, cytotactin, fibrillin, nodal, thrombomodulin, Wnt, bone morphometric ones - BMP2, BMP 4, BMP5, BMP7) and other substances, such as retinoid and folic acid. Crucial steps in cardiac organogenesis are development of the ventricle and atrial formation, as well as septation and valve formation. Any disturbances of such processes may lead to various congenital heart diseases and defects that could be initiated by various genetic, epigenetic or environmental factors. The most common heart malformations are: stenosis (coarctation) of the aorta and pulmonary trunk, bicuspid aortic valve, atrial and/or ventricular septal defect, persistent truncus arteriosus (Botallo duct), transposition of the great vessels, tricuspid atresia, hypoplastic left and right heart, as well as syndrome of Lutembachera, Cantrell, Ebstein, Eisenmenger and Shone and trilogy, tetralogy, pentalogy of Fallot."]
[24018211,0,0,0,0,2013,"Spanish evidence-based guidelines on the treatment of psoriasis with biologic agents, 2013. Part 1: on efficacy and choice of treatment. Spanish Psoriasis Group of the Spanish Academy of Dermatology and Venereology.","Puig",24018211,"Spanish evidence-based guidelines on the treatment of psoriasis with biologic agents, 2013. Part 1: on efficacy and choice of treatment. Spanish Psoriasis Group of the Spanish Academy of Dermatology and Venereology.    Abstract:   Biologic therapy is a well-established strategy for managing moderate and severe psoriasis. Nevertheless, the high cost of such therapy, the relatively short span of clinical experience with biologics, and the abundance of literature now available on these agents have made evidence-based and consensus-based clinical guidelines necessary. The ideal goal of psoriasis treatment is to achieve complete or nearly complete clearing of lesions and to maintain it over time. Failing that ideal, the goal would be to reduce involvement to localized lesions that can be controlled with topical therapy. Although current evidence allows us to directly or indirectly compare the efficacy or risk of primary or secondary failure of available biologics based on objective outcomes, clinical trial findings cannot be directly translated to routine practice. As a result, the prescribing physician must tailor the treatment regimen to the individual patient. This update of the clinical practice guidelines issued by the Spanish Academy of Dermatology and Venereology (AEDV) on biologic therapy for psoriasis incorporates information from the most recent publications on this topic."]
[24011318,0,3,0,3,2013,"Secondary bilateral striopallidodentate calcinosis associated with generalized pustular psoriasis (Von Zumbusch).","Pacheco",24011318,"Secondary bilateral striopallidodentate calcinosis associated with generalized pustular psoriasis (Von Zumbusch).    Abstract:   Bilateral striopallidodentate calcinosis (BSPDC) mentioned in the literature as Fahrs disease (a misnomer), is characterized by symmetrical and bilateral intracerebral calcifications located in the basal ganglia with or without deposits in the dentate nucleus, thalamus, and white matter. This entity is usually asymptomatic but may be manifested by neurological symptoms. Idiopathic BSPDC can occur either as sporadic or autosomal dominant familial forms. Secondary presentations of BSPDC are associated with infections, neoplastic diseases, toxicological or traumatic factors, and metabolic disorders. We describe a case of generalized pustular psoriasis associated with secondary BSPDC owing to pseudohypoparathyroidism. Laboratory tests revealed hypocalcemia, hyperphosphatemia, and a normal serum level of parathormone. The correction of the phosphorus-calcium metabolism disorder produced clinical improvement."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I69,I69)","v":23962476},{"$f":"(LEN($J69) - LEN(SUBSTITUTE(LOWER($J69),LOWER(B$3),\"\")))/LEN(B$3)","v":0},0,0,{"$f":"SUM(B69:D69)","v":0},2013,"The interferon response to intracellular DNA: why so many receptors?","Unterholzner",23962476,"The interferon response to intracellular DNA: why so many receptors?    Abstract:   The detection of intracellular DNA has emerged to be a key event in the innate immune response to viruses and intracellular bacteria, and during conditions of sterile inflammation and autoimmunity. One of the consequences of the detection of DNA as a stranger and a danger signal is the production of type I interferons and pro-inflammatory cytokines. Much work has been dedicated to the elucidation of the signalling cascades that activate this DNA-induced gene expression programme. However, while many proteins have been proposed to act as sensors for intracellular DNA in recent years, none has been met with universal acceptance, and a theory linking all the recent observations is, as yet, lacking. This review presents the evidence for the various interferon-inducing DNA receptors proposed to date, and examines the hypotheses that might explain why so many different receptors appear to be involved in the innate immune recognition of intracellular DNA."]
[23962296,1,0,0,1,2013,"25-(OH)VitD3, as a risk indicator in diagnosis of adenocarcinoma.","Cai",23962296,"25-(OH)VitD3, as a risk indicator in diagnosis of adenocarcinoma.    Abstract:   Vitamin D (VitD) comes from sunlight exposure and food intake. Apart from regulating calcium homeostasis and bone function, its levels also associate with the presence of development of adenocarcinoma. VitD can interact with VitD receptor (VDR), which heterodimerizes with retinoic X receptor (RXR) and then induces transcription of proteins that function in cell proliferation, differentiation, apoptosis, and angiogenesis. We reviewed and discussed the genes and their associated polymorphisms involved in the correlation between development of adenocarcinoma and VitD deficiency to highlight how VitD may be instrumental in cancerization. Furthermore, pilot epidemiological data show that the detection of 25-hydroxy-Vitamin D3 ((36.5±10.7 nmol/L, n=129) vs (81.4±19.8 nmol/L, n=81)) can be a promising approach in cancer diagnosis. In this review, we suggest that 25-hydroxy-Vitamin D3 can act as an indicator and/or risk assessment factor in early diagnosis, prognosis and treatment of adenocarcinoma."]
[23890557,0,0,0,0,2013,"Vitamin D in thyroid tumorigenesis and development.","Clinckspoor",23890557,"Vitamin D in thyroid tumorigenesis and development.    Abstract:   Besides its classical role in bone and calcium homeostasis, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), the active form of vitamin D, has many non-classical effects; antiproliferative, anti-apoptotic and prodifferentiating effects of 1,25(OH)2D3 have been described in several tumour types in preclinical models. This review focuses on the insights gained in the elucidation of the role of 1,25(OH)2D3 in the normal thyroid and in the pathogenesis, progression and treatment of thyroid cancer, the most common endocrine malignancy. An increasing amount of observations points towards a role for impaired 1,25(OH)2D3-VDR signalling in the occurrence and progression of thyroid cancer, and a potential for structural analogues in the multimodal treatment of dedifferentiated iodine-resistant thyroid cancer. A role for vitamin D in thyroid-related autoimmunity is less convincing and needs further study. Altered 1,25(OH)2D3-VDR signalling does not influence normal thyroid development nor thyrocyte function, but does affect C-cell function, at least in rodents. If these findings also apply to humans deserves further study."]
[23845149,2,0,0,2,2013,"Cardiovascular morbidity and mortality in psoriasis and psoriatic arthritis: a systematic literature review.","Horreau",23845149,"Cardiovascular morbidity and mortality in psoriasis and psoriatic arthritis: a systematic literature review.    Abstract:    UNLABELLEDPrevious epidemiological studies have demonstrated a high prevalence of cardiovascular (CV) risk factors in psoriasis patients, including metabolic syndrome, cigarette smoking, obesity, hypertension, diabetes mellitus, insulin resistance and dyslipidaemia. An increase in CV morbidity and mortality attributable to psoriasis is still under question.  PRIMARY OBJECTIVE : to assess CV morbidity and mortality in psoriasis and psoriatic arthritis (PsA) including stroke, coronary artery disease, myocardial infarction (MI) and peripheral artery disease.  SECONDARY OBJECTIVES : to assess if psoriasis per se is an independent CV risk factor and if psoriasis severity is a predictor of CV risk. We also evaluated the effect of conventional systemic treatments for psoriasis on CV mortality. A systematic literature search was carried out from 1980 to December 2011, in the Embase, Medline and Cochrane Library databases, in English and French using a combination of keywords including (Psoriasis) OR (Psoriatic arthritis) AND (Myocardial infarction) OR (Coronaropathy) OR (Stroke) OR (Cardiovascular) AND (Methotrexate) AND (Ciclosporin) AND (Retinoids). Of the 929 identified references, 33 observational studies evaluating the rates of cardiovascular events (CVE) in patients with psoriasis and PsA compared with controls were selected. Meta-analysis of both cohort and cross-sectional studies showed an increased risk of MI with Odds Ratio (OR) of 1.25 (95% CI 1.03-1.52) and 1.57 (95% CI 1.08-2.27) in psoriasis and PsA, respectively, compared with the general population. The risk of MI was more pronounced for patients having severe psoriasis and for patients with psoriasis of early onset. It remained significantly elevated after controlling for major CV risk factors. The meta-analysis identified a small, but significant association between psoriasis, PsA and coronary artery disease with an OR between 1.19 (95% CI 1.14-1.24) for cross-sectional studies, 1.20 (95% CI 1.13-1.27) for cohort studies and 1.84 (95% CI 1.09-3.09) for case-control studies. The risk of coronary artery disease seemed to be more pronounced in patients with severe psoriasis and in patients with psoriasis of early onset. The meta-analysis assessing the risk of stroke gave inconclusive results: analysis of cross-sectional studies suggested that psoriasis patients had a slightly higher risk of stroke with an OR of 1.14 (95% CI 1.08-1.99), whereas the meta-analysis of cohort studies failed to show an association. There was also an increased risk of peripheral artery disease in psoriasis. No significant increased risk of CV mortality could be shown for both psoriasis and PsA patients. The use of methotrexate was associated with a reduced incidence of cardiovascular disease in two studies. The use of etretinate was associated with a reduction of CV mortality in one study. Potential selection bias such as the healthy user effect prevents from drawing definite conclusions. There may be a small, but significant increased risk of CVE, but not of CV mortality in psoriasis and PsA patients. The psoriasis attributable risk remains difficult to assess due to confounding factors. The moderate quality of CV risk factors reporting in studies should be acknowledged. In addition, heterogeneity in study design, outcome definition and assessment represent major limitations. Nevertheless, screening and management of CV risk factors are important in psoriasis."]
[23823097,1,0,0,1,2013,"[Acute promyelocytic leukemia presenting with central nervous system involvement at initial diagnosis].","Sakurai",23823097,"[Acute promyelocytic leukemia presenting with central nervous system involvement at initial diagnosis].    Abstract:   We describe a rare case of acute promyelocytic leukemia (APL) presenting with central nervous system (CNS) involvement at the time of initial diagnosis. A 58-year-old male was hospitalized with palpitations, dyspnea, high grade fever, photophobia, and disturbance of consciousness in March 2010. APL was diagnosed by bone marrow (BM) examination. The cytogenetic analysis of BM cells demonstrated t(15;17)(q22;q11), and PML-RARA chimeric gene was detected by reverse transcriptase-polymerase chain reaction assay. Magnetic resonance imaging of the brain revealed several high intensity regions in the cerebrum and cerebellum. CNS involvement was diagnosed based on the appearance of APL blasts in cerebrospinal fluid (CSF). The patient was treated with all-trans retinoic acid (ATRA), and systemic chemotherapy consisting of idarubicin and cytarabine according to the Japan Adult Leukemia Study Group (JALSG) APL 204 protocol. He was then treated with continuous intrathecal administration of cytotoxic drugs (methotrexate, cytarabine, prednisolone) after systemic chemotherapy, achieving complete remission (CR) in both BM and the CNS. To date, he has been maintained in complete molecular remission in both BM and the CSF for 28 months, to date."]
[23774609,0,0,0,0,2013,"Postprandial lipoproteins and the molecular regulation of vascular homeostasis.","Botham",23774609,"Postprandial lipoproteins and the molecular regulation of vascular homeostasis.    Abstract:   Blood levels of triglyceride-rich lipoproteins (TRL) increase postprandially, and a delay in their clearance results in postprandial hyperlipidemia, an important risk factor in atherosclerosis development. Atherosclerosis is a multifactorial inflammatory disease, and its initiation involves endothelial dysfunction, invasion of the artery wall by leukocytes and subsequent formation of foam cells. TRL are implicated in several of these inflammatory processes, including the formation of damaging free radicals, leukocyte activation, endothelial dysfunction and foam cell formation. Recent studies have provided insights into the mechanisms of uptake and the signal transduction pathways mediating the interactions of TRL with leukocytes and vascular cells, and how they are modified by dietary lipids. Multiple receptor and non-receptor mediated pathways function in macrophage uptake of TRL. TRL also induce expression of adhesion molecules, cyclooxygenase-2 and heme-oxygenase-1 in endothelial cells, and activate intracellular signaling pathways involving mitogen-activated protein kinases, NF-κB and Nrf2. Many of these effects are strongly influenced by dietary components carried in TRL. There is extensive evidence indicating that raised postprandial TRL levels are a risk factor for atherosclerosis, but the molecular mechanisms involved are only now becoming appreciated. Here, we review current understanding of the mechanisms by which TRL influence vascular cell function."]
[23751781,0,0,0,0,2013,"Particulate formulations for the delivery of poly(I:C) as vaccine adjuvant.","Hafner",23751781,"Particulate formulations for the delivery of poly(I:C) as vaccine adjuvant.    Abstract:   Current research and development of antigens for vaccination often center on purified recombinant proteins, viral subunits, synthetic oligopeptides or oligosaccharides, most of them suffering from being poorly immunogenic and subject to degradation. Hence, they call for efficient delivery systems and potent immunostimulants, jointly denoted as adjuvants. Particulate delivery systems like emulsions, liposomes, nanoparticles and microspheres may provide protection from degradation and facilitate the co-formulation of both the antigen and the immunostimulant. Synthetic double-stranded (ds) RNA, such as polyriboinosinic acid-polyribocytidylic acid, poly(I:C), is a mimic of viral dsRNA and, as such, a promising immunostimulant candidate for vaccines directed against intracellular pathogens. Poly(I:C) signaling is primarily dependent on Toll-like receptor 3 (TLR3), and on melanoma differentiation-associated gene-5 (MDA-5), and strongly drives cell-mediated immunity and a potent type I interferon response. However, stability and toxicity issues so far prevented the clinical application of dsRNAs as they undergo rapid enzymatic degradation and bear the potential to trigger undue immune stimulation as well as autoimmune disorders. This review addresses these concerns and suggests strategies to improve the safety and efficacy of immunostimulatory dsRNA formulations. The focus is on technological means required to lower the necessary dosage of poly(I:C), to target surface-modified microspheres passively or actively to antigen-presenting cells (APCs), to control their interaction with non-professional phagocytes and to modulate the resulting cytokine secretion profile."]
[23731645,1,0,0,1,2013,"Pathogenesis of hyperostosis: a key role for mesenchymatous cells?","Berthelot",23731645,"Pathogenesis of hyperostosis: a key role for mesenchymatous cells?    Abstract:   The similarities between diffuse idiopathic skeletal hyperostosis (DISH) and some forms of ankylosing spondylitis suggest shared pathogenic mechanisms. Entheseal ossification progresses at the same rate in the two conditions, and spondyloarthritis was the first diagnosis considered in several families with genetically determined early-onset DISH. However, DISH may be a heterogeneous condition, as the presence of peripheral calcifications in some families suggests pathogenic similarities with several animal models combining entheseal ossification and peripheral calcifications, as well as with X-linked familial hypophosphatemia and dentin-matrix-protein mutations. In the far more common presentation of hyperostosis without calcifications, entheseal ossification may be related to abnormal osteoblastic differentiation of mesenchymatous stem cells normally found around the intervertebral disks, in the vertebral periosteum, and in the anterior and posterior longitudinal ligaments. The many factors suspected of promoting this abnormal differentiation include bone morphogenetic proteins (BMPs), retinoids, and various hormonal factors; in addition, adipokines such as leptin are the focus of growing interest based on the well-documented association between DISH and obesity. Confirmation of the role for mesenchymatous cells in DISH should encourage investigations of mesenchymatous cells as possible pathogenic contributors to the entheseal abnormalities seen in spondyloarthritis. These cells normally exert immunosuppressive effects, which may be subverted in spondyloarthritis, notably by a T-cell population that homes specifically to the entheses."]
[23720297,8,0,0,8,2013,"Vitamin a metabolism, action, and role in skeletal homeostasis.","Conaway",23720297,"Vitamin a metabolism, action, and role in skeletal homeostasis.    Abstract:   Vitamin A (retinol) is ingested as either retinyl esters or carotenoids and metabolized to active compounds such as 11-cis-retinal, which is important for vision, and all-trans-retinoic acid, which is the primary mediator of biological actions of vitamin A. All-trans-retinoic acid binds to retinoic acid receptors (RARs), which heterodimerize with retinoid X receptors. RAR-retinoid X receptor heterodimers function as transcription factors, binding RAR-responsive elements in promoters of different genes. Numerous cellular functions, including bone cell functions, are mediated by vitamin A; however, it has long been recognized that increased levels of vitamin A can have deleterious effects on bone, resulting in increased skeletal fragility. Bone mass is dependent on the balance between bone resorption and bone formation. A decrease in bone mass may be caused by either an excess of resorption or decreased bone formation. Early studies indicated that the primary skeletal effect of vitamin A was to increase bone resorption, but later studies have shown that vitamin A can not only stimulate the formation of bone-resorbing osteoclasts but also inhibit their formation. Effects of vitamin A on bone formation have not been studied in as great a detail and are not as well characterized as effects on bone resorption. Several epidemiological studies have shown an association between vitamin A, decreased bone mass, and osteoporotic fractures, but the data are not conclusive because other studies have found no associations, and some studies have suggested that vitamin A primarily promotes skeletal health. In this presentation, we have summarized how vitamin A is absorbed and metabolized and how it functions intracellularly. Vitamin A deficiency and excess are introduced, and detailed descriptions of clinical and preclinical studies of the effects of vitamin A on the skeleton are presented."]
[23669186,0,0,0,0,2013,"Gene methylation in gastric cancer.","Qu",23669186,"Gene methylation in gastric cancer.    Abstract:   Gastric cancer is one of the most common malignancies and remains the second leading cause of cancer-related death worldwide. Over 70% of new cases and deaths occur in developing countries. In the early years of the molecular biology revolution, cancer research mainly focuses on genetic alterations, including gastric cancer. Epigenetic mechanisms are essential for normal development and maintenance of tissue-specific gene expression patterns in mammals. Disruption of epigenetic processes can lead to altered gene function and malignant cellular transformation. Recent advancements in the rapidly evolving field of cancer epigenetics have shown extensive reprogramming of every component of the epigenetic machinery in cancer, including DNA methylation, histone modifications, nucleosome positioning, noncoding RNAs, and microRNAs. Aberrant DNA methylation in the promoter regions of gene, which leads to inactivation of tumor suppressor and other cancer-related genes in cancer cells, is the most well-defined epigenetic hallmark in gastric cancer. The advantages of gene methylation as a target for detection and diagnosis of cancer in biopsy specimens and non-invasive body fluids such as serum and gastric washes have led to many studies of application in gastric cancer. This review focuses on the most common and important phenomenon of epigenetics, DNA methylation, in gastric cancer and illustrates the impact epigenetics has had on this field."]
[23543539,1,0,0,1,2013,"Topical treatments for chronic plaque psoriasis.","Mason",23543539,"Topical treatments for chronic plaque psoriasis.    Abstract:    BACKGROUND : Chronic plaque psoriasis is the most common type of psoriasis, and it is characterised by redness, thickness, and scaling. First-line management of chronic plaque psoriasis is with topical treatments, including vitamin D analogues, topical corticosteroids, tar-based preparations, dithranol, salicylic acid, and topical retinoids.  OBJECTIVES : To compare the effectiveness, tolerability, and safety of topical treatments for chronic plaque psoriasis, relative to placebo, and to similarly compare vitamin D analogues (used alone or in combination) with other topical treatments.  SEARCH METHODS : We updated our searches of the following databases to February 2011: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library (2011, Issue 2), MEDLINE (from 1948), EMBASE (from 1980), Science Citation Index (from 2008), Conference Proceedings Citation Index - Science (from 2008), BIOSIS (from 1993), Dissertation Abstracts via DialogClassic (all publication years), and Inside Conferences (all publication years).We identified ongoing and unpublished studies from the UK Clinical Research Network Study Portfolio and the metaRegister of Controlled Trials. We checked the bibliographies of published studies and reviews for further references to relevant trials, and we contacted trialists and companies for information about newly published studies.A separate search for adverse effects was undertaken in February 2011 using MEDLINE and EMBASE (from 2005).Final update searches for both RCTs and adverse effects were undertaken in August 2012. Although it has not been possible to incorporate RCTs and adverse effects studies identified through these final searches within this review, we will incorporate these into the next update.  SELECTION CRITERIA : Randomised trials comparing active topical treatments against placebo or against vitamin D analogues (used alone or in combination) in people with chronic plaque psoriasis.  DATA COLLECTION AND ANALYSIS : One author extracted study data and assessed study quality. A second author checked these data. We routinely contacted trialists and companies for missing data. We also extracted data on withdrawals and on local and systemic adverse events. We defined long-term trials as those with a duration of at least 24 weeks.  MAIN RESULTS : This update added 48 trials and provided evidence on 7 new active treatments. In total, the review included 177 randomised controlled trials, with 34,808 participants, including 26 trials of scalp psoriasis and 6 trials of inverse psoriasis, facial psoriasis, or both. The number of included studies counted by Review Manager (RevMan) is higher than these figures (190) because we entered each study reporting a placebo and an active comparison into the Characteristics of included studies table as 2 studies.When used on the body, most vitamin D analogues were significantly more effective than placebo, with the standardised mean difference (SMD) ranging from -0.67 (95% CI -1.04 to -0.30; 1 study, 119 participants) for twice-daily becocalcidiol to SMD -1.66 (95% CI -2.66 to -0.67; 1 study, 11 participants) for once-daily paricalcitol. On a 6-point global improvement scale, these effects translate into 0.8 and 1.9 points, respectively. Most corticosteroids also performed better than placebo; potent corticosteroids (SMD -0.89; 95% CI -1.06 to -0.72; I² statistic = 65.1%; 14 studies, 2011 participants) had smaller benefits than very potent corticosteroids (SMD -1.56; 95% CI -1.87 to -1.26); I² statistic = 81.7%; 10 studies, 1264 participants). On a 6-point improvement scale, these benefits equate to 1.0 and 1.8 points, respectively. Dithranol, combined treatment with vitamin D/corticosteroid, and tazarotene all performed significantly better than placebo.Head-to-head comparisons of vitamin D for psoriasis of the body against potent or very potent corticosteroids had mixed findings. For both body and scalp psoriasis, combined treatment with vitamin D and corticosteroid performed significantly better than vitamin D alone or corticosteroid alone. Vitamin D generally performed better than coal tar, but findings relative to dithranol were mixed. When applied to psoriasis of the scalp, vitamin D was significantly less effective than both potent corticosteroids and very potent corticosteroids. Indirect evidence from placebo-controlled trials supported these findings.For both body and scalp psoriasis, potent corticosteroids were less likely than vitamin D to cause local adverse events, such as burning or irritation. Combined treatment with vitamin D/corticosteroid on either the body or the scalp was tolerated as well as potent corticosteroids, and significantly better than vitamin D alone. Only 25 trials assessed clinical cutaneous dermal atrophy; few cases were detected, but trials reported insufficient information to determine whether assessment methods were robust. Clinical measurements of dermal atrophy are insensitive and detect only the most severe cases. No comparison of topical agents found a significant difference in systemic adverse effects.  AUTHORS CONCLUSIONS : Corticosteroids perform at least as well as vitamin D analogues, and they are associated with a lower incidence of local adverse events. However, for people with chronic plaque psoriasis receiving long-term treatment with corticosteroids, there remains a lack of evidence about the risk of skin dermal atrophy. Further research is required to inform long-term maintenance treatment and provide appropriate safety data."]
[23542704,0,0,0,0,2013,"Regulation of macrophage and dendritic cell function by pathogens and through immunomodulation in the avian mucosa.","de Geus",23542704,"Regulation of macrophage and dendritic cell function by pathogens and through immunomodulation in the avian mucosa.    Abstract:   Macrophages (MPh) and dendritic cells (DC) are members of the mononuclear phagocyte system. In chickens, markers to distinguish MPh from DC are lacking, but whether MPh and DC can be distinguished in humans and mice is under debate, despite the availability of numerous markers. Mucosal MPh and DC are strategically located to ingest foreign antigens, suggesting they can rapidly respond to invading pathogens. This review addresses our current understanding of DC and MPh function, the receptors expressed by MPh and DC involved in pathogen recognition, and the responses of DC and MPh against respiratory and intestinal pathogens in the chicken. Furthermore, potential opportunities are described to modulate MPh and DC responses to enhance disease resistance, highlighting modulation through nutraceuticals and vaccination."]
[23500006,1,0,0,1,2013,"Effects of probiotic administration on zebrafish development and reproduction.","Carnevali",23500006,"Effects of probiotic administration on zebrafish development and reproduction.    Abstract:   As the consumption of probiotics increases worldwide, scientists focus on identifying bacterial strains able to improve human life quality and evidence the biological pathways affected by probiotic treatment. In this review, some recent observations on the effects of changes of microbiota on zebrafish metabolism were discussed. In addition, the effects of Lactobacillus rhamnosus - a component of the human gut microflora - as a diet supplement on Danio rerio were presented. When administered chronically, L. rhamnosus may affect larval development and the physiology of reproductive system in the zebrafish model. It was hypothesized exogenous L. rhamnosus accelerates larval growth and backbone development by acting on insulin-like growth factors-I (igfI) and -II (igfII), peroxisome proliferator activated receptors-α and -β, (pparα,β) vitamin D receptor-α (vdrα) and retinoic acid receptor-γ (rarγ). Gonadal differentiation was anticipated at 6weeks together with a higher expression of gnrh3 at the larval stage when L. rhamnosus was administered throughout development. Moreover, brood stock alimented with a L. rhamnosus-supplemented diet showed better reproductive performances as per follicles development, ovulated oocytes quantification and embryos quality. A plausible involvement of factors such as leptin, and kiss1 and 2 in the improvements was concluded. The observations made on the physiology of female reproduction were correlated with the gene expression of a gigantic number of factors as the aromatase cytochrome p 19 (cyp19a), the vitellogenin (vtg) and the α isoform of the E2 receptor (erα), luteinizing hormone receptor (lhr), 20-β hydroxysteroid dehydrogenase (20β-hsd), membrane progesterone receptors α and β, cyclin B, activinβA1, smad2, transforming growth factor β1 (tgfβ1), growth differentiation factor9 (gdf9) and bone morphogenetic protein15 (bmp15.) A model in which the exogenous L. rhamnosus in the digestive tract of zebrafish from the first days of life through sexual maturation positively influences the physiological performances of zebrafish was evidenced and a number of pathways that might be influenced by the presence of this human probiotic strain were proposed."]
[23476896,1,0,0,1,2013,"Multiple isolated extramedullary relapse of acute promyelocytic leukemia after allogeneic hematopoietic stem cell transplant: a case report and review of literature.","Kothari",23476896,"Multiple isolated extramedullary relapse of acute promyelocytic leukemia after allogeneic hematopoietic stem cell transplant: a case report and review of literature.    Abstract:   Isolated extramedullary disease (EMD) is uncommon, especially in acute promyelocytic leukemia (APL) after allogeneic hematopoietic stem cell transplantation (HSCT). We review the literature and present a 32 year old woman with APL who developed multiple EMDs after allogeneic HSCT within the calvarium, and later found to have various isolated lesions including femur, humerus and thoraco lumbar vertebrae. She was treated with local radiotherapy (XRT) to EMD lesions, all-trans retinoic acid, arsenic trioxide and donor lymphocyte infusion at different time points in her clinical course, without success. Out of reported cases in clinical setting as ours, average onset of isolated EMD is 25 months and median survival 14 months. Effective treatment of isolated EMD after HSCT is not yet clear, but ATO in combination with local XRT, tamibarotene and second HSCT have shown good results in some reported cases, but accumulation of more cases is needed to elucidate optimal therapy in such setting."]
[23466416,0,0,0,0,2013,"Epigenetic regulation of neural stem cell fate during corticogenesis.","MuhChyi",23466416,"Epigenetic regulation of neural stem cell fate during corticogenesis.    Abstract:   The cerebral cortex comprises over three quarters of the brain, and serves as structural basis for the sophisticated perceptual and cognitive functions. It develops from common multipotent neural stem cells (NSCs) that line the neural tube. Development of the NSCs encompasses sequential phases of progenitor expansion, neurogenesis, and gliogenesis along with the progression of developmental stages. Interestingly, NSCs steadfastly march through all of these phases and give rise to specific neural cell types in a temporally defined and highly predictable manner. Herein, we delineate the intrinsic and extrinsic factors that dictate the progression and tempo of NSC differentiation during cerebral cortex development, and how epigenetic modifications contribute to the dynamic properties of NSCs."]
[23445813,1,0,0,1,2013,"New insights into the developmental mechanisms of coronary vessels and epicardium.","Nakajima",23445813,"New insights into the developmental mechanisms of coronary vessels and epicardium.    Abstract:   During heart development, the epicardium, which originates from the proepicardial organ (PE), is a source of coronary vessels. The PE develops from the posterior visceral mesoderm of the pericardial coelom after stimulation with a combination of weak bone morphogenetic protein and strong fibroblast growth factor (FGF) signaling. PE-derived cells migrate across the heart surface to form the epicardial sheet, which subsequently seeds multipotent subepicardial mesenchymal cells via epithelial-mesenchymal transition, which is regulated by several signaling pathways including retinoic acid, FGF, sonic hedgehog, Wnt, transforming growth factor-β, and platelet-derived growth factor. Subepicardial endothelial progenitors eventually generate the coronary vascular plexus, which acquires an arterial or venous phenotype, connects with the sinus venosus and aortic sinuses, and then matures through the recruitment of vascular smooth muscle cells under the regulation of complex growth factor signaling pathways. These developmental programs might be activated in the adult heart after injury and play a role in the regeneration/repair of the myocardium."]
[23413096,1,0,0,1,2013,"Pregnane X receptor and human malignancy.","Koutsounas",23413096,"Pregnane X receptor and human malignancy.    Abstract:   Pregnane X Receptor (PXR) is a member of the nuclear receptor superfamily, expressed in liver, intestine and other tissues. PXR exerts transcriptional regulation by binding to its DNA response elements as an heterodimer with Retinoid X Receptor (RXR). This nuclear receptor is implicated in the homeostasis of numerous endobiotics, such as glucose, lipids, steroids and bile acids. Additionally, the activation of PXR induces expression of drug metabolizing enzymes (DMEs) and transporters, including multidrug resistance protein 1 (MDR1), leading to regulation of xenobiotic metabolism and drug-drug interactions. New roles for PXR have been established in inflammatory bowel disease, bone homeostasis, liver steatosis, antifibrogenesis and oxidative stress. PXR has, additionally, a multifactorial impact on cancer, either by directly affecting cell proliferation and apoptosis or by inducing chemotherapy resistance, in colon, breast, prostate, and endometrial cancer, and in osteosarcoma. PXR polymorphisms may also have clinical significance in certain types of cancer and their treatment. Further studies are needed in order to clarify the mechanisms involved in PXR-regulated carcinogenesis. PXR down-regulation could be considered as a novel therapeutic approach to overcome chemoresistance, while future research should be mainly focused on modulating PXR status in order to increase chemotherapy effectiveness and finally improve cancer patient prognosis."]
[23369858,0,0,0,0,2013,"What role (if any) does the highly conserved CSB-PGBD3 fusion protein play in Cockayne syndrome?","Weiner",23369858,"What role (if any) does the highly conserved CSB-PGBD3 fusion protein play in Cockayne syndrome?    Abstract:   The PGBD3 piggyBac transposon inserted into CSB intron 5 early in the primate lineage. As a result of alternative splicing, the human CSB gene now encodes three proteins: CSB, a CSB-PGBD3 fusion protein that joins the N-terminal CSB domain to the C-terminal PGBD3 transposase domain, and PGBD3 transposase. The fusion protein is as highly conserved as CSB, suggesting that it is advantageous in health; however, expression of the fusion protein in CSB-null cells induces a constitutive interferon (IFN) response. The fusion protein binds in vivo to PGBD3-related MER85 elements, but is also tethered to c-Jun, TEAD1, and CTCF motifs by interactions with the cognate transcription factors. The fusion protein regulates nearby genes from the c-Jun (and to a lesser extent TEAD1 and CTCF) motifs, but not from MER85 elements. We speculate that the fusion protein interferes with CSB-dependent chromatin remodeling, generating double-stranded RNA (dsRNA) that induces an IFN response through endosomal TLR or cytoplasmic RIG-I and/or MDA5 RNA sensors. We suggest that the fusion protein was fixed in primates because an elevated IFN response may help to fight viral infection. We also speculate that an inappropriate IFN response may contribute to the clinical presentation of CS."]
[23246696,0,0,0,0,2013,"Regulation of the MIR155 host gene in physiological and pathological processes.","Elton",23246696,"Regulation of the MIR155 host gene in physiological and pathological processes.    Abstract:   MicroRNAs (miRNAs), a family of small nonprotein-coding RNAs, play a critical role in posttranscriptional gene regulation by acting as adaptors for the miRNA-induced silencing complex to inhibit gene expression by targeting mRNAs for translational repression and/or cleavage. miR-155-5p and miR-155-3p are processed from the B-cell Integration Cluster (BIC) gene (now designated, MIR155 host gene or MIR155HG). MiR-155-5p is highly expressed in both activated B- and T-cells and in monocytes/macrophages. MiR-155-5p is one of the best characterized miRNAs and recent data indicate that miR-155-5p plays a critical role in various physiological and pathological processes such as hematopoietic lineage differentiation, immunity, inflammation, viral infections, cancer, cardiovascular disease, and Down syndrome. In this review we summarize the mechanisms by which MIR155HG expression can be regulated. Given that the pathologies mediated by miR-155-5p result from the over-expression of this miRNA it may be possible to therapeutically attenuate miR-155-5p levels in the treatment of several pathological processes."]
[23186772,0,0,0,0,2013,"Adjunctive skin care of the brow and periorbital region.","Bucay",23186772,"Adjunctive skin care of the brow and periorbital region.    Abstract:   This article discusses adjunctive skin care of the brow and periorbital region. Anatomic properties of eyelid skin require skin care products specifically suited to this area. Common patient concerns, including wrinkles, infraorbital dark circles, puffiness, and thinning eyebrows and eyelashes, are addressed in the context of contributing anatomic and physiologic factors and the classes of and/or specific ingredients targeting these problems."]
[23114975,0,0,0,0,2012,"Etiological and pathogenic factors in congenital diaphragmatic hernia.","Sluiter",23114975,"Etiological and pathogenic factors in congenital diaphragmatic hernia.    Abstract:   Congenital diaphragmatic hernia (CDH) is a congenital anomaly associated with an increased mortality and morbidity. In this article, we review the currently known etiological and pathogenic factors in CDH."]
[23071480,1,0,0,1,2012,"ZBTB16-RARα variant of acute promyelocytic leukemia with tuberculosis: a case report and review of literature.","Palta",23071480,"ZBTB16-RARα variant of acute promyelocytic leukemia with tuberculosis: a case report and review of literature.    Abstract:   A 23-year-old male presented with pulmonary tuberculosis and swelling of both lower limbs. He was put on antitubercular treatment. Hemogram showed mild anemia and Pseudo Pelger-huet cells. The bone marrow (BM) examination showed 52% promyelocytes with regular round to oval nuclei, few granules and were positive for CD13 and CD33, and negative for HLA-DR. Cytogenetic analysis of the BM aspirate revealed an apparently balanced t(11;17)(q23;q21). Final diagnosis rendered was acute promyelocytic leukemia (APL) with t(11;17)(q23;q21); ZBTB16/RARA. APL is a distinct subtype of acute myeloid leukemia. The variant APL with t(11;17)(q23;q21) cases that are associated with the ZBTB16/RARA fusion gene have been reported as being resistant to all-trans-retinoic acid (ATRA). Therefore, differential diagnosis of variant APL with t(11;17)(q23;q12) from classical APL with t(15;17)(q22;q12); PML-RARA is very important. Here we have discussed the importance of distinct morphology of variant APL and also significance of rare presentation with tuberculosis."]
[23043525,1,0,0,1,2012,"Oral lichen planus: a report and review of an autoimmune-mediated condition in gingiva.","Pendyala",23043525,"Oral lichen planus: a report and review of an autoimmune-mediated condition in gingiva.    Abstract:   Oral lichen planus (OLP) is a chronic autoimmune, mucocutaneous disease that affects the oral mucosa as well as the skin, genital mucosa, scalp, and nails. It is one of the most common dermatological diseases presenting in the oral cavity. An immune-mediated pathogenesis is recognized in lichen planus, although the exact etiology is unknown. The disease most commonly affects middle-aged females. It is infrequently found in children, with a prevalence of about 0.03%, and reports of this are scarce in the literature. The erosive and atrophic forms of OLP are less common, yet they are more likely to cause symptoms. OLP is the target of much controversy, especially in relation to its potential for malignancy. Thus, it is important for clinicians to maintain a high index of suspicion for all intraoral lichenoid lesions. Periodic follow-up of all patients with OLP is recommended. In view of the above, the authors highlight a case of gingival erosive lichen planus affecting a 17-year-old adolescent without concomitant cutaneous lesions, with special emphasis on clinical and microscopic characteristics of the condition and management with retinoids and steroid therapy."]
[23000736,0,0,0,0,2012,"Understanding velocardiofacial syndrome: how recent discoveries can help you improve your patient outcomes.","Chinnadurai",23000736,"Understanding velocardiofacial syndrome: how recent discoveries can help you improve your patient outcomes.    Abstract:    PURPOSE OF REVIEW : Improved recognition of velocardiofacial syndrome (VCFS) has led to increasing awareness of VCFS by otolaryngologists. Understanding the developmental biologic processes affected in VCFS patients will help improve treatment and outcomes. Advanced application of molecular labeling techniques has better outlined the role of T-Box transcription factor 1 (TBX1) as the primary genetic anomaly leading to VCFS. TBX1 plays multiple roles during branchial, cardiac, and craniofacial development and increased understanding of how these systems are affected by TBX1 mutations will improve patient outcomes. Furthermore, additional modifiers of TBX1 expression have been identified that may explain the variability of VCFS phenotypes. The phenotypic spectrum of VCFS may include cardiac anomalies, velopharyngeal insufficiency, aberrant calcium metabolism, and immune dysfunction. Recent interest has focused on the cognitive and neuropsychiatric manifestations of VCFS. Improved understanding of the biology of VCFS associated mutations has the potential to improve therapeutic outcomes.  RECENT FINDINGS : This article will discuss recent developmental biologic understanding of the role of TBX1 and genetic modifiers generating the phenotypic variability seen in VCFS patients. Special attention is given to advances in the realms of immunodeficiency, hypocalcemia, cardiac and arterial patterning anomalies, velopharyngeal insufficiency, as well as cognitive and psychiatric problems.  SUMMARY : Enhanced understanding of the multiple systems affected by TBX1 mutations will result in improved patient outcomes and improved family education. Future research will lead to improved detection of potential targets for gene therapy and change the way physicians counsel families and treat patients."]
[22963233,3,0,0,3,2013,"U.K. consensus statement on safe clinical prescribing of bexarotene for patients with cutaneous T-cell lymphoma.","Scarisbrick",22963233,"U.K. consensus statement on safe clinical prescribing of bexarotene for patients with cutaneous T-cell lymphoma.    Abstract:    BACKGROUND : Bexarotene is a synthetic retinoid from the subclass of retinoids called rexinoids which selectively activate retinoid X receptors. It has activity in cutaneous T-cell lymphoma (CTCL) and has been approved by the European Medicines Agency since 1999 for treatment of the skin manifestations of advanced-stage (IIB-IVB) CTCL in adult patients refractory to at least one systemic treatment. In vivo bexarotene produces primary hypothyroidism which may be managed with thyroxine replacement. It also affects lipid metabolism, typically resulting in raised triglycerides, which requires prophylactic lipid-modification therapy. Effects on neutrophils, glucose and liver function may also occur. These side-effects are dose dependent and may be controlled with corrective therapy or dose adjustments.  OBJECTIVES :   To produce a U.K. statement outlining a bexarotene dosing schedule and monitoring protocol to enable bexarotene prescribers to deliver bexarotene safely for optimal effect.  METHODS :  Leaders from U.K. supraregional centres produced this consensus statement after a series of meetings and a review of the literature.  RESULTS :  The statement outlines a bexarotene dosing schedule and monitoring protocol. This gives instructions on monitoring and treating thyroid, lipid, liver, blood count, creatine kinase, glucose and amylase abnormalities. The statement also includes algorithms for a bexarotene protocol and lipid management, which may be used in the clinical setting.  CONCLUSION :  Clinical prescribing of bexarotene for patients with CTCL requires careful monitoring to allow safe administration of bexarotene at the optimal dose."]
[22945385,1,0,0,1,2012,"Does the cranial mesenchyme contribute to neural fold elevation during neurulation?","Zohn",22945385,"Does the cranial mesenchyme contribute to neural fold elevation during neurulation?    Abstract:   The central nervous system is derived from the neural plate, which undergoes a series of complex morphogenetic events resulting in formation of the neural tube in a process known as neurulation. The cellular behaviors driving neurulation in the cranial region involve forces generated by the neural tissue itself as well as the surrounding epithelium and mesenchyme. Of interest, the cranial mesenchyme underlying the neural plate undergoes stereotypical rearrangements hypothesized to drive elevation of the neural folds. As the neural folds rise, the hyaluronate-rich extracellular matrix greatly expands resulting in increased space between individual cranial mesenchyme cells. Based on inhibitor studies, expansion of the extracellular matrix has been implicated in driving neural fold elevation; however, because the surrounding neural and epidermal ectoderm were also affected by inhibitor exposure, these studies are inconclusive. Similarly, treatment of neurulating embryos with teratogenic doses of retinoic acid results in altered organization of the cranial mesenchyme, but alterations in surrounding tissues are also observed. The strongest evidence for a critical role for the cranial mesenchyme in neural fold elevation comes from studies of genes expressed exclusively in the cranial mesenchyme that when mutated result in exencephaly associated with abnormal organization of the cranial mesenchyme. Twist is the best studied of these and is expressed in both the paraxial mesoderm and neural crest derived cranial mesenchyme. In this article, we review the evidence implicating the cranial mesenchyme in providing a driving force for neural fold elevation to evaluate whether there are sufficient data to support this hypothesis."]
[22895955,0,0,0,0,2012,"Vitamin A supplementation for cystic fibrosis.","Bonifant",22895955,"Vitamin A supplementation for cystic fibrosis.    Abstract:    BACKGROUND : People with cystic fibrosis and pancreatic insufficiency are at risk of fat soluble vitamin deficiency as these vitamins (A, D, E and K) are co-absorbed with fat. Thus, some cystic fibrosis centres routinely administer these vitamins as supplements but the centres vary in their approach of addressing the possible development of deficiencies in these vitamins. Vitamin A deficiency causes predominantly eye and skin problems while supplementation of vitamin A to excessive levels may cause harm to the respiratory and skeletal systems in children. Thus a systematic review on vitamin A supplementation in people with cystic fibrosis would help guide clinical practice.  OBJECTIVES : To determine if vitamin A supplementation in children and adults with CF: 1. reduces the frequency of vitamin A deficiency disorders; 2. improves general and respiratory health; 3. increases the frequency of vitamin A toxicity.  SEARCH METHODS : We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of the most recent search of the Groups Cystic Fibrosis Trials Register: 23 May 2012.  SELECTION CRITERIA : All randomised or quasi-randomised controlled trials comparing all preparations of oral vitamin A used as a supplement compared to either no supplementation (or placebo) at any dose and for any duration, in children or adults with cystic fibrosis (defined by sweat tests or genetic testing) with and without pancreatic insufficiency.  DATA COLLECTION AND ANALYSIS : No relevant studies for inclusion were identified in the search.  MAIN RESULTS : No studies were included in this review.  AUTHORS CONCLUSIONS : As there were no randomised or quasi-randomised controlled trials identified, we cannot draw any conclusions on the benefits (or otherwise) of regular administration of vitamin A in people with cystic fibrosis. Until further data are available, country or region specific guidelines on the use of vitamin A in people with cystic fibrosis should be followed."]
[22888564,1,0,0,1,2012,"Provocative pearls in diagnosing and treating acute promyelocytic leukemia.","Stein",22888564,"Provocative pearls in diagnosing and treating acute promyelocytic leukemia.    Abstract:   The introduction of all-trans retinoic acid (ATRA) into routine clinical practice changed the outcome of acute promyelocytic leukemia (APL) from the most fatal to the most curable subtype of acute myeloid leukemia (AML). Patients who do not survive generally succumb within the first 30 days after presentation or diagnosis, often from intracranial or pulmonary hemorrhage caused by the characteristic coagulopathy associated with this disease. For the majority of patients who avoid hemorrhagic complications, the goals of decreasing the side effects of diagnosis and treatment-including pain, inpatient hospital days, and late sequelae of cytotoxic chemotherapy-have emerged as paramount. Here, we discuss novel and provocative observations regarding diagnostic and treatment strategies for APL that are likely to emerge as standards of care in the next 5 years, and that may improve the rate of early hemorrhagic death and decrease diagnosis- and treatment-related morbidity."]
[22784035,1,0,0,1,2012,"Nail psoriasis: a review.","Tan",22784035,"Nail psoriasis: a review.    Abstract:   Nail psoriasis is common, occurring in up to half of patients with psoriasis and in 90% of patients with psoriatic arthritis. Left untreated, it may progress to debilitating nail disease, which leads to significant functional impairment. The most common clinical signs of nail psoriasis are nail plate pitting and onycholysis. Other classical signs include oil drop discoloration, subungual hyperkeratosis, and splinter hemorrhages. The modified Nail Psoriasis Severity Index (mNAPSI) can be used to grade the severity of nail psoriasis, while the Nail Psoriasis Quality of Life Scale (NPQ10) is a questionnaire that evaluates the impact of nail psoriasis on the patients functional status and quality of life. Treatment of nail psoriasis should be individualized according to the patients preferences, severity of nail changes, and presence of skin and/or joint involvement. Both topical and intralesional therapies are safe and effective treatment modalities for nail disease, but are limited by poor adherence and pain, respectively. Systemic therapy such as oral retinoids may be considered for widespread nail disease causing significant morbidity. Among biologic agents, tumor necrosis factor-α inhibitors and T-cell-targeted therapies such as ustekinumab may be useful for refractory severe nail psoriasis."]
[22782502,1,0,0,1,2013,"Molecular mechanisms of vitamin D action.","Haussler",22782502,"Molecular mechanisms of vitamin D action.    Abstract:   The hormonal metabolite of vitamin D, 1α,25-dihydroxyvitamin D(3) (1,25D), initiates biological responses via binding to the vitamin D receptor (VDR). When occupied by 1,25D, VDR interacts with the retinoid X receptor (RXR) to form a heterodimer that binds to vitamin D responsive elements in the region of genes directly controlled by 1,25D. By recruiting complexes of either coactivators or corepressors, ligand-activated VDR-RXR modulates the transcription of genes encoding proteins that promulgate the traditional functions of vitamin D, including signaling intestinal calcium and phosphate absorption to effect skeletal and calcium homeostasis. Thus, vitamin D action in a particular cell depends upon the metabolic production or delivery of sufficient concentrations of the 1,25D ligand, expression of adequate VDR and RXR coreceptor proteins, and cell-specific programming of transcriptional responses to regulate select genes that encode proteins that function in mediating the effects of vitamin D. For example, 1,25D induces RANKL, SPP1 (osteopontin), and BGP (osteocalcin) to govern bone mineral remodeling; TRPV6, CaBP(9k), and claudin 2 to promote intestinal calcium absorption; and TRPV5, klotho, and Npt2c to regulate renal calcium and phosphate reabsorption. VDR appears to function unliganded by 1,25D in keratinocytes to drive mammalian hair cycling via regulation of genes such as CASP14, S100A8, SOSTDC1, and others affecting Wnt signaling. Finally, alternative, low-affinity, non-vitamin D VDR ligands, e.g., lithocholic acid, docosahexaenoic acid, and curcumin, have been reported. Combined alternative VDR ligand(s) and 1,25D/VDR control of gene expression may delay chronic disorders of aging such as osteoporosis, type 2 diabetes, cardiovascular disease, and cancer."]
[22649910,1,0,0,1,2012,"Determination of vitamin A in infant formula and adult nutritionals by UPLC-UV: First Action 2011.07.","Trisconi",22649910,"Determination of vitamin A in infant formula and adult nutritionals by UPLC-UV: First Action 2011.07.    Abstract:   Vitamin A, a fat-soluble vitamin, is essential for health and plays an important part in vision, bone growth, reproduction, regulating the immune system, cell function, and skin health. Due to the advances in technology and the expansion of its uses, LC technologies are being studied for effectiveness in detecting and quantifying vitamin A in an effort to help determine the amount of vitamin A in various types of samples. For this reason, an Expert Review Panel agreed on June 29, 2011, at the quot;Standards Development and International Harmonization: AOAC INTERNATIONAL Mid-Year Meeting,quot; to approve quot;Determination of Vitamin A in Infant Formula and Adult Nutritionals by UPLC-UVquot; as AOAC Official Method 2011.07. To move from First to Final Action status, it was recommended that additional information be generated for all types of infant formulas and adult nutritional formula matrixes at varied concentration levels, as indicated in the standard method performance requirements. International units or retinol equivalents typically represent the concentration of vitamin A in food and supplements. However, for the purpose of this method, the concentration represented is presented in microg/100 g."]
[22595346,1,0,0,1,2012,"The neural crest in cardiac congenital anomalies.","Keyte",22595346,"The neural crest in cardiac congenital anomalies.    Abstract:   This review discusses the function of neural crest as they relate to cardiovascular defects. The cardiac neural crest cells are a subpopulation of cranial neural crest discovered nearly 30 years ago by ablation of premigratory neural crest. The cardiac neural crest cells are necessary for normal cardiovascular development. We begin with a description of the crest cells in normal development, including their function in remodeling the pharyngeal arch arteries, outflow tract septation, valvulogenesis, and development of the cardiac conduction system. The cells are also responsible for modulating signaling in the caudal pharynx, including the second heart field. Many of the molecular pathways that are known to influence specification, migration, patterning and final targeting of the cardiac neural crest cells are reviewed. The cardiac neural crest cells play a critical role in the pathogenesis of various human cardiocraniofacial syndromes such as DiGeorge, Velocardiofacial, CHARGE, Fetal Alcohol, Alagille, LEOPARD, and Noonan syndromes, as well as Retinoic Acid Embryopathy. The loss of neural crest cells or their dysfunction may not always directly cause abnormal cardiovascular development, but are involved secondarily because crest cells represent a major component in the complex tissue interactions in the head, pharynx and outflow tract. Thus many of the human syndromes linking defects in the heart, face and brain can be better understood when considered within the context of a single cardiocraniofacial developmental module with the neural crest being a key cell type that interconnects the regions."]
[22521611,1,0,0,1,2012,"New developments in the second heart field.","Zaffran",22521611,"New developments in the second heart field.    Abstract:   During cardiac looping the heart tube elongates by addition of progenitor cells from adjacent pharyngeal mesoderm to the arterial and venous poles. This cell population, termed the second heart field, was first identified ten years ago and many studies in the intervening decade have refined our understanding of how heart tube elongation takes place and identified signaling pathways that regulate proliferation and differentiation during progressive contribution of second heart field cells to the embryonic heart. It has also become apparent that defective second heart field development results in common congenital heart anomalies affecting both the conotruncal region and venous pole of the heart, including atrial and atrioventricular septal defects. In this review we focus on a series of recent papers that have identified new regulators of second heart field development, in particular the retinoic acid signaling pathway and HOX, SIX and EYA transcription factors. We also discuss new findings concerning the regulation of fibroblast growth factor signaling during second heart field deployment and studies that have implicated FGF10 and FGF3 in outflow tract development in addition to FGF8. Second heart field derived parts of the heart share common progenitor cells in pharyngeal mesoderm with craniofacial skeletal muscles and recent findings from xenopus, zebrafish and the protochordate Ciona intestinalis provide insights into the evolution of the second heart field during vertebrate radiation."]
[22463723,1,0,0,1,2012,"Classical to current approach for treatment of psoriasis: a review.","Rahman",22463723,"Classical to current approach for treatment of psoriasis: a review.    Abstract:   Psoriasis is a genetic predisposition with T-cell mediated autoimmune inflammatory skin disorder, characterized by cutaneous inflammation, increased epidermal proliferation, hyperkeratosis, angiogenesis, and abnormal keratinization that affects up to 2 - 3% of the population worldwide. Common therapies that are used for the treatment of psoriasis include topical, systemic, phototherapy, combination, herbal therapy and novel molecules. Topically used agents include Vit D, calcipotriol, corticosteroids, dithranol and retinoids etc. Systemically used agents include methotrexate and cyclosporine etc. Phototherapy includes UV-B, Psoralen plus ultraviolet therapy and excimer laser etc. These therapies have a number of potential problems, such as limited in efficacy, inconvenience, organ toxicity, carcinogenic and broadband immunosuppression. In natural treatment a variety of natural agents such as methanolic extracts of duzhong (Eucommia ulmoides Oliv.), yerba mate (Ilex paraguariensis,) linseed oil, fish oil, and Indigo naturalis etc., that modulates T cell and cytokine action at various steps along with the pathogenic sequence have been developed. But till now there is no more in vivo, dose and its efficacy data has been established. Current therapy includes biologicals, small molecules inhibitor and enzyme inhibitors etc, which serve as novel therapeutic options for psoriasis treatment. All these avoid the side effects of the prebiologically developed systemic agents including hepatotoxicity, nephrotoxicity, and bone marrow suppression. Currently, Denilukin diftitox, Efalizumab, Alefacept, Ustekinumab and Etanercept are approved by the FDA, and others molecules are at clinical stage. Patents issued by the US office are also included in current psoriasis treatment scenario. In the United States, biologicals are widely used for moderate-to-severe psoriasis. But because of the high cost of medication and their availability in injection form, it remains to be seen how widely these agents will be utilized worldwide. Still, developing countries prefer conventional drugs."]
[22361284,4,0,0,4,2012,"Vitamin a: history, current uses, and controversies.","Chapman",22361284,"Vitamin a: history, current uses, and controversies.    Abstract:   Vitamin A is required for the proper functioning of many important metabolic and physiologic activities, including vision, gene transcription, the immune system and skin cell differentiation. Both excessive and deficient levels of vitamin A lead to poor functioning of many human systems. The biologically active form, retinoic acid, binds to nuclear receptors that facilitate transcription that ultimately leads to its physiological effects. Retinoids are derivatives of vitamin A that are medications used to treat acne vulgaris, psoriasis, ichthyosis (and other disorders of keratinization), skin cancer prevention as well as several bone marrow derived neoplasias. Systemic retinoids are teratogenic and have to be prescribed with caution and close oversight. Other potential adverse events are controversial. These include the relationship of retinoid derivatives in sunscreens, their effects on bone mineral density, depression and suicidal ideation and inflammatory bowel disease. These controversies will be discussed in detail."]
[22292422,9,0,0,9,2012,"Roles of vitamin A status and retinoids in glucose and fatty acid metabolism.","Zhao",22292422,"Roles of vitamin A status and retinoids in glucose and fatty acid metabolism.    Abstract:   The rising prevalence of metabolic diseases, such as obesity and diabetes, has become a public health concern. Vitamin A (VA, retinol) is an essential micronutrient for a variety of physiological processes, such as tissue differentiation, immunity, and vision. However, its role in glucose and lipid metabolism has not been clearly defined. VA activities are mediated by the metabolite of retinol catabolism, retinoic acid, which activates the retinoic acid receptor and retinoid X receptor (RXR). Since RXR is an obligate heterodimeric partner for many nuclear receptors involved in metabolism, it is reasonable to assume that VA status and retinoids contribute to glucose and lipid homeostasis. To date, the impacts of VA and retinoids on energy metabolism in animals and humans have been demonstrated in some basic and clinical investigations. This review summarizes the effects of VA status and retinoid treatments on metabolism of the liver, adipocytes, pancreatic β-cells, and skeletal muscle. It proposes a mechanism by which the dietary and hormonal signals converge on the promoter of sterol regulatory element-binding protein 1c gene to induce its expression, and in turn, the expression of lipogenic genes in hepatocytes. Future research projects relevant to the VAs roles in metabolic diseases are also discussed."]
[22220265,2,0,0,2,2011,"Pathogenesis and treatment of thrombohemorrhagic diathesis in acute promyelocytic leukemia.","Falanga",22220265,"Pathogenesis and treatment of thrombohemorrhagic diathesis in acute promyelocytic leukemia.    Abstract:   Acute promyelocytic leukemia (APL) is a distinct subtype of myeloid leukemia characterized by t(15;17) chromosomal translocation, which involves the retinoic acid receptor-alpha (RAR-alpha). APL typically presents with a life-threatening hemorrhagic diathesis. Before the introduction of all-trans retinoic acid (ATRA) for the cure of APL, fatal hemorrhages due, at least in part, to the APL-associated coagulopathy, were a major cause of induction remission failure. The laboratory abnormalities of blood coagulation found in these patients indicate the occurrence of a hypercoagulable state. Major determinants of the coagulopathy of APL are endogenous factors expressed by the leukemic cells, including procoagulant factors, fibrinolytic proteins, and non-specific proteolytic enzymes. In addition, these cells have an increased capacity to adhere to the vascular endothelium, and to secrete inflammatory cytokines [i.e. interleukin-1beta (IL-1beta) and tumor necrosis factor (TNF-alpha)], which in turn stimulate the expression of prothrombotic activities by endothelial cells and leukocytes. ATRA can interfere with each of the principal hemostatic properties of the leukemic cell, thus reducing the APL cell procoagulant potential, in parallel to the induction of cellular differentiation. This effect occurs in vivo, in the bone marrow of APL patients receiving ATRA, and is associated with the improvement of the bleeding symptoms. Therapy with arsenic trioxide (ATO) also beneficially affects coagulation in APL. However, early deaths from bleeding still remain a major problem in APL and further research is required in this field. In this review, we will summarize our current knowledge of the pathogenesis of the APL-associated coagulopathy and will overview the therapeutic approaches for the management of this complication."]
[22214468,1,0,0,1,2012,"Congenital diaphragmatic hernia.","Tovar",22214468,"Congenital diaphragmatic hernia.    Abstract:   Congenital Diaphragmatic Hernia (CDH) is defined by the presence of an orifice in the diaphragm, more often left and posterolateral that permits the herniation of abdominal contents into the thorax. The lungs are hypoplastic and have abnormal vessels that cause respiratory insufficiency and persistent pulmonary hypertension with high mortality. About one third of cases have cardiovascular malformations and lesser proportions have skeletal, neural, genitourinary, gastrointestinal or other defects. CDH can be a component of Pallister-Killian, Fryns, Ghersoni-Baruch, WAGR, Denys-Drash, Brachman-De Lange, Donnai-Barrow or Wolf-Hirschhorn syndromes. Some chromosomal anomalies involve CDH as well. The incidence is lt; 5 in 10,000 live-births. The etiology is unknown although clinical, genetic and experimental evidence points to disturbances in the retinoid-signaling pathway during organogenesis. Antenatal diagnosis is often made and this allows prenatal management (open correction of the hernia in the past and reversible fetoscopic tracheal obstruction nowadays) that may be indicated in cases with severe lung hypoplasia and grim prognosis. Treatment after birth requires all the refinements of critical care including extracorporeal membrane oxygenation prior to surgical correction. The best hospital series report 80% survival but it remains around 50% in population-based studies. Chronic respiratory tract disease, neurodevelopmental problems, neurosensorial hearing loss and gastroesophageal reflux are common problems in survivors. Much more research on several aspects of this severe condition is warranted."]
[22177102,0,0,0,0,2011,"Emerging treatments and signaling pathway inhibitors.","Tang",22177102,"Emerging treatments and signaling pathway inhibitors.    Abstract:   A number of therapies that target components of the Hedgehog signaling pathway currently are in clinical trials. The specific molecules that seem most promising in basal cell carcinoma and a number of other cancers are those that target the Smoothened transmembrane protein. The pivotal phase II trials have been completed on the Smoothened inhibitor known as GDC-0449; five other agents (BMS-833923, LDE225, LEQ506, IPI926, and TAK-441) have also shown promise in animal studies and early clinical trials and have shown some efficacy in a variety of cancers that are affected by the Hedgehog signaling pathway."]
[22166416,1,0,0,1,2012,"Neurorestoration.","Airavaara",22166416,"Neurorestoration.    Abstract:   Although initially thought to be important primarily in neural development, a number of trophic proteins have been found to have neuroprotective and neuroregenerative activity in the adult central nervous system, particularly for midbrain dopamine neurons (MDN). Neurorestoration is potentially feasible for MDN since there is an initial loss of phenotype for these neurons in Parkinsons disease (PD) rather than neuronal death. There is a considerable recent literature on trophic properties of TGF-β superfamily proteins for MDNs, including glial cell-derived neurotrophic factor (GDNF), neurturin, and bone morphogenetic proteins (BMPs). This paper will review studies with the factors listed above, as well as describe more recent studies with two newly described trophic proteins, MANF and CDNF. Data will be presented from various animal models of PD suggesting that these trophic proteins may eventually lead to PD therapeutics in man. In addition, some data on small molecules with neuroprotective properties (AP(4)A, retinoic acid and vitamin D(3)) will also be described."]
[22167840,1,0,0,1,2011,"[Matrix Gla-protein and its role in vascular wall calcification].","Harbuzova",22167840,"[Matrix Gla-protein and its role in vascular wall calcification].    Abstract:   Data on the structure of matrix Gla-protein (MGP), its chemical characteristics, regulation of synthesis and post-translational modifications are described. The information on the structure of the MGP gene, its well distributed polymorphisms are presented. Factors that regulate expression and activity of MGP include vitamin D, retinoic acid, extracellular calcium ions, cytokines, and some hormones. It is emphasized that MGP is an important inhibitor of calcification of soft tissues. These properties of this protein are associated with the presence of residues of gamma-carboxiglutamic acid of its molecule. Four possible mechanisms of anticalcinogenic action of MGP are described: binding with calcium ions and crystals of hydroxyapatite, binding to extracellular matrix components, interaction with bone morphogenetic protein (BMP-2) and elimination the effects of the latter, participation in the regulation of apoptosis. It is emphasized that the study of allelic variants of the MGP gene is important in the context of their possible association with the development of cardiovascular and other diseases."]
[22007948,1,0,0,1,2012,"Long-term treatment of severe SAPHO syndrome with adalimumab: case report and a review of the literature.","Garcovich",22007948,"Long-term treatment of severe SAPHO syndrome with adalimumab: case report and a review of the literature.    Abstract:   SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome defines an association of inflammatory cutaneous disorders with osteoarticular manifestations and represents a clinical and therapeutic challenge. We report a case of severe SAPHO syndrome with acne conglobata and a diffuse involvement of the anterior chest wall and sacroiliac joints that required treatment with isotretinoin and adalimumab, a new fully human anti-tumor necrosis factor (TNF)-α monoclonal antibody. Combination treatment determined a complete clinical remission of cutaneous and osteoarticular manifestations after 48 weeks. Despite maintenance of clinical remission, follow-up imaging studies after 24 months of adalimumab monotherapy revealed osteoarticular disease progression, with features of inflammatory osteitis. TNFα antagonists have been used as third-line therapy for SAPHO syndrome in single case reports or case series, but these lack consistent long-term follow-up. SAPHO syndrome can present an intermittent-favorable course in the majority of cases as well as a chronic-progressive course, the latter requiring aggressive combination treatment with TNFα antagonists and conventional systemic agents."]
[21967161,0,0,3,3,2011,"Vitamin A and clefting: putative biological mechanisms.","Ackermans",21967161,"Vitamin A and clefting: putative biological mechanisms.    Abstract:   Nutritional factors such as vitamin intake contribute to the etiology of cleft palate. Vitamin A is a regulator of embryonic development. Excess vitamin A can cause congenital malformations such as spina bifida and cleft palate. Therefore, preventive nutritional strategies are required. This review identifies putative biological mechanisms underlying the association between maternal vitamin A intake and cleft palate. Excessive vitamin A may disturb all three stages of palatogenesis: 1) during shelf outgrowth, it may decrease cell proliferation and thus prevent tissue development; 2) it may prevent shelf elevation by affecting extracellular matrix composition and hydration; and 3) during shelf fusion, it may affect epithelial differentiation and apoptosis, which precludes the formation of a continuous palate. In general, high doses of vitamin A affect palatogenesis through interference with cell proliferation and growth factors such as transforming growth factor β and platelet-derived growth factor. The effects of lower doses of vitamin A need to be investigated in greater depth in order to improve public health recommendations."]
[21967159,1,0,0,1,2011,"Vitamins and bone health: beyond calcium and vitamin D.","Ahmadieh",21967159,"Vitamins and bone health: beyond calcium and vitamin D.    Abstract:   Osteoporosis is a major health disorder associated with an increased risk of fracture. Nutrition is among the modifiable factors that influence the risk of osteoporosis and fracture. Calcium and vitamin D play important roles in improving bone mineral density and reducing the risk of fracture. Other vitamins appear to play a role in bone health as well. In this review, the findings of studies that related the intake and/or the status of vitamins other than vitamin D to bone health in animals and humans are summarized. Studies of vitamin A showed inconsistent results. Excessive, as well as insufficient, levels of retinol intake may be associated with compromised bone health. Deficiencies in vitamin B, along with the consequent elevated homocysteine level, are associated with bone loss, decreased bone strength, and increased risk of fracture. Deficiencies in vitamins C, E, and K are also associated with compromised bone health; this effect may be modified by smoking, estrogen use or hormonal therapy after menopause, calcium intake, and vitamin D. These findings highlight the importance of adequate nutrition in preserving bone mass and reducing the risk of osteoporosis and fractures."]
[21952113,7,0,0,7,2011,"Interaction of the retinoic acid signaling pathway with spicule formation in the marine sponge Suberites domuncula through activation of bone morphogenetic protein-1.","Müller",21952113,"Interaction of the retinoic acid signaling pathway with spicule formation in the marine sponge Suberites domuncula through activation of bone morphogenetic protein-1.    Abstract:    BACKGROUND : The formation of the spicules in siliceous sponges involves the formation of cylinder-like structures in the extraspicular space, composed of the enzyme silicatein and the calcium-dependent lectin.  SCOPE OF REVIEW : Molecular cloning of the cDNAs (carotene dioxygenase, retinal dehydrogenase, and BMB-1 [bone morphogenic protein-1]) from the demosponge Suberites domuncula was performed. These tools were used to understand the retinoid metabolism in the animal by qRT-PCR, immunoblotting and TEM.  MAJOR CONCLUSIONS : We demonstrate that silintaphin-2, a silicatein-interacting protein, is processed from a longer-sized 15-kDa precursor to a truncated, shorter-sized 13kDa calcium-binding protein via proteolytic cleavage at the dipeptide Ala↓Asp, mediated by BMP-1. The expression of this protease as well as the expression of two key enzymes of the carotinoid metabolism, the β,β-carotene-15,15-dioxygenase and the retinal dehydrogenase/reductase, were found to be strongly up-regulated by retinoic acid. Hence retinoic acid turned out to be a key factor in skeletogenesis in the most ancient still existing metazoans, the sponges.  GENERAL SIGNIFICANCE : It is shown that retinoic acid regulates the formation of the organic cylinder that surrounds the axis of the spicules and enables, as a scaffold, the radial apposition of new silica layers and hence the growth of the spicules."]
[21932165,0,0,0,0,2012,"The role of vitamin D in the FGF23, klotho, and phosphate bone-kidney endocrine axis.","Haussler",21932165,"The role of vitamin D in the FGF23, klotho, and phosphate bone-kidney endocrine axis.    Abstract:   1,25-dihydroxyvitamin D (1,25D), through association with the nuclear vitamin D receptor (VDR), exerts control over a novel endocrine axis consisting of the bone-derived hormone FGF23, and the kidney-expressed klotho, CYP27B1, and CYP24A1 genes, which together prevent hyperphosphatemia/ectopic calcification and govern the levels of 1,25D to maintain bone mineral integrity while promoting optimal function of other vital tissues. When occupied by 1,25D, VDR interacts with RXR to form a heterodimer that binds to VDREs in the region of genes directly controlled by 1,25D (e.g., FGF23, klotho, Npt2c, CYP27B1 and CYP24A1). By recruiting complexes of comodulators, activated VDR initiates a series of events that induces or represses the transcription of genes encoding proteins such as: the osteocyte-derived hormone, FGF23; the renal anti-senescence factor and protein co-receptor for FGF23, klotho; other mediators of phosphate transport including Npt2a/c; and vitamin D hormone metabolic enzymes, CYP27B1 and CYP24A1. The mechanism whereby osteocytes are triggered to release FGF23 is yet to be fully defined, but 1,25D, phosphate, and leptin appear to play major roles. The kidney responds to FGF23 to elicit CYP24A1-catalyzed detoxification of the 1,25D hormone while also repressing both Npt2a/c to mediate phosphate elimination and CYP27B1 to limit de novo 1,25D synthesis. Comprehension of these skeletal and renal actions of 1,25D should facilitate the development of novel mimetics to prevent ectopic calcification, chronic renal and vascular disease, and promote healthful aging."]
[21924649,0,0,0,0,2013,"When urothelial differentiation pathways go wrong: implications for bladder cancer development and progression.","DeGraff",21924649,"When urothelial differentiation pathways go wrong: implications for bladder cancer development and progression.    Abstract:   Differentiation is defined as the ability of a cell to acquire full functional behavior. For instance, the function of bladder urothelium is to act as a barrier to the diffusion of solutes into or out of the urine after excretion by the kidney. The urothelium also serves to protect the detrusor muscle from toxins present in stored urine. A major event in the initiation and progression of bladder cancer is loss of urothelial differentiation. This is important because less differentiated urothelial tumors (higher histologic tumor grade) are typically associated with increased biologic and clinical aggressiveness. The differentiation status of urothelial carcinomas can be assessed by histopathologic examination and is reflected in the assignment of a histologic grade (low-grade or high-grade). Although typically limited to morphologic evaluation in most routine diagnostic practices, tumor grade can also be assessed using biochemical markers. Indeed, current pathological analysis of tumor specimens is increasingly reliant on molecular phenotyping. Thus, high priorities for bladder cancer research include identification of (1) biomarkers that will enable the identification of high grade T1 tumors that pose the most threat and require the most aggressive treatment; (2) biomarkers that predict the likelihood that a low grade, American Joint Committee on Cancer stage pTa bladder tumor will progress into an invasive carcinoma with metastatic potential; (3) biomarkers that indicate which pTa tumors are most likely to recur, thus enabling clinicians to prospectively identify patients who require aggressive treatment; and (4) how these markers might contribute to biological processes that underlie tumor progression and metastasis, potentially through loss of terminal differentiation. This review will discuss the proteins associated with urothelial cell differentiation, with a focus on those implicated in bladder cancer, and other proteins that may be involved in neoplastic progression. It is hoped that ongoing discoveries associated with the study of these differentiation-promoting proteins can be translated into the clinic to positively impact patient care."]
[21872797,1,0,0,1,2011,"Vitamin D receptor (VDR)-mediated actions of 1α,25(OH)₂vitamin D₃: genomic and non-genomic mechanisms.","Haussler",21872797,"Vitamin D receptor (VDR)-mediated actions of 1α,25(OH)₂vitamin D₃: genomic and non-genomic mechanisms.    Abstract:   The conformationally flexible secosteroid, 1α,25(OH)₂vitamin D₃ (1α,25(OH)₂D₃) initiates biological responses via binding to the vitamin D receptor (VDR). The VDR contains two overlapping ligand binding sites, a genomic pocket (VDR-GP) and an alternative pocket (VDR-AP), that respectively bind a bowl-like ligand configuration (gene transcription) or a planar-like ligand shape (rapid responses). When occupied by 1α,25(OH)₂D₃, the VDR-GP interacts with the retinoid X receptor to form a heterodimer that binds to vitamin D responsive elements in the region of genes directly controlled by 1α,25(OH)₂D₃. By recruiting complexes of either coactivators or corepressors, activated VDR modulates the transcription of genes encoding proteins that promulgate the traditional genomic functions of vitamin D, including signaling intestinal calcium and phosphate absorption to effect skeletal and calcium homeostasis. 1α,25(OH)₂D₃/VDR control of gene expression and rapid responses also delays chronic diseases of aging such as osteoporosis, cancer, type-1 and -2 diabetes, arteriosclerosis, vascular disease, and infection."]
[21810483,11,0,0,11,2012,"Retinoid metabolism and its effects on the vasculature.","Rhee",21810483,"Retinoid metabolism and its effects on the vasculature.    Abstract:   Retinoids, the metabolically-active structural derivatives of vitamin A, are critical signaling molecules in many fundamental biological processes including cell survival, proliferation and differentiation. Emerging evidence, both clinical and molecular, implicates retinoids in atherosclerosis and other vasculoproliferative disorders such as restenosis. Although the data from clinical trials examining effect of vitamin A and vitamin precursors on cardiac events have been contradictory, this data does suggest that retinoids do influence fundamental processes relevant to atherosclerosis. Preclinical animal model and cellular studies support these concepts. Retinoids exhibit complex effects on proliferation, growth, differentiation and migration of vascular smooth muscle cells (VSMC), including responses to injury and atherosclerosis. Retinoids also appear to exert important inhibitory effects on thrombosis and inflammatory responses relevant to atherogenesis. Recent studies suggest retinoids may also be involved in vascular calcification and endothelial function, for example, by modulating nitric oxide pathways. In addition, established retinoid effects on lipid metabolism and adipogenesis may indirectly influence inflammation and atherosclerosis. Collectively, these observations underscore the scope and complexity of retinoid effects relevant to vascular disease. Additional studies are needed to elucidate how context and metabolite-specific retinoid effects affect atherosclerosis. This article is part of a Special Issue entitled: Retinoid and Lipid Metabolism."]
[21768880,1,0,0,1,2011,"Bone effects of cancer therapies: pros and cons.","Silbermann",21768880,"Bone effects of cancer therapies: pros and cons.    Abstract:    PURPOSE OF REVIEW : Agents used for systemic chemotherapy can alter normal bone homeostasis through mechanisms that affect both osteoblast and osteoclast function. The identification of those agents that influence maintenance of the bone-remodeling compartment is an important component of the drug development and testing process. This brief review focuses on preclinical and clinical data illustrating the effect of several classes of chemotherapeutic agents on skeletal development and bone remodeling.  RECENT FINDINGS : New preclinical data demonstrate that several classes of chemotherapeutic agents, including histone deacetylase inhibitors and proteasome inhibitors, alter osteoblast and osteoclast function. Preclinical data on retinoic acid analogues demonstrate that these agents inhibit osteoclastogenesis. In addition, a dose-dependent effect of methotrexate treatment on growth plate thickness and primary spongiosa height in rats has been demonstrated. Two recently published analyses of clinical data from trials of bortezomib in myeloma patients found increased biochemical markers of bone formation and evidence of increased bone deposition after bortezomib treatment.  SUMMARY : Several classes of chemotherapeutic agents alter bone metabolism and negatively impact bone homeostasis. Bone mineral density (BMD) monitoring guidelines for patients receiving systemic chemotherapy are not established. Limited guidelines exist for BMD monitoring in patients receiving long-term hormonal modulation; however, the negative effect of other chemotherapeutic agents on the skeleton is underappreciated."]
[21723946,2,0,0,2,2012,"Retinoid-related orphan receptor alpha and the regulation of lipid homeostasis.","Fitzsimmons",21723946,"Retinoid-related orphan receptor alpha and the regulation of lipid homeostasis.    Abstract:   Many nuclear hormone receptors (NRs) control lipid, glucose and energy homeostasis in an organ specific manner. Concordantly, dysfunctional NR signalling results in metabolic disease. The Retinoic acid receptor-related orphan receptor alpha (RORα), a member of the NR1F subgroup, is expressed in metabolic tissues. Previous studies identified the role of this NR in dyslipidemia, apo-lipoprotein metabolism and atherosclerosis. Recent data is underscoring the significant role of this orphan NR in the regulation of phase I/II metabolism (bile acids, xenobiotics, steroids etc.), adiposity, insulin signalling, and glucose tolerance. Moreover, oxygenated sterols, have been demonstrated to function as native ligands and inverse agonists. This review focuses on the rapidly emerging and evolving role of RORα in the control of lipid and glucose homeostasis in major mass metabolic tissues. Article from the special issue orphan receptors."]
[21669299,9,0,0,9,2012,"Lipid metabolism in mammalian tissues and its control by retinoic acid.","Bonet",21669299,"Lipid metabolism in mammalian tissues and its control by retinoic acid.    Abstract:   Evidence has accumulated that specific retinoids impact on developmental and biochemical processes influencing mammalian adiposity including adipogenesis, lipogenesis, adaptive thermogenesis, lipolysis and fatty acid oxidation in tissues. Treatment with retinoic acid, in particular, has been shown to reduce body fat and improve insulin sensitivity in lean and obese rodents by enhancing fat mobilization and energy utilization systemically, in tissues including brown and white adipose tissues, skeletal muscle and the liver. Nevertheless, controversial data have been reported, particularly regarding retinoids effects on hepatic lipid and lipoprotein metabolism and blood lipid profile. Moreover, the molecular mechanisms underlying retinoid effects on lipid metabolism are complex and remain incompletely understood. Here, we present a brief overview of mammalian lipid metabolism and its control, introduce mechanisms through which retinoids can impact on lipid metabolism, and review reported activities of retinoids on different aspects of lipid metabolism in key tissues, focusing on retinoic acid. Possible implications of this knowledge in the context of the management of obesity and the metabolic syndrome are also addressed. This article is part of a Special Issue entitled Retinoid and Lipid Metabolism."]
[21558193,0,0,0,0,2010,"Palaeophylogenomics of the vertebrate ancestor--impact of hidden paralogy on hagfish and lamprey gene phylogeny.","Kuraku",21558193,"Palaeophylogenomics of the vertebrate ancestor--impact of hidden paralogy on hagfish and lamprey gene phylogeny.    Abstract:   In dissecting the transition from invertebrates to vertebrates at the molecular level, whole-genome duplications are recognized as a key event. This gave rise to more copies of genes in jawed vertebrates (gnathostomes), such as the four Hox clusters in the human, compared to the single ancestral cluster in invertebrates. To date, as the most early-branching lineages in vertebrates, cyclostomes (hagfishes and lampreys) have been used for comparative analyses of gene regulations and functions. However, assignment of orthology/paralogy for cyclostomes genes is not unambiguously demonstrated. Thus, there is a high degree of incongruence in tree topologies between gene families, although whole genome duplications postulate uniform patterns in gene phylogeny. In this review, we demonstrate how expansion of an ancient genome before the cyclostome-gnathostome split, followed by reciprocal gene loss, can cause this incongruence. This is sometimes referred to as hidden paralogy."]
[21545756,1,0,0,1,2011,"Smith-Magenis syndrome: haploinsufficiency of RAI1 results in altered gene regulation in neurological and metabolic pathways.","Elsea",21545756,"Smith-Magenis syndrome: haploinsufficiency of RAI1 results in altered gene regulation in neurological and metabolic pathways.    Abstract:   Smith-Magenis syndrome (SMS) is a complex neurobehavioural disorder characterised by intellectual disability, self-injurious behaviours, sleep disturbance, obesity, and craniofacial and skeletal anomalies. Diagnostic strategies are focused towards identification of a 17p11.2 microdeletion encompassing the gene RAI1 (retinoic acid induced 1) or a mutation of RAI1. Molecular evidence shows that most SMS features are due to RAI1 haploinsufficiency, whereas variability and severity are modified by other genes in the 17p11.2 region for 17p11.2 deletion cases. The functional role of RAI1 is not completely understood, but it is probably a transcription factor acting in several different biological pathways that are dysregulated in SMS. Functional studies based on the hypothesis that RAI1 acts through phenotype-specific pathways involving several downstream genes have shown that RAI1 gene dosage is crucial for normal regulation of circadian rhythm, lipid metabolism and neurotransmitter function. Here, we review the clinical and molecular features of SMS and explore more recent studies supporting possible therapeutic strategies for behavioural management."]
[21524412,0,0,0,0,2011,"[Human pluripotent stem cells: opening key for pathological modeling].","Maury",21524412,"[Human pluripotent stem cells: opening key for pathological modeling].    Abstract:  "]
[21504909,1,0,0,1,2011,"A clinical and experimental overview of sirenomelia: insight into the mechanisms of congenital limb malformations.","Garrido-Allepuz",21504909,"A clinical and experimental overview of sirenomelia: insight into the mechanisms of congenital limb malformations.    Abstract:   Sirenomelia, also known as sirenomelia sequence, is a severe malformation of the lower body characterized by fusion of the legs and a variable combination of visceral abnormalities. The causes of this malformation remain unknown, although the discovery that it can have a genetic basis in mice represents an important step towards the understanding of its pathogenesis. Sirenomelia occurs in mice lacking Cyp26a1, an enzyme that degrades retinoic acid (RA), and in mice that develop with reduced bone morphogenetic protein (Bmp) signaling in the caudal embryonic region. The phenotypes of these mutant mice suggest that sirenomelia in humans is associated with an excess of RA signaling and a deficit in Bmp signaling in the caudal body. Clinical studies of sirenomelia have given rise to two main pathogenic hypotheses. The first hypothesis, based on the aberrant abdominal and umbilical vascular pattern of affected individuals, postulates a primary vascular defect that leaves the caudal part of the embryo hypoperfused. The second hypothesis, based on the overall malformation of the caudal body, postulates a primary defect in the generation of the mesoderm. This review gathers experimental and clinical information on sirenomelia together with the necessary background to understand how deviations from normal development of the caudal part of the embryo might lead to this multisystemic malformation."]
[21495966,2,0,0,2,2011,"Neural induction and patterning in Mammalian pluripotent stem cells.","Osakada",21495966,"Neural induction and patterning in Mammalian pluripotent stem cells.    Abstract:   Embryonic stem (ES) cells are derived from the inner cell mass (ICM) of blastocyst stage embryos, while induced pluripotent stem (iPS) cells are generated from somatic cells through transient overexpression of defined transcription factors. When transplanted into a preimplantation embryo, ES cells and iPS cells can differentiate into any cell type, including germ cells. Moreover, they can grow in culture indefinitely while maintaining pluripotency. In vitro differentiation of ES cells and iPS cells recapitulates many aspects of in vivo embryogenesis. The acquisition of neural fates (neural induction) in ES cells can be controlled by bone morphogenetic protein (BMP), fibroblast growth factor (FGF), and Wnt signaling, while the production of specific neural cell types (neural patterning) can be controlled by exogenous patterning signals such as Wnt, BMP, Shh, FGF, and retinoic acid. In response to these signals, ES cells can differentiate into a wide range of neural cell types that correlate with their positions along the anterior-posterior and dorsal-ventral axes. ES cell and iPS cell culture systems will provide materials for cell replacement therapy, and can be used as in vitro models for disease and drug testing as well as development. Here we review spatiotemporal control of neural differentiation of mammalian pluripotent stem cells, with a special emphasis on the relationship between in vivo embryogenesis and in vitro ES cell differentiation. Retinal differentiation from ES cells and iPS cells is also outlined."]
[21493923,2,0,0,2,2011,"The PPAR-RXR transcriptional complex in the vasculature: energy in the balance.","Plutzky",21493923,"The PPAR-RXR transcriptional complex in the vasculature: energy in the balance.    Abstract:   The peroxisome proliferator-activated receptors (PPARs) and the retinoid X receptors (RXRs) are ligand-activated transcription factors that coordinately regulate gene expression. This PPAR-RXR transcriptional complex plays a critical role in energy balance, including triglyceride metabolism, fatty acid handling and storage, and glucose homeostasis: processes whose dysregulation characterize obesity, diabetes, and atherosclerosis. PPARs and RXRs are also involved directly in inflammatory and vascular responses in endothelial and vascular smooth muscle cells. New insights into fundamental aspects of PPAR and RXR biology, and their actions in the vasculature, continue to appear. Although RXRs are obligate heterodimeric partners for PPAR action, the part that RXRs, and their endogenous retinoid mediators, exert in the vessel wall is less well understood. Biological insights into PPAR-RXRs may help inform interpretation of clinical trials with synthetic PPAR agonists and prospects for future PPAR therapeutics. Importantly, the extensive data establishing a key role for PPARs and RXRs in energy balance, inflammation, and vascular biology stands separately from the clinical experience with any given synthetic PPAR agonist. Both the basic science data and the clinical experience with PPAR agonists identify the need to better understand these important transcriptional regulators."]
[21482859,0,0,0,0,2011,"Development of extraocular muscles requires early signals from periocular neural crest and the developing eye.","Bohnsack",21482859,"Development of extraocular muscles requires early signals from periocular neural crest and the developing eye.    Abstract:    OBJECTIVES : To identify and explain morphologic changes of the extraocular muscles (EOMs) in anophthalmic patients.  METHODS : Retrospective medical record review of patients with congenital anophthalmia, using magnetic resonance imaging and intraoperative findings to characterize EOM morphology. We then used molecular biology techniques in zebrafish and chick embryos to determine the relationships among the developing eye, periocular neural crest, and EOMs.  RESULTS : In 3 human patients with bilateral congenital anophthalmia and preoperative orbital imaging, we observed a spectrum of EOM morphologies ranging from indiscernible muscle tissue to well-formed, organized EOMs. Timing of eye loss in zebrafish and chick embryos correlated with the morphology of EOM organization in the orbit (eye socket). In congenitally eyeless Rx3 zebrafish mutants, or following genetic ablation of the cranial neural crest cells, EOMs failed to organize, which was independent of other craniofacial muscle development.  CONCLUSIONS : Orbital development is dependent on interactions between the eye, neural crest, and developing EOMs. Timing of the ocular insult in relation to neural crest migration and EOM development is a key determinant of aberrant EOM organization. Additional research will be required to study patients with unilateral and syndromic anophthalmia and assess for possible differences in clinical outcomes of patients with varied EOM morphology.  CLINICAL RELEVANCE : The presence and organization of EOMs in anophthalmic eye sockets may serve as a markers for the timing of genetic or teratogenic insults, improving genetic counseling, and assisting with surgical reconstruction and family counseling efforts."]
[21442438,1,0,0,1,2011,"An algorithm for chemotherapy treatment of recurrent glioma patients after temozolomide failure in the general oncology setting.","Kyritsis",21442438,"An algorithm for chemotherapy treatment of recurrent glioma patients after temozolomide failure in the general oncology setting.    Abstract:    PURPOSE : The standard therapy for newly diagnosed malignant gliomas comprises surgery, radiotherapy, and commonly temozolomide chemotherapy. For recurrent or progressive disease after temozolomide failure, there is no consensus and only limited options for chemotherapy.  METHODS : We reviewed the English literature for phase II trials of therapies for recurrent malignant glioma conducted between January 2000 and September 2010. The search was supplemented by a review of articles published prior to 2000 on chemotherapy regimens that had shown activity on recurrent gliomas.  RESULTS : To guide practice in the general oncology setting, an algorithm was constructed according to the activity of the reported chemotherapies at the time of writing. Some molecular studies performed on tumor tissue may help guide the selection of chemotherapy. Methylated MGMT in tumor tissue correlates with increased sensitivity to alkylating agents such as fotemustine or other nitrosoureas. Depending on MGMT status and bone marrow reserve, treatment with fotemustine, bevacizumab, bevacizumab with irinotecan, or cis-retinoic acid (cRA), might be of value.  CONCLUSION : Unfortunately, progress in the development of new and more effective chemotherapy agents has been very limited and leaves the clinician treating high-grade glioma patients at relapse with few good options. The suggested algorithm is our objective evaluation of the currently existing knowledge. Hopefully, the ongoing phase II and III trials will provide us the needed chemotherapy agents in the years to come."]
[21388456,13,0,0,13,2011,"Efficacy and safety of oral retinoids in different psoriasis subtypes: a systematic literature review.","Sbidian",21388456,"Efficacy and safety of oral retinoids in different psoriasis subtypes: a systematic literature review.    Abstract:    BACKGROUND : There is limited evidence regarding the efficacy and safety of retinoids in different psoriasis subtypes.  OBJECTIVE : To systematically review the available literature on: (i) modalities of administration and prescription of oral retinoids as single agent or combined therapy for the treatment of plaque-type psoriasis (PV), nail psoriasis and localized and generalized pustular psoriasis : initial and optimal dosage; (ii) skeletal toxicity of retinoid for the treatment of psoriasis.  METHODS : A systematic literature search was carried out in MEDLINE, EMBASE, and Cochrane Library databases from 1975 to 2010 searching for randomized controlled trials and observational studies evaluating 1) various dosages of retinoid in psoriasis and 2) skeletal toxicity of retinoid in psoriasis. Articles were limited to human subjects and English/French languages.  RESULTS : Efficacy of retinoids in psoriasis. Among 1348 identified references, 44 published studies were included. Starting daily dosages between 10 and 25 mg and stepwise escalation were associated with higher clinical efficacy and lower incidence of adverse events in comparison with higher doses and regimens rapidly reaching optimal dose. Retinoids as single agent therapy appeared to show limited efficacy in PV, while the good clinical efficacy reported in pustular forms should be cautiously considered, given the spontaneously remitting course of the disease. Combining retinoids with phototherapy appeared to be highly effective in patients with PV. Potential skeletal toxicity of retinoids. 15 published studies out of 105 identified references were included. There is no strong evidence of an increased risk of skeletal abnormalities in psoriasis patients treated with retinoids.  CONCLUSION : Acitretin appears to provide better efficacy in pustular psoriasis than in PV as a single agent treatment. There is no evidence for skeletal toxicity of retinoids in the setting of psoriasis, and accordingly monitoring this risk through X-ray is not warranted."]
[21350678,15,0,0,15,2011,"Vitamin A metabolism: an update.","DAmbrosio",21350678,"Vitamin A metabolism: an update.    Abstract:   Retinoids are required for maintaining many essential physiological processes in the body, including normal growth and development, normal vision, a healthy immune system, normal reproduction, and healthy skin and barrier functions. In excess of 500 genes are thought to be regulated by retinoic acid. 11-cis-retinal serves as the visual chromophore in vision. The body must acquire retinoid from the diet in order to maintain these essential physiological processes. Retinoid metabolism is complex and involves many different retinoid forms, including retinyl esters, retinol, retinal, retinoic acid and oxidized and conjugated metabolites of both retinol and retinoic acid. In addition, retinoid metabolism involves many carrier proteins and enzymes that are specific to retinoid metabolism, as well as other proteins which may be involved in mediating also triglyceride and/or cholesterol metabolism. This review will focus on recent advances for understanding retinoid metabolism that have taken place in the last ten to fifteen years."]
[21339420,3,0,0,3,2011,"Harlequin ichthyosis: a review of clinical and molecular findings in 45 cases.","Rajpopat",21339420,"Harlequin ichthyosis: a review of clinical and molecular findings in 45 cases.    Abstract:    OBJECTIVE : To assess the clinical outcomes of 45 cases of harlequin ichthyosis and review the underlying ABCA12 gene mutations in these patients.  DESIGN : Multicenter, retrospective, questionnaire-based survey.  SETTING : Dermatology research institute.  PARTICIPANTS : Patients with harlequin ichthyosis for whom we had performed ABCA12 mutation analysis.  MAIN OUTCOME MEASURES : Referring physicians were asked to complete a questionnaire using the patients notes, detailing the clinical outcome of the affected child. In each case, the causative ABCA12 mutation was identified using standard polymerase chain reaction and sequencing techniques.  RESULTS : Of the 45 cases, the ages of the survivors ranged from 10 months to 25 years, with an overall survival rate of 56%. Death usually occurred in the first 3 months and was attributed to sepsis and/or respiratory failure in 75% of cases. The early introduction of oral retinoids may improve survival, since 83% of those treated survived, whereas 76% who were not given retinoids died. Recurrent skin infections in infancy affected one-third of patients. Problems maintaining weight affected 44%. Three children developed an inflammatory arthritis, and developmental delay was reported in 32%. Mutation analysis revealed that 52% of survivors had compound heterozygous mutations, whereas all deaths were associated with homozygous mutations.  CONCLUSIONS : Harlequin ichthyosis should be regarded as a severe chronic disease that is not invariably fatal. With improved neonatal care and probably the early introduction of oral retinoids, the number of survivors is increasing. Compound heterozygotes appear to have a survival advantage."]
[21313915,3,0,0,3,2010,"The histopathalogical effects of retinoic acid on the tissues.","Yousefi",21313915,"The histopathalogical effects of retinoic acid on the tissues.    Abstract:   The aim of this study is to sum up the important information that has emerged from the last 10 years of experimental investigations over the effects of retinoic acid (RA) on embryonic structure and adult tissues. Administration of exogenous RA can affect the connective tissues including enhancement of myeloid compartment and suppression of erythroid cells and conversion of hematopoietic stem cells to erythroid progenitors. Also, it is able to induce osteogenic differentiation of stem cells derived from adipose tissues and etc. Examining the neural tissue highlighted that disruption of RA signaling in the adult leads to degeneration of motor neurons and development of some diseases. In vitro administration of All-Trans Retinoic Acid (ATRA) increased dendritic growth and synaptophysin puncta intensity and increased expressions of neuronal nuclei, neuron specific enolase, synaptophysin. RA also promotes expression of a marker of mature astrocytes. On muscular tissue, it can inhibit proliferation of smooth muscle cells (SMC) while promoting differentiation of SMC in vitro instead. The ATRA stimulates skeletal myogenesis while inhibiting cardiomyogenesis and hypertrophy and proliferation of cultured neonatal cardiomyocytes and cardiofibroblasts. In addition, differences in levels of embryonic RA may contribute to variability in great artery anomalies. In epithelial tissue, the squamous epithelium exposed to ATRA showed the columnar differentiation independent to proliferation. Also RA seems able to rescue the regeneration process of injured gut and revealing a better wound healing of the intestine undergone intra-operative radiotherapy. It can interrupt the process of progressive fibrosis, enhancements of the langerhans islets, exocrine pancreas, modulate the health of the mammary glands and repairs the lung cell. Thus, differences in levels of endogenous RA in embryonic and adult tissues may contribute to anomalies and pathogenesis of disease, furthermore RA has paradoxical effects on the parts forming the connective and muscles tissue in equal conditions."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I133,I133)","v":21295138},{"$f":"(LEN($J133) - LEN(SUBSTITUTE(LOWER($J133),LOWER(B$3),\"\")))/LEN(B$3)","v":2},0,0,{"$f":"SUM(B133:D133)","v":2},2011,"Nuclear receptor PXR, transcriptional circuits and metabolic relevance.","Ihunnah",21295138,"Nuclear receptor PXR, transcriptional circuits and metabolic relevance.    Abstract:   The pregnane X receptor (PXR, NR1I2) is a ligand activated transcription factor that belongs to the nuclear hormone receptor (NR) superfamily. PXR is highly expressed in the liver and intestine, but low levels of expression have also been found in many other tissues. PXR plays an integral role in xenobiotic and endobiotic metabolism by regulating the expression of drug-metabolizing enzymes and transporters, as well as genes implicated in the metabolism of endobiotics. PXR exerts its transcriptional regulation by binding to its DNA response elements as a heterodimer with the retinoid X receptor (RXR) and recruitment of a host of coactivators. The biological and physiological implications of PXR activation are broad, ranging from drug metabolism and drug-drug interactions to the homeostasis of numerous endobiotics, such as glucose, lipids, steroids, bile acids, bilirubin, retinoic acid, and bone minerals. The purpose of this article is to provide an overview on the transcriptional circuits and metabolic relevance controlled by PXR. This article is part of a Special Issue entitled: Translating Nuclear Receptors from Health to Disease."]
[21269590,1,0,0,1,2011,"Unusual acute promyelocytic leukemia following de novo renal transplant: case report and literature review.","Lai",21269590,"Unusual acute promyelocytic leukemia following de novo renal transplant: case report and literature review.    Abstract:   Acute promyelocytic leukemia (APL) with transcripting three isoforms of mRNA from PML-RAR alpha fusion genes following renal transplantation has never been reported in the literature. A 39-year-old man received a cadaveric renal allograft for IgA chronic kidney disease in 2006 and was consecutively immunosuppressed by tacrolimus, mycophenolate mofetil, and prednisolone. In 2008, he presented with gum bleeding and weight loss. Following bone marrow biopsy, we diagnosed acute promyelocytic leukemia. Molecular analysis demonstrated atypical presence consisting of three isoforms of mRNA from PML-RAR alpha fusion genes. The patient was administered with three courses of consolidation chemotherapy plus atretinoin, resulting in complete remission and did not jeopardize his allograft function. This novel finding suggests that the leukemogenesis of APL may be polyclonal, sharing similar progenitor targeting on complicated karyotypes, responding well to current chemotherapy."]
[21150176,1,0,0,1,2011,"Recent developments in the genetic factors underlying congenital diaphragmatic hernia.","Brady",21150176,"Recent developments in the genetic factors underlying congenital diaphragmatic hernia.    Abstract:   Congenital diaphragmatic hernia (CDH) is a birth defect affecting around 1 in 3,000 births and is associated with high mortality and morbidity. It has become increasingly apparent that genetic factors underlie many forms of CDH. We review the recent developments in the area of the genetics of CDH, including potential candidate genes supported by evidence from animal models. We also discuss the possible role in the pathogenesis of CDH of defective retinoid signalling and abnormal mesenchymal cell function."]
[21134875,0,0,0,0,2011,"Medications that affect calcium.","Ruppe",21134875,"Medications that affect calcium.    Abstract:    OBJECTIVE : To review medications that can affect serum calcium concentrations.  METHODS : The literature was reviewed for articles pertaining to medications that affect calcium concentrations.  RESULTS : The serum calcium concentration is tightly regulated because of the importance of this mineral in diffuse cellular processes. Many medications have been reported to cause changes in serum calcium levels by influencing intestinal calcium absorption, renal calcium resorption, and bone remodeling or through altering parathyroid or 1,25-dihydroxyvitamin D-mediated regulation. Some medications are used specifically to alter serum calcium as a therapeutic intervention. With others, the calcium disturbances are viewed as a side effect of the treatment.  CONCLUSION : It is important to be aware of the influence that medications can have on serum calcium levels when evaluating patients with disorders of calcium homeostasis."]
[20938219,1,0,0,1,2010,"The role of PPARγ for the osteoblastic differentiation.","Viccica",20938219,"The role of PPARγ for the osteoblastic differentiation.    Abstract:   Peroxisome proliferator-activated receptor γ (PPARγ) is a ligand-activated transcription factor that belongs to the nuclear hormone receptor superfamily and functions as a heterodimer with a retinoid X receptor by binding to PPAR responsive elements. PPARγ plays an important role in adipocyte differentiation and is activated by long-chain fatty acid, peroxisome proliferators, and thiazolidinedione (TZD). TZD are agonists of PPARγ, act as insulin-sensitizing agents, and are widely prescribed in the management of different conditions characterized by insulin resistance. Osteoblasts and marrow adipocytes derive from common multipotential mesenchymal stem cell (MSC) progenitors. Lineage commitment of MSC is determined by expression and/or activation of specific transcription factors, such as Runx2 and Osterix in the case of osteoblasts, and PPARγ in the case of adipocytes. Many evidences indicate an important role of PPARγ in bone metabolism. Heterozygous PPARγ-deficient (PPARγ +/-) mice exhibit enhanced bone formation with increased osteoblastogenesis. Embryonic stem cells derived from PPARγ +/- mice spontaneously differentiate into osteoblasts. In mice and rats, the activation of PPARγ by TZD treatment, such as rosiglitazone (Rosi), causes bone loss, which results from an increase of marrow adipocytes and a decrease of osteoblasts, leading to a reduction of bone formation rate. Human studies have shown that pre- and post-menopausal women treated with Rosi have an increased risk of fracture compared to women treated with metformin and glyburide. Moreover, the modulation of the PPARγ expression is also implicated in the effects of mechanical loading on bone and in age-related bone loss."]
[20932317,1,0,0,1,2010,"Frameshift mutation hotspot identified in Smith-Magenis syndrome: case report and review of literature.","Truong",20932317,"Frameshift mutation hotspot identified in Smith-Magenis syndrome: case report and review of literature.    Abstract:   Smith-Magenis syndrome (SMS) is a complex syndrome involving intellectual disabilities, sleep disturbance, behavioural problems, and a variety of craniofacial, skeletal, and visceral anomalies. While the majority of SMS cases harbor an ~3.5 Mb common deletion on 17p11.2 that encompasses the retinoic acid induced-1 (RAI1) gene, some patients carry small intragenic deletions or point mutations in RAI1. We present data on two cases of Smith-Magenis syndrome with mutation of RAI1. Both cases are phenotypically consistent with SMS and RAI1 mutation but also have other anomalies not previously reported in SMS, including spontaneous pneumothoraces. These cases also illustrate variability in the SMS phenotype not previously shown for RAI1 mutation cases, including hearing loss, absence of self-abusive behaviours, and mild global delays. Sequencing of RAI1 revealed mutation of the same heptameric C-tract (CCCCCCC) in exon 3 in both cases (c.3103delC one case and and c.3103insC in the other), resulting in frameshift mutations. Of the seven reported frameshift mutations occurring in poly C-tracts in RAI1, four cases (~57%) occur at this heptameric C-tract. Collectively, these results indicate that this heptameric C-tract is a preferential hotspot for single nucleotide insertion/deletions (SNindels) and therefore, should be considered a primary target for analysis in patients suspected for mutations in RAI1. We expect that as more patients are sequenced for mutations in RAI1, the incidence of frameshift mutations in this hotspot will become more evident."]
[20850526,1,0,0,1,2011,"Aberrant forebrain signaling during early development underlies the generation of holoprosencephaly and coloboma.","Gongal",20850526,"Aberrant forebrain signaling during early development underlies the generation of holoprosencephaly and coloboma.    Abstract:   In this review, we highlight recent literature concerning the signaling mechanisms underlying the development of two neural birth defects, holoprosencephaly and coloboma. Holoprosencephaly, the most common forebrain defect, occurs when the cerebral hemispheres fail to separate and is typically associated with mispatterning of embryonic midline tissue. Coloboma results when the choroid fissure in the eye fails to close. It is clear that Sonic hedgehog (Shh) signaling regulates both forebrain and eye development, with defects in Shh, or components of the Shh signaling cascade leading to the generation of both birth defects. In addition, other intercellular signaling pathways are known factors in the incidence of holoprosencephaly and coloboma. This review will outline recent advances in our understanding of forebrain and eye embryonic pattern formation, with a focus on zebrafish studies of Shh and retinoic acid pathways. Given the clear overlap in the mechanisms that generate both diseases, we propose that holoprosencephaly and coloboma can represent mild and severe aspects of single phenotypic spectrum resulting from aberrant forebrain development. This article is part of a Special Issue entitled Zebrafish Models of Neurological Diseases."]
[20818443,1,0,0,1,2011,"Role of autotransplantation in the treatment of acute promyelocytic leukemia patients in remission: Fukuoka BMT Group observations and a literature review.","Kamimura",20818443,"Role of autotransplantation in the treatment of acute promyelocytic leukemia patients in remission: Fukuoka BMT Group observations and a literature review.    Abstract:   We retrospectively analyzed the outcomes of 26 patients with acute promyelocytic leukemia (APL) in the first CR (CR1) or second CR (CR2), who underwent autologous PBSCT (auto-PBSCT) between 1992 and 2008. All patients received all-trans retinoic acid-based induction therapy. After two courses of consolidation chemotherapy, upfront auto-PBSCT was performed in 20 patients in the CR1. Five patients had a high WBC count of more than 10 × 10(9)/L (high risk), while 15 patients had a count of less than 10 × 10(9)/L (low risk) at initial presentation. In addition, six patients, who were considered as low-risk patients at presentation, had a relapse after three cycles of consolidation and 2 years of maintenance therapy, but gained the molecular remission after re-induction and consolidation, and underwent auto-PBSCT in the CR2. In 26 recipients, engraftment was rapid and no TRM was documented. All 20 patients autotransplanted in CR1 were still in CR at a median of 133 months (73-193 months), and six patients who underwent auto-PBSCT in CR2 were also still in CR at a median of 41 months (2-187 months) without maintenance therapy. PML/RARα chimeric mRNA was undetectable in PBSC or BM samples examined before auto-PBSCT. Despite a small number of cases studied, our retrospective observations suggest that auto-PBSCT may be an effective treatment option to continue durable CR in the treatment of high-risk APL. We review previous reports and discuss the role of autotransplantation in the treatment of APL patients in CR."]
[20706998,2,0,0,2,2010,"Genetic and pathologic aspects of retinoic acid-induced limb malformations in the mouse.","Lee",20706998,"Genetic and pathologic aspects of retinoic acid-induced limb malformations in the mouse.    Abstract:   Because all-trans retinoic acid (atRA) is teratogenic in all species tested and many of the specific defects induced are common across the phylogenetic spectrum, it would be logical to predict that murine strain differences in teratology to this agent are minimal. However, for specific defects, strain susceptibilities are vastly different. Studies with atRA have shown stark differences between C57BL/6 and SWV mouse strains in susceptibility to postaxial forelimb ectrodactyly and ectopic hindlimb formation, with the C57 strain being more susceptible for both defects. Various approaches were used to determine why these strains differ in susceptibility, but the mechanisms remain unknown. Hindlimb duplications were hypothesized to be caused by the formation of ectopic posterior body axes. For forelimb ectrodactyly, a locus on chromosome 11, Rafar, has linkage to the strain difference, and mRNA localization has shown that specific genes (Fgf8, Dlx3, Bmp4, and Sp8) in the postaxial preAER (prior to formation of the apical ectodermal ridge) of the developing limb bud (the site of the defect) were downregulated hours after atRA administration more in the susceptible C57 than in the SWV strain. Because both atRA and divalent cadmium induce postaxial forelimb ectrodactyly (right-sided predominance) at a high rate in C57BL/6 and low in the SWV strain, there is debate as to whether they share a common mechanism. These teratogens cause a greater-than-additive level of forelimb ectrodactyly when coadministered at low doses, but cadmium does not induce ectopic hindlimb formation. The hypothesis is that these agents have separate molecular pathologic pathways that converge to perturb a common anatomic structure."]
[20638138,5,0,0,5,2010,"Development of canal cholesteatoma in a patient with prenatal isotretinoin exposure.","Van Abel",20638138,"Development of canal cholesteatoma in a patient with prenatal isotretinoin exposure.    Abstract:    PURPOSE : To describe the clinical and radiologic findings in a case of isotretinoin embryopathy-like syndrome and discuss management of hearing loss, congenital external auditory canal (EAC) stenosis, and EAC cholesteatoma.  METHODS : Review of medical, audiological, and radiological records.  RESULTS : An 8 year old female presented with bilateral moderate conductive hearing loss, bilateral microtia, left EAC stenosis, and right EAC atresia, secondary to prenatal isotretinoin exposure. Comorbidities included developmental delay, ventricular septal defect, hypotonia, and retinal maldevelopment. The left EAC was sharply upsloping with a 2mm-diameter meatus. Computed tomography (CT) scan of the temporal bone demonstrated normal middle and inner ears bilaterally; serial CT scans over 6 years demonstrated progressive development of left canal cholesteatoma. Implantation of a right BAHA system was performed, followed by left canalplasty and excision of cholesteatoma with facial nerve monitoring. An endaural incision was utilized to avoid compromising future microtia repair. Postoperative left-sided hearing improved to mild low-frequency conductive hearing loss rising to normal at 2000 Hz and above.  CONCLUSIONS : Despite extensive precautions for its use, isotretinoin remains a cause of major birth defects, including sensorineural, conductive or mixed hearing loss. Congenital EAC stenosis is much less common than congenital atresia or acquired stenosis; optimal surgical approaches vary depending on hearing status and facial nerve anatomy. Close monitoring for development of canal cholesteatoma is necessary."]
[20596911,1,0,0,1,2010,"The role of mesodermal signals during liver organogenesis in zebrafish.","Niu",20596911,"The role of mesodermal signals during liver organogenesis in zebrafish.    Abstract:   Three germ cell layers, the ectoderm, mesoderm and endoderm, are established during the gastrulation stage. All cell types in different organs and tissues are derived from these 3 germ cell layers at later stages. For example, skin epithelial cells and neuronal cells are derived from the ectoderm, while endothelial cells and muscle cells from the mesoderm and lung, and intestine epithelial cells from the endoderm. While in a normal situation different germ cells are destined to specific cell fates in different organs and tissues, each type of germ cells or its derivatives also produce extracellular signaling molecules to direct and facilitate the specification and differentiation of other germ cells during organogenesis. Liver is derived from the endoderm, but completion of liver organogenesis is regulated at different levels. While the pan-endoderm factors (e.g. FoxA and Gata families) and liver specific factors (e.g. Prox1 and Hhex) are essential intrinsic factors for endoderm cells to be differentiated into hepatoblasts, the role of signals produced by neighboring mesoderm cells for liver organogenesis is equally important. This review summarizes recent progress in studying the role of Bone morphogenetic proteins (Bmp), Fibroblast growth factors (Fgf), retinoic acid (RA) and Wingless and Int (Wnt), the 4 types of signaling molecules produced by the mesoderm cells, in liver organogenesis in zebrafish."]
[20590580,1,0,0,1,2010,"Current status and new developments in the treatment of psoriasis and psoriatic arthritis with biological agents.","Weger",20590580,"Current status and new developments in the treatment of psoriasis and psoriatic arthritis with biological agents.    Abstract:   Psoriasis is a chronic inflammatory disease affecting 1-3% of the general population. Among psoriatic patients, 5-40% are affected by psoriatic arthritis. Due to the chronic nature of the disease, patients suffer from substantial psychological and financial burdens, thus adding to a significantly impaired quality of life. Traditional systemic therapies for psoriasis, such as methotrexate, cyclosporin A, retinoids or PUVA therapy, have a potential for long-term toxicity and may not always provide sufficient improvement of the disease. The development of novel therapies targeting key steps in the pathogenesis of psoriasis and psoriatic arthritis now provide new and efficient treatment options. Biological therapies for the treatment of psoriasis and/or psoriatic arthritis are defined by their mode of action and can be classified into three categories: the T-cell modulating agents (alefacept and efalizumab), the inhibitors of tumour necrosis factor-alpha (TNFalpha blockers, e.g. adalimumab, certolizumab, etanercept, golimumab and infliximab) and the inhibitors of interleukin (IL) 12 and IL-23 (e.g. ustekinumab and briakinumab). This article provides a brief overview of the currently approved biological agents in the European Union and of some newer agents, such as briakinumab, certolizumab and golimumab."]
[20575083,1,0,0,1,2010,"In vitro derivation of germ cells from embryonic stem cells in mammals.","Zhou",20575083,"In vitro derivation of germ cells from embryonic stem cells in mammals.    Abstract:   Previous reports have shown that embryonic stem (ES) cells, derived from the inner cell mass of mouse or human blastocysts, could differentiate in vitro into female and male germ cells as well as into the cell types of all three germ layers. While in one case, the ES cell-derived germ cells have been reported to give birth to live offspring in the mouse, these cells differ in fertilization capacity from the sperm and oocytes produced in vivo as they cannot complete meiosis under in vitro conditions. The efficiency of functional germ cell isolation from ES cells is also low. According to published reports, factors such as the proper selection of feeder cells, including ovarian granulosa cells and those which could secrete bone morphogenic protein-4 (BMP4), and the addition of retinoic acid into culture medium, could to some extent establish and improve the microenvironment ES cells rely on for differentiation into germ cells. This review briefly describes the progress of deriving germ cells from ES cells and discusses possible factors that could improve in vitro gamete production."]
[20537528,0,0,0,0,2010,"The temporal dynamics of vertebrate limb development, teratogenesis and evolution.","Zeller",20537528,"The temporal dynamics of vertebrate limb development, teratogenesis and evolution.    Abstract:   Recent genetic and functional analysis of vertebrate limb development begins to reveal how the functions of particular genes and regulatory hierarchies can drastically change over time. The temporal and spatial interplay of the two instructive signalling centres are part of a larger signalling system that orchestrates limb bud morphogenesis in a rather self-regulatory manner. It appears that mesenchymal cells are specified early and subsequently, the progenitors for the different skeletal elements are expanded and determined progressively during outgrowth. Mutations and teratogens that disrupt distal progression of limb development most often cause death of the early-specified progenitors rather than altering their fates. The proliferative expansion and distal progression of paired appendage development was one of the main driving forces behind the transition from fin to limb buds during paired appendage evolution. Finally, the adaptive diversification or loss of modern tetrapod limbs in particular phyla or species appear to be a consequence of evolutionary tampering with the regulatory systems that control distal progression of limb development."]
[20506379,1,0,0,1,2010,"The biology and pathology of vitamin D control in bone.","Bell",20506379,"The biology and pathology of vitamin D control in bone.    Abstract:   Vitamin D is a steroid pro-hormone, whose active metabolite binds the vitamin D receptor (VDR) which, in turn, binds to DNA sequences on target genes as a heterodimer with the retinoid-X receptor, resulting in regulation of gene expression. The vitamin D pro-hormone can be synthesized in the skin, in response to ultraviolet radiation; however, dietary sources have become increasingly important as a result of cultural changes over the past few centuries. Based on its initial discovery as an anti-rachitic factor, studies of the role of vitamin D and its receptor have largely focused on the skeleton. Investigations into the pathophysiologic basis and therapeutic responses of skeletal disorders associated with impaired vitamin D action have led to the identification of the molecular pathways involved in hormone activation and regulation of gene expression by the liganded VDR. These studies have also demonstrated that the skeletal actions of the VDR and its ligand are largely redundant if normal mineral ion homeostasis can be maintained by other means. However, investigations in animal models with tissue-specific ablation of the VDR or the enzyme required for hormone activation have demonstrated novel actions in skeletal tissues. The active vitamin D metabolite has been shown to have both paracrine and endocrine actions in other tissues as well."]
[20434005,2,0,0,2,2010,"Open issues on bleeding and thrombosis in acute promyelocytic leukemia.","Sanz",20434005,"Open issues on bleeding and thrombosis in acute promyelocytic leukemia.    Abstract:   Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia characterized by a specific genetic alteration, affecting the retinoic acid receptor-alpha (RAR-alpha), and leading to the accumulation of the promyelocytic blasts in the bone marrow and blood which is frequently associated with a life-threatening consumptive coagulopathy. The body of biological information on APL establishes this leukemia as a unique entity that has to be promptly recognized to counteract the coagulopathy, especially in light of its striking response to treatment with all-trans retinoic acid. In fact, the current standard for induction therapy results in extremely high antileukemic efficacy, achieving 90 to 95% complete remission rate. However, while primary leukemia resistance has virtually disappeared as a cause of remission induction failure, death due to hemorrhage remains the major problem during the early treatment phase. As a part of the clotting activation commonly present in APL, thrombosis is a less recognized and probably underestimated life-threatening manifestation in patients with this disease. In addition to reviewing the available data on the incidence, outcome and prognostic factors of bleeding and thrombosis in APL, we discuss the current consensus and controversies on the most appropriate management of these complications."]
[20398728,1,0,0,1,2010,"Pituitary tumors: cell type-specific roles for BMP-4.","Labeur",20398728,"Pituitary tumors: cell type-specific roles for BMP-4.    Abstract:   BMP-4 plays a crucial role not only in the formation of the anterior pituitary during embryo development but also in the pathogenesis of pituitary tumors in adults. In tumor cells, BMP-4 promotes prolactin secretion and lactotroph cell proliferation through a Smad-estrogen receptor crosstalk but it inhibits ACTH production and cell proliferation of corticotrophs. In addition, BMP-4 increases GH secretion in rat pituitary tumor somatolactotroph GH3 cells and FSHbeta subunit gene transcription in the murine gonadotroph cell line, LbetaT2. Therefore, BMP-4 has a differential role on different types of pituitary tumors: it promotes pituitary prolactinoma while it inhibits corticotroph pathogenesis in Cushings disease. The modulation of BMP-4 also plays an important role in the therapeutic mechanism of action of bromocriptine, somatostatin analogs and retinoic acid."]
[20388135,1,0,0,1,2010,"Phytanic acid--an overlooked bioactive fatty acid in dairy fat?","Hellgren",20388135,"Phytanic acid--an overlooked bioactive fatty acid in dairy fat?    Abstract:   Phytanic acid is a multibranched fatty acid with reported retinoid X receptor (RXR) and peroxisome proliferator-activated receptor-alpha (PPAR-alpha) agonist activity, which have been suggested to have preventive effects on metabolic dysfunctions. Serum level in man is strongly correlated to the intake of red meat and dairy products and the concentration in these products is strongly correlated to the chlorophyll content in the feed of the cattle. Available data suggest that phytanic acid is a natural agonist for RXR at physiological concentrations, while it is more likely that it is the metabolite pristanic acid, rather than phytanic acid itself, that acts as PPAR-alpha agonist. Animal studies show increased expression of genes involved in fatty acid oxidation, after intake of phytol, the metabolic precursor of phytanic acid, but it is at present not possible to deduce whether phytanic acid is useful in the prevention of ectopic lipid deposition. Phytanic acid is an efficient inducer of the expression of uncoupler protein 1 (UCP1). UCP1 is expressed in human skeletal muscles, were it might be important for the total energy balance. Therefore, phytanic acid may be able to stimulate energy dissipation in skeletal muscles. Phytanic acid levels in serum are associated with an increased risk of developing prostate cancer, but the available data do not support a general causal link between circulating phytanic acid and prostate cancer risk. However, certain individuals, with specific single-nucleotide polymorphisms in the gene for the enzyme alpha-methylacyl-CoA racemase, might be susceptible to raised phytanic acid levels."]
[20369703,1,0,0,1,2010,"[STRA8 as a specific expression marker in postnatal male germ cells].","Lu",20369703,"[STRA8 as a specific expression marker in postnatal male germ cells].    Abstract:   Stimulated by retinoic acid gene 8 (STRA8) is specifically expressed in mammalian germ cells before their transition from mitosis to meiosis. STRA8 expression is observed only in the postnatal testis. Single nucleotide polymorphisms but no mutations were identified in the coding or proximal promoter region of STRA8 in some gonadal dysgenesis patients. Studies on the teratocarcinoma cells and embryonic stem cells (ESC) transfected with STRA8-EGFP, a fusion construct harboring the promoter and coding region of the enhanced green fluorescence protein, have shown that the STRA8-EGFP positive cells may undergo meiosis, develop into sperm and generate live offspring mice. STRA8-EGFP positive cells derived from the bone marrow are able to differentiate into spermatogenic cells, but arrest in the premeiotic stage, and those from the adult mouse testis, when cultured in ESC culture conditions, may acquire ESC properties, pluripotency and redifferentiation capacity and act as a new stem cell source for tissue regeneration. The presence of oocytes renewed in postnatal mouse ovaries calls in question the absence of STRA8 in postnatal mouse ovaries."]
[20224268,1,0,0,1,2010,"Isochromosome der(17)(q10)t(15;17) in acute promyelocytic leukemia resulting in an additional copy of the RARA-PML fusion gene: report of 4 cases and review of the literature.","Manola",20224268,"Isochromosome der(17)(q10)t(15;17) in acute promyelocytic leukemia resulting in an additional copy of the RARA-PML fusion gene: report of 4 cases and review of the literature.    Abstract:   Isochromosome of the long arm of the derivative chromosome 17, originating from the translocation t(15;17) [ider(17)(q10)t(15;17) or ider(17q)] in acute promyelocytic leukemia (APL), is a rare chromosome aberration which has been associated with a poor prognosis. In the present study, we report on 4 male APL patients with ider(17q) and review the clinical, cytogenetic and molecular characteristics of all previously reported APL patients with ider(17q) in order to clarify the clinical features and outcome of these patients. The data presented in this study demonstrated that ider(17q), which resulted in an extra RARA-PML fusion gene, was more frequent in males than females (male/female ratio of 2.12/1), was associated with a rather low initial white blood cell count and did not confer an adverse prognosis in APL patients treated with all-trans-retinoic acid and chemotherapy. The most frequent additional chromosome change to ider(17q) was trisomy 8. Ider(17q) was observed in all subtypes of the PML-RARA fusion gene, but the frequency of the bcr1 subtype was increased. Cases of overrepresentation of the RARA-PML fusion gene and ider(17q) cases may help in elucidating the role of RARA-PML in leukemogenesis."]
[20090511,1,0,0,1,2010,"Unicuspid aortic valve, hand anomalies: a heart-hand syndrome.","Nanda",20090511,"Unicuspid aortic valve, hand anomalies: a heart-hand syndrome.    Abstract:   Embryonic heart and limb development are closely related with gt;100 known inherited disorders affecting both. Common limb defects include duplication, deficiencies, and hypoplasia. Ventricular septal defects and atrial septal defects are the commonest associated cardiac conditions. A positive association exists between heart defects and limb disorders when these disorders are analyzed separately. Closer associations exist between heart defects and upper limb defects compared with lower limb defects. The majority of limb defects occur in the more distal parts of the affected limb. Genes expressed in both the heart and limb development include TGF-beta, BMP4, Msx transcription factor, HAND gene, retinoic acid receptor, and sonic hedgehog gene. Radial ray-heart syndromes are better described than ulnar ray-hand syndromes. There is significant variability of malformations. Partial phenocopies that are not genetically linked are well documented. An appreciation of ulnar anomalies should always provoke an evaluation of the heart for potential abnormalities. Although heart-hand syndromes are rare, valvular abnormalities and aortic aneurysms can lead to significant complications unless identified in time. The presence of radial or ulnar ray anomalies merit a detailed cardiac examination and a low threshold for cardiac imaging."]
[20083217,0,0,0,0,2010,"Evolving maps in craniofacial development.","Gitton",20083217,"Evolving maps in craniofacial development.    Abstract:   The shaping of the vertebrate head results from highly dynamic integrated processes involving the growth and exchange of signals between the ectoderm, the endoderm, the mesoderm and Cephalic Neural Crest Cells (CNCCs). During embryonic development, these tissues change their shape and relative position rapidly and come transiently in contact with each other. Molecular signals exchanged in restricted regions of tissue interaction are crucial in providing positional identity to the mesenchymes which will form the different skeletal and muscular components of the head. Slight spatio-temporal modifications of these signalling maps can result in profound changes in craniofacial development and might have contributed to the evolution of facial diversity. Abnormal signalling patterns could also be at the origin of congenital craniofacial malformations. This review brings into perspective recent work on spatial and temporal aspects of facial morphogenesis with particular focus on the molecular mechanisms of jaw specification."]
[20066096,1,0,0,1,2009,"Vertebrate limb development: moving from classical morphogen gradients to an integrated 4-dimensional patterning system.","Bénazet",20066096,"Vertebrate limb development: moving from classical morphogen gradients to an integrated 4-dimensional patterning system.    Abstract:   A wealth of classical embryological manipulation experiments taking mainly advantage of the chicken limb buds identified the apical ectodermal ridge (AER) and the zone of polarizing activity (ZPA) as the respective ectodermal and mesenchymal key signaling centers coordinating proximodistal (PD) and anteroposterior (AP) limb axis development. These experiments inspired Wolperts French flag model, which is a classic among morphogen gradient models. Subsequent molecular and genetic analysis in the mouse identified retinoic acid as proximal signal, and fibroblast growth factors (FGFs) and sonic hedgehog (SHH) as the essential instructive signals produced by AER and ZPA, respectively. Recent studies provide good evidence that progenitors are specified early with respect to their PD and AP fates and that morpho-regulatory signaling is also required for subsequent proliferative expansion of the specified progenitor pools. The determination of particular fates seems to occur rather late and depends on additional signals such as bone morphogenetic proteins (BMPs), which indicates that cells integrate signaling inputs over time and space. The coordinate regulation of PD and AP axis patterning is controlled by an epithelial-mesenchymal feedback signaling system, in which transcriptional regulation of the BMP antagonist Gremlin1 integrates inputs from the BMP, SHH, and FGF pathways. Vertebrate limb-bud development is controlled by a 4-dimensional (4D) patterning system integrating positive and negative regulatory feedback loops, rather than thresholds set by morphogen gradients."]
[20054531,1,0,0,1,2010,"22q11 deletion syndrome: a role for TBX1 in pharyngeal and cardiovascular development.","Scambler",20054531,"22q11 deletion syndrome: a role for TBX1 in pharyngeal and cardiovascular development.    Abstract:   Tbx1 is a member of the Tbox family of binding domain transcription factors. TBX1 maps within the region of 22q11 deleted in humans with DiGeorge or velocardiofacial syndrome. Mice haploinsufficient for Tbx1 have phenotypes that recapitulate major features of the syndrome, notably abnormal growth and remodelling of the pharyngeal arch arteries. The Tbx1 haploinsufficiency phenotype is modified by genetic background and by mutations in putative downstream targets. Homozygous null mutations of Tbx1 have more severe defects including failure of outflow tract septation, and absence of the caudal pharyngeal arches. Tbx1 is a transcriptional activator, and loss of this activity has been linked to alterations in the expression of various genes involved in cardiovascular morphogenesis. In particular, Fgf and retinoic acid signalling are dysregulated in Tbx1 mutants. This article summarises the tissue specific and temporal requirements for Tbx1, and attempts to synthesis what is know about the developmental pathways under its control."]
[21516863,0,0,0,0,2010,"[The treatment of secondary Sjogren syndrome].","Vultur",21516863,"[The treatment of secondary Sjogren syndrome].    Abstract:   Sjogren syndrome is a chronic autoimmune disease witch affects mostly lachrymal and salivary glands. The exocrinopathy can be encountered alone (primary Sjogren syndrome) or in association with other autoimmune disorders (secondary Sjogren syndrome). Visual prognosis of the patients with secondary Sjogren syndrome depends on the early diagnosis, applied therapy follow-up controls along with an effective collaboration between ophthalmologist and rheumatologist. We present therapeutic options in secondary Sjogren syndrome: hygiene and protective measures, medical nonspecific substitution treatment, treatment to stimulate tear secretion, autoimmune disease-specific medical treatment and surgery."]
[20026355,1,0,0,1,2010,"Peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) acts as regulator of metabolism linked to multiple cellular functions.","Wagner",20026355,"Peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) acts as regulator of metabolism linked to multiple cellular functions.    Abstract:   Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors. They function as ligand activated transcription factors. They exist in three isoforms, PPARalpha, PPARbeta (formerly PPARdelta), and PPARgamma. For all PPARs lipids are endogenous ligands, linking them directly to metabolism. PPARs form heterodimers with retinoic X receptors, and, upon ligand binding, modulate gene expression of downstream target genes dependent on the presence of co-repressors or co-activators. This results in cell-type specific complex regulations of proliferation, differentiation and cell survival. Specific synthetic agonists for all PPARs are available. PPARalpha and PPARgamma agonists are already in clinical use for the treatment of hyperlipidemia and type 2 diabetes, respectively. More recently, PPARbeta activation came into focus as an interesting novel approach for the treatment of metabolic syndrome and associated cardiovascular diseases. Although the initial notion was that PPARbeta is expressed ubiquitously, more recently extensive investigations have been performed demonstrating high PPARbeta expression in a variety of tissues, e.g. skin, skeletal muscle, adipose tissue, inflammatory cells, heart, and various types of cancer. In addition, in vitro and in vivo studies using specific PPARbeta agonists, tissue-specific over-expression or knockout mouse models have demonstrated a variety of functions of PPARbeta in adipose tissue, muscle, skin, inflammation, and cancer. We will focus here on functions of PPARbeta in adipose tissue, skeletal muscle, heart, angiogenesis and cancer related to modifications in metabolism and the identified underlying molecular mechanisms."]
[20009973,5,0,0,5,2009,"All-trans retinoic acid-induced focal myositis, synovitis, and mononeuritis.","Yu",20009973,"All-trans retinoic acid-induced focal myositis, synovitis, and mononeuritis.    Abstract:   All-trans retinoic acid has revolutionized the treatment of acute promyelocytic leukemia, but this therapy is often complicated by the all-trans retinoic acid syndrome. Here we report a patient with newly diagnosed acute promyelocytic leukemia who developed acute focal myositis, synovitis, and possible vasculitis, after receiving all-trans retinoic acid therapy. We review the existing literature on this rare clinical entity, all-trans retinoic acid-induced myositis. This condition can manifest as fever, myalgia, arthralgia, and Sweet syndrome, accompanied by distinct magnetic resonance findings involving the lower extremity musculature. Treatment consists of discontinuation of the offending drug and often high dose corticosteroids."]
[19932324,2,0,0,2,2009,"Acne and systemic disease.","Lolis",19932324,"Acne and systemic disease.    Abstract:   Acne is the most common disease of the skin. It affects 85% of teenagers, 42.5% of men, and 50.9% of women between the ages of 20 and 30 years.96,97 The role of hormones, particularly as a trigger of sebum production and sebaceous growth and differentiation, is well known. Excess production of hormones, specifically androgens, GH, IGF-1, insulin, CRH, and glucocorticoids, is associated with increased rates of acne development. Acne may be a feature in many endocrine disorders, including polycystic ovary disease, Cushing syndrome, CAH, androgen-secreting tumors, and acromegaly. Other nonendocrine diseases associated with acne include Apert syndrome, SAPHO syndrome, Behçet syndrome and PAPA syndrome. Acne medicamentosa is the development of acne vulgaris or an acneiform eruption with the use of certain medications. These medications include testosterone, progesterone,steroids, lithium, phenytoin, isoniazid, vitamins B2, B6, and B12, halogens, and epidermal growth factor inhibitors. Management of acne medicamentosa includes standard acne therapy. Discontinuation of the offending drug may be necessary in recalcitrant cases. Basic therapeutic interventions for acne include topical therapy, systemic antibiotics,hormonal agents, isotretinoin, and physical treatments. Generally, the severity of acne lesions determines the type of acne regimen necessary. The emergence of drug-resistant P acnes and adverse side effects are current limitations to effective acne management."]
[19906796,0,0,0,0,2010,"Selective peroxisome proliferator-activated receptor gamma (PPARgamma) modulation as a strategy for safer therapeutic PPARgamma activation.","Higgins",19906796,"Selective peroxisome proliferator-activated receptor gamma (PPARgamma) modulation as a strategy for safer therapeutic PPARgamma activation.    Abstract:   Peroxisome proliferator-activated receptor gamma (PPARgamma) is a clinically validated target for treatment of insulin resistance. PPARgamma activation by full agonists such as thiazolidinediones has shown potent and durable glucose-lowering activity in patients with type 2 diabetes without the concern for hypoglycemia or gastrointestinal toxicities associated with some other medications used to treat this disease. However, thiazolidinediones are linked to safety and tolerability issues such as weight gain, fluid retention, edema, congestive heart failure, and bone fracture. Distinctive properties of PPARgamma provide the opportunity for selective modulation of the receptor such that desirable therapeutic effects may be attained without the unwanted effects of full activation. PPARgamma is a nuclear receptor that forms a complex with coreceptor RXR and a cell type- and cell state-specific array of coregulators to control gene transcription. PPARgamma affinity for these components, and hence transcriptional response, is determined by the conformational changes induced by ligand binding within a complex pocket with multiple interaction points. This molecular mechanism thereby offers the opportunity for selective modulation. A desirable selective PPARgamma modulator profile would include high-affinity interaction with the PPARgamma-binding pocket in a manner that leads to retention of the insulin-sensitizing activity that is characteristic of full agonists as well as mitigation of the effects leading to increased adiposity, fluid retention, congestive heart failure, and bone fracture. Examples of endogenous and synthetic selective PPARgamma modulator (SPPARM) ligands have been identified. SPPARM drug candidates are being tested clinically and provide support for this strategy."]
[19863475,1,0,0,1,2009,"Nutrition and bone: it is more than calcium and vitamin D.","Morgan",19863475,"Nutrition and bone: it is more than calcium and vitamin D.    Abstract:   Unlike pharmacological agents that are taken for proscribed periods of time, food and nutrient intakes have the possibility of affecting bone health over the entire lifespan. While deficiencies or excesses of individual nutrients have been shown to affect bone, it is likely that individual foods or dietary patterns have important effects related to skeletal health. While biochemical mechanisms exist to relate a deficiency of vitamin K to altered bone metabolism, clinical trials related to supplementation of this nutrient have been confusing. It is likely that these disparate results are related to the fact that interactions of nutrients have not been considered or the possibility that suboptimal nutrient status is a marker of poor nutritional status. Vitamin A excess has been postulated to be related to high fracture risk; however, it is likely that retinol is not the best marker for the proposed interaction. Altering whole food patterns, such as the Dietary Approaches to Stop Hypertension diet, have demonstrated beneficial effects on bone metabolism. Individuals who select some vegetarian patterns may need to consider supplementation with nutrients such as calcium and protein. Future studies should center on whole food and dietary patterns and their relationship to bone metabolism and fracture risk."]
[19818218,1,0,0,1,2009,"Vitamin D endocrine system and psoriasis vulgaris--review of the literature.","Rucević",19818218,"Vitamin D endocrine system and psoriasis vulgaris--review of the literature.    Abstract:   Vitamin D exerts its physiological functions on calcium and bone metabolism in humans through the active metabolite 1,25-dihydroxyvitamin D3(1,25(OH)2D3). The other spectrum of vitamin D activities includes important effects on cellular proliferation, differentiation and the immune system. These effects are mediated through the intracellularly located vitamin D receptor (VDR). VDR is a member of the steroid, estrogen and retinoid receptor gene family of proteins that mediate transcriptional activities of the respective ligands. The VDR complex binds in the nucleus to the vitamin D responsive element on the gene. Several polymorphisms of the vitamin D receptor (VDR) gene have been described including FokI in exon 2, BsmI and ApaI in intron 8 and TaqI in exon 9. Alterations in vitamin D-1,25 (OH)2D3 levels and polymorphisms of VDR gene have been shown to be associated with several malignant or autoimmune diseases such as sclerosis multiplex, breast cancer, diabetes mellitus, malignant melanoma, and psoriasis vulgaris. The effects of VDR gene polymorphisms including immunomodulation, stimulation of cellular differentiation and inhibition of proliferation make it a possible candidate for therapy of psoriasis as well as for the psoriasis gene modification. The objective of this article is to present the state-of-the-art in the VDR gene polymorphism research in psoriasis vulgaris."]
[19807660,0,0,0,0,2010,"Epigenetic remodeling of chromatin architecture: exploring tumor differentiation therapies in mesenchymal stem cells and sarcomas.","Siddiqi",19807660,"Epigenetic remodeling of chromatin architecture: exploring tumor differentiation therapies in mesenchymal stem cells and sarcomas.    Abstract:   Sarcomas are the mesenchymal-derived malignant tumors of connective tissues (e.g., fat, bone, and cartilage) presumed to arise from aberrant development or differentiation of mesenchymal stem cells (MSCs). Appropriate control of stem cell maintenance versus differentiation allows for normal connective tissue development. Current theories suggest that loss of this control--through accumulation of genetic lesions in MSCs at various points in the differentiation process--leads to development of sarcomas, including undifferentiated, high grade sarcoma tumors. The initiation of stem cell differentiation is highly associated with alteration of gene expression, which depends on chromatin remodeling. Epigenetic chromatin modifying agents have been shown to induce cancer cell differentiation and are currently being used clinically to treat cancer. This review will focus on the importance of epigenetic chromatin remodeling in the context of mesenchymal stem cells, sarcoma tumorigenesis and differentiation therapy."]
[19697097,1,0,0,1,2009,"Type II collagen oral tolerance; mechanism and role in collagen-induced arthritis and rheumatoid arthritis.","Park",19697097,"Type II collagen oral tolerance; mechanism and role in collagen-induced arthritis and rheumatoid arthritis.    Abstract:   Oral tolerance means a diminished immune response to previously fed antigens. Repeated oral administrations of type II collagen (CII) induce oral tolerance and inhibit the development of collagen-induced arthritis (CIA). Dendritic cells (DCs) in the gut-associated lymphoid tissue (GALT) take up the CII and then present it to T cells to generate regulatory T cells (Tregs), which induce systemic immune tolerance to CII. Inhibitory cytokines, such as transforming growth factor (TGF)-beta and interleukin (IL)-10, and several immune regulatory molecules, including indoleamine 2,3-dioxygenase (IDO) and retinoic acid, play an important role in Treg generation. Each DC subset may play different roles, and CD11c+CD11b+DCs and IDO+DCs are important in the generation of antigen-inducible Tregs in CII oral tolerance. Upon stimulation with the antigen involved in its generation, Treg is activated and regulates the immune response through inhibitory cytokine production, cell-to-cell contact-dependent mechanisms, DC modification, and bystander suppression. The DCs and Tregs are deeply involved in oral tolerance through reciprocal interactions. Several clinical trials have been conducted in RA patients to examine the efficacy of CII oral tolerance. An understanding the mechanism of oral tolerance to CII would give clinicians new insights into the development of natural immune tolerance and new therapeutic approaches for the treatment of autoimmune diseases."]
[19651306,1,0,0,1,2009,"Establishment of Hox vertebral identities in the embryonic spine precursors.","Iimura",19651306,"Establishment of Hox vertebral identities in the embryonic spine precursors.    Abstract:   The vertebrate spine exhibits two striking characteristics. The first one is the periodic arrangement of its elements-the vertebrae-along the anteroposterior axis. This segmented organization is the result of somitogenesis, which takes place during organogenesis. The segmentation machinery involves a molecular oscillator-the segmentation clock-which delivers a periodic signal controlling somite production. During embryonic axis elongation, this signal is displaced posteriorly by a system of traveling signaling gradients-the wavefront-which depends on the Wnt, FGF, and retinoic acid pathways. The other characteristic feature of the spine is the subdivision of groups of vertebrae into anatomical domains, such as the cervical, thoracic, lumbar, sacral, and caudal regions. This axial regionalization is controlled by a set of transcription factors called Hox genes. Hox genes exhibit nested expression domains in the somites which reflect their linear arrangement along the chromosomes-a property termed colinearity. The colinear disposition of Hox genes expression domains provides a blueprint for the regionalization of the future vertebral territories of the spine. In amniotes, Hox genes are activated in the somite precursors of the epiblast in a temporal colinear sequence and they were proposed to control their progressive ingression into the nascent paraxial mesoderm. Consequently, the positioning of the expression domains of Hox genes along the anteroposterior axis is largely controlled by the timing of Hox activation during gastrulation. Positioning of the somitic Hox domains is subsequently refined through a crosstalk with the segmentation machinery in the presomitic mesoderm. In this review, we focus on our current understanding of the embryonic mechanisms that establish vertebral identities during vertebrate development."]
[19646777,1,0,0,1,2010,"Psoriasis in patients with HIV infection: from the medical board of the National Psoriasis Foundation.","Menon",19646777,"Psoriasis in patients with HIV infection: from the medical board of the National Psoriasis Foundation.    Abstract:    BACKGROUND : Patients with psoriasis and HIV infection often present with more severe and treatment-refractory cutaneous disease. In addition, many of these patients have significant psoriatic arthritis. Many effective drugs for psoriasis and psoriatic arthritis are immunosuppressive. Therefore, therapy for the HIV-infected patient is more challenging, requiring both careful consideration of the potential risks and benefits of treatment and more fastidious monitoring for potential adverse events.  OBJECTIVE : A task force of the National Psoriasis Foundation Medical Board was convened to evaluate treatment options. Our aim was to arrive at a consensus on therapy for psoriasis in patients with HIV.  METHODS : A MEDLINE search of the terms quot;psoriasis,quot; quot;psoriatic arthritis,quot; quot;human immunodeficiency virus (HIV),quot; and quot;HIV skin diseasesquot; was performed and literature relevant to HIV-associated psoriasis and the treatment of HIV-associated psoriasis were reviewed.  RESULTS : Based on a review of the literature, 29 reports were included as evidence in this review. Topical therapy is the first-line recommended treatment for mild to moderate disease. For moderate to severe disease, phototherapy and antiretrovirals are the recommended first-line therapeutic agents. Oral retinoids may be used as second-line treatment. For more refractory, severe disease, cautious use of cyclosporine, methotrexate, hydroxyurea, and tumor necrosis factor-alpha inhibitors may also be considered.  LIMITATIONS : There are no randomized, placebo-controlled trials evaluating the therapeutic efficacy or safety of treatments for patients with HIV-associated psoriasis; consequently, the evidence supporting this review consists mainly of case reports or case series.  CONCLUSIONS : HIV-associated psoriasis is often refractory to traditional treatments. Treatment is challenging and requires careful consideration and should be tailored to patients based on disease severity and the input from an infectious disease specialist. Close monitoring for potential adverse events is necessary."]
[19567986,0,0,0,0,2009,"[Hormones and osteoporosis update. Vitamin D and bone].","Endo",19567986,"[Hormones and osteoporosis update. Vitamin D and bone].    Abstract:   Calcium homeostasis is maintained by parathyroid hormone and vitamin D. Mechanisms of action of these calcium-regulating hormones have been extensively examined, and the intracellular signaling pathways as well as transcriptional regulation of their target genes have been elucidated. Epidemiological studies revealed the importance of vitamin D sufficiency, and efforts have been made to implement the diagnostic criteria for vitamin D insufficiency. As a therapeutic agent, a new active vitamin D analog with anti-fracture efficacy has been developed for the treatment of osteoporosis."]
[27265273,6,0,0,6,2009,"Acute promyelocytic leukemia and differentiation therapy: molecular mechanisms of differentiation, retinoic acid resistance and novel treatments.","Özpolat",27265273,"Acute promyelocytic leukemia and differentiation therapy: molecular mechanisms of differentiation, retinoic acid resistance and novel treatments.    Abstract:   Incorporation of all-trans-retinoic acid (ATRA) into the treatment of acute promyelocytic leukemia (APL), a type of acute myeloid leukemia (AML), revolutionized the therapy of cancer in the last decade and introduced the concept of differentiation therapy. ATRA, a physiological metabolite of vitamin A (retinol), induces complete clinical remissions (CRs) in about 90% of patients with APL. In contrast to the cytotoxic chemotherapeutics, ATRA can selectively induce terminal differentiation of promyelocytic leukemic cells into normal granulocytes without causing bone marrow hypoplasia or exacerbation of the frequently occurring fatal hemorrhagic syndromes in patients with APL. However, remissions induced by ATRA alone are transient and the patients commonly become resistant to the therapy, leading to relapses in most patients and thus limiting the use of ATRA as a single agent. Therefore, ATRA is currently combined with anthracycline-based chemotherapy, and this regimen dramatically improves patient survival compared to chemotherapy alone, curing about 70% of the patients. However, 30% of APL patients still relapse and die in five years. Recently, arsenic trioxide (As2O3) was proven to be highly effective in inducing CRs not only in APL patients relapsed after ATRA treatment and conventional chemotherapy but also in primary APL patients. Despite the well-documented clinical efficacy of ATRA, molecular mechanisms responsible for development of ATRA resistance are not well understood. Based on in vitro and clinical observations, several mechanisms, including induction of accelerated metabolism of ATRA, decreased bioavailability and plasma drug levels, point mutations in the ATRA-binding domain of promyelocytic leukemia (PML)-retinoic acid receptor-alpha (RARα) and other molecular events have been proposed to explain ATRA resistance. In this review, the molecular mechanisms of ATRA-induced myeloid cell differentiation and resistance are discussed, together with novel clinical approaches to overcome ATRA resistance in APL. Son 10 yıl içerisinde, all-trans retinoik asidin (ATRA) bir akut miyeloid lösemi (AML) tipi olan akut promiyelositik lösemi (APL) tedavisinde kullanılmaya başlanması, kanser tedavisinde kökten değişiklik yapmış ve diferansiyasyon tedavisi kavramının ortaya çıkmasına neden olmuştur. A vitamininin (retinol) fizyolojik bir metaboliti olan ATRA, APL’li hastaların yaklaşık %90’ında tam klinik remisyonları (KR) indükler. Sitotoksik kemoterapötiklerin tersine, ATRA, APL’li hastalarda kemik iliği hipoplazisi oluşumunu veya sık oluşan ölümcül hemorajik sendromların alevlenmesini önleyerek, seçici bir şekilde promiyelositik lösemik hücrelerin normal granülositlere terminal diferansiyasyonunu indükler. Buna rağmen, sadece ATRA tarafından indüklenen remisyonlar geçicidir ve çoğunlukla hastalar tedaviye direnç kazanırlar, bu da pek çok hastada hastalığın nüksüne neden olur; bu nedenle, ATRA’ nın tek ajan olarak kullanımı sınırlı hale gelir. Bu nedenle, ATRA halen antrasiklin bazlı kemoterapi ile kombine haldedir ve bu rejim sadece kemoterapi kullanımı ile karşılaştırıldığında, hastaların yaklaşık %70’ini iyileştirerek, hasta sağkalımını önemli ölçüde arttırmaktadır. Buna rağmen, APL hastalarının halen %30’unda hastalık nüks etmekte ve 5 yıl içerisinde ölüm gerçekleşmektedir. Son zamanlarda, arsenik trioksit (As2O3)’ in, sadece ATRA tedavisi ve klasik kemoterapiden sonra nükseden APL hastalarında değil, aynı zamanda, primer APL hastalarında da KR’leri indüklemede yüksek oranda etkili olduğu ispatlanmıştır. ATRA’nın yazılı kanıtlara dayanan klinik etkinliğine rağmen, ATRA direncinin gelişmesinden sorumlu olan moleküler mekanizmalar tam olarak anlaşılmamıştır. İnvitro ve klinik gözlemlere dayanarak, ATRA’nın hızlanmış metabolizmasının indüksiyonu, azalmış olan biyoyararlanım ve plazma ilaç düzeyleri dahil çeşitli mekanizmalar, PML-RARα’nın ATRA-bağlayan domain yapısında nokta mutasyonu ve diğer moleküler olaylar ATRA direncini açıklamak üzere öne sürülmüştür. Bu derlemede, APL’de ATRA direncinin üstesinden gelmek için, ATRA ile-indüklenmiş miyeloid hücre farklılaşmasının, direncin ve yeni klinik yaklaşımların moleküler mekanizmalarını ele alacağım."]
[19485900,1,0,0,1,2010,"Thromboembolic complications in malignant haematological disorders.","Castelli",19485900,"Thromboembolic complications in malignant haematological disorders.    Abstract:   It is well known that solid cancers are associated with thromboembolic complications, but recent studies have shown that the incidence of thrombosis may be as high (or even higher) in patients with malignant haematological disorders. However, this may be obscured by the significant morbidity and mortality due to other complications of haematological malignancies, such as bleeding and infections. The vast majority of patients with haematological neoplasias also have clinically silent haemostatic abnormalities, but some may show clinical manifestations, including venous thromboembolism, pulmonary embolism, disseminated intravascular coagulation and life-threatening thrombohaemorrhagic syndrome in acute leukaemias. The pathogenesis of thromboembolic disease in haematological malignancies is complex and multifactorial: tumour cell-derived procoagulant, fibrinolytic or proteolytic factors and inflammatory cytokines affect clotting activation, and chemotherapy and anti-angiogenic drugs increase thrombotic risk in patients with lymphoma, acute leukaemia and multiple myeloma. Infectious complications are another important factor: endotoxins from gram-negative bacteria induce the release of tissue factor (TF), Tumor Necrosis Factor (TNF) and interleukin-1b (IL-1b), and gram-positive organisms can release bacterial mucopolysaccharides that directly activate factor XII. Leukaemic patients may be affected by other prothrombotic factors, including hyperleukocytosis, increased TF expression and activation, and the prothrombotic properties of therapeutic agents such as all-trans retinoic acid and L-asparaginase, which can induce thrombosis involving multiple organs. The very high risk of haemorrhaging in these patients warrants prospective randomised trials evaluating optimal anti-thrombotic prophylaxis and treatment."]
[19464395,0,0,0,0,2009,"The etiology of congenital diaphragmatic hernia: still largely unknown?","Klaassens",19464395,"The etiology of congenital diaphragmatic hernia: still largely unknown?    Abstract:   Congenital diaphragmatic hernia (CDH) is a severe birth defect characterized by a defect in the diaphragm associated with pulmonary hypoplasia and postnatal pulmonary hypertension. Half of the cases present with other non-pulmonary congenital anomalies (so called non-isolated CDH) and in 5-10% of cases there is a chromosomal etiology. The clinical aspects of CDH are well documented but knowledge on the etiology of CDH is largely lacking. Worldwide many researchers have focused research efforts on CDH. Their findings have led to several hypotheses proposing roles for genetic and environmental factors. In this review we have combined these findings with our own research on the genetics of CDH in results from recent literature and propose a theory on the etiology of CDH. We also propose a protocol for the CDH patient that will help clinicians and researchers to obtain maximal success out of their collaborations that will eventually lead to unravelling the etiology of this intriguing birth defect."]
[19390062,1,0,0,1,2009,"Signaling pathways controlling second heart field development.","Rochais",19390062,"Signaling pathways controlling second heart field development.    Abstract:   Insight into the mechanisms underlying congenital heart defects and the use of stem cells for cardiac repair are major research goals in cardiovascular biology. In the early embryo, progenitor cells in pharyngeal mesoderm contribute to the rapid growth of the heart tube during looping morphogenesis. These progenitor cells constitute the second heart field (SHF) and were first identified in 2001. Direct or indirect perturbation of SHF addition to the heart results in congenital heart defects, including arterial pole alignment defects. Over the last 3 years, a number of studies have identified key intercellular signaling pathways that control the proliferation and deployment of SHF progenitor cells. Here, we review data concerning Wnt, fibroblast growth factor, bone morphogenetic protein, Hedgehog, and retinoic acid signaling that have begun to identify the ligand sources and responding cell types controlling SHF development. These studies have revealed the importance of signals from pharyngeal mesoderm itself, as well as critical inputs from adjacent pharyngeal epithelia and neural crest cells. Proliferation is emerging as a central checkpoint in the regulation of SHF development. Together, these studies contribute to defining the niche of cardiac progenitor cells in the early embryo, and we discuss the implications of these findings for the regulation of resident stem cell populations in the fetal and postnatal heart. Characterization of signals that maintain, expand, and regulate the differentiation of cardiac progenitor cells is essential for understanding both the etiology of congenital heart defects and the biomedical application of stem cell populations for cardiac repair."]
[19370616,1,0,0,1,2009,"Topical treatments for chronic plaque psoriasis.","Mason",19370616,"Topical treatments for chronic plaque psoriasis.    Abstract:    BACKGROUND : Chronic plaque psoriasis is the most common type of psoriasis and is characterised by redness, thickness and scaling. First line management of chronic plaque psoriasis is with topical treatments, including vitamin D analogues, topical corticosteroids, tar-based preparations, dithranol, salicylic acid and topical retinoids.  OBJECTIVES : To compare the effectiveness, tolerability and safety of topical treatments for chronic plaque psoriasis with placebo; to compare vitamin D analogues with other topical treatments.  SEARCH STRATEGY : The Cochrane Skin Groups Trials Register was searched (2004/12). To update an unpublished 2002 review we also searched CENTRAL in The Cochrane Library (Issue 1,2005); MEDLINE (to 2005/02); EMBASE (to 2005/08); Science Citation Index (to 2005); Biosis (to 2005); Dissertation Abstracts (all publication years); Inside Conferences (all publication years); SIGLE (to 2005); National Research Register (all projects with a start date of 2001 to 2005); metaRegister of Current Controlled Trials.  SELECTION CRITERIA : Randomised trials comparing treatments against placebo or against vitamin D analogues in people with chronic plaque psoriasis.  DATA COLLECTION AND ANALYSIS : One author extracted study data and assessed study quality. A second author checked these data. We routinely contacted triallists and companies for missing data. We extracted data on withdrawals and adverse events.  MAIN RESULTS : The review included 131 RCTs with 21,448 participants. Vitamin D was significantly more effective than placebo, although there was a wide variation in effect size with the standardised mean difference (SMD) ranging from -0.82 (95% CI -1.34 to -0.29) to -1.90 (95% CI -2.09 to -1.71). With one exception, all corticosteroids performed better than placebo, with potent corticosteroids (SMD: -0.95 (95% CI: -1.11 to -0.80; I(2): 61.1%; 17 studies; 2386 participants)) having smaller benefits than very potent corticosteroids (SMD: -1.29 (95% CI: -1.45 to -1.13; I(2): 53.2%; 11 studies; 1571 participants)). Dithranol and tazarotene performed better than placebo. Head-to-head comparisons of vitamin D against potent or very potent corticosteroids found no significant differences. However, combined treatment with vitamin D /corticosteroid performed significantly better than either vitamin D alone or corticosteroid alone. Vitamin D performed better than coal tar, but findings relative to dithranol were mixed. Potent corticosteroids were less likely than vitamin D to cause local adverse events. No comparison of topical agents found a significant difference in systemic adverse effects.  AUTHORS CONCLUSIONS : Corticosteroids perform as well as vitamin D analogues and are associated with a lower incidence of local adverse events. Further research is required to inform long-term maintenance treatment."]
[19334283,0,0,0,0,2009,"Xenopus pancreas development.","Pearl",19334283,"Xenopus pancreas development.    Abstract:   Understanding how the pancreas develops is vital to finding new treatments for a range of pancreatic diseases, including diabetes and pancreatic cancer. Xenopus is a relatively new model organism for the elucidation of pancreas development, and has already made contributions to the field. Recent studies have shown benefits of using Xenopus for understanding both early patterning and lineage specification aspects of pancreas organogenesis. This review focuses specifically on Xenopus pancreas development, and covers events from the end of gastrulation, when regional specification of the endoderm is occurring, right through metamorphosis, when the mature pancreas is fully formed. We have attempted to cover pancreas development in Xenopus comprehensively enough to assist newcomers to the field and also to enable those studying pancreas development in other model organisms to better place the results from Xenopus research into the context of the field in general and their studies specifically. Developmental Dynamics 238:1271-1286, 2009. (c) 2009 Wiley-Liss, Inc."]
[19306896,1,0,0,1,2009,"Multilevel targeting of hematopoietic stem cell self-renewal, differentiation and apoptosis for leukemia therapy.","Tsiftsoglou",19306896,"Multilevel targeting of hematopoietic stem cell self-renewal, differentiation and apoptosis for leukemia therapy.    Abstract:   Human leukemias are considered clonal hematological malignancies initiated by chromosomal aberrations or epigenetic alterations occurring at the level of either pluripotent hematopoietic stem cells (HSCs) or early multipotent progenitors (MPPs). Leukemic cells are transformed, immortalized, actively proliferating cells that are still able to differentiate into cells resembling mature blood cells. Future therapies of leukemias require identification of molecular targets involved in hematopoiesis under normal and leukemic conditions and detailed understanding of the interactions between normal hematopoietic and leukemic cells within the bone marrow micro-environment. This review presents the basic aspects of hematopoiesis and highlights multilevel exploitable targets for leukemia therapy. These include HSC niche components, signaling pathways (SCF/c-kit-R, EPO-R-JAK2/STAT, Wnt, Notch, HOX), inducer-receptor interactions, superfine chromatin structure modifications, fused transcription factors, microRNAs and signaling of cell death through the Bcl-2 apoptotic switch (BH3-only proteins). The classes of therapeutics developed or being under development to eradicate human leukemias include novel antimetabolites, DNA hypomethylating agents, histone deacetylation inhibitors (HDACIs), retinoids and other inducers of differentiation, targeted monoclonal antibodies raised against cell surface proteins, pro-apoptotic receptor agonists (PARAs), BH3 peptidomimetics, cell cycle inhibitors, siRNAs and perhaps microRNAs. Some of these agents induce terminal differentiation while others promote cell cycle arrest and apoptosis in leukemia cells. At last but not least, this article describes the mechanisms of removal of damaged/harmful cells from organs since impairment in clearance of such cells can lead to autoimmune disorders by self-antigens."]
[19286352,0,0,0,0,2009,"Dendritic cells as controllers of antigen-specific Foxp3+ regulatory T cells.","Yamazaki",19286352,"Dendritic cells as controllers of antigen-specific Foxp3+ regulatory T cells.    Abstract:   Regulatory T cells (Treg) are a subpopulation of CD4(+) lymphocytes that maintain immunological self-tolerance in the periphery. Treg also regulate or suppress other classes of immune response such as allograft rejection, allergy, tumor immunity, and responses to microbes. Treg express the Foxp3 transcription factor and CD25, the high affinity interleukin-2 receptor (IL-2R). Treg are divided into two types: naturally occurring Treg derived from thymus (natural Treg) and Treg induced from Foxp3(-) CD4(+) T cells in the periphery (induced Treg). It would be valuable to understand how to control the generation of antigen-specific Treg, which could also provide a new approach to treat autoimmunity, allergy or allograft rejection without suppressing immune responses to tumor and microbes. In this review, we will discuss the role of dendritic cells (DCs) in controlling antigen-specific natural Treg and induced Treg. Natural Treg are anergic upon T cell receptor stimulation generally, however, we found that the antigen-specific natural Treg can be expanded by antigen-presenting mature bone marrow-derived dendritic cells (BM-DCs). Furthermore, recent studies showed that antigen-specific Treg can be induced from Foxp3(-) CD25(-) CD4(+) T cells by antigen-presenting DCs, particularly select subsets of DCs in the periphery. These findings need to be pursued to develop novel immune suppressive therapies using antigen-specific Treg educated by DCs."]
[19247958,2,0,0,2,2009,"The road to the vertebral formula.","Mallo",19247958,"The road to the vertebral formula.    Abstract:   In vertebrates, the paraxial mesoderm differentiates into several structures, including the axial skeleton. The genetic mechanisms that control positional information in the paraxial mesoderm along the anterior-posterior axis are responsible for the development of a skeleton with the appropriate vertebral formula, i.e. a specific number of cervical, thoracic, lumbar, sacral and caudal vertebrae. These control mechanisms are complex and involve molecules of different kinds, including transcription factors, like those encoded by the Hox genes, and signalling molecules, like those involved in Gdf11, FGF, retinoic acid or WNT signalling. Recent experiments indicate that most of the positional information for the paraxial mesoderm is encoded during the initial steps of its development in the presomitic mesoderm, although it is only decoded later during differentiation of the somites. The genesis of positional identity may be linked to the process of somitogenesis, which also occurs in the presomitic mesoderm as a result of complex interactions involving oscillatory activity of components of the Notch and WNT signalling pathways and antagonistic gradients of FGF/WNT and retinoic acid. The possible connections between Hox genes and all these signalling processes to generate a properly patterned axial skeleton are discussed in this review."]
[19189637,0,0,0,0,2008,"Identification of parental chromosomes involved in translocations BCR-ABL, t(9;22) and PML-RARA, t(15;17).","Chaudhuri",19189637,"Identification of parental chromosomes involved in translocations BCR-ABL, t(9;22) and PML-RARA, t(15;17).    Abstract:   Cells of blood and bone marrow often exhibit a genome- or ploidywise organization of the two haploid sets, representing apparently maternal and paternal chromosomes in interphase nuclei and in metaphase spreads. This provides the opportunity to perform quot;genomic karyotyping.quot; Such application of karyotyping may indicate whether two chromosomes involved in a translocation are both maternal, both paternal, or intermingled, i.e., one maternal and the other paternal (we refer to this as mixed). The parental origin for these translocations likely has profound differences and implications in disease expression and response to treatments, making such information very important to personalized medicine. In this mini-review, we present our observations from specimens with translocations BCR-ABL, t(9;22) and PML-RARA, t(15;17). About 20% metaphases of these specimens indicated ploidywise organization and were amenable to genomic karyotyping analysis. Fluorescence in situ hybridization (FISH) probes for BCR-ABL translocation suggest a close approximation of the HSA 9 and 22, as control values for false-positive signals run from approximately 5-10%. Given a ploidywise distribution of the maternal and paternal sets of chromosomes, it would be expected that the chromosomes involved in the translocation t(9;22) would more often belong to one of the two genomes, either maternal or paternal. Contrastingly, HSA 15 and 17 are not considered as spatially close to each other and therefore an intragenomic involvement would be rarer for translocation t(15;17). In 14 out of the 21 (66.6%) specimens with informative metaphases, the chromosomes involved in the translocation BCR-ABL were restricted to one of the two genomes--either maternal or paternal. In cases of translocation PML-RARA only 4 out of 21 (19.1%) specimens indicated an intragenomic involvement. These simple yet informative analyses of cancer-related translocations show profound underlying genomic origins and lend support to genomic karyotyping."]
[19084074,1,0,0,1,2009,"Balancing segmentation and laterality during vertebrate development.","Brend",19084074,"Balancing segmentation and laterality during vertebrate development.    Abstract:   Somites are the mesodermal segments of vertebrate embryos that become the vertebral column, skeletal muscle and dermis. Somites arise within the paraxial mesoderm by the periodic, bilaterally symmetric process of somitogenesis. However, specification of left-right asymmetry occurs in close spatial and temporal proximity to somitogenesis and involves some of the same cell signaling pathways that govern segmentation. Here, we review recent evidence that identifies cross-talk between these processes and that demonstrates a role for retinoic acid in maintaining symmetrical somitogenesis by preventing impingement of left-right patterning signals upon the paraxial mesoderm."]
[19075782,9,0,0,9,2008,"Roles of retinoic acid in induction of immunity and immune tolerance.","Kim",19075782,"Roles of retinoic acid in induction of immunity and immune tolerance.    Abstract:   It has long been recognized that vitamin A and its metabolites have immune-regulatory roles but the mechanism has been unclear. Recently, there has been a significant progress in elucidating the functions of retinoic acid in regulation of immune cell development. Retinoic acid (all-trans and 9-cis retinoic acid) is produced from the cells of the intestine such as dendritic cells and provides an intestine-specific environmental cue to differentiating immune cells. When T cells and B cells are activated in the intestine and associated-lymphoid tissues, gut homing receptors are induced on the cells in a retinoic acid and antigen-dependent manner. Retinoic acid, produced by gut dendritic cells, is also an important signal that induces IgA-producing B cells. The gut homing T cells and B cells play essential roles in protecting the digestive tract from pathogens. Retinoic acid is required also for production of mature phagocytes in bone marrow. On the other hand, retinoic acid induces a subset of FoxP3+ regulatory T cells which is important for maintaining immune tolerance in the gut. Therefore, retinoids provide both positive and negative regulatory signals to fine-control the mucosal immune system."]
[18341851,1,0,0,1,2008,"[Long-term control of psoriasis is necessary].","Sánchez Carazo",18341851,"[Long-term control of psoriasis is necessary].    Abstract:   Psoriasis is an immune mediated, inflammatory skin condition affecting approximately 1.43% of Spanish population. In clinical practice, physicians use PASI index to assess the severity. Psoriasis causes physical and mental disability comparable to other chronic diseases and affects seriously the patients quality of life. For treatment we have different options. Conventional systemic treatment such as methotrexate, cyclosporine and acitretin may be associated with relevant side effects, and organ toxicity that avoid long term therapy. Several psoriasis patients have other comorbid disorders like obesity, diabetes, dyslipemia, hypertension and an increased rate of cardiovascular disease and metabolic syndrome and these patients need safer treatments. The accumulating clinical experience with new therapies consistent on biological agents like efalizumab indicates that are effective therapies, with safety profile and no evidence of cumulative toxicity that allows a long term use. A better control of psoriasis improves patients quality of life."]
[18844852,1,0,0,1,2008,"Vitamin D receptor: molecular signaling and actions of nutritional ligands in disease prevention.","Haussler",18844852,"Vitamin D receptor: molecular signaling and actions of nutritional ligands in disease prevention.    Abstract:   The human vitamin D receptor (VDR) is a key nuclear receptor that binds nutritionally derived ligands and exerts bioeffects that contribute to bone mineral homeostasis, detoxification of exogenous and endogenous compounds, cancer prevention, and mammalian hair cycling. Liganded VDR modulates gene expression via heterodimerization with the retinoid X receptor and recruitment of coactivators or corepressors. VDR interacts with the corepressor hairless (Hr) to control hair cycling, an action independent of the endocrine VDR ligand, 1,25-dihydroxyvitamin D(3). We report novel dietary ligands for VDR including curcumin, gamma-tocotrienol, and essential fatty acid derivatives that likely play a role in the bioactions of VDR."]
[19030789,1,0,0,1,2008,"Treatment of mice with retinoids in vivo and in vitro.","Morriss-Kay",19030789,"Treatment of mice with retinoids in vivo and in vitro.    Abstract:  "]
[19027486,1,0,0,1,2008,"Acute promyelocytic leukemia relapsing as secondary acute myelogenous leukemia with translocation t(3;21)(q26;q22) and RUNX1-MDS1-EVI1 fusion transcript.","Park",19027486,"Acute promyelocytic leukemia relapsing as secondary acute myelogenous leukemia with translocation t(3;21)(q26;q22) and RUNX1-MDS1-EVI1 fusion transcript.    Abstract:   Acute promyelocytic leukemia (APL) is a subtype of acute myelogenous leukemia (AML) that is characterized by peculiar clinical and biologic features, including severe hemorrhagic diathesis, specific recurrent chromosomal aberration, and distinct morphologic features with predominant pathologic promyelocytes. A reciprocal translocation involving chromosomes 15 and 17, t(15;17)(q22;q21), is a characteristic feature of APL that represents approximately 5-8% of AML. The rearranged gene created by this translocation encodes a chimeric protein PML-RARA that is a transcriptional repressor. In contrast to other AML subtypes, APL is particularly sensitive to treatment with all trans-retinoic acid (ATRA) combined with chemotherapy, converting this once fatal leukemia to a highly curable disease. Nonetheless, therapy-related myelodysplastic syndrome-acute myelogenous leukemia (t-MDS/AML) has been reported as a rare complication of chemotherapy in APL. Of 30 APL cases described as t-MDS/AML in the literature, only 1 case relapsed as acute leukemia with t(3;21)(q26;q22). Here we describe a rare case of APL relapsing as secondary AML with t(3;21)(q26;q22) and clinically characterize this patient using the RUNX1 (previously AML1)-MDS1-EVI1 fusion transcript (with follow-up for 55 months), and review the relevant literature."]
[18759328,0,0,0,0,2008,"Neural differentiation of human embryonic stem cells.","Dhara",18759328,"Neural differentiation of human embryonic stem cells.    Abstract:   Availability of human embryonic stem cells (hESC) has enhanced human neural differentiation research. The derivation of neural progenitor (NP) cells from hESC facilitates the interrogation of human embryonic development through the generation of neuronal subtypes and supporting glial cells. These cells will likely lead to novel drug screening and cell therapy uses. This review will discuss the current status of derivation, maintenance and further differentiation of NP cells with special emphasis on the cellular signaling involved in these processes. The derivation process affects the yield and homogeneity of the NP cells. Then when exposed to the correct environmental signaling cues, NP cells can follow a unique and robust temporal cell differentiation process forming numerous phenotypes."]
[18755362,2,0,0,2,2008,"Systemic therapies for psoriasis: methotrexate, retinoids, and cyclosporine.","Warren",18755362,"Systemic therapies for psoriasis: methotrexate, retinoids, and cyclosporine.    Abstract:   Despite the current use and ongoing development of the biological therapies traditional systemic agents will continue to form a key part of the therapeutic armamentarium for patients with severe psoriasis. Long-term maintenance therapy with retinoids and methotrexate is cost-effective and, for many patients with psoriasis, life changing. Regular monitoring is required for both treatments, particularly methotrexate to prevent significant bone marrow suppression and hepatotoxicity. Ideally, cyclosporine should be used for short courses of 3 to 4 months duration, within which it provides excellent disease control. Close assessment of renal function and blood pressure is essential."]
[18752475,1,0,0,1,2008,"Are low tolerable upper intake levels for vitamin A undermining effective food fortification efforts?","Kraemer",18752475,"Are low tolerable upper intake levels for vitamin A undermining effective food fortification efforts?    Abstract:   Vitamin A deficiency (VAD) is a major health problem, particularly in low-resource countries, putting an estimated 125-130 million preschool-aged children at increased risk of morbidity and mortality from infectious diseases. Vitamin A supplementation reduces VAD and increases child survival; it is complemented by fortifying foods with vitamin A. Concern over increased risk of bone fracture associated with vitamin A intakes below the tolerable upper intake level (UL) among populations in affluent countries conflicts with the need to increase intakes in less developed countries, where populations are at greater risk of VAD and intakes are unlikely to reach the UL as diets include fewer foods containing retinol while vitamin A from carotenoids poses no risk of overdose. With the implementation of recently developed risk management tools, vitamin A can be used safely in food fortification, including point-of-use fortification in the context of supplementation among specific target groups in low-resource countries."]
[18692690,2,0,0,2,2008,"Acute promyelocytic leukemia: recent advances in diagnosis and management.","Lo-Coco",18692690,"Acute promyelocytic leukemia: recent advances in diagnosis and management.    Abstract:   Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia (AML) characterized by a specific genetic alteration, affecting the retinoic acid receptor-alpha (RARalpha), and leading to a blockage in the differentiation of the granulocytic cells. The accumulation of the promyelocytic blasts in the bone marrow produces intense peripheral blood cytopenias or, less commonly, hyperleucocytosis, both of which are frequently associated with a life-threatening consumptive coagulopathy. The body of available biological information on APL establishes this leukemia as a unique entity that has to be promptly recognized and clearly distinguished from all other acute leukemias, especially in light of its striking response to treatment with anthracyclines and differentiating agents such as all-trans retinoic acid (ATRA) or arsenic trioxide (ATO). Current state-of-the-art treatments, which include simultaneous administration of ATRA and anthracycline-based chemotherapy for induction and consolidation, as well as ATRA-based maintenance, have dramatically transformed APL into the most curable acute leukemia in adults, with approximately 80% of long-term survivors. Risk-adapted strategies to modulate treatment intensity may be an effective approach to minimizing therapy-related morbidity and mortality while maintaining the potential of cure. Nonetheless, a sizeable proportion of patients will relapse after the ATRA-based upfront therapy. Given the high anti-leukemic efficacy observed with ATO in patients who relapse, this agent is currently regarded as the best treatment option in this setting. In this article, we will review the current treatment strategies in the management of newly diagnosed and relapsed APL. We also highlight other aspects that can be crucial for the outcome of individual patients, including supportive care, recognition and treatment of life-threatening complications, management of ATRA- and ATO-associated adverse events, and the role of minimal residual disease (MRD) monitoring."]
[18690950,1,0,0,1,2007,"Musculoskeletal adverse drug reactions: a review of literature and data from ADR spontaneous reporting databases.","Conforti",18690950,"Musculoskeletal adverse drug reactions: a review of literature and data from ADR spontaneous reporting databases.    Abstract:   The musculoskeletal system can be a target organ for adverse drug reactions (ADRs). Drug-induced muscle, bone or connective tissue injuries may be due to, i), primary direct drug action, or, ii), undirected consequence of generalized drug-induced disease. Musculoskeletal ADRs may be only temporarily disabling, such as muscle cramps, as well as in other cases may be serious and life-threatening, such as rhabdomyolysis. In the last few years there has been an increasing awareness of musculoskeletal ADRs. Some recent drug safety issues dealt with serious or uncommon musculoskeletal reactions like rhabdomyolysis associated to statins and tendon rupture associated to fluoroquinolones. In this review, we firstly selected those drug classes having a significantly high percentage of musculoskeletal disorder reports in the WHO adverse drug reaction database, maintained by the Uppsala Monitoring Centre. Secondly, the different musculoskeletal ADRs were closely analyzed through the data obtained from an Italian interregional ADRs spontaneous reporting database. The findings on drugs associated to different musculoskeletal disorders, have been integrated with a review of the epidemiological data available in the literature. For the most involved drugs (HMG-CoA reductase inhibitors, fluoroquinolones, corticosteroids, bisphosphonates, retinoids) the underlying musculoskeletal ADR mechanisms were also reviewed and discussed."]
[18650721,1,0,0,1,2008,"Prevention and management of hypertrophic scars and keloids after burns in children.","Berman",18650721,"Prevention and management of hypertrophic scars and keloids after burns in children.    Abstract:   Hypertrophic scars and keloids are challenging to manage, particularly as sequelae of burns in children in whom the psychologic burden and skin characteristics differ substantially from adults. Prevention of hypertrophic scars and keloids after burns is currently the best strategy in their management to avoid permanent functional and aesthetical alterations. Several actions can be taken to prevent their occurrence, including parental and children education regarding handling sources of fire and flammable materials, among others. Combination of therapies is the mainstay of current burn scar management, including surgical reconstruction, pressure therapy, silicon gels and sheets, and temporary garments. Other adjuvant therapies such as topical imiquimod, tacrolimus, and retinoids, as well as intralesional corticosteroids, 5-fluorouracil, interferons, and bleomycin, have been used with relative success. Cryosurgery and lasers have also been reported as alternatives. Newer treatments aimed at molecular targets such as cytokines, growth factors, and gene therapy, currently in developing stages, are considered the future of the treatment of postburn hypertrophic scars and keloids in children."]
[18566348,1,0,0,1,2009,"Bone pain, growth failure, and skin rash after an upper respiratory illness in a boy with autism: possible association with altered retinoid metabolism.","Mawson",18566348,"Bone pain, growth failure, and skin rash after an upper respiratory illness in a boy with autism: possible association with altered retinoid metabolism.    Abstract:   Symptoms of bone pain and skin rashes are not uncommon following a variety of infectious illnesses, but the underlying mechanisms are not well understood. The case of a 9-year-old boy with autism was recently described, who was hospitalized because of pain in the right hip, refusal to walk, fatigue, irritability, skin rash, and subsequent gingival swelling after an unspecified upper respiratory illness. The boy was diagnosed with scurvy. However, the gingival symptoms occurred after treatment with indomethacin, which lowers vitamin C levels; severe bone pain and fatigue are also well-documented symptoms of hypervitaminosis A. This review of a case report of a boy with autism provides an opportunity to present a new hypothesis of the mechanism of these postinfection symptoms in the context of an increasingly common condition of childhood."]
[18563503,3,0,0,3,2008,"Neuronal differentiation of synovial sarcoma and its therapeutic application.","Ishibe",18563503,"Neuronal differentiation of synovial sarcoma and its therapeutic application.    Abstract:   Synovial sarcoma is a rare sarcoma of unknown histologic origin. We previously reported the gene expression profile of synovial sarcoma was closely related to that of malignant peripheral nerve sheath tumors, and the fibroblast growth factor (FGF) signal was one of the main growth signals in synovial sarcoma. Here we further demonstrate the neural origin of synovial sarcoma using primary tumors and cell lines. The expression of neural tissue-related genes was confirmed in synovial sarcoma tumor tissues, but the expression of some genes was absent in synovial sarcoma cell lines. Treatment of synovial sarcoma cell lines with BMP4 or FGF2 enhanced or restored the expression of neural tissue-related genes and induced a neuron-like morphology with positive Tuj-1 expression. Treatment with all-trans-retinoic acid also induced the expression of neural tissue-related genes in association with growth inhibition, which was not observed in other cell lines except a malignant peripheral nerve sheath tumor cell line. A growth-inhibitory effect of all-trans-retinoic acid was also observed for xenografted tumors in athymic mice. The simultaneous treatment with FGF signal inhibitors enhanced the growth-inhibitory effect of all-trans-retinoic acid, suggesting the combination of growth signaling inhibition and differentiation induction could be a potential molecular target for treating synovial sarcoma."]
[18313476,1,0,0,1,2008,"Growth and differentiation factors for cartilage healing and repair.","Gaissmaier",18313476,"Growth and differentiation factors for cartilage healing and repair.    Abstract:   Chondrocyte differentiation and the maintenance of function requires both transient and long-lasting control through humoral factors, particularly under stress, repair and regeneration in vivo or in vitro as in cell and tissue culture. To date, humoral factors from all major classes of molecules are known to contribute: ions (calcium), steroids (estrogens), terpenoids (retinoic acid), peptides (PTHRP, PTH, insulin, FGFs) and complex proteins (IGF-1, BMPs). They may act indirectly through membrane receptors and signal pathways or directly on transcriptional control elements. Those molecules may reach chondrocytes via free diffusion or may be bound to collagens or proteoglycans on extracellular matrix superstructures becoming available on metabolic processing of collagens and/or proteoglycans. Depending on their position in the metabolic cascade controlling chondrocyte development and homeostasis, they may be used in tissue engineering and regenerative approaches towards cartilage repair by direct application, carrier-mediated release or genetic delivery."]
[18459983,1,0,0,1,2008,"The autopod: its formation during limb development.","Tamura",18459983,"The autopod: its formation during limb development.    Abstract:   The autopod, including the mesopodium and the acropodium, is the most distal part of the tetrapod limb, and developmental mechanisms of autopod formation serve as a model system of pattern formation during development. Cartilage rudiments of the autopod develop after proximal elements have differentiated. The autopod region is marked by a change in the expression of two homeobox genes: future autopod cells are first Hoxa11/Hoxa13-double-positive and then Hoxa13-single-positive. The change in expression of these Hox genes is controlled by upstream mechanisms, including the retinoic acid pathway, and the expression of Hoxa13 is connected to downstream mechanisms, including the autopod-specific cell surface property mediated by molecules, including cadherins and ephrins/Ephs, for cell-to-cell communication and recognition. Comparative analyses of the expression of Hox genes in fish fins and tetrapod limb buds support the notion on the origin of the autopod in vertebrates. This review will focus on the cellular and molecular regulation of the formation of the autopod during development and evolutionary developmental aspects of the origin of the autopod."]
[18430162,0,0,0,0,2008,"Elucidation of the role of activin in organogenesis using a multiple organ induction system with amphibian and mouse undifferentiated cells in vitro.","Asashima",18430162,"Elucidation of the role of activin in organogenesis using a multiple organ induction system with amphibian and mouse undifferentiated cells in vitro.    Abstract:   Studies performed over the last century have clarified the mechanisms of organ and tissue formation. Mesoderm formation is one of the most important events in early body pattern determination during embryogenesis. In 1988, we found that activin A has mesoderm-inducing activity. As activin A could induce dorsal mesoderm formation, unlike fibroblast growth factor and bone morphogenetic protein, this factor was thought to be the molecular entity of the Spemann-Mangold organizer. Subsequently, the mechanisms of early embryogenesis have been clarified using molecular biological techniques, resulting in the identification of many genes that are involved in organ and tissue development. This finding that activin A could induce dorsal mesoderm formation spurred research into the application of agents that induce organs and tissues in vitro. In this regard, we have shown that many organ types can be induced by activin A in vitro. Moreover, we have found that other types of organs can be induced by changing the conditions of treatment. To date, more than 20 different types of tissues and organs have been successfully induced from Xenopus undifferentiated cells in vitro. In recent years, we have applied these protocols to mouse embryonic stem cells, and we have successfully induced several tissues, such as the pancreas and cardiomyocytes. We are also investigating how the pluripotency of undifferentiated stem cells is regulated. In this review, we summarize the current knowledge regarding activin as a mesoderm-inducing factor and its application for the induction of tissues and organs from undifferentiated cells. Moreover, we provide some examples of in vitro tissue differentiation from mouse embryonic stem cells, which may prove useful in regenerative medicine."]
[18423260,0,0,0,0,2008,"Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 1. Overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics.","Menter",18423260,"Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 1. Overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics.    Abstract:   Psoriasis is a common, chronic, inflammatory, multisystem disease with predominantly skin and joint manifestations affecting approximately 2% of the population. In this first of 5 sections of the guidelines of care for psoriasis, we discuss the classification of psoriasis; associated comorbidities including autoimmune diseases, cardiovascular risk, psychiatric/psychologic issues, and cancer risk; along with assessment tools for skin disease and quality-of-life issues. Finally, we will discuss the safety and efficacy of the biologic treatments used to treat patients with psoriasis."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I197,I197)","v":18418469},{"$f":"(LEN($J197) - LEN(SUBSTITUTE(LOWER($J197),LOWER(B$3),\"\")))/LEN(B$3)","v":4},0,0,{"$f":"SUM(B197:D197)","v":4},2006,"Retinoid-related Orphan Receptors (RORs): Roles in Cellular Differentiation and Development.","Jetten",18418469,"Retinoid-related Orphan Receptors (RORs): Roles in Cellular Differentiation and Development.    Abstract:   Retinoid-related orphan receptors RORalpha, -beta, and -gamma are transcription factors belonging to the steroid hormone receptor superfamily. During embryonic development RORs are expressed in a spatial and temporal manner and are critical in the regulation of cellular differentiation and the development of several tissues. RORalpha plays a key role in the development of the cerebellum particularly in the regulation of the maturation and survival of Purkinje cells. In RORalpha-deficient mice, the reduced production of sonic hedgehog by these cells appears to be the major cause of the decreased proliferation of granule cell precursors and the observed cerebellar atrophy. RORalpha has been implicated in the regulation of a number of other physiological processes, including bone formation. RORbeta expression is largely restricted to several regions of the brain, the retina, and pineal gland. Mice deficient in RORbeta develop retinal degeneration that results in blindness. RORgamma is essential for lymph node organogenesis. In the intestine RORgamma is required for the formation of several other lymphoid tissues: Peyers patches, cryptopatches, and isolated lymphoid follicles. RORgamma plays a key role in the generation of lymphoid tissue inducer (LTi) cells that are essential for the development of these lymphoid tissues. In addition, RORgamma is a critical regulator of thymopoiesis. It controls the differentiation of immature single-positive thymocytes into double-positive thymocytes and promotes the survival of double-positive thymocytes by inducing the expression of the anti-apoptotic gene Bcl-X(L). Interestingly, all three ROR receptors appear to play a role in the control of circadian rhythms. RORalpha positively regulates the expression of Bmal1, a transcription factor that is critical in the control of the circadian clock. This review intends to provide an overview of the current status of the functions RORs have in these biological processes."]
[18290716,1,0,0,1,2007,"Substrate and enzyme trafficking as a means of regulating 1,25-dihydroxyvitamin D synthesis and action: the human innate immune response.","Adams",18290716,"Substrate and enzyme trafficking as a means of regulating 1,25-dihydroxyvitamin D synthesis and action: the human innate immune response.    Abstract:   Tissue availability of the active vitamin D metabolite, 1,25-dihydroxyvitamin D [1,25(OH)(2)D] is dependent on expression of the activating enzyme 1alpha-hydroxylase (CYP27b1) and its catabolic counterpart 24-hydroxylase (CYP24). The activity of these two enzymes is in turn controlled by factors including affinity of the serum vitamin D-binding protein (DBP) for 25-hydroxyvitamin D [25(OH)D]; the availability of enzyme cofactors; and the relative amount of hydroxylase gene product expressed. In recent years, it has become clear that directed trafficking of substrate and enzyme is also a pivotal component of the regulated process of hormone synthesis by both renal and extrarenal tissues expressing the CYP27b1 and CYP24 genes. Extracellular regulatory trafficking events are defined by the quantity of substrate 25(OH)D entering the circulatory pool. Entry into some target cells in vivo, such as the macrophage and proximal renal tubular epithelial cells, requires 25(OH)D binding to serum DBP, followed by recognition, internalization, and intracellular release. The quot;releasedquot; intracellular substrate is moved to specific intracellular destinations (i.e., the mitochondrial CYP enzymes and the vitamin D receptor [VDR]) by the hsc70 family of chaperone proteins. Synthesis of 1,25(OH)(2)D is also regulated by CYP24 and its metabolically inactive splice variant CYP24-SV. Finally, initiation of transcription of 1,25(OH)(2)D-regulated genes, such as the CYP24, requires movement of the CYP27b1 product, 1,25(OH)(2)D, to the VDR in the same cell for intracrine action or export to another cell for paracrine action. In either case, the 1,25(OH)(2)D ligand is required for the VDR to heterodimerize with the retinoid x receptor and compete away the dominant-negative acting, heterogeneous nuclear ribonucleoprotein (hnRNP)-related, vitamin D response element-binding proteins that inhibit hormone-directed transactivation of genes. In this review, we use vitamin D-directed events in the human innate immune response to Mycobacterium tuberculosis as a physiologically relevant model system in which to highlight the importance of these intracellular traffic patterns."]
[18306849,0,0,0,0,2008,"Nevoid basal cell carcinoma syndrome (Gorlin syndrome): updated review of minimally invasive treatments.","Mitropoulos",18306849,"Nevoid basal cell carcinoma syndrome (Gorlin syndrome): updated review of minimally invasive treatments.    Abstract:   An updated review of management of nevoid basal cell carcinoma syndrome (NBCCS) is presented. An ideal treatment of NBCCS does not exist, and surgical intervention has been the most commonly used treatment, as it provides excellent cure rates. However, patients with NBCCS typically present with a large number of basal cell carcinomas (BCCs) with repeated occurrence throughout life. Surgical intervention, although efficient, may be too painful and discomforting, especially if it has to be frequently performed. Additionally, depending on the location and extent of the tumor, the risk for cosmetic or functional defects exists. This article investigates and compares current alternative, minimally invasive treatment modalities and their potential benefits and success rates."]
[18291307,1,0,0,1,2008,"Nutritargeting.","Biesalski",18291307,"Nutritargeting.    Abstract:   The term quot;nutritargetingquot; in analogy to the term quot;drug targetingquot; means targeting nutrients to specific quot;targetquot; tissues. What is the rationale for this idea? Some tissues obviously are able to accumulate micronutrients selectively and to use them predominantly for specific functions. It has, for instance, been known for a long time that the accumulation of beta-carotene in the skin does not only provide a quot;golden-yellowquot; color but considerable antioxidative protection as well. Yet beta-carotene is only one of many antioxidants, which can be detected in the skin. Other carotenoids, for example, lutein and zeaxanthine, are preferentially found in the macula lutea, the so-called yellow spot in the eye. Here, carotenoids are subject to a metabolism typical for that tissue, which cannot be found in other tissues (e.g., formation of meso-zeaxanthine). In addition, they can specifically be absorbed into the macula. In the macula, they protect the retinal pigment epithelial cells against oxidative damage from UV light. Indeed, these two carotenoids can be protective against age-dependent macula degeneration. Another example is the tissues that are particularly rich in vitamin C, for example, the cortex of the suprarenal gland or the lens: here, vitamin C fulfills both antioxidative functions and metabolic ones as it helps in the formation of collagen structures. Approximately 40% of the bodys ascorbate is stored in skeletal muscle because this tissue is relatively abundant and its cellular concentration is tenfold higher than the plasma level. Similarly, the intracellular ascorbate concentration in the brain (3 mM) greatly exceeds the level in the extracellular fluid (200-400 muM). The majority of ascorbate is stored in the astroglial cells that are capable of reducing great quantities of DHAA to ascorbate, which then becomes available for release back into the extracellular fluid. Thus, the accumulation of vitamins respectively micronutrients in single tissues is not limited to a pure storage process like the storage of vitamin A in the liver, but is often connected with important and tissue-specific metabolic functions. When single micronutrients are applied for prevention or even intervention in diseases of organs or tissues, they are usually administered in higher doses for a longer period of time. The hope is to accumulate it this way sufficiently in the tissue and to thus be able to ensure the therapeutic success. This procedure, however, leads to a quot;floodingquot; of the whole organism with micronutrients and their potential enrichment in tissues which would usually not accumulate the respective micronutrient. Thus, unexpected side effects may occur. An attractive solution to these problems in the future could be to wrap up or apply micronutrients in such a way that they can selectively reach the targeted tissue. For this approach, called quot;drug targetingquot; by pharmacologists, one could introduce the analogous expression quot;nutritargetingquot; with respect to micronutrients. For such a nutritargeting there are already a lot of examples and developments which show that it is possible to accumulate micronutrients in target tissues while simultaneously circumventing or protecting other tissues. A substantial requirement for the development of quot;carriersquot; for nutritargeting is the availability of procedures or specific carriers, which allow the selected nutrients to bypass the main barriers that are encountered when, for example, circumventing the enteral route in the targeting process. The entrance areas for such a targeting are the nasal mucosa, the oral mucosa, the cornea, the skin, or the lung. In the case of enteral application of proteins, the packaging has to resist gastric digestion and the body must be able to absorb the particles through the intestinal mucosa without hydrolyzing the proteins in order for them to reach the systemic circulation. Another field in which nutritargeting may play an important role is the diseases where either systemic absorption is not possible (e.g., malabsorption/maldigestion) or where local deficits occur, which may not or only inadequately be supplied by systemic application."]
[18254115,0,0,0,0,2008,"Vitamin A supplementation for cystic fibrosis.","ONeil",18254115,"Vitamin A supplementation for cystic fibrosis.    Abstract:    BACKGROUND : People with cystic fibrosis and pancreatic insufficiency are at risk of fat soluble vitamin deficiency as these vitamins (A, D, E and K) are co-absorbed with fat. Thus, some cystic fibrosis centres routinely administer these vitamins as supplements but the centres vary in their approach of addressing the possible development of deficiencies in these vitamins. Vitamin A deficiency causes predominantly eye and skin problems while supplementation of vitamin A to excessive levels may cause harm to the respiratory and skeletal systems in children. Thus a systematic review on vitamin A supplementation in people with cystic fibrosis would help guide clinical practice.  OBJECTIVES : To determine if vitamin A supplementation in children and adults with CF:(1) reduces the frequency of vitamin A deficiency disorders;(2) improves general and respiratory health;(3) increases the frequency of vitamin A toxicity.  SEARCH STRATEGY : We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Date of the most recent search of the Groups Cystic Fibrosis Trials Register: July 2007.  SELECTION CRITERIA : All randomised or quasi-randomised controlled trials comparing all preparations of oral vitamin A used as a supplement compared to either no supplementation (or placebo) at any dose and for any duration, in children or adults with cystic fibrosis (defined by sweat tests or genetic testing) with and without pancreatic insufficiency.  DATA COLLECTION AND ANALYSIS : No relevant studies were identified in the search.  MAIN RESULTS : No studies were included in this review.  AUTHORS CONCLUSIONS : As there were no randomised or quasi-randomised controlled trials identified, we cannot draw any conclusions on the benefits (or otherwise) of regular administration of vitamin A in people with cystic fibrosis. Until further data are available, country or region specific guidelines on the use of vitamin A in people with cystic fibrosis should be followed."]
[18240599,20,0,0,20,2008,"[New drug therapy for retinal degeneration].","Ohguro",18240599,"[New drug therapy for retinal degeneration].    Abstract:   Retinitis pigmentosa (RP) is an inherited retinal degeneration characterized by nyctalopia, ring scotoma, and bone-spicule pigmentation of the retina. So far, no effective therapy has been found for RP. As a possible molecular etiology of RP, retina-specific gene deficits are most likely involved, but little has been identified in terms of intracellular mechanisms leading to retinal photoreceptor cell death at post-translational levels. In order to find an effective therapy for RP, we must look for underlying common mechanisms that are responsible for the development of RP, instead of designing a specific therapy for each of the RP types with different causes. Therefore, in the present study, several animal models with different causes of RP were studied, including (1)Royal College of Surgeons (RCS) rats with a deficit of retinal pigment epithelium (RPE) function caused by rhodopsin mutation; (2) P23H rats, (3) S334ter rats, (4) photo stress rats, (5) retinal degeneration (rd) mice with a deficit of phosphodiesterase(PDE) function; and (6) cancer-associated retinopathy (CAR) model rats with a deficit of recoverin-dependent photoreceptor adaptation function. In each of these models, the following assessments were made in order to elucidate common pathological mechanisms among the models: (1) retinal function assessed by electroretinogram (ERG), (2) retinal morphology, (3) retinoid analysis, (4) rhodopsin regeneration, (5) rhodopsin phosphorylation and dephosphorylation, and (6) cytosolic cGMP levels. We found that unregulated photoreceptor adaptation processes caused by an imbalance of rhodopsin phosphorylation and dephosphorylation caused retinal dysfunction leading to photoreceptor cell death. As possible candidate drugs for normalizing these retinal dysfunctions and stopping further retinal degeneration, nilvadipine, a Ca channel blocker, retinoid derivatives, and anthocyanine were chosen and tested to determine their effect on the above animal models with retinal degeneration. Nilvadipine showed beneficial effects against retinal degeneration in all models tested, but retinoid derivatives and anthocyanine showed these beneficial effects in only some models. Thus our present data allowed us to test the effectiveness of nilvadipine in the treatment of human RP patients."]
[18231123,1,0,0,1,2008,"Smith-Magenis syndrome.","Elsea",18231123,"Smith-Magenis syndrome.    Abstract:   Smith-Magenis syndrome (SMS) is a complex neurobehavioral disorder caused by haploinsufficiency of the retinoic acid-induced 1 (RAI1) gene on chromosome 17p11.2. Diagnostic strategies include molecular identification of a 17p11.2 microdeletion encompassing RAI1 or a mutation in RAI1. G-banding and fluorescent in situ hybridization (FISH) are the classical methods used to detect the SMS deletions, while multiplex ligation-dependent probe amplification (MLPA) and real-time quantitative PCR are the newer, cost-effective, and high-throughput technologies. Most SMS features are due to RAI1 haploinsufficiency, while the variability and severity of the disorder are modified by other genes in the 17p11.2 region. The functional role for RAI1 is not completely understood, but it is likely involved in transcription, based on homology and preliminary studies. Management of SMS is primarily a multidisciplinary approach and involves treatment for sleep disturbance, speech and occupational therapies, minor medical interventions, and management of behaviors."]
[18228215,1,0,0,1,2007,"Distant metastases of differentiated thyroid cancer: diagnosis, treatment and outcome.","Toubert",18228215,"Distant metastases of differentiated thyroid cancer: diagnosis, treatment and outcome.    Abstract:   The remarkably good prognosis and long-term survival in differentiated thyroid cancer (DTC) are significantly reduced in patients with distant metastasis (DM). Multi-site metastases are associated with a high mortality rate reaching 92% at 5 years necessitating early diagnosis and treatment. The most common site of metastases are the lungs, followed by the bone, with the former having better prognosis than the latter due to late detection. A number of factors contribute to the development of DM including large and multifocal primary tumour, extrathyroidal extension, aggressive histology and advanced age. In patients with good (131)I uptake, (131)I therapy appears highly effective and should be offered up to a cumulative activity of 22 GBq. Other measures such as surgery, radiotherapy, arterial embolisation and cementoplasty may be required. If there is low or no (131)I uptake, FDG-PET should be obtained due to its prognostic impact. It may help in selecting patients for other modalities such as cytotoxic chemotherapy and redifferentiation therapy by 13-cis retinoic acid. The development of tyrosine kinase inhibitors has raised hopes in providing alternative therapy for bone metastasis, especially in older age groups with poorly differentiated tumours with no (131)I uptake but good uptake of FDG."]
[18195085,1,0,0,1,2008,"Hepatic stellate cells: protean, multifunctional, and enigmatic cells of the liver.","Friedman",18195085,"Hepatic stellate cells: protean, multifunctional, and enigmatic cells of the liver.    Abstract:   The hepatic stellate cell has surprised and engaged physiologists, pathologists, and hepatologists for over 130 years, yet clear evidence of its role in hepatic injury and fibrosis only emerged following the refinement of methods for its isolation and characterization. The paradigm in liver injury of activation of quiescent vitamin A-rich stellate cells into proliferative, contractile, and fibrogenic myofibroblasts has launched an era of astonishing progress in understanding the mechanistic basis of hepatic fibrosis progression and regression. But this simple paradigm has now yielded to a remarkably broad appreciation of the cells functions not only in liver injury, but also in hepatic development, regeneration, xenobiotic responses, intermediary metabolism, and immunoregulation. Among the most exciting prospects is that stellate cells are essential for hepatic progenitor cell amplification and differentiation. Equally intriguing is the remarkable plasticity of stellate cells, not only in their variable intermediate filament phenotype, but also in their functions. Stellate cells can be viewed as the nexus in a complex sinusoidal milieu that requires tightly regulated autocrine and paracrine cross-talk, rapid responses to evolving extracellular matrix content, and exquisite responsiveness to the metabolic needs imposed by liver growth and repair. Moreover, roles vital to systemic homeostasis include their storage and mobilization of retinoids, their emerging capacity for antigen presentation and induction of tolerance, as well as their emerging relationship to bone marrow-derived cells. As interest in this cell type intensifies, more surprises and mysteries are sure to unfold that will ultimately benefit our understanding of liver physiology and the diagnosis and treatment of liver disease."]
[18047848,1,0,0,1,2007,"Lipids, lipoproteins, and peroxisome proliferator activated receptor-delta.","Sprecher",18047848,"Lipids, lipoproteins, and peroxisome proliferator activated receptor-delta.    Abstract:   Peroxisome proliferator activated receptors (PPARs) are nuclear receptors activated by small, lipophilic compounds. Typically resident on nuclear DNA, full activation requires heterodimer formation with retinoid X receptor and ligand binding, leading to modulation in the expression of hundreds of genes. Of the 3 described forms, (PPAR-alpha, PPAR-gamma, and PPAR-delta), PPAR-delta has been the least investigated. Preclinical in vitro data show that activation of PPAR-delta, like PPAR-alpha, results in enhancement of fatty acid oxidation, leading to increased energy production in the form of adenosine triphosphate and of energy uncoupling. Microarray data in preclinical models suggest substantial PPAR-delta expression in skeletal muscle. Exercise, which induces upregulation of PPAR-delta in muscle tissue, leads to an increased requirement for an external or serum derived triacylglycerol energy source. This suggests that upregulation of skeletal muscle PPAR-delta would influence lipoprotein composition, this being the major source of combustible substrate. In the first human study using a PPAR-delta agonist, experimental data obtained with GW 501516 (a highly specific PPAR-delta agonist) suggested that upregulated enzymes critical to fatty acid oxidation in human cells enhanced fatty acid and beta-oxidation in skeletal muscle."]
[18047466,3,0,0,3,2008,"Vitamin A: a drug for prevention of restenosis/reocclusion after percutaneous coronary intervention?","Gidlöf",18047466,"Vitamin A: a drug for prevention of restenosis/reocclusion after percutaneous coronary intervention?    Abstract:   The re-establishment of adequate blood flow in a vessel with a reduced lumen due to an atherosclerotic plaque by percutaneous vascular intervention is a well established procedure. However, the long-term outcome of such interventions is negatively influenced by the development of intimal hyperplasia/restenosis. Although extensively researched, this still represents a significant clinical problem. Retinoids, i.e. natural and synthetic derivates of vitamin A, represent a potential therapeutic compound, since they have been shown to influence the vast majority of processes that ultimately lead to reocclusion of the injured vessel. Retinoids exert their effects at the transcriptional level through their nuclear receptors. Targeting multiple processes, i.e. proliferation, migration, extracellular matrix composition and cell differentiation, as well as coagulation/fibrinolysis, should increase their future role in the prevention of restenosis. The purpose of this review is to summarize the diverse effects of retinoids on pathobiological and biological processes activated at sites of vascular injury with particular emphasis on intimal hyperplasia/restenosis after endovascular interventions."]
[17972437,1,0,0,1,2007,"Vitamin A: is it a risk factor for osteoporosis and bone fracture?","Ribaya-Mercado",17972437,"Vitamin A: is it a risk factor for osteoporosis and bone fracture?    Abstract:   Results from observational studies of the association between vitamin A intake or serum concentration and bone mineral density or fracture are mixed. The inconsistencies may be due, in part, to difficulties in obtaining an accurate assessment of vitamin A intake or status. Serum retinol is a poor measure of vitamin A status because it is subject to homeostatic control. Stable-isotope-dilution methodology gives a validated assessment of the total-body and liver vitamin A stores and is recommended in future studies on vitamin A status and osteoporosis. The potential for exacerbating an already serious public health problem with intakes of vitamin A currently considered safe indicates further research into this matter is warranted."]
[17929994,1,0,0,1,2007,"Key mechanisms of early lung development.","Kimura",17929994,"Key mechanisms of early lung development.    Abstract:   Lung morphogenesis requires the integration of multiple regulatory factors, which results in a functional air-blood interface required for gas exchange at birth. The respiratory tract is composed of endodermally derived epithelium surrounded by cells of mesodermal origin. Inductive signaling between these 2 tissue compartments plays a critical role in formation and differentiation of the lung, which is mediated by evolutionarily conserved signaling families used reiteratively during lung formation, including the fibroblast growth factor, hedgehog, retinoic acid, bone morphogenetic protein, and Wnt signaling pathways. Cells coordinate their response to these signaling proteins largely through transcription factors, which determine respiratory cell fate and pattern formation via the activation and repression of downstream target genes. Gain- and loss-of-function studies in null mutant and transgenic mice models have greatly facilitated the identification and hierarchical classification of these molecular programs. In this review, we highlight select molecular events that drive key phases of pulmonary development, including specification of a lung cell fate, primary lung bud formation, tracheoesophageal septation, branching morphogenesis, and proximal-distal epithelial patterning. Understanding the genetic pathways that regulate respiratory tract development is essential to provide insight into the pathogenesis of congenital anomalies and to develop innovative strategies to treat inherited and acquired lung disease."]
[17886256,1,0,0,1,2007,"Integration of signaling pathways regulating chondrocyte differentiation during endochondral bone formation.","Adams",17886256,"Integration of signaling pathways regulating chondrocyte differentiation during endochondral bone formation.    Abstract:   During endochondral bone formation, chondrocytes undergo a process of terminal differentiation or maturation, during which the rate of proliferation decreases, cells become hypertrophic, and the extracellular matrix is altered by production of a unique protein, collagen X, as well as proteins that promote mineralization. The matrix surrounding the hypertrophic chondrocytes eventually becomes mineralized, and the mineralized matrix serves as a template for bone deposition. This process is responsible for most longitudinal bone growth, both during embryonic development and in the postnatal long bone growth plates. Chondrocyte maturation must be precisely controlled, balancing proliferation with terminal differentiation; changes in the rate of either proliferation or differentiation result in shortened bones. Numerous signaling molecules have been implicated in regulation of this process. These include the negative regulators Indian hedgehog (Ihh) and parathyroid hormone-related protein (PTHrP; Pthlh, PTH-like hormone), as well as a number of positive regulators. This review will focus on several positive regulators which exert profound effects on chondrocyte maturation: the thyroid hormones T3 and T4, retinoic acid (the major active metabolite of vitamin A) and bone morphogenetic proteins (BMPs), as well as the transcription factor Runx2. Each of these molecules is essential for endochondral bone formation and cannot compensate for the others; abrogation of any one of them prevents differentiation. The important features of each of these signaling pathways will be discussed as they relate to chondrocyte maturation, and a model will be proposed suggesting how these pathways may converge to regulate this process."]
[17826041,1,0,0,1,2007,"Diabetes mellitus and macrovascular disease: mechanisms and mediators.","Boyle",17826041,"Diabetes mellitus and macrovascular disease: mechanisms and mediators.    Abstract:   Atherosclerosis is a chronic inflammatory condition initiated in the endothelium in response to injury and maintained through the interactions between modified lipoproteins, macrophages, and arterial wall constituents. Risk for macrovascular disease is substantially increased in patients with type 2 diabetes mellitus. Factors underlying the link between insulin resistance/type 2 diabetes and macrovascular disease include reduced adiponectin concentration, increased expression of vascular cell adhesion molecule-1 and consequent adhesion of T-lymphocytes to the coronary endothelium, procoagulability with increased expression of plasminogen activator inhibitor-1 (PAI)-1, and instability of atherosclerotic plaques resulting from increased expression by macrophages of matrix metalloproteinases (MMPs). Thiazolidinediones (TZDs) are agonists of peroxisome proliferator-activated receptor (PPAR)-gamma and increase adiponectin. TZD therapy is associated with decreases in hepatic fat content and glycosylated hemoglobin and an increase in hepatic glucose disposal. TZDs lower circulating free fatty acid concentration and triglyceride content in the liver, but not in skeletal muscle. Effects of PPAR-gamma agonists in vitro and in animal models provide evidence for additional potential antiatherosclerotic benefits in patients with diabetes beyond the treatment of hyperglycemia and dyslipidemia, including the reduction of expression of macrophage MMPs and scavenger receptor-1, and indirect reduction of PAI-1 and inhibition of vascular smooth muscle cell proliferation, via suppression of type 1 angiotensin-2 receptor expression. Dual PPAR-alpha/gamma agonists, retinoid receptor agonists, and, to a lesser extent, TZDs, also stimulate cholesterol efflux from macrophages in vitro."]
[17802952,0,0,3,3,2006,"[Chief teratogenic factors in facial abnormalities].","Scutariu",17802952,"[Chief teratogenic factors in facial abnormalities].    Abstract:   Congenital anomalies of the face mainly originate in chromosomal and teratogenic factors. Cleft lip and cleft palate are common anomalies of the face and palate. Cleft lip, with or without cleft palate, occurs about once in 1000 births. Cleft palate occurs about once in 2500 births. Most cases of cleft lip and palate are determined by multiple factors, genetic and nongenetic, each causing only a minor developmental disturbance. This is called multifactorial inheritance. The purpose of this study is a review on teratogenic factors with action on the newborn face."]
[17764205,0,0,0,0,2006,"Multivitamin/mineral supplements and prevention of chronic disease.","Huang",17764205,"Multivitamin/mineral supplements and prevention of chronic disease.    Abstract:    OBJECTIVES : To review and synthesize published literature on the efficacy of multivitamin/mineral supplements and certain single nutrient supplements in the primary prevention of chronic disease in the general adult population, and on the safety of multivitamin/mineral supplements and certain single nutrient supplements, likely to be included in multivitamin/mineral supplements, in the general population of adults and children.  DATA SOURCES : All articles published through February 28, 2006, on MEDLINE, EMBASE, and the Cochrane databases.  REVIEW METHODS : Each article underwent double reviews on title, abstract, and inclusion eligibility. Two reviewers performed data abstraction and quality assessment. Differences in opinion were resolved through consensus adjudication.  RESULTS : Few trials have addressed the efficacy of multivitamin/mineral supplement use in chronic disease prevention in the general population of the United States. One trial on poorly nourished Chinese showed supplementation with combined Beta-carotene, vitamin E and selenium reduced gastric cancer incidence and mortality, and overall cancer mortality. In a French trial, combined vitamin C, vitamin E, Beta-carotene, selenium, and zinc reduced cancer risk in men but not in women. No cardiovascular benefit was evident in both trials. Multivitamin/mineral supplement use had no benefit for preventing cataract. Zinc/antioxidants had benefits for preventing advanced age-related macular degeneration in persons at high risk for the disease. With few exceptions, neither Beta-carotene nor vitamin E had benefits for preventing cancer, cardiovascular disease, cataract, and age-related macular degeneration. Beta-carotene supplementation increased lung cancer risk in smokers and persons exposed to asbestos. Folic acid alone or combined with vitamin B12 and/or vitamin B6 had no significant effects on cognitive function. Selenium may confer benefit for cancer prevention but not cardiovascular disease prevention. Calcium may prevent bone mineral density loss in postmenopausal women, and may reduce vertebral fractures, but not non-vertebral fractures. The evidence suggests dose-dependent benefits of vitamin D with/without calcium for retaining bone mineral density and preventing hip fracture, non-vertebral fracture and falls. We found no consistent pattern of increased adverse effects of multivitamin/mineral supplements except for skin yellowing by Beta-carotene.  CONCLUSIONS : Multivitamin/mineral supplement use may prevent cancer in individuals with poor or suboptimal nutritional status. The heterogeneity in the study populations limits generalization to United States population. Multivitamin/mineral supplements conferred no benefit in preventing cardiovascular disease or cataract, and may prevent advanced age-related macular degeneration only in high-risk individuals. The overall quality and quantity of the literature on the safety of multivitamin/mineral supplements is limited."]
[17609502,2,0,0,2,2007,"Signal transduction in early heart development (II): ventricular chamber specification, trabeculation, and heart valve formation.","Wagner",17609502,"Signal transduction in early heart development (II): ventricular chamber specification, trabeculation, and heart valve formation.    Abstract:   The formation of a four-chambered heart with ventricular chambers aligned in a left-right orientation begins with the rightward looping of the linear heart tube in accordance with the left-right embryonic axis. The functional specification of the ventricular chambers in the looped heart occurs with the formation of a trabeculated myocardium along the outer curvature of the realigned heart tube. Two major signal transduction pathways are involved in this process, the retinoic acid and neuregulin signaling pathways, with the retinoic acid pathway also participating in rightward heart tube looping. With the establishment of the atrial and ventricular chambers, maintenance of a unidirectional flow of blood between the two chambers must be ensured. To achieve this, heart valves develop at the atrioventricular juncture. This process begins with formation of endocardial cushions, the primordia of heart valves, and ends with formation of heart valve leaflets. Underlying this process is a complex network of signal transduction pathways that mediate communication between the endocardial and myocardial cell layers to form the endocardial cushions and nascent heart valve. Some of the signaling molecules involved are vascular endothelial growth factor, Wnts, bone morphogenetic proteins, epidermal growth factor, hyaluronic acid, neurofibromin, and calcium."]
[17600783,1,0,0,1,2007,"Genetic analysis of molecular oscillators in mammalian somitogenesis: clues for studies of human vertebral disorders.","Sewell",17600783,"Genetic analysis of molecular oscillators in mammalian somitogenesis: clues for studies of human vertebral disorders.    Abstract:   The repeating pattern of the human vertebral column is shaped early in development, by a process called somitogenesis. In this embryonic process, pairs of mesodermal segments called somites are serially laid down along the developing neural tube. Somitogenesis is an iterative process, repeating at regular time intervals until the last somite is formed. This process lays down the vertebrate body axis from head to tail, making for a progression of developmental steps along the rostral-caudal axis. In this review, the roles of the Notch, Wnt, fibroblast growth factor, retinoic acid and other pathways are described during the following key steps in somitogenesis: formation of the presomitic mesoderm (PSM) and establishment of molecular gradients; prepatterning of the PSM by molecular oscillators; patterning of rostral-caudal polarity within the somite; formation of somite borders; and maturation and resegmentation of somites to form musculoskeletal tissues. Disruption of somitogenesis can lead to severe vertebral birth defects such as spondylocostal dysostosis (SCD). Genetic studies in the mouse have been instrumental in finding mutations in this disorder, and ongoing mouse studies should provide functional insights and additional candidate genes to help in efforts to identify genes causing human spinal birth defects."]
[17600782,0,0,0,0,2007,"Disruption of the somitic molecular clock causes abnormal vertebral segmentation.","Sparrow",17600782,"Disruption of the somitic molecular clock causes abnormal vertebral segmentation.    Abstract:   Somites are the precursors of the vertebral column. They segment from the presomitic mesoderm (PSM) that is caudally located and newly generated from the tailbud. Somites form in synchrony on either side of the embryonic midline in a reiterative manner. A molecular clock that operates in the PSM drives this reiterative process. Genetic manipulation in mouse, chick and zebrafish has revealed that the molecular clock controls the activity of the Notch and WNT signaling pathways in the PSM. Disruption of the molecular clock impacts on somite formation causing abnormal vertebral segmentation (AVS). A number of dysmorphic syndromes manifest AVS defects. Interaction between developmental biologists and clinicians has lead to groundbreaking research in this area with the identification that spondylocostal dysostosis (SCD) is caused by mutation in Delta-like 3 (DLL3), Mesoderm posterior 2 (MESP2), and Lunatic fringe (LFNG); three genes that are components of the Notch signaling pathway. This review describes our current understanding of the somitic molecular clock and highlights how key findings in developmental biology can impact on clinical practice."]
[17522095,0,0,0,0,2007,"The antioxidant vitamins A, C, E and selenium in the treatment of arthritis: a systematic review of randomized clinical trials.","Canter",17522095,"The antioxidant vitamins A, C, E and selenium in the treatment of arthritis: a systematic review of randomized clinical trials.    Abstract:    OBJECTIVE : To systematically review the evidence from randomized clinical trials (RCTs) for the effectiveness of the antioxidant vitamins A, C, E or selenium or their combination in the treatment of arthritis. METHODSL: A systematic search of computerized databases from inception to September 2006 for relevant RCTs, application of pre-defined inclusion/exclusion criteria and independent data extraction by two authors. Methodological quality was assessed using the Jadad scale.  RESULTS : The searches identified 20 unique RCTs meeting the inclusion criteria: 11 in inflammatory arthritis and 9 in osteoarthritis (OA). The studies included are generally of poor quality. They fall into three main clusters: selenium for rheumatoid arthritis (n = 5); vitamin E for inflammatory arthritis (n = 5) and vitamin E for OA (n = 7). One RCT suggests superiority of vitamin E over placebo and three RCTs suggest equivalence between vitamin E and diclofenac in the treatment of inflammatory arthritis. In OA, four RCTs compared vitamin E with placebo. Two shorter-term studies were positive and two longer-term studies were negative. Two further RCTs suggest equivalence between vitamin E and diclofenac in the treatment of OA. Findings for selenium, vitamin A and a combination product in inflammatory arthritis and for vitamin A, and a combination product in OA were negative. An isolated positive result for vitamin C in OA is of doubtful clinical significance.  CONCLUSIONS : Clinical trials testing the efficacy of vitamin E in the treatment of OA and inflammatory arthritis have been methodologically weak and have produced contradictory findings. There is presently no convincing evidence that selenium, vitamin A, vitamin C or the combination product selenium ACE is effective in the treatment of any type of arthritis."]
[17515122,1,0,0,1,2007,"[Acute promyelocytic leukemia associated with hemophagocytic syndrome].","Jinta",17515122,"[Acute promyelocytic leukemia associated with hemophagocytic syndrome].    Abstract:   A 19-year-old man was referred to our hospital with pancytopenia and disseminated intravascular coagulation (DIC). Bone marrow aspiration revealed 93.6% of atypical promyelocytes and marked hemophagocytosis by macrophages. The diagnosis of acute promyelocytic leukemia (APL) associated with hemophagocytic syndrome (HPS) was made. As there was no evidence of infection, collagen diseases, or abuse of medicine, his HPS was classified as malignancy-associated HPS (MAHS). The DIC improved after administration of idarubicin and all-trans-retinoic acid (ATRA). On the 11th day, however, DIC and elevation of serum LDH recurred with the appearance of hepatosplenomegaly. Although APL cells had decreased in the bone marrow, hemophagocytes persisted. After administration of dexamethasone and etoposide, DIC and HPS improved, and complete remission of APL was obtained. ATRA was implicated in the aggravation of APL-induced MAHS in the present case."]
[17510980,1,0,0,1,2007,"Regulatory factor X4 variant 3: a transcription factor involved in brain development and disease.","Zhang",17510980,"Regulatory factor X4 variant 3: a transcription factor involved in brain development and disease.    Abstract:   Regulatory factor X4 variant 3 (RFX4_v3) is a recently identified transcription factor specifically expressed in the brain. Gene disruption in mice demonstrated that interruption of a single allele (heterozygous, +/-) prevented formation of the subcommissural organ (SCO), resulting in congenital hydrocephalus, whereas interruption of two alleles (homozygous, -/-) caused fatal failure of dorsal midline brain structure formation. These mutagenesis studies implicated RFX4_v3 in early brain development as well as the genesis of the SCO. Rfx4_v3 deficiency presumably causes abnormalities in brain by altering the expression levels of many genes that are crucial for brain morphogenesis, such as the signaling components in the Wnt, bone morphogenetic protein, and retinoic acid pathways. RFX4_v3 might affect these critical signaling pathways in brain development. Cx3cl1, a chemokine gene highly expressed in brain, was identified as a direct target for RFX4_v3, indicating that RFX4_v3 possesses trans-acting activity to stimulate gene expression. Rfx4_v3 is highly expressed in the suprachiasmatic nucleus and might be involved in regulating the circadian clock. One haplotype in RFX4_v3 gene is linked to a higher risk of bipolar disorder, suggesting that this protein might contribute to the pathogenesis of the disease. This Mini-Review describes our current knowledge about RFX4_v3, an important protein that appears to be involved in many aspects of brain development and disease."]
[17495601,3,0,0,3,2007,"Lipids in the heart: a source of fuel and a source of toxins.","Park",17495601,"Lipids in the heart: a source of fuel and a source of toxins.    Abstract:    PURPOSE OF REVIEW : How do lipids arrive in the heart and other tissues? This review focuses on new information on pathways of lipid uptake into the heart.  RECENT FINDINGS : Fatty acids, the major cardiac fuel, are obtained from either lipoproteins or free fatty acids associated with albumin. The heart is the tissue with the most robust expression of lipoprotein lipase, and recent data attest to the importance of this enzyme in supplying optimal amounts of fatty acids for the heart. Genetic deletion of CD36 also shows that this transporter is important for cardiac uptake of lipids. Retinoid acquisition by the heart involves pathways parallel to those used for fatty acid uptake: a pathway for acquisition of core lipoprotein retinyl ester and another for nonlipoprotein retinol. Dilated lipotoxic cardiomyopathy is the consequence of excess lipid uptake.  SUMMARY : Genetic modifications that affect lipid uptake, oxidation, and storage are being exploited to elucidate the pathophysiology of cardiomyopathies and to discover how lipids relate to heart failure in humans with obesity and diabetes mellitus. This information is likely to lead to new diagnostic categories of cardiomyopathy and more pathophysiologically appropriate treatments."]
[17469205,2,0,0,2,2007,"Linking animal models to human congenital diaphragmatic hernia.","Beurskens",17469205,"Linking animal models to human congenital diaphragmatic hernia.    Abstract:    BACKGROUND : Congenital diaphragmatic hernia (CDH) is a major life-threatening malformation, occurring in approximately 1 in 3,000 live births. Over the years, different animal models have been used to gain insight into the etiology of this complex congenital anomaly and to develop treatment strategies. However, to date the pathogenic mechanism is still not understood, and treatment remains difficult because of the associated pulmonary hypoplasia and pulmonary hypertension.  METHODS : In this review, data available from several animal models will be discussed. The retinoic acid signaling pathway (RA pathway, retinoid pathway) will be addressed as a developmental pathway that is potentially disrupted in the pathogenesis of CDH. Furthermore, genetic factors involved in diaphragm and lung development will be discussed.  CONCLUSIONS : With this review article, we aim to provide a concise overview of the current most important experimental genetic data available in the field of CDH."]
[17436305,0,0,0,0,2007,"Vitamin A deficiency (VAD), teratogenic, and surgical models of congenital diaphragmatic hernia (CDH).","Kling",17436305,"Vitamin A deficiency (VAD), teratogenic, and surgical models of congenital diaphragmatic hernia (CDH).    Abstract:   Congenital diaphragmatic hernia (CDH) is a congenital malformation that occurs with a frequency of 0.08 to 0.45 per 1,000 births. Children with CDH are born with the abdominal contents herniated through the diaphragm and exhibit an associated pulmonary hypoplasia which is frequently accompanied by severe morbidity and mortality. Although the etiology of CDH is largely unknown, considerable progress has been made in understanding its molecular mechanisms through the usage of genetic, teratogenic, and surgical models. The following review focuses on the teratogenic and surgical models of CDH and the possible molecular mechanisms of nitrofen (a diphenyl ether, formerly used as an herbicide) in both induction of CDH and pulmonary hypoplasia. In addition, the mechanisms of other compounds including several anti-inflammatory agents that have been linked to CDH will be discussed. Furthermore, this review will also explore the importance of vitamin A in lung and diaphragm development and the possible mechanisms of teratogen interference in vitamin A homeostasis. Continued exploration of these models will bring forth a clearer understanding of CDH and its molecular underpinnings, which will ultimately facilitate development of therapeutic strategies."]
[17436238,1,0,0,1,2007,"Genetic factors in congenital diaphragmatic hernia.","Holder",17436238,"Genetic factors in congenital diaphragmatic hernia.    Abstract:   Congenital diaphragmatic hernia (CDH) is a relatively common birth defect associated with high mortality and morbidity. Although the exact etiology of most cases of CDH remains unknown, there is a growing body of evidence that genetic factors play an important role in the development of CDH. In this review, we examine key findings that are likely to form the basis for future research in this field. Specific topics include a short overview of normal and abnormal diaphragm development, a discussion of syndromic forms of CDH, a detailed review of chromosomal regions recurrently altered in CDH, a description of the retinoid hypothesis of CDH, and evidence of the roles of specific genes in the development of CDH."]
[17416055,0,0,0,0,2006,"[Psoriasis].","Guilhou",17416055,"[Psoriasis].    Abstract:  "]
[17402564,15,0,0,15,2007,"[Novel approach for management of age-related macular degeneration--antiangiogenic therapy and retinal regenerative therapy].","Tamaki",17402564,"[Novel approach for management of age-related macular degeneration--antiangiogenic therapy and retinal regenerative therapy].    Abstract:   Age-related macular degeneration (AMD) is a leading cause of legal blindness in developed countries. Even with the recent advent of several treatment options, treatment of exudative AMD, characterized by choroidal neovascularization (CNV), remains difficult. Thus, in this review article, we report on the investigation of novel approaches for the management of AMD, antiangiogenic therapy for CNV, and retinal regenerative therapy. Polyion complex(PIC) micelles have a range in size of several tens of nanometers formed through an electrostatic interaction, and accumulate in solid tumors through an enhanced permeability and retention(EPR) effect. In this study, we examined the distribution of the PIC micelles which encapsulate fluorescein isothiocyanate-labeled poly-L-lysine{FITC-P(Lys)} in experimental CNV in rats, to investigate whether PIC micelles can be used for the treatment of CNV. We demonstrated that PIC micelles accumulate in the CNV lesions and are retained in the lesions for as long as 168 hours after intravenous administration. These results raise the possibility that PIC micelles can be used for achieving an effective drug delivery system against CNV. Although photodynamic therapy (PDT) is a very promising treatment for AMD, most patients require repeated treatments. For effective PDT against AMD, the selective delivery of a photosensitizer to the CNV lesions and an effective photochemical reaction at the CNV site are necessary. The characteristic dendritic structure of the photosensitizer prevents aggregation of its core sensitizer, thereby inducing a highly effective photochemical reaction. We present an effective PDT for AMD employing a supramolecular nanomedical device, i.e., a novel dendritic photosensitizer encapsulated in a polymeric micelle formulation. With its highly selective accumulation in CNV lesions, this treatment resulted in a remarkably efficacious CNV occlusion with minimal unfavorable phototoxicity. Our results will provide a basis for an effective approach to PDT for AMD. Spatial control of gene transfection in the body is a core issue in the gene therapy for ocular diseases including AMD. Photochemical internalization (PCI) is a technology that effects light-induced delivery of DNA directly inside cells. PCI usually requires that a photosensitizer be added to the drug-delivery system to photochemically destabilize the endosomal membrane. We have developed a ternary complex composed of a core containing DNA packaged with cationic peptides and enveloped in the anionic dendrimer, phthalocyanine, which provides the photosensitizing action. Subconjunctival injection of the ternary complex followed by laser irradiation resulted in transgene expression only in the laser-irradiated site in rats. This PCI-mediated gene delivery system is potentially useful in gene therapy for ophthalmic diseases. Accumulation of lipofuscin is related to an increased risk of AMD. We report that a major lipofuscin component, A2E(N-retinyledin-N-retinylethanolamin), activates the retinoic acid receptor (RAR). In vivo experiments suggest that A2E accumulation results in the pro-angiogenic conversion of retinal pigment epithelial(RPE) cell phenotype. This physiological consequence of A2E accumulation may be related to a novel potential therapeutic target for CNV. To recover visual function damaged by AMD, retinal regenerative therapy is essential. We investigated whether subretinal transplantation of bone marrow mesenchymal stem cells(MSCs) promotes photoreceptor survival in a rat model of retinal degeneration. Morphological and functional studies in vivo, including histological analysis and electrophysiological studies, indicate that the subretinal transplantation of MSCs delays retinal degeneration and preserves retinal function. These results suggest that MSC is a useful cell source for cell-transplantation therapy for retinal degeneration. In order to elucidate the molecular mechanisms of development of the fovea, which is composed mainly of cone photoreceptors and is susceptible to injury from AMD, we performed a comparative gene expression analysis between the central and peripheral regions of the monkey retina using monkey (rhesus macaque) genome microarray chips. We then selected the clones which were expressed at significantly higher levels in the central region and confirmed their expression in the monkey retina by section in situ hybridization. This study sheds light on the mechanisms of foveal development and may lead to the development of regenerative medicine for cone photoreceptors."]
[17337883,1,0,0,1,2007,"Pituitary action of cytokines: focus on BMP-4 and gp130 family.","Giacomini",17337883,"Pituitary action of cytokines: focus on BMP-4 and gp130 family.    Abstract:   The anterior pituitary can develop benign tumors of different sizes, classified as micro- and macroadenomas, frequently associated with high levels of hormone production, leading to different associated syndromes like Cushings disease, acromegaly or prolactinomas. Much work has been done in order to understand the signaling pathways and the factors and hormones involved in the pituitary tumorigenic process. In recent years, much evidence has been collected and it is now well documented that cytokines of the gp130 family, such as interleukin-6, that use gp130 as a common signaling protein stimulate not only the proliferation but also the hormone secretion of pituitary cells. Experiments in vivo have shown that the overexpression of the gp130 receptor resulted in pituitary abnormal growth. Moreover, it has been recently described that bone morphogenetic protein-4 (BMP-4), a member of the TGF-beta family, has a stimulatory role on lactosomatotropic cells promoting the development of prolactinomas but it has an inhibitory action on the corticotropic lineage. This inhibitory action prevents Cushings disease progression. Furthermore, BMP-4 mediates the antiproliferative action of retinoic acid in these cells. The present review highlights the most recent work about gp130 and TGF-beta cytokine families and their role in pituitary tumorigenesis."]
[17337858,0,0,0,0,2007,"[Possibility of alveolar regeneration].","Ishizawa",17337858,"[Possibility of alveolar regeneration].    Abstract:  "]
[17336257,1,0,0,1,2007,"The role of autologous transplantation for acute myeloid leukemia in first and second remission.","Linker",17336257,"The role of autologous transplantation for acute myeloid leukemia in first and second remission.    Abstract:   Since 1986, the University of California San Francisco has developed novel approaches to autologous transplantation for acute myeloid leukemia (AML). Strategies have included intensive preparative regimens using busulfan and etoposide, and evolving strategies for pre-transplant consolidation and stem cell collection. Treatment-related mortality has been low (lt;5%), and after problems with slow engraftment and extended mucosal and skin toxicity in initial studies using 4-hydroperoxycyclophosphamide (4-HC)-purged bone marrow, peripheral blood autologous stem cell transplantation (ASCT) has been well tolerated even in older patients. In particular, careful attention to avoiding neurotoxicity associated with the use of high-dose cytarabine has limited dropout rates. Long-term event-free survival (EFS) has been excellent in first remission (CR1) cytogenetically favorable groups, particularly with post-transplant treatment for acute promyelocytic leukemia (APL) patients with all-trans retinoic acid (ATRA; EFS 88%). ASCT in advanced disease showed overall long-term EFS of 44%; patients with APL in second remission achieved long-term EFS of 64%. Even among those failing primary induction, after remission induction with an alternative regimen, EFS was 61%. ASCT appears to be a treatment of choice for those in APL CR2, and offers some curative potential for AML CR2. The role of ASCT for those in CR1 is less clear, in part because high dropout rates in large randomized studies complicates interpretation of those studies. New directions for ASCT in the treatment of AML should focus on improving therapy, including calibrated intensification of induction regimens using plasma-kinetics targeting of dosages and the development and incorporation of immunotherapies into consolidation regimens."]
[17326003,6,0,0,6,2007,"Vitamins as hormones.","Reichrath",17326003,"Vitamins as hormones.    Abstract:   Vitamins A and D are the first group of substances that have been reported to exhibit properties of skin hormones, such as organized metabolism, activation, inactivation, and elimination in specialized cells of the tissue, exertion of biological activity, and release in the circulation. Vitamin A and its two important metabolites, retinaldehyde and retinoic acids, are fat-soluble unsaturated isoprenoids necessary for growth, differentiation and maintenance of epithelial tissues, and also for reproduction. In a reversible process, vitamin A is oxidized IN VIVO to give retinaldehyde, which is important for vision. The dramatic effects of vitamin A analogues on embryogenesis have been studied by animal experiments; the clinical malformation pattern in humans is known. Retinoic acids are major oxidative metabolites of vitamin A and can substitute for it in vitamin A-deficient animals in growth promotion and epithelial differentiation. Natural vitamin A metabolites are vitamins, because vitamin A is not synthesized in the body and must be derived from carotenoids in the diet. On the other hand, retinoids are also hormones - with intracrine activity - because retinol is transformed in the cells into molecules that bind to and activate specific nuclear receptors, exhibit their function, and are subsequently inactivated. The mechanisms of action of natural vitamin A metabolites on human skin are based on the time- and dose-dependent influence of morphogenesis, epithelial cell proliferation and differentiation, epithelial and mesenchymal synthetic performance, immune modulation, stimulation of angiogenesis and inhibition of carcinogenesis. As drugs, vitamin A and its natural metabolites have been approved for the topical and systemic treatment of mild to moderate and severe, recalcitrant acne, photoaging and biologic skin aging, acute promyelocytic leukaemia and Kaposis sarcoma. On the other hand, the critical importance of the skin for the human bodys vitamin D endocrine system is documented by the fact that the skin is both the site of vitamin D (3)- and 1,25-dihydroxyvitamin D (3) [1, 25(OH) (2)D (3)]-synthesis and a target organ for 1,25(OH) (2)D (3). 1,25(OH) (2)D (3) is not only essential for mineral homeostasis and bone integrity, but also for numerous further physiologic functions including regulation of growth and differentiation in a broad variety of normal and malignant tissues, including cells derived from prostate, breast and bone. In keratinocytes and other cell types, 1,25(OH) (2)D (3) regulates growth and differentiation. Consequently, vitamin D analogues have been introduced for the treatment of the hyperproliferative skin disease psoriasis. Other newly detected functions of vitamin D analogues include profound effects on the immune system as well as protection against cancer and other diseases, including autoimmune and infectious diseases, in various tissues. Current investigation of the biological effects of vitamin D analogues are likely to lead to new therapeutic applications that, besides cancer prevention, may include the prevention and treatment of infectious as well as of inflammatory skin diseases. This review summarizes existing knowledge on vitamins A and D, the major vitamin-hormones of the skin."]
[17317642,3,0,0,3,2007,"Treatment of acute promyelocytic leukaemia with all-trans retinoic acid and arsenic trioxide: a paradigm of synergistic molecular targeting therapy.","Zhou",17317642,"Treatment of acute promyelocytic leukaemia with all-trans retinoic acid and arsenic trioxide: a paradigm of synergistic molecular targeting therapy.    Abstract:   To turn a disease from highly fatal to highly curable is extremely difficult, especially when the disease is a type of cancer. However, we can gain some insight into how this can be done by looking back over the 50-year history of taming acute promyelocytic leukaemia (APL). APL is the M3 type of acute myeloid leukaemia characterized by an accumulation of abnormal promyelocytes in bone marrow, a severe bleeding tendency and the presence of the chromosomal translocation t(15;17) or variants. APL was considered the most fatal type of acute leukaemia five decades ago and the treatment of APL was a nightmare for physicians. Great efforts have been made by scientists worldwide to conquer this disease. The first use of chemotherapy (CT) was unsuccessful due to lack of supportive care and cytotoxic-agent-related exacerbated coagulopathy. The first breakthrough came from the use of anthracyclines which improved the complete remission (CR) rate, though the 5-year overall survival could only be attained in a small proportion of patients. A rational and intriguing hypothesis, to induce differentiation of APL cells rather than killing them, was raised in the 1970s. Laudably, the use of all-trans retinoic acid (ATRA) in treating APL resulted in terminal differentiation of APL cells and a 90-95% CR rate of patients, turning differentiation therapy in cancer treatment from hypothesis to practice. The combination of ATRA with CT further improved the 5-year overall survival. When arsenic trioxide (ATO) was used to treat relapsed APL not only the patients but also the ancient drug were revived. ATO exerts dose-dependent dual effects on APL cells: at low concentration, ATO induces partial differentiation, while at relatively high concentration, it triggers apoptosis. Of note, both ATRA and ATO trigger catabolism of the PML-RARalpha fusion protein which is the key player in APL leukaemogenesis generated from t(15;17), targeting the RARalpha (retinoic acid receptor alpha) or promyelocytic leukaemia (PML) moieties, respectively. Hence, in treating APL both ATRA and ATO represent paradigms for molecularly targeted therapy. At molecular level, ATRA and ATO synergistically modulate multiple downstream pathways/cascades. Strikingly, a clearance of PML-RARalpha transcript in an earlier and more thorough manner, and a higher quality remission and survival in newly diagnosed APL are achieved when ATRA is combined with ATO, as compared to either monotherapy, making APL a curable disease. Thus, the story of APL can serve as a model for the development of curative approaches for disease; it suggests that molecularly synergistic targeted therapies are powerful tools in cancer, and dissection of disease pathogenesis or anatomy of the cancer genome is critical in developing molecular target-based therapies."]
[17289546,0,0,0,0,2007,"What is after cytokine-blocking therapy, a novel therapeutic target--synovial Epstein-Barr virus for rheumatoid arthritis.","Sawada",17289546,"What is after cytokine-blocking therapy, a novel therapeutic target--synovial Epstein-Barr virus for rheumatoid arthritis.    Abstract:   There has been significant progress in cytokine-blocking therapy for treatment of rheumatoid arthritis (RA) However, inhibition of cytokines involved in immune defense raises severe side effects. The cost of cytokine-blocking treatment is another major issue. Why are levels of inflammatory cytokines increased in RA patients? We have a large amount of circumstantial and direct evidence for the presence of Epstein-Barr virus (EBV) in RA synovial cells. Here, we provide an overview of the implications for novel approaches to therapy for RA patients, based on the most recent available evidences of anti-viral agents."]
[17268237,1,0,0,1,2007,"Intestinal morphogenesis.","Rubin",17268237,"Intestinal morphogenesis.    Abstract:    PURPOSE OF REVIEW : The molecular basis of endoderm differentiation and interaction with mesoderm to generate the mature intestine has been the focus of intensive investigation. Signaling pathways relevant to organogenesis may be recapitulated during oncogenesis. This review highlights recent studies of endoderm specification, differentiation and formation of the gut tube, the ontogeny of regional differentiation along the anterior-posterior and crypt-villus axes, and mechanisms of epithelial differentiation and epithelial-mesenchymal interactions during gut morphogenesis.  RECENT FINDINGS : Model organisms include zebrafish, Xenopus, Drosophila and the mouse. Fibroblast growth factors play critical roles in early endoderm differentiation and anterior-posterior patterning, and retinoids regulate left-right asymmetry and gut looping/rotation. Embryoid bodies derived from embryonic stem cells recapitulate many aspects of gut epithelial morphogenesis. Novel regulators of epithelial cell differentiation and epithelial-mesenchymal interactions have been identified (e.g. Mtgr1), and several known genes modulate these processes (e.g. PPARbeta/delta, Ptk6, GATA4). The role of Bmp, Hh and wnt signaling in morphogenesis continues to be elucidated.  SUMMARY : The complex process of intestinal morphogenesis involves interactions among multiple signaling pathways. Studies of morphogenesis are critical for elucidating the molecular basis of congenital gut defects and provide novel insight into intestinal oncogenic processes."]
[17241599,14,0,0,14,2006,"Lack of significant skeletal changes after long-term, low-dose retinoid therapy: case report and review of the literature.","Halverstam",17241599,"Lack of significant skeletal changes after long-term, low-dose retinoid therapy: case report and review of the literature.    Abstract:    BACKGROUND : Long-term systemic retinoid therapy has been associated with skeletal side effects. There have been reports of diffuse idiopathic skeletal hyperostosis (DISH) syndrome, calcification of ligaments, and osteoporosis, as well as premature fusion of epiphyses and modeling abnormalities of long bones, occurring in patients on chronic high-dose isotretinoin, etretinate, and acitretin therapy. Low-dose acitretin has been used for many years as monotherapy or in combination with other systemic therapies for psoriasis. Evidence to date suggests that the frequency of symptomatic bony effects is quite low in these patients.  OBJECTIVE : To present the radiologic findings of a patient on long-term, low-dose acitretin and etretinate and to review the literature on the radiologic evidence of skeletal side effects during retinoid therapy.  METHODS : Case report and literature search.  RESULTS : A patient on low-dose acitretin had no significant radiologic abnormalities associated with retinoid use after 9 years of treatment. A review of the literature revealed conflicting reports on the incidence of radiologic abnormalities in patients on retinoid treatment.  CONCLUSION : The evidence to date does not substantiate a clear link between radiologic skeletal abnormalities and long-term, low-dose acitretin or etretinate therapy."]
[17214727,7,0,0,7,2007,"Multiple keratoacanthomas in a young woman: report of a case emphasizing medical management and a review of the spectrum of multiple keratoacanthomas.","Feldman",17214727,"Multiple keratoacanthomas in a young woman: report of a case emphasizing medical management and a review of the spectrum of multiple keratoacanthomas.    Abstract:   A 27-year-old white woman was referred for consultation with regard to the presence of extensive multiple keratotic lesions. She began to develop these lesions at the age of 9 years, with healing of the lesions resulting in scar formation. A biopsy was performed at the age of 16 years, but the patient was unsure of the results. Since then, she had not had any treatment or biopsies, and stated that she had not suffered from any health problems during the intervening period. She was most concerned about the tumors on her heels and soles, which caused difficulty with ambulation. The family history was negative for skin diseases, including melanoma, nonmelanoma skin cancer, psoriasis, and eczema, and positive for Type II diabetes mellitus. A relative reported that the patients grandfather had similar lesions, but the patients parents and siblings were healthy. She was married and had one child, a 9-year-old daughter. Her child had no skin lesions. The patients only medication was Ortho-Tricyclene birth control pills. She had no known drug allergies. Physical examination revealed the presence of multiple lesions on her body (Fig. 1). Her left superior helix contained a well-demarcated, dome-shaped nodule with a rolled, mildly erythematous border with a central hyperkeratotic plug. A similar lesion was present in the scaphoid fossa of the left ear and smaller lesions were scattered on her face. Numerous lesions were present on the arms and legs bilaterally, with the majority of lesions being located on the anterior lower legs. There were also lesions present on the palms and soles. The lesions ranged in size from 5 mm to 3 cm, the largest being a verrucous exophytic nodule on the anterior aspect of her left leg. Overall, there appeared to be two distinct types of lesion. One type appeared round, oval, and symmetric with a central keratotic plug, similar to that on the ear. The other type was larger, more exophytic, and verrucous, including the lesions on the volar surfaces. Also present were numerous, irregularly shaped atrophic scars where previous lesions had healed spontaneously. There were no oral lesions or lesions on her fingernails or toenails, and her teeth and hair were normal. A biopsy was obtained from an early lesion on the right dorsal forearm. Histology revealed an exo-/endophytic growth having a central crater containing keratinous material (Fig. 2). The crater was surrounded by markedly hyperplastic squamous epithelium with large squamous epithelial cells having abundant glassy cytoplasm. Some cells were dyskeratotic. Within the dermis was a dense, chiefly mononuclear inflammatory infiltrate. A buttress of epidermis surrounded the crater. The clinical and pathologic data were consistent with keratoacanthomas. Initial laboratory screenings revealed elevated triglycerides and total cholesterol, 537 mg/dL (normal, lt; 150 mg/dL) and 225 mg/dL (normal, lt; 200 mg/dL), respectively, with all other laboratory results within normal limits. In anticipation of starting oral retinoid therapy for her multiple keratoacanthomas, she was referred to her primary care physician for control of hyperlipidemia. After her lipids had been controlled, she was placed on isotretinoin (Accutane) 40 mg/day. There was some interval improvement with regression of some lesions leaving atrophic scars. She was also started on topical application of tazarotene (Tazorac) for all nonresolving lesions. Possible side-effects from the isotretinoin occurred, including dry mouth and eyes. After 8 months of isotretinoin, the patient was switched to acitretin (Soriatane) 25 mg to determine whether it might have a more beneficial effect on the resistant lesions. Many of the larger lesions regressed leaving atrophic scars. The dose of acitretin was subsequently increased to 35 mg because the lesions on her heel and the ball of her foot persisted. Almost all of the lesions resolved, except those on her feet, which are slowly regressing. Currently, the patient is on a regimen of acitretin 25 mg once a day with tazarotene 0.1% gel applied directly to the few residual keratoacanthomas on her feet, which are slowly improving."]
[17211986,1,0,1,2,2006,"Cell cycle proteins in normal and chemically induced abnormal secondary palate development: a review.","Dhulipala",17211986,"Cell cycle proteins in normal and chemically induced abnormal secondary palate development: a review.    Abstract:   Cell cycle progression and thus proper cell number is essential for normal development of organs and organisms. Craniofacial tissues including the secondary palate are vulnerable to disruption of cell cycle progression and proliferation by many chemicals including mycotoxin, secalonic acid D (SAD), glucocorticoids, retinoic acid and 2,3,7,8-tetrachlorodibenzodioxin. Induction of cleft palate (CP) by SAD in mice occurs from a reduction in the size of developing palatal shelves. This is associated with an inhibition of proliferation of murine and human embryonic palatal mesenchymal (MEPM and HEPM) cells as well as a G1/S block of cell cycle. In murine embryonic palates and HEPM cells, SAD inhibited G1/S-phase-specific cyclin-dependent kinase (CDK)2 activity, reduced the level of cyclin E and increased the level of the CDK2 inhibitor, p21. These results, together with those from other laboratories, suggest that common cell cycle protein targets (biomarkers), relevant to the pathogenesis of CP by multiple chemical exposures, that can form the basis for the diagnosis and the development of preventive strategies, are likely to exist."]
[17148746,1,0,0,1,2006,"Targeting components of the stress system as potential therapies for the metabolic syndrome: the peroxisome-proliferator-activated receptors.","Yumuk",17148746,"Targeting components of the stress system as potential therapies for the metabolic syndrome: the peroxisome-proliferator-activated receptors.    Abstract:   The three peroxisome-proliferator-activated receptor (PPAR) subtypes PPAR-alpha, PPAR-gamma, and PPAR-delta are ligand-activated transcription factors of the nuclear receptor family. PPARs form obligate heterodimers with the retinoid X receptor, which bind to peroxisome-proliferator-response elements (PPREs). PPAR-alpha is expressed mainly in liver, brown fat, kidney, heart, and skeletal muscle; PPAR-gamma in intestine and adipose tissue; PPAR-alpha and PPAR-gamma are both expressed in vascular endothelium, smooth muscle cells, macrophages, and foam cells; PPAR-delta in skeletal muscle, human embryonic kidney, intestine, heart, adipose tissue, developing brain, and keratinocytes. Intense interest in the development of drugs with new mechanisms of action for the metabolic syndrome has focused attention on nuclear receptors, such as PPARs that function as regulators of energy homeostasis. Agonists of PPAR-alpha and PPAR-gamma are currently used to treat diabetic dyslipidemia and type 2 diabetes. Dual PPAR-alpha/gamma agonists and PPAR-alpha/gamma/delta pan-agonists are under investigation for treatment of cardiovascular disease and the metabolic syndrome. Selective PPAR modulators (SPPARMs) are PPAR ligands that possess desirable efficacy and improved tolerance. Efforts are being made to identify novel partial agonists or antagonists for PPAR-gamma in order to combine their antidiabetic and antiobesity effects. Glucocorticoids are major mediators of the stress response and could be the link between stress and PPAR activator signaling and thus may affect the downstream metabolic pathways involved in fuel homeostasis."]
[17101024,0,1,0,1,2006,"Fetal alcohol syndrome and developing craniofacial and dental structures--a review.","SantAnna",17101024,"Fetal alcohol syndrome and developing craniofacial and dental structures--a review.    Abstract:    OBJECTIVES : Fetal alcohol syndrome (FAS) is a collection of signs and symptoms seen in children exposed to alcohol in the prenatal period. It is characterized mainly by a distinct pattern of craniofacial malformations, physical and mental retardation. However, with the increased incidence of FAS, there is a great variation in the clinical features of FAS.  DESIGN : Narrative review.  RESULTS : This review describes data from clinical and experimental studies, and in vitro models. Experimental studies have shown that alcohol has a direct toxic effect on the ectodermal and mesodermal cells of the developing embryo, particularly in the cells destined to give rise to dentofacial structures (i.e. cranial neural crest cells). Other effects, such as, abnormal pattern of cranial and mandibular growth and altered odontogenesis are described in detail. The exact mechanism by which alcohol induces its teratogenic effects remains still unknown. The possible mechanisms are outlined here, with an emphasis on the developing face and tooth. Possible future research directions and treatment strategies are also discussed.  CONCLUSION : Early identification of children affected by prenatal alcohol exposure leads to interventions, services, and improved outcomes. FAS can be prevented with the elimination of alcohol consumption during pregnancy. We need to provide education, target high-risk groups, and make this issue a high priority in terms of public health."]
[17086935,1,0,0,1,2006,"Vitamin D receptor ligands for osteoporosis.","Cheskis",17086935,"Vitamin D receptor ligands for osteoporosis.    Abstract:   1alpha,25-Dihydroxyvitamin D3 (1,25-(OH)2D3), the biologically active metabolite of vitamin D, mediates its actions via the vitamin D receptor (VDR), a member of the superfamily of steroid/thyroid hormone/retinoid receptors. 1,25-(OH)2D3 is required for calcium and phosphorus homeostasis, and for normal skeletal development as well as maintenance of skeletal architecture. Two VDR ligands, calcitriol (1,25-(OH)2D3) and its synthetic analog alfacalcidol (1alpha-hydroxyvitamin D3), have been approved for the treatment of osteoporosis. However, the use of calcitriol and alfacalcidol is limited by their major side effect, hypercalcemia, which is mediated mainly by VDR activity in the small intestine. In order to identify VDR ligands with less hypercalcemia liability, a number of pharmaceutical companies are pursuing efforts to develop synthetic vitamin D analogs. This review discusses the mechanism of action of vitamin D, and summarizes the currently approved anti-osteoporotic VDR agonists and compounds that are under development. The future directions of vitamin D research for the discovery of novel VDR agonists for osteoporosis are also discussed."]
[17061260,2,0,0,2,2006,"Genetic patterning of the mammalian telencephalon by morphogenetic molecules and transcription factors.","Takahashi",17061260,"Genetic patterning of the mammalian telencephalon by morphogenetic molecules and transcription factors.    Abstract:   Patterning centers that produce gradients of morphogenetic molecules, including fibroblast growth factor (FGF), bone morphogenetic proteins (BMP), Wnt, Sonic hedgehog (Shh), and retinoic acid (RA), are located in telencephalic anlage during early stages of development. Genetic evidence based on loss-of-function and gain-of-function studies indicate that they are involved in regional specification of the dorsal, ventral, and lateral telencephalon. For patterning of the dorsal telencephalon, FGF8 controls the anteroposterior patterning, while BMP and Wnt molecules regulate the mediolateral patterning. Shh and retinoic acid regulate patterning of the ventral and the lateral telencephalon. The regionalization of telencephalon is accompanied by expression of region-specific codes of transcription factors, which in turn regulate different phases of neuronal development to generate different cell types in each brain region. Therefore, bioactive signals of morphogenetic molecules are translated into transcription factor codes for regional specification, which subsequently leads to neurogenesis of the diversity of cell types in different regions of the telencephalon."]
[17014561,1,0,0,1,2006,"Molecular mechanisms mediating vascular calcification: role of matrix Gla protein.","Proudfoot",17014561,"Molecular mechanisms mediating vascular calcification: role of matrix Gla protein.    Abstract:   Patients with chronic kidney disease (CKD) have a higher incidence of vascular calcification and a greatly increased risk of cardiovascular death. The mechanisms involved in the accelerated vascular calcification observed in CKD have recently become clearer, leading to the hypothesis that a lack of natural inhibitors of calcification may trigger calcium deposition. One of these inhibitory factors, matrix Gla protein (MGP), is the focus of the present review. MGP, originally isolated from bone, is a vitamin K-dependent protein that is also highly expressed by vascular smooth muscle cells. MGP has been confirmed as a calcification-inhibitor in numerous studies; however, its mechanism of action is not completely understood. It potentially acts in several ways to regulate calcium deposition including: (i) binding calcium ions and crystals; (ii) antagonizing bone morphogenetic protein and altering cell differentiation; (iii) binding to extracellular matrix components; and (iv) regulating apoptosis. Its expression is regulated by several factors including retinoic acid, vitamin D and extracellular calcium ions, and a reduced form of vitamin K (KH2) is important in maintaining MGP in an active form. Therefore, strategies aimed at increasing its expression and activity may be beneficial in tipping the balance in favour of inhibition of calcification in CKD."]
[17014486,7,0,0,7,2006,"Skin cancer chemoprevention with systemic retinoids: an adjunct in the management of selected high-risk patients.","Campbell",17014486,"Skin cancer chemoprevention with systemic retinoids: an adjunct in the management of selected high-risk patients.    Abstract:   Systemic retinoids (isotretinoin, etretinate, and acitretin) have been shown to be effective chemotherapeutic agents in studies of patients with xeroderma pigmentosum, the nevoid basal cell carcinoma syndrome, and recipients of organ or bone marrow transplantation. In addition, patients who do not have these disorders but who are actively developing large numbers of new skin cancers may also benefit from this approach. All patients developing large numbers of skin cancers need rigorous UV protection and frequent dermatologic examinations. Although isotretinoin and acitretin share overlapping toxicities, there are differences that may affect drug choice. Because low doses may be effective, there are advantages to beginning treatment at a low dose, and subsequently, increasing dose if necessary, based on patient response. Laboratory monitoring including pregnancy testing should be performed before and during treatment. Long-term toxicity, primarily involving the skeletal system, can be monitored with imaging studies."]
[16972684,0,0,0,0,2006,"[Nutrition-related bone disease].","Hirota",16972684,"[Nutrition-related bone disease].    Abstract:   Bone disorders clearly related to nutrition are osteomalacia and osteoporosis. Osteomalacia is caused by a deficiency of vitamin D or a disturbance of its metabolism. Dietary deficiency of phosphate or excess of aluminum or cadmium will also cause osteomalacia. Osteoporosis is associated with low intake of calcium and other nutrients. Dietary copper deficiency might stimulate bone metabolism and increase in hip fractures. Excess vitamin A intake was also associated with lower bone mineral density and higher risk of hip fractures. Excess vitamin D sometimes causes mental simplicity, congenital heart disease and calcification of soft tissue. Therefore not only diet but also drugs and supplements of nutrients should be carefully observed in older women."]
[16937924,0,0,0,0,2006,"[Diagnosis and treatment for myelodysplastic syndrome (MDS)].","Tamura",16937924,"[Diagnosis and treatment for myelodysplastic syndrome (MDS)].    Abstract:  "]
[16910258,1,0,0,1,2006,"[Psoriasis and psoriatic arthritis].","Henno",16910258,"[Psoriasis and psoriatic arthritis].    Abstract:   Psoriasis is a frequent multifactorial chronic skin disease that can lead to a decreased quality of life. Some patients also present arthritis. Those two complex inflammatory diseases share some of their characteristics, but several clinical manifestations can be distinguished in each of them. In addition to classical medications (constituted of topical treatments, methotrexate, ciclosporin and retinoids for cutaneous psoriasis and non steroidal anti-inflammatory drugs or methotrexate for psoriatic arthritis), they are the target of a new generation of therapies: the biologics."]
[16894622,0,0,0,0,2006,"Anteroposterior patterning in the limb and digit specification: contribution of mouse genetics.","Robert",16894622,"Anteroposterior patterning in the limb and digit specification: contribution of mouse genetics.    Abstract:   The limb has been a privileged object of investigation and reflection for scientists over the past two centuries and continues to provide a heuristic framework to analyze vertebrate development. Recently, accumulation of new data has significantly changed our view on the mechanisms of limb patterning, in particular along the anterior-posterior axis. These data have led us to revisit the mode of action of the zone of polarizing activity. They shed light on the molecular and cellular mechanisms of patterning linked to the Shh-Gli3 signaling pathway and give insights into the mechanism of activation of these cardinal factors, as well as the consequences of their activity. These new data are in good part the result of systematic Application of tools used in contemporary mouse molecular genetics. These have extended the power of mouse genetics by introducing mutational strategies that allow fine-tuned modulation of gene expression, interchromosomal deletions and duplication. They have even made the mouse embryo amenable to cell lineage analysis that used to be the realm of chick embryos. In this review, we focus on the data acquired over the last five years from the analysis of mouse limb development and discuss new perspectives opened by these results."]
[16886661,1,0,0,1,2006,"Vitamin D compounds: activity against microbes and cancer.","Gombart",16886661,"Vitamin D compounds: activity against microbes and cancer.    Abstract:   Vitamin D3 is produced in skin and is sequentially metabolized by the liver and kidney to the biologically active form 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. It is a seco-steroid hormone that regulates calcium homeostasis within the body. The genomic actions of 1,25(OH)2D3 are modulated through the vitamin D receptor (VDR). VDR belongs to a superfamily of nuclear receptors that transduce hormonal signals from the immediate environment and transactivate genes in response to these signals. Target genes contain hormone response elements (VDREs) in their promoters to which heterodimers of VDR and retinoid X receptors (RXR) can bind and transactivate expression of the target genes. The VDR is expressed in at least 30 different target tissues including bone, kidney, blood, breast, prostate, gut, activated B- and T- lymphocytes, monocytes and keratinocytes). Most dividing cell types, normal and malignant, can express VDR and respond to 1,25(OH)2D3. Although 1,25(OH)2D3 and its analogs (termed deltanoids) are important regulators of calcium and bone metabolism, their non-calciotropic activities that include inhibition of cell proliferation, promotion of cell differentiation and modulation of immune cell function have spurred interest in therapeutic applications in a wide variety of diseases. In this report, the anticancer and newly discovered antimicrobial actions of 1,25(OH)2D3 and deltanoids are reviewed."]
[16819260,9,0,0,9,2006,"[Retinoid therapy for autoimmune diseases].","Fukasawa",16819260,"[Retinoid therapy for autoimmune diseases].    Abstract:   Retinoid is a collective term for compounds which bind to and activate retinoic acid receptors (RARalpha, beta, gamma and RXRalpha, beta, gamma), members of nuclear hormone receptor superfamily. The most important endogeneous retinoid is all-trans-retinoic acid (ATRA) which is an RARalpha, beta and gamma ligand. ATRA and its mimics have been in clinical use for treatment of acute promyelocytic leukemia (APL) and some skin diseases. Many synthetic retinoids have been developed and attempts to improve their medicinal properties have been made. Among them, tamibarotene (Am80) is an RARalpha- and RARbeta-specific (but RARgamma- and RXRs-nonbinding) synthetic retinoid that is effective in the treatment of psoriasis patients and relapsed APL. Experimentally, this compound is also active in animal models of rheumatoid arthritis and experimental autoimmune encephalomyelitis. On this background, possible application of retinoids for the treatment of autoimmune diseases was discussed. In particular, Th1 dominant autoimmune diseases may be the targets of the retinoids."]
[16809920,3,0,0,3,2006,"Bone morphogenetic protein-4 control of pituitary pathophysiology.","Giacomini",16809920,"Bone morphogenetic protein-4 control of pituitary pathophysiology.    Abstract:   Bone morphogenetic protein-4 (BMP-4), a member of the transforming growth factor-Beta(TGF-Beta) family, is overexpressed in different prolactinoma models and induces the development of these lineage adenomas. SMAD proteins activated by growth factors of the TGF-Beta and BMP family interact with estrogen receptors to stimulate the proliferation of prolactin and growth hormone-secreting cells. Furthermore, BMP-4 presents differential expression in normal and adenomatous corticotropes and inhibitory action on corticotropinoma cell proliferation. Moreover, BMP-4 mediates the antiproliferative action of retinoic acid in these cells. The present review highlights not only the crucial and opposite role of BMP-4 in the progression of pituitary adenomas but also that BMP-4 and retinoic acid interaction might serve as a potential new mechanism target for therapeutic approaches for Cushing disease."]
[16789901,1,0,0,1,2006,"Proteomic strategies for individualizing therapy of acute myeloid leukemia (AML).","Sjøholt",16789901,"Proteomic strategies for individualizing therapy of acute myeloid leukemia (AML).    Abstract:   Acute myeloid leukemia (AML) is an aggressive hematological malignancy characterized by accumulating myeloid precursor cells in the bone marrow, with approximately 2-3 months 50% survival if left untreated. With current treatment modalities the five years overall survival hardly exceeds 50%. Cytogenetics and molecular diagnostics guide the clinician to select individualized therapy in certain subsets of AML, achieving long-term survival above 70% of these cases. However, approximately half of the AML patients have no risk stratifying features, and early reports indicate that proteomic approaches may be utilized for disease classification as well as development of novel biomarkers related to prognosis, diagnosis, and choice of therapeutic regimen. Proteomics, here defined as the analysis of all proteins in a cell, in a cell compartment or in a signaling pathway, has probably its greatest potential in investigating pathways that are easily targeted by small molecules or therapeutic antibodies. The major methodological challenges include detection sensitivity in a limited clinical material, a problem that in some cases can be solved through designated multiplexed protein assays based on single cells or cell extracts. In this review we will discuss pharmacoproteomic studies of drugs regulating leukemia specific targets like all-trans retinoic acid, histone deacetylase inhibitors, proteasome inhibitors and tyrosine kinase inhibitors, as well as studies on drug resistance and graft-versus-host studies during stem cell transplantations. These studies indicate new avenues in AML diagnostics, individualized therapy design and therapy response surveillance for the clinician."]
[16782410,1,0,0,1,2006,"Peroxisome proliferator-activated receptors in vascular biology-molecular mechanisms and clinical implications.","Touyz",16782410,"Peroxisome proliferator-activated receptors in vascular biology-molecular mechanisms and clinical implications.    Abstract:   Peroxisome proliferator-activated receptors (PPAR)alpha, gamma and beta/delta belong to the nuclear receptor family of ligand-activated transcription factors. PPARs heterodimerize with the retinoid X receptor (RXR) and then act as transcription factors to modulate the function of many target genes. PPARalpha, gamma and beta/delta subtypes have significant differences in their ligand and gene specificities. PPARalpha is activated by polyunsaturated fatty acids and by fibrate drugs (fenofibrate and gemfibrozil) and controls expression of genes involved in lipid metabolism. PPARgamma is activated by fatty acid derivatives, such as hydroxyoctadecadienoic acid (HODEs), prostaglandin derivatives, such as 15-deoxy-Delta12,14-prostaglandin J2, and thiazolidinedione (glitazone) drugs, such as pioglitazone and rosiglitazone. PPARgamma is a key regulator of glucose homeostasis and adipogenesis. PPARbeta/delta ligands include polyunsaturated fatty acids, prostaglandins and synthetic compounds and stimulate fatty acid oxidation. All PPARs are expressed in vascular cells where they exert antiatherogenic, anti-inflammatory and vasculoprotective actions. Activators of PPARalpha (fibrates) and PPARgamma (thiazolidinediones or glitazones) antagonize angiotensin II effects in vivo and in vitro and have cardiovascular antioxidant and anti-inflammatory actions. PPAR agonists slightly reduce blood pressure are cardio-protective and correct vascular structure and endothelial dysfunction in experimental models of hypertension. Because of these beneficial effects, activators of PPARs may have therapeutic potential in the prevention of cardiovascular disease beyond their actions on carbohydrate and lipid metabolism. The present chapter focuses on the role of PPARs in vascular biology and discusses the clinical implications of using PPAR agonists in the management of vascular disease."]
[16737919,0,0,0,0,2006,"A complex, four-way variant t(15;17) in acute promyelocytic leukemia.","Yoo",16737919,"A complex, four-way variant t(15;17) in acute promyelocytic leukemia.    Abstract:   Complex variant 15;17 translocations are increasingly recognized in acute promyelocytic leukemia (APL). We report the case of a 47-year-old woman with APL harboring a novel four-way translocation. She presented with persistent bleeding after a tooth extraction. Blood cell counts at admission were hemoglobin at 9.0 g/dL, platelets at 15 x 10(9)/L, and white blood cells at 0.460 x 10(9)/L with abnormal promyelocytes. Most nucleated cells of bone marrow aspirates were abnormal promyelocytes with Auer rods. Chromosome analysis of unstimulated bone marrow cell cultures revealed a variant t(15;17) in the form of t(10;17;15;22)(q22;q21;q22;q11.2). Fluorescence in situ hybridization with a PML/RARA dual-color DNA probe showed the fusion signals on der(15) and the residual PML signals on der(22). RT-PCR showed long-form PML/RARA fusion transcripts. A complete remission was attained with a course of conventional chemotherapy including ATRA. A literature review revealed that our case is one of the very rare four-way translocations and the first report of the involvement of chromosomes 10 and 22 in a variant t(15;17)."]
[16724326,1,0,0,1,2006,"The long and short of it: somite formation in mice.","Gridley",16724326,"The long and short of it: somite formation in mice.    Abstract:   A fundamental characteristic of the vertebrate body plan is its segmentation along the anterior-posterior axis. This segmental pattern is established during embryogenesis by the formation of somites, the transient epithelial blocks of cells that derive from the unsegmented presomitic mesoderm. Somite formation involves a molecular oscillator, termed the segmentation clock, in combination with gradients of signaling molecules such as fibroblast growth factor 8, WNT3A, and retinoic acid. Disruption of somitogenesis in humans can result in disorders such as spondylocostal dysostosis, which is characterized by vertebral malformations. This review summarizes recent findings concerning the role of Notch signaling in the segmentation clock, the complex regulatory network that governs somitogenesis, the genes that cause inherited spondylocostal dysostosis, and the mechanisms that regulate bilaterally symmetric somite formation."]
[16721130,1,0,0,1,2006,"Targeting angiogenesis for the treatment of sarcoma.","Balasubramanian",16721130,"Targeting angiogenesis for the treatment of sarcoma.    Abstract:    PURPOSE OF REVIEW : More therapeutic options are needed for bone and soft tissue sarcomas, especially for patients with metastatic disease. Recent randomized clinical trials conducted in colon, breast and lung cancer have shown the anti-vascular endothelial growth factor agent, bevacizumab, alone or in combination with chemotherapy, improves response and survival. Preclinical studies have demonstrated the anti-tumor effects of varied anti-angiogenic agents in sarcoma cell lines and tumor models.  RECENT FINDINGS : Preclinical studies in sarcomas have evaluated the role of targeted agents including platelet-derived growth factor, matrix metalloproteinases, urokinase receptor and varied small-molecule tyrosine kinase inhibitors. Novel angiogenesis inhibitors are being studied in the treatment of sarcoma, including monoclonal antibodies against vascular endothelial growth factor, cis- and trans-retinoic acids, thalidomide, and tyrosine kinase inhibitors. Phase I, II and III clinical trials continue to evaluate these agents alone, in combinations together and combined with standard chemotherapy. We review herein the preclinical rationale and clinical trial results of anti-angiogenesis therapy in the treatment of soft tissue and bone sarcoma.  SUMMARY : Preclinical mechanistic study and clinical trials are continuing in order to evaluate the therapeutic role and ultimately validate the efficacy of the varied anti-angiogenesis agents in soft tissue and bone sarcoma."]
[16720557,2,0,0,2,2006,"Bilateral osteonecrosis of the head of the femur during treatment with retinoic acid in a young patient with acute promyelocytic leukemia.","Sakakura",16720557,"Bilateral osteonecrosis of the head of the femur during treatment with retinoic acid in a young patient with acute promyelocytic leukemia.    Abstract:   All-trans retinoic acid (ATRA) is the drug of choice for the treatment of acute promyelocytic leukemia (APL). In general, ATRA is well tolerated, but it does have side effects, the most severe of which is ATRA syndrome. We report the case of a young patient with APL treated with ATRA for induction and maintenance therapy who then developed avascular necrosis of both femoral heads. We also review cases of APL patients with osteonecrosis of the femoral head after ATRA therapy."]
[16706264,0,0,0,0,2006,"Diagnosis, screening, prevention, and treatment of osteoporosis.","Mauck",16706264,"Diagnosis, screening, prevention, and treatment of osteoporosis.    Abstract:   Osteoporosis is the most common bone disease in humans and affects both men and women. The clinical and public health implications of the disease are substantial because of the mortality, morbidity, and cost of medical care associated with osteoporotic fractures. Osteoporosis is diagnosed on the basis of a low-impact or fragility fracture or low bone mineral density, which was best assessed by central dual-energy x-ray absorptiometry. Both nonpharmacological therapy (calcium and vitamin D supplementation, weight-bearing exercise, and fall prevention) and pharmacological treatments (antiresorptive and anabolic agents) may be helpful in the prevention and treatment of osteoporosis. Therefore, clinicians need to be vigilant in instituting primary prevention measures for those at high risk for osteoporosis and in instituting treatment for patients diagnosed as having the disease either by screening or a history of fracture. This article provides an overview of the diagnosis, screening, prevention, and treatment of osteoporosis."]
[16678459,1,0,0,1,2006,"Molecular targets and the treatment of myeloid leukemia.","Ikeda",16678459,"Molecular targets and the treatment of myeloid leukemia.    Abstract:   Leukemia is a multistep process involving accumulation of genetic alterations over time. These genetic mutations destroy the delicate balance between cell proliferation, differentiation, and apoptosis. Traditional approaches to treatment of leukemia involve chemotherapy, radiation, and bone marrow transplantation. In recent years, specific targeted therapies have been developed for the treatment of leukemia. The success of treatment of acute promyelocytic leukemia with All Trans Retinoic Acid (ATRA) and CML with imatinib have lead to increased efforts to identify targets that can be inhibited by small molecules for treatment of hematological malignancies. In this review, we describe the current advances in the development of targeted therapy in acute myeloid leukemia."]
[16632271,0,0,0,0,2006,"Oral pityriasis rubra pilaris.","Martinez Calixto",16632271,"Oral pityriasis rubra pilaris.    Abstract:   Pityriasis rubra pilaris is a chronic, papulosquamous dermatosis of unknown etiology. Oral mucosal involvement of this condition is rare with only 3 previously reported cases in the English literature. A case of a 68-year-old man with pityriasis rubra pilaris with involvement of tongue and palate is presented. Clinical features, histopathologic features, and management of pityriasis rubra pilaris are discussed. We hereby present an additional case, the fourth worldwide, and review the literature."]
[16628264,2,0,0,2,2006,"Retinoic acid receptor-related orphan receptor alpha as a therapeutic target in the treatment of dyslipidemia and atherosclerosis.","Jakel",16628264,"Retinoic acid receptor-related orphan receptor alpha as a therapeutic target in the treatment of dyslipidemia and atherosclerosis.    Abstract:   Retinoic acid receptor-related orphan receptor alpha (RORalpha) is a member of the nuclear receptor family. Recently, cholesterol (derivatives) has been identified as an RORalpha ligand and deorphanized this receptor. RORalpha is expressed in many tissues and is therefore a regulator of multiple biological processes. Studies of staggerer mice and in vitro assays indicate a beneficial modulatory role of RORalpha in the pathogenesis of dyslipidemia, inflammation and atherosclerosis. This paper provides an overview on the role of RORalpha in lipid metabolism and discusses its potential therapeutic option for treating lipid and inflammatory disorders leading to atherosclerosis."]
[16622850,1,0,0,1,2006,"Parabronchial smooth muscle cells and alveolar myofibroblasts in lung development.","Kim",16622850,"Parabronchial smooth muscle cells and alveolar myofibroblasts in lung development.    Abstract:   Epithelial-mesenchymal interactions and extracellular matrix remodeling are key processes of embryonic lung development. Lung smooth muscle cells, which are derived from the mesenchyme, form a sheath around bronchi and blood vessels. During lung organogenesis, smooth muscle differentiation coincides with epithelial branching morphogenesis and closely follows developing airways spatially and temporally. The precise function of parabronchial smooth muscle (PBSM) cells in healthy adult lung remains unclear. However, PBSM may regulate epithelial branching morphogenesis during lung development by the induction of mechanical stress or through regulation of paracrine signaling pathways. Alveolar myofibroblasts are interstitial contractile cells that share features and may share an origin with smooth muscle cells. Alveolar myofibroblasts are essential for secondary septation, a process critical for the development of the gas-exchange region of the lung. Dysregulation of PBSM or alveolar myofibroblast development is thought to underlie the pathogenesis of many lung diseases, including bronchopulmonary dysplasia, asthma, and interstitial fibrosis. We review the current understanding of the regulation of PBSM and alveolar myofibroblast development, and discuss the role of PBSM in lung development. We specifically focus on the role of these cells in the context of fibroblast growth factor-10, sonic hedgehog, bone morphogenetic protein-4, retinoic acid, and Wnt signaling pathways in the regulation of lung branching morphogenesis."]
[16613830,1,0,0,1,2006,"Regulation of early lung morphogenesis: questions, facts and controversies.","Cardoso",16613830,"Regulation of early lung morphogenesis: questions, facts and controversies.    Abstract:   During early respiratory system development, the foregut endoderm gives rise to the tracheal and lung cell progenitors. Through branching morphogenesis, and in coordination with vascular development, a tree-like structure of epithelial tubules forms and differentiates to produce the airways and alveoli. Recent studies have implicated the fibroblast growth factor, sonic hedgehog, bone morphogenetic protein, retinoic acid and Wnt signaling pathways, and various transcription factors in regulating the initial stages of lung development. However, the precise roles of these molecules and how they interact in the developing lung is subject to debate. Here, we review early stages in lung development and highlight questions and controversies regarding their molecular regulation."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I261,I261)","v":16503871},{"$f":"(LEN($J261) - LEN(SUBSTITUTE(LOWER($J261),LOWER(B$3),\"\")))/LEN(B$3)","v":1},0,0,{"$f":"SUM(B261:D261)","v":1},2005,"Peroxisome proliferator-activated receptor alpha (PPARalpha) and athero-sclerosis.","Gouni-Berthold",16503871,"Peroxisome proliferator-activated receptor alpha (PPARalpha) and athero-sclerosis.    Abstract:   The peroxisome proliferator-activated receptors (PPARs) alpha, beta/delta and gamma are ligand-activated transcription factors belonging to the nuclear receptor superfamily. PPARs heterodimerize with the retinoid X receptor (RXR) and modulate the function of many target genes. They were originally described as regulators of various metabolic, pathways, but have been recently found to also exert modulating actions in the vascular wall. PPARalpha is activated by endogenous ligands, such as polyunsaturated fatty acids and by synthetic agonists such as the fibrates. PPARalpha is expressed mainly in the liver, kidney and skeletal muscle and is involved in fatty acid oxidation. However, it is also expressed in vascular cells such as the endothelial cells, vascular smooth muscle cells and macrophages, where it exerts anti-inflammatory and antioxidant effects. Since atherosclerosis is both a chronic inflammatory and a lipid disorder and since PPARalpha is expressed in vascular cells and regulates the expression of genes involved in lipid metabolism and inflammation, PPARalpha activators may constitute useful agents for the prevention of atherosclerosis, beyond their effects on lipid metabolism. This review will focus on the functions of PPARalpha on lipid metabolism, on vascular inflammation and its relationship to atherosclerosis. Furthermore, the currently available preclinical and clinical data on PPARalpha activators as well as their future perspectives will be discussed."]
[16488334,0,0,0,0,2006,"The treatment of psoriasis and psoriatic arthritis: an interdisciplinary approach.","Gordon",16488334,"The treatment of psoriasis and psoriatic arthritis: an interdisciplinary approach.    Abstract:   Psoriatic arthritis is a common inflammatory arthritis associated with psoriasis, occurring in 5% to 40% of patients with cutaneous disease. Recently, there has been an increased appreciation of the need to use an integrated approach to these 2 diseases, considering both entities when determining therapeutic choices. In this review, the available therapeutic options for psoriatic arthritis are considered, along with the potential benefit that these medications may have for cutaneous psoriasis. Finally, a conceptual model for the therapy of psoriasis and psoriatic arthritis, the Four Quadrant Model, is presented as a simplified framework to use when considering treatment for psoriatic disease."]
[16487086,1,0,0,1,2006,"Staging and management of cutaneous T-cell lymphoma.","Scarisbrick",16487086,"Staging and management of cutaneous T-cell lymphoma.    Abstract:   Cutaneous T-cell lymphoma (CTCL) accounts for two-thirds of cases of primary cutaneous lymphoma. Most variants of CTCL are indolent lymphoma, the most common being mycosis fungoides. In addition, Sézary syndrome, the leukaemic variant, has an aggressive clinical course. Accurate diagnosis and staging is critical in determining the prognosis of those with CTCL. The tumour, node, metastasis and blood stage needs to be documented and used to determine an overall stage from IA to IVB. Management of patients should be carried out by a multidisciplinary team. A full clinical examination should be made at all visits. Thorough investigations are needed at diagnosis and should be repeated during disease progression to allow initial staging and restaging. Treatment of patients with early-stage disease (IA-IIB) should be limited to skin-directed therapy. More advanced or resistant disease may be treated with systemic therapies such as extracorporeal photopheresis, immunotherapy, monoclonal antibody therapy, novel retinoids or chemotherapy, and where possible, patients should be entered into clinical trials."]
[16469975,2,0,0,2,2006,"The acute and chronic toxic effects of vitamin A.","Penniston",16469975,"The acute and chronic toxic effects of vitamin A.    Abstract:   The acute and chronic effects of vitamin A toxicity are well documented in the literature. Emerging evidence suggests that subtoxicity without clinical signs of toxicity may be a growing concern, because intake from preformed sources of vitamin A often exceeds the recommended dietary allowances (RDA) for adults, especially in developed countries. Osteoporosis and hip fracture are associated with preformed vitamin A intakes that are only twice the current RDA. Assessing vitamin A status in persons with subtoxicity or toxicity is complicated because serum retinol concentrations are nonsensitive indicators in this range of liver vitamin A reserves. The metabolism in well-nourished persons of preformed vitamin A, provided by either liver or supplements, has been studied by several research groups. To control vitamin A deficiency, large therapeutic doses are administered in developing countries to women and children, who often are undernourished. Nevertheless, little attention has been given to the short-term kinetics (ie, after absorption but before storage) of a large dose of vitamin A or to the short- and long-term effects of such a dose given to lactating women on serum and breast-milk concentrations of retinol and its metabolites. Moreover, appropriate dosing regimens have not been systematically evaluated to ascertain the quantitative improvement in vitamin A status of the women and children who receive these supplements. The known acute and chronic effects of vitamin A toxicity have been reported previously. However, further research is needed to ascertain the areas of the world in which subclinical toxicity exists and to evaluate its effects on overall health and well-being."]
[16456374,1,0,0,1,2006,"New insights into the pathogenesis and drug treatment of myelofibrosis.","Tefferi",16456374,"New insights into the pathogenesis and drug treatment of myelofibrosis.    Abstract:    PURPOSE OF REVIEW : Myelofibrosis with myeloid metaplasia was first described in 1879, classified as a myeloproliferative disorder in 1951, and characterized as a clonal stem cell disorder in 1978. Despite the passing of time, the molecular basis of the disease has remained elusive although substantial progress has been made regarding the pathogenesis of the associated bone marrow stromal reaction. Advances have also been meager in terms of treatment for disease complications, including anemia, splenomegaly, and leukemic transformation.  RECENT FINDINGS : At the molecular level, a JAK2 tyrosine kinase mutation (JAK2) has recently been described in a spectrum of myeloproliferative disorders including myelofibrosis with myeloid metaplasia with the reported mutational frequency ranging from 35% to 57% with 9-29% homozygosity. To date, the presence of JAK2 in myelofibrosis with myeloid metaplasia has not been shown to have prognostic relevance. Other recent observations of potential pathogenetic relevance in this disease include the description of a highly specific chromosomal translocation {der(6)t(1;6)(q23;p21)}, the demonstration of an epigenetic downregulation of the retinoic acid receptor-beta2 expression in CD34 cells, and the direct implication of transforming growth factor-beta1 in thrombopoietin-driven experimental myelofibrosis in mice. From a therapeutic standpoint, benefit to a subset of patients has been demonstrated for both allogeneic stem cell transplantation and novel drugs, including thalidomide and lenalidomide.  SUMMARY : Recent advances in the pathogenesis of myelofibrosis with myeloid metaplasia are expected to facilitate the development of molecularly targeted therapy. In the mean time, current management strategies include observation, participation in experimental drug therapy, and allogeneic stem cell transplantation for low-risk, intermediate-risk, and high-risk disease, respectively."]
[16452274,0,0,0,0,2006,"Vitamins.","Sethuraman",16452274,"Vitamins.    Abstract:  "]
[16433796,22,0,0,22,2006,"Oral retinoid therapy for disorders of keratinization: single-centre retrospective 25 years experience on 23 patients.","Katugampola",16433796,"Oral retinoid therapy for disorders of keratinization: single-centre retrospective 25 years experience on 23 patients.    Abstract:    BACKGROUND : Over the last three decades, the oral retinoids etretinate and acitretin have revolutionized the treatment of disorders of keratinization (DOK). Many patients with DOK require life-long treatment with oral retinoids. However, the longest follow-up data of patients with DOK on oral retinoid therapy is 10 years for adults and up to 11 years for children.  OBJECTIVES : The aim of our study was to collect long-term retrospective data including disease response, side-effects and pregnancy outcome in a cohort of patients with DOK who were among the first in the world to commence oral retinoids 25 years ago.  METHODS : Between 1979 and 1981, 30 patients with DOK were commenced on oral etretinate in our department. Case notes of these patients were reviewed retrospectively, and patients interviewed where possible to obtain the following information: diagnosis, age when treatment commenced, duration of treatment, reason for discontinuation of therapy, side-effects, abnormal investigation results and pregnancy outcomes.  RESULTS : Case notes of 23 of the 30 patients were available for review; of these, two patients were deceased and 14 were interviewed. In the 23 patients, the mean age of commencing treatment was 33.5 years (range 4.2-61) and the mean duration of etretinate therapy was 5.2 years (range 1 month to 14 years). Reasons for discontinuing treatment were an overall improvement in the skin disease (six of 23), no benefit +/- side-effects (11 of 23) and noncompliance (one of 23). Two patients died of causes unrelated to their skin disease or treatment, 12 and 4 years after stopping etretinate. Five patients (one female, four males) subsequently changed to acitretin and are currently continuing therapy. The mean total duration of retinoid therapy (etretinate and acitretin) for the four males was 23.7 years (range 20.6-25.1). The female patient continued intermittent courses (due to planned pregnancies) of oral retinoids for a total of 10.1 years over the last 25 years. Abnormal investigation results included elevated serum triglycerides and cholesterol (two of 23), isolated high triglycerides (three of 23), isolated high cholesterol (three of 23), worsening of liver enzymes in a patient with alcohol dependence, and elevated serum alkaline phosphatase (ALP) in healthy adults (three of 23). In two children, the elevated pretreatment ALP levels increased further after commencing etretinate but returned to normal in adulthood while treatment continued. One patient developed diffuse idiopathic skeletal hyperostosis after 21 years of retinoid therapy. One female patient had two early spontaneous abortions 2.75 and 3.2 years after discontinuing etretinate; she subsequently had two normal children. Two other females had normal children 1, 3 and 5 years after stopping etretinate. Two male patients fathered a total of three healthy children while on etretinate.  CONCLUSIONS : This study provides the longest available follow-up data of children and adults with DOK on oral retinoid therapy. Such information is essential for clinicians and their patients with DOK embarking on life-long treatment with retinoids."]
[16406653,1,0,0,1,2006,"Vitamin D signaling is modulated on multiple levels in health and disease.","Ebert",16406653,"Vitamin D signaling is modulated on multiple levels in health and disease.    Abstract:   Vitamin D signaling is dependent on the availability and turnover of the active Vitamin D receptor (VDR) ligand 1,25-dihydroxycholecalciferol and on the efficiency of VDR transactivation. Activating and inactivating secosteroid metabolizing p450 enzymes, e.g. 25-hydroxylases, 1alpha-hydroxylase and 24-hydroxylase, are responsible for ligand availability on the basis of substrate production in the skin and of nutritional intake of precursors. Net availability of active hormone depends on the delivery of substrate and the balance of activating and inactivating enzymes. 1Alpha-hydroxylase is the critical activating enzyme. It is expressed in the kidney for systemic supply and in target tissues for local secosteroid activation. It is upregulated in the kidney by low calcium intake and parathyroid hormone, downregulated by phosphatonins and proinflammatory signal transduction. Transactivation of VDR depends on the correct molecule structure, effective nuclear translocation and the presence of the unliganded heterodimer partner retinoid X-receptor (RXR) and other nuclear cofactors. Rapid Vitamin D-dependent membrane associated effects and consecutive second messenger activation exert an own pattern of gene regulation. A membrane receptor for these effects is hypothesized but not yet identified. Rickets is the long known clinical syndrome of impaired Vitamin D signaling due to Vitamin D3 deficiency. It can be caused by inherited defects of the cascade, nutritional deficits, lack of sunlight exposure, malabsorption and underlying diseases like chronic inflammation. It has been shown during the last decades that many modifiers of Vitamin D signaling are targets of disease in terms of inherited and acquired syndromes and that Vitamin D signaling is modulated at multiple levels and is more complex than mere mechanistic ligand/receptor/DNA interaction."]
[16249271,1,0,0,1,2005,"Effect of vitamin A on fracture risk.","Jackson",16249271,"Effect of vitamin A on fracture risk.    Abstract:    OBJECTIVE : To describe current data evaluating the effect of vitamin A intake on fracture risk.  DATA SOURCES : A literature search using MEDLINE (1966-March 2005) was conducted using the search terms bone density, fractures, osteoporosis, retinol, and vitamin A to identify published studies evaluating the effects of vitamin A on bone.  DATA SYNTHESIS : Studies evaluating vitamin A consumption and fracture risk were reviewed. Current data suggest a potential inverse relationship between excess vitamin A consumption and bone mineral density leading to an increased risk for fracture.  CONCLUSIONS : Although current data are limited, consumption of large amounts of vitamin A may be associated with decreased bone mineral density and increased fracture risk. Until further information is available, patients should be made aware of the potential risks of consuming vitamin A in amounts that exceed the recommended dietary allowance. Further research is needed to clarify the relationship between vitamin A and fracture risk."]
[16197378,0,0,0,0,2005,"Myelofibrosis in a patient with pachydermoperiostosis.","Bachmeyer",16197378,"Myelofibrosis in a patient with pachydermoperiostosis.    Abstract:   Pachydermoperiostosis (idiopathic or primary hypertrophic osteoarthropathy) is a rare condition of unknown origin involving the skin and the skeleton, with an autosomal dominant transmission. We report a case of anaemia in a patient with pachydermoperiostosis indicating myelofibrosis, and review the literature and the pathogenetic mechanisms."]
[20527403,0,0,0,0,2005,"[Unexpected failure of antioxidant clinical trials].","Wierzba",20527403,"[Unexpected failure of antioxidant clinical trials].    Abstract:   Data from a variety of experimental studies suggesting benefits of the antioxidant supplementation were confronted with those from clinical trials and large metaanalyses which have failed to prove those benefits. Major directions of the biological effects of reactive oxygen species (ROS) and antioxidants were specified. In particular, plausible mechanisms through antioxidants may disturb physiological functions were discussed. The regulatory aspects of ROS potency, and the ways antioxidants may disturb homeostasis were taken particularly into account. Directions of prospective research towards practical use of antioxidants were suggested."]
[16167012,1,0,0,1,2005,"Acute promyelocytic leukemia: current strategies for the treatment of newly diagnosed disease.","Sirulnik",16167012,"Acute promyelocytic leukemia: current strategies for the treatment of newly diagnosed disease.    Abstract:   Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia that comprises about 10% of cases. It is characterized by the accumulation of granulocytic cells blocked at the promyelocytic stage of differentiation in the bone marrow and the peripheral blood, life-threatening coagulopathy, and a remarkable response to treatment with all-trans-retinoic acid (ATRA), arsenic trioxide, and anthracyclines. Current treatment strategies with ATRA and anthracycline-based chemotherapy has dramatically transformed APL into the most curable of all acute leukemias. Advances in supportive care together with the early recognition of treatment-related complications have also contributed significantly to increased cure rates. In this review we explore current treatment strategies in the management of newly diagnosed APL. We also highlight practical points that may serve as a guideline for the treating physician and address current controversies in the choice of treatment."]
[16129372,15,0,0,15,2005,"Retinoic acid and retinoid receptors: potential chemopreventive and therapeutic role in cervical cancer.","Abu",16129372,"Retinoic acid and retinoid receptors: potential chemopreventive and therapeutic role in cervical cancer.    Abstract:   Retinoids are natural and synthetic derivatives of vitamin A, which can be obtained from animal products (milk, liver, beef, fish oils, and eggs) and vegetables (carrots, mangos, sweet potatoes, and spinach). Retinoids regulate various important cellular functions in the body through specific nuclear retinoic-acid receptors and retinoid-X receptors, which are encoded by separate genes. Retinoic-acid receptors specifically bind tretinoin and alitretinoin, whereas retinoid-X receptors bind only alitretinoin. Retinoids have long been established as crucial for several essential life processes-healthy growth, vision, maintenance of tissues, reproduction, metabolism, tissue differentiation (normal, premalignant cells, and malignant cells), haemopoiesis, bone development, spermatogenesis, embryogenesis, and overall survival. Therefore, deficiency of vitamin A can lead to various unwanted biological effects. Several experimental and epidemiological studies have shown the antiproliferative activity of retinoids and their potential use in cancer treatment and chemoprevention. Emerging clinical trials have shown the chemotherapeutic and chemopreventive potential of retinoids in cancerous and precancerous conditions of the uterine cervix. In this review, we explore the potential chemopreventive and therapeutic roles of retinoids in preinvasive and invasive cervical neoplasia."]
[16109139,1,0,0,1,2005,"Parathyroid cell growth in patients with advanced secondary hyperparathyroidism: vitamin D receptor, calcium sensing receptor, and cell cycle regulating factors.","Tokumoto",16109139,"Parathyroid cell growth in patients with advanced secondary hyperparathyroidism: vitamin D receptor, calcium sensing receptor, and cell cycle regulating factors.    Abstract:   The parathyroid gland (PTG) is a unique endocrine organ in which the quiescent glandular cells begin to proliferate in response to the demand for maintaining calcium (Ca) homeostasis in the progressive course of renal failure, leading to secondary hypereparathyroidism (SHPT). SHPT is characterized with continuous over-secretion of parathyroid hormone (PTH) and high turn-over bone disease, osteitis fibrosa, and the major factors include a deficiency of active vitamin D, hypocalcemia, and phosphate retention. With long-term end-stage renal failure, SHPT becomes resistant to conventional medical treatment such as phosphate binders and active vitamin D supplementation, and the growth of the PTG accelerates with the pattern of hyperplasia changing from diffuse to nodular type. In this process, the sigmoid curve between extracellular Ca concentration (exCa) and the plasma level of PTH shifts to the upper-rightward, indicating both an absolute increase in PTH secretion and the resistance of PT cells to exCa. Many experimental and human studies have revealed down-regulation of vitamin D receptor (VDR), calcium-sensing receptor (CaSR), and retinoid X receptor (RXR) in PT cells. The sustained proliferation of PT cells after obtaining autonomicity is another characteristic feature of SHPT. In this context, it has been demonstrated that the cell cycle is markedly progressed, where the expression of cyclin-dependent kinase inhibitor (CDKI), p21 and p27, is depressed in a VDR-dependent manner. These pathological features are most evident in nodular hyperplasia, in which monoclonal proliferation is obvious, indicating the phenotypic changes have occured in PT cells. It has been observed by Fukagawa and colleagues that pharmacologically high dose of active vitamin D administered orally can cause small-size PTG hyperplasia to regress in patients with advanced SHPT. Successful renal transplantation may also restore VDR and CaSR expressions in the diffuse type, in association with increasing TUNEL-positive cells. Thus, it is important to vigorously treat SHPT when the PT cell proliferation is in the reversible stage of diffuse hyperplasia."]
[16107759,1,0,0,1,2005,"Regulation of mast cell development.","Shiohara",16107759,"Regulation of mast cell development.    Abstract:   Human mast cells originated from multipotential hematopoietic progenitors in bone marrow (BM). A large proportion of these progenitors were CD34+CD38-c-kit+ cells and CD34+CD38+c-kit+ cells. Cloning of stem cell factor (SCF) contributed to the development of culture systems of human mast cells from different sources including BM mononuclear cells, CD34+ cord blood (CB) cells, and fetal liver cells. SCF could support mast cell development from CD34+ CB cells in the serum-deprived culture system. The cumulative mast cell number reached 10(10)-fold the input quantity at 50 weeks of SCF-containing serumdeprived culture. CB-derived mast cells expressed tryptase, chymase, and histamine similar to mast cells residing in tissues. The surface expression of FcepsilonRI, however, was very low on fetal liver- or CB-derived mast cells. Factors that had effects on SCF-dependent human mast cell development were divided into four types: (1) factors that stimulated both proliferation and maturation: SCF; (2) factors that stimulated only proliferation: thrombopoietin, interleukin (IL)-9; (3) factors that inhibited proliferation, but stimulated maturation: IL-4, IL-6, and (4) factors that inhibited proliferation and maturation: retinoids."]
[16101412,1,0,0,1,2005,"Vitamin D receptor modulators for inflammation and cancer.","Yee",16101412,"Vitamin D receptor modulators for inflammation and cancer.    Abstract:   1alpha, 25-Dihydroxyvitamin D3 [1,25-(OH)2D3], the biologically active form of vitamin D, is an important hormone that is critically required for the maintenance of mineral homeostasis and structural integrity of bones. 1,25-(OH)2D3 accomplishes this by facilitating calcium absorption from the gut and by a direct action on osteoblasts, the bone forming cells. Apart form its classical actions on the gut and bone, 1,25-(OH)2D3 and its synthetic analogs also possess potent anti-proliferative, differentiative and immunomodulatory activities. 1,25-(OH)2D3 exerts these effects through vitamin D receptor (VDR), a ligand-dependent transcription factor that belongs to the superfamily of steroid/thyroid hormone/retinoid nuclear receptors. The presence of VDR in various tissues other than gut and bone, along with their ability to exert differentiation, growth inhibitory and anti-inflammatory action, has set the stage for therapeutic exploitation of VDR ligands for the treatment of various inflammatory indications and cancer. However, the use of VDR ligands in clinic is limited by their major dose-related side effect, namely hypercalcemia/hypercalciuria. Efforts are being undertaken to develop vitamin D receptor modulators (VDRMs) that are tissue-selective and/or gene-selective in their action and these ligands may exhibit increased therapeutic indices. This review explores the recent advances in VDR biology, non-secosteroidal VDR ligands and the current and potential clinical applications of VDR ligands in inflammation and cancer."]
[16041760,0,0,0,0,2005,"Role of morphogens in neural crest cell determination.","Jones",16041760,"Role of morphogens in neural crest cell determination.    Abstract:   The neural crest is a transient, migratory cell population found in all vertebrate embryos that generate a diverse range of cell and tissue derivatives including, but not limited, to the neurons and glia of the peripheral nervous system, smooth muscle, connective tissue, melanocytes, craniofacial cartilage, and bone. Over the past few years, many studies have provided tremendous insights into understanding the mechanisms regulating the induction and migration of neural crest cell development. This review highlights the surprising and perhaps unexpected roles for morphogens in these distinct processes. A comparison of studies performed in several different vertebrates emphasizes the requirement for coordination between multiple signaling pathways in the induction and migration of neural crest cells in the developing embryo."]
[16041757,1,0,0,1,2005,"CNS regeneration: a morphogens tale.","Vergara",16041757,"CNS regeneration: a morphogens tale.    Abstract:   Tissue regeneration will soon become an avenue for repair of damaged or diseased tissues as stem cell niches have been found in almost every organ of the vertebrate body including the CNS. In addition, different animals display an array of regenerative capabilities that are currently being researched to dissect the molecular mechanisms involved. This review concentrates on the different ways in which CNS tissues such as brain, spinal cord and retina can regenerate or display neurogenic potential and how these abilities are modulated by morphogens."]
[15981190,6,0,0,6,2005,"Congenital diaphragmatic hernia: a retinoid-signaling pathway disruption during lung development?","Gallot",15981190,"Congenital diaphragmatic hernia: a retinoid-signaling pathway disruption during lung development?    Abstract:   Congenital diaphragmatic hernia (CDH) usually occurs sporadically. The prognosis remains poor, with a 50% perinatal mortality rate. Most deaths result from hypoxemia due to lung hypoplasia and abnormal development of pulmonary vasculature that results in persistent pulmonary hypertension. Our current understanding of the pathogenesis of CDH is based on an assumption linking herniation of abdominal viscera into the thorax with compression of the developing lung. Pulmonary hypoplasia, however, can also result from reduced distension of the developing lung secondary to impaired fetal breathing movements. Moreover, a nitrofen-induced CDH model shows that lung hypoplasia precedes the diaphragmatic defect, leading to a quot;dual-hit hypothesis.quot; Recent data reveal the role of a retinoid-signaling pathway disruption in the pathogenesis of CDH. We describe the clinical and epidemiological aspects of human CDH, the metabolic and molecular aspects of the retinoid-signaling pathway, and the implications of retinoids in the development of the diaphragm and the lung. Finally, we highlight the existing links between CDH and disruption of the retinoid-signaling pathway, which may suggest an eventual use of retinoids in the treatment of CDH."]
[15964534,0,0,0,0,2005,"[Fat-soluble vitamins in infants].","Salle",15964534,"[Fat-soluble vitamins in infants].    Abstract:   Vitamins are micronutrients not synthesised by the human body and should be provided by the nutrition. Liposoluble vitamins include vitamins A, E, D and K. Vitamins A and E are two potent antioxidant nutrients and play a significant role in immune function. Vitamin D plays a major role in intestinal calcium absorption and bone mineralization. Vitamin K intervenes in the synthesis of coagulation factors particularly in the prothrombin synthesis. Vitamin metabolism, placental transfer, vitamin status in newborns and infants are reported. Finally requirements of these vitamins are defined."]
[15959399,1,0,0,1,2005,"[PPAR receptors: recent data].","Vidal",15959399,"[PPAR receptors: recent data].    Abstract:   The nuclear receptors PPAR (Peroxisome Proliferator-Activated Receptors) are transcription factors which form with the retinoid receptor RXR, a PPAR/RXR heterodimer, the functional transcription factor within cells. PPAR receptors are activated by their ligands, either naturals or synthetics, and modulate target gene transcription. There are three PPAR subtypes (PPARalpha, PPARbeta/delta et PPARgamma) coded by different genes, and two isoforms of PPARgamma proteins have been detected in humans (PPARgamma1 and PPARgamma2). PPAR are mainly modulators of lipid metabolism, but each receptor subtype is pharmacologically distinct, and development of synthetic PPAR agonists has shown their role in cellular (mainly adipocyte) differentiation and in glucose homeostasis. This review summarise the main data, currently available, on expression, biological functions, natural and synthetic (activators) ligands for the PPAR receptor subtypes. PPAR receptors key-role in lipid and glucose métabolisms, has lead to a large clinical use of pharmacological agents acting as PPAR ligands: fibrates, PPARalpha agonists as hypolipidaemic treatment, thiazolidinediones (glitazones), PPARalpha agonists as antidiabetics. Lipid metabolism is impaired in insulin resistant skeletal muscles, fatty acids role in the pathophysiology of insulin resistance generates several hypothesis we briefly describe. Finally, we present and discuss experimental data, suggesting the activation of PPARbeta/delta in skeletal muscle to be a potential new approach in the treatment of insulin resistance and metabolic syndrome."]
[15958702,5,0,0,5,2005,"Distinct gene expression pattern of malignant hematopoietic stem and progenitor cells in polycythemia vera.","Steidl",15958702,"Distinct gene expression pattern of malignant hematopoietic stem and progenitor cells in polycythemia vera.    Abstract:   Polycythemia vera (PV) is a chronic myeloproliferative disorder with an expansion of multipotent hematopoietic progenitor cells. Although it is known that hematopoietic progenitors in PV are erythropoietin independent and hypersensitive to several cytokines, the molecular oncogenic mechanisms in PV are largely unknown. In this study, we examined gene expression profiles of CD34(+) cells from bone marrow of patients with de novo PV and from healthy volunteers to identify molecular changes associated with the malignant growth of hematopoietic stem and progenitor cells in this myeloproliferative disorder. Using cDNA arrays, we found significant differences (P lt; .01) in the expression of 107 genes. Proapoptotic genes (CASP2, CASP3, DAPK1, ALG2) were expressed at lower levels in PV-CD34(+) cells, reflecting a lower apoptotic activity. Fibrosis-stimulating growth factors (transforming growth factor beta1, transforming growth factor beta2, bone morphogenetic protein 2, and endothelial growth factor) were expressed at significantly higher levels in PV-CD34(+) cells. Furthermore, PV-CD34(+) cells overexpressed several receptors, protein kinases, and proteasome subunits, which might be targets for directed therapeutic approaches. It is interesting that three retinoid receptors were overexpressed in PV-CD34(+) cells--retinoic acid receptor beta (RARbeta), retinoid X receptor beta (RXRbeta), and cellular retinoic acid binding protein 2 (CRABP2). Using methylcellulose colony-forming assays, we found that the formation of erythroid colonies derived from PV hematopoietic progenitors was inhibited by all-trans-retinoic acid (ATRA), a natural ligand of those receptors, in a dose-dependent manner, showing a maximum inhibition of 89% at 10 microM; the growth of myelomonocytic colonies was not significantly affected. These data suggest that the use of ATRA could be of therapeutic benefit for patients with PV."]
[15956766,1,0,0,1,2005,"Genesis of alcohol-induced craniofacial dysmorphism.","Sulik",15956766,"Genesis of alcohol-induced craniofacial dysmorphism.    Abstract:   The initial diagnosis of fetal alcohol syndrome (FAS) in the United States was made because of the facial features common to the first cohort of patients. This article reviews the development of an FAS mouse model whose craniofacial features are remarkably similar to those of affected humans. The model is based on short-term maternal treatment with a high dosage of ethanol at stages of pregnancy that are equivalent to Weeks 3 and 4 of human gestation. At these early stages of development, alcohols insult to the developing face is concurrent with that to the brain, eyes, and inner ear. That facial and central nervous system defects consistent with FAS can be induced by more quot;realisticquot; alcohol dosages as illustrated with data from an oral alcohol intake mouse model in which maternal blood alcohol levels do not exceed 200 mg/dl. The ethanol-induced pathogenesis involves apoptosis that occurs within 12 hrs of alcohol exposure in selected cell populations of Day 7, 8, and 9 mouse embryos. Experimental evidence from other species also shows that apoptosis underlies ethanol-induced malformations. With knowledge of sensitive and resistant cell populations at specific developmental stages, studies designed to identify the basis for these differing cellular responses and, therefore, to determine the primary mechanisms of ethanols teratogenesis are possible. For example, microarray comparisons of sensitive and resistant embryonic cell populations have been made, as have in situ studies of gene expression patterns in the populations of interest. Studies that illustrate agents that are effective in diminishing or exacerbating ethanols teratogenesis have also been helpful in determining mechanisms. Among these agents are antioxidants, sonic hedgehog protein, retinoids, and the peptides SAL and NAP."]
[15936325,1,0,0,1,2005,"The mechanisms of dorsoventral patterning in the vertebrate neural tube.","Wilson",15936325,"The mechanisms of dorsoventral patterning in the vertebrate neural tube.    Abstract:   We describe the essential features of and the molecules involved in dorsoventral (DV) patterning in the neural tube. The neural tube is, from its very outset, patterned in this axis as there is a roof plate, floor plate, and differing numbers and types of neuroblasts. These neuroblasts develop into different types of neurons which express a different range of marker genes. Early embryological experiments identified the notochord and the somites as being responsible for the DV patterning of the neural tube and we now know that 4 signaling molecules are involved and are generated by these surrounding structures. Fibroblast growth factors (FGFs) are produced by the caudal mesoderm and must be down-regulated before neural differentiation can occur. Retinoic acid (RA) is produced by the paraxial mesoderm and is an inducer of neural differentiation and patterning and is responsible for down-regulating FGF. Sonic hedgehog (Shh) is produced by the notochord and floor plate and is responsible for inducing ventral neural cell types in a concentration-dependent manner. Bone morphogenetic proteins (BMPs) are produced by the roof plate and are responsible for inducing dorsal neural cell types in a concentration-dependent manner. Subsequently, RA is used twice more. Once from the somites for motor neuron differentiation and secondly RA is used to define the motor neuron subtypes, but in the latter case it is generated within the neural tube from differentiating motor neurons rather than from outside. These 4 signaling molecules also interact with each other, generally in a repressive fashion, and DV patterning shows how complex these interactions can be."]
[15922648,0,1,0,1,2005,"Skeletal muscle and nuclear hormone receptors: implications for cardiovascular and metabolic disease.","Smith",15922648,"Skeletal muscle and nuclear hormone receptors: implications for cardiovascular and metabolic disease.    Abstract:   Skeletal muscle is a major mass peripheral tissue that accounts for approximately 40% of the total body mass and a major player in energy balance. It accounts for gt;30% of energy expenditure, is the primary tissue of insulin stimulated glucose uptake, disposal, and storage. Furthermore, it influences metabolism via modulation of circulating and stored lipid (and cholesterol) flux. Lipid catabolism supplies up to 70% of the energy requirements for resting muscle. However, initial aerobic exercise utilizes stored muscle glycogen but as exercise continues, glucose and stored muscle triglycerides become important energy substrates. Endurance exercise increasingly depends on fatty acid oxidation (and lipid mobilization from other tissues). This underscores the importance of lipid and glucose utilization as an energy source in muscle. Consequently skeletal muscle has a significant role in insulin sensitivity, the blood lipid profile, and obesity. Moreover, caloric excess, obesity and physical inactivity lead to skeletal muscle insulin resistance, a risk factor for the development of type II diabetes. In this context skeletal muscle is an important therapeutic target in the battle against cardiovascular disease, the worlds most serious public health threat. Major risk factors for cardiovascular disease include dyslipidemia, hypertension, obesity, sedentary lifestyle, and diabetes. These risk factors are directly influenced by diet, metabolism and physical activity. Metabolism is largely regulated by nuclear hormone receptors which function as hormone regulated transcription factors that bind DNA and mediate the patho-physiological regulation of gene expression. Metabolism and activity, which directly influence cardiovascular disease risk factors, are primarily driven by skeletal muscle. Recently, many nuclear receptors expressed in skeletal muscle have been shown to improve glucose tolerance, insulin resistance, and dyslipidemia. Skeletal muscle and nuclear receptors are rapidly emerging as critical targets in the battle against cardiovascular disease risk factors. Understanding the function of nuclear receptors in skeletal muscle has enormous pharmacological utility for the treatment of cardiovascular disease. This review focuses on the molecular regulation of metabolism by nuclear receptors in skeletal muscle in the context of dyslipidemia and cardiovascular disease."]
[15876415,0,0,0,0,2005,"Phytoestrogens derived from red clover: an alternative to estrogen replacement therapy?","Beck",15876415,"Phytoestrogens derived from red clover: an alternative to estrogen replacement therapy?    Abstract:   The benefits of plant extracts from soy and red clover as alternatives to conventional hormone replacement therapy (HRT) have been debated in the past. Here, an attempt has been made to summarize the biochemical and pharmacological data in the light of clinical aspects. Red clover and soy extracts contain isoflavones, which have a high affinity to estrogen receptor alpha (ERalpha), estrogen receptor beta (ERbeta), progesterone receptor (PR) and androgen receptor (AR). The higher affinity to ERbeta compared to ERalpha has been used as an explanation why red clover extracts function as food additives to treat menopausal disorders and may reduce risk of breast cancer. Biochemical analysis shows that these representatives of phytoestrogens have multiple actions beside selective estrogen receptor modulator (SERM)-activity. They act as selective estrogen enzyme modulators (SEEMs), have antioxidant activity and interact with transcription factors such as NF-kappaB. Furthermore, it is indicated that they have protective effects on osteoporosis and the cardiovascular system. Currently 40-50mg of isoflavones (biochanin A, daidzein, formononetin and genistein) are recommended as daily dose. This recommendation is based on the daily intake of phytoestrogens in a traditional Japanese diet."]
[15854063,0,0,0,0,2005,"Possible contraindications and adverse reactions associated with the use of ocular nutritional supplements.","Bartlett",15854063,"Possible contraindications and adverse reactions associated with the use of ocular nutritional supplements.    Abstract:   The role of oxidation in the development of age-related eye disease has prompted interest in the use of nutritional supplementation for prevention of onset and progression. Our aim is to highlight possible contraindications and adverse reactions of isolated or high dose ocular nutritional supplements. Web of Science and PubMed database searches were carried out, followed by a manual search of the bibliographies of retrieved articles. Vitamin A should be avoided in women who may become pregnant, in those with liver disease, and in people who drink heavily. Relationships have been found between vitamin A and reduced bone mineral density, and beta-carotene and increased risk of lung cancer in smoking males. Vitamin E and Ginkgo biloba have anticoagulant and anti-platelet effects respectively, and high doses are contraindicated in those being treated for vascular disorders. Those patients with contraindications or who are considered at risk of adverse reactions should be advised to seek specialist dietary advice via their medical practitioner."]
[15851961,1,0,0,1,2005,"[Surgical management of cervical radiculopathy in Forestiers disease. Case report and review].","Matgé",15851961,"[Surgical management of cervical radiculopathy in Forestiers disease. Case report and review].    Abstract:   Forestiers disease now called DISH (diffuse idiopathic skeletal hyperostosis) is a non inflammatory enthesopathy ossifying the anterolateral spine and sparing the disc and joint space in elderly men, mostly at thoracic levels. Radiology performed for minor trauma or to explore a stiff neck provides the diagnosis. The main differential diagnosis is ankylosing spondylitis presenting an inflammatory profile as well as previously existing alterations of the sacroiliac joint. Retinoic acid treatment or ossification of the posterior longitudinal ligament should also be discussed. Dysphagia is the most frequent symptom, but neurological signs are rarely observed. We report a case observed at the cervical level. Anterior decompression and cage-fusion was indicated. Ongoing hyperostosis was also documented. Surgery in DISH is mainly indicated for dysphagia and rarely after cervical trauma. Of note are associated lesions such as OPLL (ossification of the posterior longitudinal ligament) or synovial cysts responsible for the exceptional and severe myelopathy presentation. The neurosurgical community should become better aware of Forestiers disease."]
[15846704,0,0,0,0,2005,"Vitamins for epilepsy.","Ranganathan",15846704,"Vitamins for epilepsy.    Abstract:    BACKGROUND : Vitamins have been reported to be effective in controlling certain types of seizures and to prevent some of the harmful effects of antiepileptic drugs (AEDs). In this review we will summarize evidence from randomized controlled trials.  OBJECTIVES : To assess if vitamins improve seizure control, reduce adverse effects of AEDs or improve the quality of life in people with epilepsy.  SEARCH STRATEGY : We searched MEDLINE from 1966 to 2004, the Cochrane Epilepsy Group trials register (December 2004), CENTRAL (the Cochrane Controlled Trials Register) (TheCochraneLibrary Issue 4, 2004), and cross-references from identified studies.  SELECTION CRITERIA : Randomized or quasi-randomized studies investigating the effects of one or more vitamins given alone or in addition to AEDs to people of any age with any type of epilepsy.  DATA COLLECTION AND ANALYSIS : Both reviewers assessed the trials for inclusion and extracted the data. Outcomes assessed included seizure frequency, gingival hyperplasia, neuropathy, changes in bone mineral content, serum calcium, alkaline phosphatase, hemogram, serum levels of AEDs, neuropsychological and quality of life outcomes. Primary analyses were by intention to treat.  MAIN RESULTS : Fifteen studies met our inclusion criteria and were of poor methodological quality. None described randomization methods and most enrolled small numbers of participants. Nine studies (331 participants) investigated folic acid. Two studies (75 participants) found no effect for the outcome 50% or greater reduction in seizure frequency (OR 0.96; 95% CI 0.32 to 2.29). Also, no evidence was found for an effect on gingival health, intelligence, behavior, mental health or personality, or measures of red blood volume and hemoglobin content. Folic acid was not associated with any consistent changes in serum phenytoin or phenobarbitone levels or improvement in the mean motor conduction velocities of peripheral nerves. One small study (72 participants) found that thiamine improves neuropsychological functions related to psychomotor speed, visuospatial abilities, selective attention and verbal abstracting ability. One study (226 participants) found a significantly higher bone mineral content (BMC) among patients with epilepsy taking AEDs with vitamin D supplementation compared to controls who were not given supplementation (OR 3.6; 95% CI 2.48 to 4.72; p lt; 0.00001). The studies found no significant effects on serum calcium, alkaline phosphatase or general well-being. One small study (24 participants) found a significant decrease in seizure frequency in those treated with vitamin E compared to placebo (p = 0.00005; Peto OR 26.73; 95% CI 5.46 to 130.92).  AUTHORS CONCLUSIONS : In view of methodological deficiencies and limited number of individual studies, we have found no reliable evidence to support the routine use of vitamins in patients with epilepsy. Further trials are needed, especially to assess the utility of vitamin D supplementation to prevent osteomalacia and the role of vitamin E on seizures and thiamine in improving cognitive functions."]
[15838445,2,0,0,2,2005,"Congenital oculomotor nerve synkinesis associated with fetal retinoid syndrome.","Morrison",15838445,"Congenital oculomotor nerve synkinesis associated with fetal retinoid syndrome.    Abstract:    INTRODUCTION : Isotretinoin (RA), used for the treatment of cystic acne, is a powerful teratogen, causing craniofacial dysmorphisms and neural tube defects. We present two patients with RA embryopathy and oculomotor nerve synkinesis.  METHODS : Retrospective review of patient records.  RESULTS : Two patients presented with third nerve synkinesis and fetal RA exposure. Both had marked elevation of the upper eyelids on adduction such that the lid fissures alternately opened and closed on gaze from side to side. Both patients showed typical dysmorphisms of RA embryopathy. The first patient had complete agenesis of the cerebellar vermix and died at 2 years. The second patient had restricted extraocular muscles in one eye and was exotropic and hypotropic.  DISCUSSION : Both patients demonstrated simultaneous innervation of the medial rectus and levator palpebrae muscles causing coincident lid elevation in adduction. This evidence of oculomotor nerve synkinesis is consistent with animal studies showing abnormalities in the formation of cranial nerve ganglia following fetal RA exposure.  CONCLUSION : RA is a powerful teratogen. These patients provide additional clinical evidence of its influence on neural migration during early development."]
[15786708,0,0,0,0,2004,"Inositide-modifying enzymes: a cooperative role in regulating nuclear morphology during differentiation of myeloid cells.","Bertagnolo",15786708,"Inositide-modifying enzymes: a cooperative role in regulating nuclear morphology during differentiation of myeloid cells.    Abstract:   Differentiation and functional response of mature myeloid cells require cytoskeleton remodelling in a dynamic system that involves subcellular organization and regional signalling. Within the myeloid lineage, neutrophils constitute a cell type in which different cell compartments, and predominantly the nucleus, undergo distinctive large changes involving actin reorganization. In the context of the progressive elucidation of the nuclear structure and composition that has been achieved in the last two decades, it is now clear that the nucleus possesses an ordered and dynamic skeletal structure which shares many properties with the cytoskeleton, and the full set of substrates and enzymes that participate in the inositol lipid metabolism. Consolidated evidence indicate that the changes in cytoskeleton assembly are regulated also by phosphoinositides in a way dependent on their local concentration and availability. Indeed, enzymes able to affect the amount and phosphorylation of inositol lipids can play fundamental roles in determining the architectural transitions of the cell. The expression pattern and the changes of activity of PLC and PI 3-K in the nucleus during differentiation of tumoral myeloid precursors suggest that these enzymes play a crucial role in modifying the intranuclear pool of phosphoinositides, which in turn induce the changes in nucleoskeleton associated to granulocytic maturation. It can be speculated that defective control of nucleoskeleton assembly is one of the causes of dysregulated cell maturation or differentiative block in the course of myeloid leukemias. Inositide modifying enzymes can thus be regarded as potential targets for molecularly designed therapeutic intervention on hematological malignancies."]
[15776785,2,0,0,2,2005,"Scrotal ulceration as a consequence of all-trans-retinoic acid (ATRA) for the treatment of acute promyelocytic leukemia.","Simzar",15776785,"Scrotal ulceration as a consequence of all-trans-retinoic acid (ATRA) for the treatment of acute promyelocytic leukemia.    Abstract:   Induction therapy with all-trans-retinoic acid (ATRA), an oral vitamin A derivative, has been shown to improve the short and long-term outcome of patients with acute promyelocytic leukemia (APML). Common side effects include headache, fever, dry skin, and bone pain, and approximately 25% of treated patients experience ATRA syndrome, which includes fever, dyspnea, weight gain, pulmonary infiltrates, and pleural or pericardial effusions. Scrotal ulcerations due to ATRA are rare with 16 previously documented cases, most of whom were Asian. We report a Caucasian male with APML who developed scrotal ulceration during ATRA induction therapy and review the previously reported cases. Physicians and patients should be aware of this disturbing, but self-limited, dermatologic complication of ATRA."]
[15747784,0,0,0,0,2005,"Advances in understanding the biology and genetics of acute myelocytic leukemia.","McKenzie",15747784,"Advances in understanding the biology and genetics of acute myelocytic leukemia.    Abstract:   Acute myelocytic leukemia (AML) is a malignant neoplasm of hematopoietic cells characterized by an abnormal proliferation of myeloid precursor cells, decreased rate of self-destruction and an arrest in cellular differentiation. The leukemic cells have an abnormal survival advantage. Thus, the bone marrow and peripheral blood are characterized by leukocytosis with a predominance of immature cells, primarily blasts. As the immature cells accumulate in the bone marrow, they replace the normal myelocytic cells, megakaryocytes, and erythrocytic cells. This leads to a loss of normal bone marrow function and associated complications of bleeding, anemia, and infection. The incidence of AML increases with age, peaking in the sixth decade of life. In the United States, there are about 10,000 new cases of AML and 7,000 deaths in those with an AML diagnosis per year. Current molecular studies of AML demonstrate that it is a heterogeneous disorder of the myeloid cell lineage. This paper will discuss the most recent understanding and research of the cellular origin of AML and associated common genetic mutations that fuel the neoplastic process. Also discussed are how these advances have impacted the classification, selection of therapy, and definition of complete remission in AML. Promyelocytic leukemia will be discussed in detail as this AML subtype reveals how our understanding of the biology and genetics of the disease has led to targeted therapy that results in a cure in up to 80% of patients."]
[15708946,0,0,0,0,2005,"Psoriasis treatment: current and emerging directed therapies.","Winterfield",15708946,"Psoriasis treatment: current and emerging directed therapies.    Abstract:   Quality of life studies in patients with cutaneous psoriasis attest to its significant impact on day to day activities and personal social interactions. Up to 40% of patients with psoriasis may develop psoriatic arthritis, usually within 5-10 years after onset of the cutaneous disease, heightening quality of life issues. These data have prompted an increased awareness and interest in more aggressive management of psoriasis; coupled with a better understanding of immunopathogenesis, this has led to the development of new agents targeting specific cells and molecules involved in the development and maintenance of psoriatic plaques. Although non-biological therapies, including methotrexate and ciclosporin, show significant efficacy their side effect profiles have precluded their long term use for moderate to severe psoriasis. This review concentrates on new biological agents, focusing on the three agents approved for psoriasis within the past 18 months (alefacept, efalizumab, and etanercept). Phase II and III trial data on other agents in development (adalimumab and infliximab) are also presented. Surveys show many patients want to be treated more aggressively. It is hoped that the introduction of new agents that are more targeted and that hold the promise of fewer side effects will cause patients and their physicians to reconsider systemic treatment and, as a consequence, stimulate other patients to reconsider treatment for psoriasis. Close cooperation between dermatologists and rheumatologists, particularly in the area of psoriatic joint disease, will enhance these considerations."]
[15682880,0,0,0,0,2004,"Diffuse idiopathic skeletal hyperostosis: Forestiers disease.","Childs",15682880,"Diffuse idiopathic skeletal hyperostosis: Forestiers disease.    Abstract:   Diffuse idiopathic skeletal hyperostosis (DISH) or Forestiers disease is characterized by calcification and ossification of soft tissue entheses of ligaments and tendons. DISH is believed to be a variant of osteoarthritis (OA) without the degenerative intervertebral disc and joint degenerative qualities seen in classic OA. The likely pathoetiologic causes of DISH are presented."]
[15675886,11,0,0,11,2005,"Retinoid therapy for acne. A comparative review.","Chivot",15675886,"Retinoid therapy for acne. A comparative review.    Abstract:   Retinoids play a vital role in the treatment of acne because they act on the primary lesion, the microcomedo. They are synthetic derivatives of vitamin A (retinol), and are selected for their effectiveness. Several compounds are used for acne, either in topical or systemic form.We describe and compare the different topical retinoids, tretinoin (all-trans-retinoic acid), isotretinoin (13-cis-retinoic acid), adapalene (derived from naphthoic acid), and tazarotene (acetylenic retinoid). They act mainly as comedolytics, but anti-inflammatory actions have also been discovered recently. The retinoids have great beneficial effects, but also some adverse effects, the main one being teratogenicity. It is preferable not to use them in topical form for pregnant women, although a pregnancy test is only compulsory for tazarotene. Only isotretinoin is used in systemic form. It acts on all the factors of acne and offers long remissions, and sometimes complete cures. Precautions must be taken for women of childbearing age due to its teratogenicity. It is also important to be aware of its other adverse effects, explain them to the patient and, if possible, deal with them in advance."]
[15671709,9,0,0,9,2004,"Vitamin A intake and osteoporosis: a clinical review.","Crandall",15671709,"Vitamin A intake and osteoporosis: a clinical review.    Abstract:    BACKGROUND : If osteoporosis is linked with vitamin A (Vit A) A consumption, millions of people could be affected.  METHODS : A MEDLINE search was performed with keywords retinol, beta-carotene, and osteoporosis.  RESULTS : Of 20 clinical studies, 3 were randomized controlled trials (RCTs), 14 were observational studies, and 3 were case reports. Most (8) observational studies were cross-sectional. Oral retinoyl palmitate (RP) in high doses induces fractures and radiographic osteoporosis in animals. Retinol intake from diet or supplements is negatively associated with lumbar, femoral neck, and trochanter bone mineral density (BMD). There is a graded increase in relative risk of hip fracture with increasing retinol intake, attributable primarily to retinol (either from diet or supplements) but not beta-carotene intake. Higher serum retinol levels are associated with higher risk of any fracture and with higher risk of hip fracture, whereas there is no evidence of harm associated with beta-carotene intake. The few RCTs involve serum markers of bone metabolism, not bone density or fracture outcomes. Observational studies are generally consistent in finding harm from either dietary or supplemental retinol intake on BMD and hip fracture risk. Total Vit A intake is more important than source in determining harm. Adverse effects may occur at a level of retinol intake that is only about twice the current recommendation for adult females.  CONCLUSIONS : It is not yet possible to set a specific level of retinol intake above which bone health is compromised. Pending further investigation, Vit A supplements should not be used with the express goal of improving bone health."]
[15647709,2,0,0,2,2004,"Advances in diabetes for the millennium: vitamins and oxidant stress in diabetes and its complications.","Chertow",15647709,"Advances in diabetes for the millennium: vitamins and oxidant stress in diabetes and its complications.    Abstract:   Hyperinduced oxidant stress may have a role in the pathogenesis of diabetes and its micro- and macrovascular complications. Attaining euglycemia and the use of antioxidant vitamins could reduce oxidant stress and complications. In general, evidence does not support the use of supplements, and supplements are not recommended unless patients are deficient. Use of vitamins in excess may have adverse effects. Vitamin supplements are indicated in patients deficient in vitamins due to inadequate dietary intake or intestinal disease. Treatment with proper amounts of vitamins and antioxidants is best accomplished with a balanced diet including 3 servings of vegetables and 2 servings of fruits. Regarding supplementation of specific vitamins: carotene cannot be recommended in view of the possible harm and lack of benefit in clinical studies. Vitamin A (retinol) and Vitamin D should be repleted if deficient by laboratory assay. Excesses should be avoided. Vitamin A supplements, particularly in pregnancy, should not exceed 10,000 IU daily or a supplement should not exceed 25,000 units weekly. Vitamin E (alpha-tocopherol) alone in doses of 400 units is of questionable value, and larger doses may cause intracranial hemorrhage or interact negatively with lipid-lowering drugs. Vitamin E should not be used in patients who have bleeding disorders or patients on anticoagulants or acetylsalicylic acid (ASA). Vitamin C (ascorbic acid) losses in urine may be excessive in diabetic patients and may require repletion to 200 mg in nonsmokers and 250 mg in smokers. Further studies are needed testing: (1) vitamin supplementation in subgroups of patients at high risk for specific complications using tissue-specific indicators of oxidative stress; (2) the role of oxidative stress in nephropathy, diabetic myocardiopathy, dermopathy, joint limitation syndromes, peripheral edema, metabolic bone disease, and pregnancy; (3) the impact of renal failure on oxidative stress; and (4) the effects of diabetes and dietary vitamins on the relative amounts of retinoids, carotenoids, and vitamin E in the chylomicron and lipoproteins, and how this affects assimilation, oxidation of lipids, and atherosclerotic plaque formation."]
[15612519,1,0,0,1,2004,"[Peroxisome proliferator-activated receptors (PPARs) in obesity and insulin resistance development].","Alemán",15612519,"[Peroxisome proliferator-activated receptors (PPARs) in obesity and insulin resistance development].    Abstract:   The peroxisome proliferator-activated receptors (PPARs) are a family of nuclear transcription factors that belong to the steroid receptor superfamily. PPARs family includes PPARalpha, PPARbeta/delta, PPARgamma1 and PPARgamma2. PPARs form an heterodimer with the 9-cis retinoic acid receptor (RXR) and bind to response elements present in target genes activated by these transcription factors. PPARs control the expression of genes involved in fatty acid synthesis, oxidation and storage. PPARs are present in most tissues, where PPARalpha is most abundant in liver and skeletal muscle, whereas PPARgamma is found mainly in adipose tissue. Natural ligands for PPARs are polyunsaturated fatty acids (PUFAs) and some eicosanoids, however they are also activated by compounds such as fibrates and thiazolidinediones (TZDs). In this review is shown the different PPARs isoforms, identification, and regulation of their expression and activity. Also shows which are the natural ligands, and the chemical compounds that activate PPARs. Finally, it shows the target genes activated by the different isoforms of PPARs, the metabolic integration between the different PPAR isoforms to maintain a balance between fatty acid synthesis and oxidation and the association with the development of obesity and insulin resistance. Also shows information about the nutritional requirements of PUFAs that are the main natural ligands of PPARs."]
[15610503,1,0,0,1,2004,"Retinoids: inducers of tumor/growth suppressors.","Nagpal",15610503,"Retinoids: inducers of tumor/growth suppressors.    Abstract:  "]
[15584888,3,0,0,3,2004,"Recent advances in the mechanisms of action and physiological functions of the retinoid-related orphan receptors (RORs).","Jetten",15584888,"Recent advances in the mechanisms of action and physiological functions of the retinoid-related orphan receptors (RORs).    Abstract:   Retinoid-related orphan receptors ROR alpha, -beta, and -gamma are evolutionarily related transcription factors belonging to the steroid hormone receptor superfamily. Studies of ROR mutant mice revealed that these receptors are critical in the regulation of a number of physiological processes. ROR alpha plays a key role in the development of the cerebellum particularly in the regulation of Purkinje cell differentiation and proliferation of granule cell progenitors. ROR alpha has also been implicated in the maintenance of bone tissue and mice deficient in ROR alpha exhibit a greater susceptibility to atherosclerosis. ROR gamma is essential for lymph node organogenesis and plays a key role in the generation or survival of lymphoid tissue inducer (Lti) cells. ROR gamma is also critical in thymopoiesis where it controls differentiation and promotes the survival of thymocytes by positively regulating Bcl-X(L) expression. Several studies have indicated a regulatory role for RORs in circadian behavior. In several tissues, the expression of RORs oscillates during circadian rhythm while mice deficient in ROR beta exhibit an altered circadian rhythm. ROR alpha and ROR gamma have been implicated in the control of various immune responses. Mice deficient in ROR gamma exhibit a reduced susceptibility to allergen-induced airway inflammation while ROR alpha null mice show a prolonged inflammatory response to lipopolysaccharide. Recent analyses of the crystal structure and transcriptional activity of RORs revealed that cholesterol and specific cholesterol derivatives behave as agonists of ROR alpha while certain retinoids function as partial antagonists of ROR beta and ROR gamma. These studies indicate that ROR activity and, as a consequence physiological processes regulated by RORs, can be modulated by exogenous (ant)agonists. Therefore, the discovery of new (ant)agonists may lead to the development of novel therapeutic strategies for human disease in which RORs have been implicated."]
[15577021,0,0,0,0,2004,"[Vitamin K and bone quality].","Kishimoto",15577021,"[Vitamin K and bone quality].    Abstract:   Dietary vitamin K intakes becomes reduced with aging. Low vitamin K intakes are associated with an increased incidence of hip fractures and an increase of under carboxylated osteocalcin in elderly men and women. The increase of under carboxylated osteocalcin is a risk factor for fractures in osteoporosis. Vitamin K2 treatment is effective for the prevention of fractures, but not for the increase of bone mineral density in osteoporosis. Vitamin K2 administration could be a potential treatment to improve the bone quality."]
[15573865,7,0,0,7,2004,"Selective retinoic acid receptor ligands for rheumatoid arthritis.","Beehler",15573865,"Selective retinoic acid receptor ligands for rheumatoid arthritis.    Abstract:   Retinoids, modulators of retinoic acid receptors (RARs), have been studied for over 20 years as potential therapeutic agents for rheumatoid arthritis (RA). Early successes at the in vitro and in vivo levels were overshadowed by disappointing clinical trials that yielded poor efficacy and unacceptable side effects. A greater understanding of retinoid biology has led to the development of many synthetic retinoids that selectively modulate the RAR isotypes. RAR selective retinoids have a high potential for improved pharmacology with reduced toxicity, thereby renewing interest for the use of retinoids in RA."]
[15563242,3,0,0,3,2004,"Tamibarotene: AM 80, retinobenzoic acid, Tamibaro.","Beehler",15563242,"Tamibarotene: AM 80, retinobenzoic acid, Tamibaro.    Abstract:   Tamibarotene [AM 80, retinobenzoic acid, Amnoid, Tamibaro] is a novel synthetic retinoid that is in development with Nippon Shinyaku as a potential treatment for acute promyelocytic leukaemia (APL) and is pending approval in Japan. Tamibarotene was being developed by Shionogi in Japan but the company subsequently discontinued its involvement. Various nonindustrial sources, such as the University of Tokyo, Japan, have also played a role in the development of tamibarotene. Nippon Shinyaku has licensed the rights to tamibarotene from Toko Pharmaceutical Industries for the treatment of acute promyelocytic leukaemia, according to Nippon Shinyakus June 2004 pipeline update. However it is unclear when Toko Pharmaceutical Industries acquired rights to the compound."]
[15523196,2,0,0,2,2004,"Ocular manifestations of graft versus host disease.","Anderson",15523196,"Ocular manifestations of graft versus host disease.    Abstract:    PURPOSE OF REVIEW : A review of the current literature regarding the ocular manifestations and management of graft versus host disease is presented.  RECENT FINDINGS : A variety of systemic and topical anti-inflammatory or immunomodulatory agents, including prednisolone acetate, cyclosporine A, FK506, autologous serum, and retinoic acid show promise in controlling ocular graft versus host disease.  SUMMARY : Graft versus host disease is a common manifestation of allogeneic stem cell transplantation. Ocular manifestations are found in a majority of patients and may be the presenting symptom. Ocular findings include keratoconjunctivitis sicca, pseudomembranous conjunctivitis, corneal ulceration and perforation, and microvascular retinopathy. Systemic and local therapy may be used to control ocular disease."]
[15522654,1,0,0,1,2004,"New therapeutic approaches for adult T-cell leukaemia.","Bazarbachi",15522654,"New therapeutic approaches for adult T-cell leukaemia.    Abstract:   Adult T-cell leukaemia or lymphoma is an aggressive malignant disease of mature activated T cells caused by human T-cell lymphotropic virus type I. Patients with this disease have a very poor outlook because of intrinsic chemoresistance and severe immunosuppression. In acute adult T-cell leukaemia, clinical trials in Japan show that although non-targeted combinations of chemotherapy improve response, they do not have a significant effect on complete remission and survival. Antiretroviral therapy with combination zidovudine and interferon alfa, which induces a high rate of complete remission and lengthens survival, should be the first treatment option in acute adult T-cell leukaemia. Patients with adult T-cell lymphoma might benefit from initial aggressive chemotherapy followed by antiretroviral therapy. To prevent relapse in all patients allogeneic bone-marrow transplantation when feasible, or additional targeted therapy, should be mandatory. Based on current pathophysiology, we discuss promising new drugs such as arsenic trioxide, proteasome inhibitors, retinoids, and angiogenesis inhibitors, as well as cellular immunotherapy."]
[15380252,2,0,0,2,2004,"Retinoic acid signalling in the development of branchial arches.","Mark",15380252,"Retinoic acid signalling in the development of branchial arches.    Abstract:   Branchial arches develop through a complex sequence of interactions between migrating cells, derived from neural crest and mesoderm, and epithelia of ectodermal and endodermal origin, to yield a variety of derivatives, notably skeletal elements, arteries and glands. In all vertebrate species, dramatic malformations generated by experimental blocks or activations of retinoic acid signalling highlight key roles for this molecule in the endoderm for branchial arch formation and morphogenesis."]
[15374828,1,0,0,1,2005,"Peroxisome proliferator-activated receptors and cardiovascular remodeling.","Schiffrin",15374828,"Peroxisome proliferator-activated receptors and cardiovascular remodeling.    Abstract:   Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that heterodimerize with the retinoid X receptor and then modulate the function of many target genes. Three PPARs are known: alpha, beta/delta, and gamma. The better known are PPAR-alpha and PPAR-gamma, which may be activated by different synthetic agonists, although the endogenous ligands are unknown. PPAR-alpha is involved in fatty acid oxidation and expressed in the liver, kidney, and skeletal muscle, whereas PPAR-gamma is involved in fat cell differentiation, lipid storage, and insulin sensitivity. However, both have been shown to be present in variable amounts in cardiovascular tissues, including endothelium, smooth muscle cells, macrophages, and the heart. The activators of PPAR-alpha (fibrates) and PPAR-gamma (thiazolidinediones or glitazones) antagonized the actions of angiotensin II in vivo and in vitro and exerted cardiovascular antioxidant and anti-inflammatory effects. PPAR activators lowered blood pressure, induced favorable effects on the heart, and corrected vascular structure and endothelial dysfunction in several rodent models of hypertension. Activators of PPARs may become therapeutic agents useful in the prevention of cardiovascular disease beyond their effects on carbohydrate and lipid metabolism. Some side effects, such as weight gain, as well as documented aggravation of advanced heart failure through fluid retention by glitazones, may, however, limit their therapeutic application in prevention of cardiovascular disease."]
[15356647,1,0,0,1,2004,"Riddle: what do aplastic anemia, acute promyelocytic leukemia, and chronic myeloid leukemia have in common?","Brodsky",15356647,"Riddle: what do aplastic anemia, acute promyelocytic leukemia, and chronic myeloid leukemia have in common?    Abstract:   Secondary myelodysplastic syndrome (MDS)/acute leukemia frequently evolves from severe aplastic anemia (SAA) following immunosuppressive therapy. Secondary clonal cytogenetic abnormalities have now been reported after noncytotoxic therapy in two additional settings: all trans retinoic acid (ATRA) treatment of acute promyelocytic leukemia (APL) and imatinib for chronic myeloid leukemia (CML). We propose that SAA, APL, CML, and MDS represent different manifestations of generalized insults to the bone marrow. In SAA, the insult to hematopoietic progenitors leads to an immune attack, while in APL, CML, and MDS, it gives rise to the malignant clones. A primary insult to bone marrow could simultaneously lead to several abnormal hematopoietic cell clones, with one dominating and the others present but below the level of detection. Such a field leukemogenic effect would be analogous to the field cancerization effect described in solid tumors. Nonspecific cytotoxic therapies, including antileukemic chemotherapy and allogeneic transplantation, have broad activity that could inhibit both the overt disease and other undetectable coexistent abnormal clones. In contrast, disease-specific targeted therapy such as immunosuppressive therapy in aplastic anemia, ATRA in APL, or imatinib in CML would have no activity against other abnormal clones, allowing them to expand and become detectable as the dominant clone declines."]
[15320736,8,0,0,8,2004,"Retinoid-induced limb malformations.","Lee",15320736,"Retinoid-induced limb malformations.    Abstract:   The developing limb has been studied extensively and is a useful model to study morphogenesis. During embryogenesis, limb formation is initiated as a budding off from the embryonic lateral body wall. Limb pattern is specified by a series of epithelial-mesenchymal interactions, directing proximodistal, dorsoventral and anteroposterior axes. Vitamin A metabolites, especially retinoic acid, are known to play an important role in limb development, and the effects of retinoic acid may be mediated through the retinoid receptor signaling pathways. Accumulated evidence has shown that inadequate levels (excess or deficiency) of retinoic acid cause a wide range of limb malformations. Some species have the capacity to regenerate amputated limbs, and retinoids certainly affect this process, but there is debate regarding the extent that regeneration recapitulates development. In this review, phenotypic features, pathogenesis and the molecular basis of retinoid-induced limb malformations are discussed with a description of normal limb development and endogenous retinoid pathways."]
[15296972,0,0,0,0,2004,"The chick embryo: a leading model in somitogenesis studies.","Pourquié",15296972,"The chick embryo: a leading model in somitogenesis studies.    Abstract:   The vertebrate body is built on a metameric organization which consists of a repetition of functionally equivalent units, each comprising a vertebra, its associated muscles, peripheral nerves and blood vessels. This periodic pattern is established during embryogenesis by the somitogenesis process. Somites are generated in a rhythmic fashion from the presomitic mesoderm and they subsequently differentiate to give rise to the vertebrae and skeletal muscles of the body. Somitogenesis has been very actively studied in the chick embryo since the 19th century and many of the landmark experiments that led to our current understanding of the vertebrate segmentation process have been performed in this organism. Somite formation involves an oscillator, the segmentation clock whose periodic signal is converted into the periodic array of somite boundaries by a spacing mechanism relying on a traveling threshold of FGF signaling regressing in concert with body axis extension."]
[15293809,1,0,0,1,2004,"Exploring the mechanisms regulating regeneration of deer antlers.","Price",15293809,"Exploring the mechanisms regulating regeneration of deer antlers.    Abstract:   Deer antlers are the only mammalian appendages capable of repeated rounds of regeneration; every year they are shed and regrow from a blastema into large branched structures of cartilage and bone that are used for fighting and display. Longitudinal growth is by a process of modified endochondral ossification and in some species this can exceed 2 cm per day, representing the fastest rate of organ growth in the animal kingdom. However, despite their value as a unique model of mammalian regeneration the underlying mechanisms remain poorly understood. We review what is currently known about the local and systemic regulation of antler regeneration and some of the many unsolved questions of antler physiology are discussed. Molecules that we have identified as having potentially important local roles in antlers include parathyroid hormone-related peptide and retinoic acid (RA). Both are present in the blastema and in the rapidly growing antler where they regulate the differentiation of chondrocytes, osteoblasts and osteoclasts in vitro. Recent studies have shown that blockade of RA signalling can alter cellular differentiation in the blastema in vivo. The trigger that regulates the expression of these local signals is likely to be changing levels of sex steroids because the process of antler regeneration is linked to the reproductive cycle. The natural assumption has been that the most important hormone is testosterone, however, at a cellular level oestrogen may be a more significant regulator. Our data suggest that exogenous oestrogen acts as a brake, inhibiting the proliferation of progenitor cells in the antler tip while stimulating their differentiation, thus inhibiting continued growth. Deciphering the mechanism(s) by which sex steroids regulate cell-cycle progression and cellular differentiation in antlers may help to address why regeneration is limited in other mammalian tissues."]
[15264367,0,0,0,0,2004,"2003 Keio Medical Science Prize commemorative lecture. PPARs and the complex journey to obesity.","Evans",15264367,"2003 Keio Medical Science Prize commemorative lecture. PPARs and the complex journey to obesity.    Abstract:  "]
[15212235,0,0,0,0,2004,"[Recent advances in neuroblastoma research].","Imaizumi",15212235,"[Recent advances in neuroblastoma research].    Abstract:  "]
[15147236,3,0,0,3,2004,"1alpha,25-dihydroxyvitamin D3 inducible transcription factor and its role in the vitamin D action.","Nezbedova",15147236,"1alpha,25-dihydroxyvitamin D3 inducible transcription factor and its role in the vitamin D action.    Abstract:   Vitamin D is considered multifunctional steroid hormone that modulates calcium homeostasis through actions predominantly in kidney, bone and the intestinal tract. Nuclear vitamin D receptor (VDR) is a specific nuclear protein, a member of steroid hormone receptor superfamily. The amino acid sequence of the VDR shows a significant homology with other members of the nuclear hormone receptor superfamily, including receptors for glucocorticoids (GR), oestrogen (ER), androgen (AR), progesteron (PR), thyroid hormone (T3R), retinoic acid (RAR), retinoid X (RXR) and over 150 orphan receptors. VDR is known to mediate the pleiotropic biological actions of 1a,25-dihydroxyvitamin D3 through its ability to modulate the expression of target genes. VDR upon binding 1a,25-dihydroxyvitamin D3 regulates specific gene transcription predominantly by binding as a heterodimer with the retinoid X receptor (RXR) to DNA enhancer sequence, termed the vitamin D-responsive element (VDRE) that is present within the promoter region of vitamin D-controlled genes. The VDR has been shown to associate with several additional molecules to form the active transcriptional complex required for gene regulation. The regulation of this ligand-activated cellular transcription factor occurs at both transcriptional and posttranslational levels. This article summarizes a variety of effects of 1a,25-dihydroxyvitamin D3, acting through its cognate nuclear receptor, and its use in chemotherapy and chemoprevention of cancer."]
[15142970,0,0,0,0,2004,"Peroxisome proliferator-activated receptors and atherogenesis: regulators of gene expression in vascular cells.","Marx",15142970,"Peroxisome proliferator-activated receptors and atherogenesis: regulators of gene expression in vascular cells.    Abstract:   A large body of data gathered over the past couple of years has identified the peroxisome proliferator-activated receptors (PPAR) alpha, gamma, and beta/delta as transcription factors exerting modulatory actions in vascular cells. PPARs, which belong to the nuclear receptor family of ligand-activated transcription factors, were originally described as gene regulators of various metabolic pathways. Although the PPARalpha, gamma, and beta/delta subtypes are approximately 60% to 80% homologous in their ligand- and DNA-binding domains, significant differences in ligand and target gene specificities are observed. PPARalpha is activated by polyunsaturated fatty acids and oxidized derivatives and by lipid-modifying drugs of the fibrate family, including fenofibrate or gemfibrozil. PPARalpha controls expression of genes implicated in lipid metabolism. PPARgamma, in contrast, is a key regulator of glucose homeostasis and adipogenesis. Ligands of PPARgamma include naturally occurring FA derivatives, such as hydroxyoctadecadienoic acids (HODEs), prostaglandin derivatives such as 15-deoxyDelta12,14-prostaglandin J2, and glitazones, insulin-sensitizing drugs presently used to treat patients with type 2 diabetes. Ligands for PPARbeta/delta are polyunsaturated fatty acids, prostaglandins, and synthetic compounds, some of which are presently in clinical development. PPARbeta/delta stimulates fatty acid oxidation predominantly acting in muscle. All PPARs are expressed in vascular cells, where they exhibit antiinflammatory and antiatherogenic properties. In addition, studies in various animal models as well as clinical data suggest that PPARalpha and PPARgamma activators can modulate atherogenesis in vivo. At present, no data are available relating to possible effects of PPARbeta/delta agonists on atherogenesis. Given the widespread use of PPARalpha and PPARgamma agonists in patients at high risk for cardiovascular disease, the understanding of their function in the vasculature is not only of basic interest but also has important clinical implications. This review will focus on the role of PPARs in the vasculature and summarize the present understanding of their effects on atherogenesis and its cardiovascular complications."]
[15125707,5,0,0,5,2004,"Detection and treatment of minimal residual disease in high-risk neuroblastoma.","Reynolds",15125707,"Detection and treatment of minimal residual disease in high-risk neuroblastoma.    Abstract:   Intensive, myeloablative therapy supported by autologous hematopoietic stem-cell transplantation (AHSCT) has improved the outcome for children with high-risk neuroblastoma. However, gt;50% of patients develop recurrent neuroblastoma, often from minimal residual disease (MRD). Immunocytological and reverse transcriptase polymerase chain reaction (RT-PCR) for genes highly expressed in neuroblastoma both can detect small amounts of MRD in blood and bone marrow, and detection of MRD at certain levels during therapy has prognostic value. Radionucleotide scans using meta-iodobenzaguanidine (MIBG) imaging allows sensitive detection of neuroblastoma in patients, but whether or not all MIBG-positive disease detected after AHSCT will progress remains to be defined and is complicated by use of post-AHSCT therapy. Selective removal of tumor cells from marrow or blood stem cells harvested for AHSCT could decrease recurrence by preventing infusion of tumorigenic cells with AHSCT. Treating MRD after AHSCT with the differentiation-inducing retinoid 13-cis-retinoic acid significantly /improved EFS of high-risk neuroblastoma patients. Randomized clinical trials in the Childrens Oncology Group are testing the value of purging blood stem cells and also whether post-AHSCT therapy with an anti-GD2 monoclonal antibody (combined with cytokines) improves outcome over use of 13-cis-retinoic acid alone. New approaches to treating neuroblastoma MRD that are in early clinical trials include the cytotoxic retinoid fenretinide and the hu14.18-IL2 immunocytokine. It is anticipated that testing novel approaches to treating neuroblastoma MRD will be the subject of future phase-III randomized trials."]
[15103938,1,0,0,1,2004,"[Acute promyelocytic leukemia after living donor partial orthotopic liver transplantation].","Sato",15103938,"[Acute promyelocytic leukemia after living donor partial orthotopic liver transplantation].    Abstract:   We encountered a 12-year-old girl with acute promyelocytic leukemia (APL) that occurred 21 months after a living donor partial orthotopic liver transplantation from her father for ornithine transcarbamylase deficiency. FK-506 had been administered for prophylaxis against graft-versus-host reaction. The bone marrow specimen revealed a massive infiltration of promyelocytic blasts (M3 by FAB classification) with chromosome 46, XX, t (15; 17) (q22; q12), being the recipient origin. A PML/RAR alpha chimeric gene was detected by RT-PCR. The patient was diagnosed as having APL and successfully induced to complete remission by chemotherapy including daunorubicin (DNR), cytarabine (araC), and all-trans retinoic acid (ATRA). She has been in continuous remission for 12 months after the treatment. Leukemia after liver transplantation is generally taken as a rare complication. However, recent advances in the survival rate of patients who have undergone liver transplantation will lead to an increase of such cases."]
[15083599,1,0,0,1,2004,"Vitamin D analogs as therapeutic agents: a clinical study update.","Wu-Wong",15083599,"Vitamin D analogs as therapeutic agents: a clinical study update.    Abstract:   Vitamin D3 is modified by vitamin D3-25-hydroxylase in the liver and 25-hydroxyvitamin D3-1 alpha-hydroxylase in the kidney to form the active metabolite 1 alpha,25-dihydroxyvitamin D3. The binding of 1 alpha,25-dihydroxyvitamin D3 to the vitamin D receptor (VDR), a nuclear receptor, activates VDR to interact with retinoid X receptor (RXR) and form the VDR/RXR/co-factor complex, which binds to vitamin D response elements in the promoter region of target genes to regulate gene transcription. 1 alpha,25-dihydroxyvitamin D3 regulates the homeostasis of calcium and phosphorus, and also controls the expression of parathyroid hormone. Chronic renal disease is characterized by reduced synthesis of 1 alpha,25-dihydroxyvitamin D3, inadequate renal phosphate clearance and calcium imbalance, over-stimulation of the parathyroid gland, and increased parathyroid hormone synthesis. This secondary hyperparathyroidism (HPT) can cause renal osteodystrophy unless treated. Several vitamin D analogs are currently available or under investigation for the treatment of secondary HPT, psoriasis and osteoporosis. Additional clinical studies are being conducted for a variety of indications, including bone diseases, cell proliferation disorders and autoimmune diseases. Different vitamin D analogs seem to exhibit differential effects as exemplified by the survival benefit provided by paricalcitol over 1 alpha,25-dihydroxyvitamin D3 for end-stage renal disease patients on hemodialysis. Elucidation of the mechanism of action for the different vitamin D analogs will enhance our understanding of the vitamin D pathway and improve therapeutic uses of these analogs. This review discusses recent progress on the use of vitamin D and its analogs in the management of HPT secondary to chronic renal disease."]
[15082912,1,0,0,1,2004,"Meningeal relapse in a patient with acute promyelocytic leukemia: a case report and review of the literature.","Bae",15082912,"Meningeal relapse in a patient with acute promyelocytic leukemia: a case report and review of the literature.    Abstract:   The involvement of central nervous system is rare in acute promyelocytic leukemia (APL). We report a APL patient of a 41 yr-old Korean male who presented with fever and petechia. Complete molecular remission was achieved with all-trans retinoic acid (ATRA), idarubicin, and cytarabine. Ten months later, he complained of a mild headache. The results of the physical examination and the complete blood counts were normal. The examination of cerebrospinal fluid showed the presence of promyelocyte. Bone marrow studies showed cytogenetic remission but with molecular relapse. He was treated with intrathecal and systemic chemotherapy."]
[15080368,1,0,0,1,2004,"Vitamin A supplementation and risk of skeletal fracture.","Genaro",15080368,"Vitamin A supplementation and risk of skeletal fracture.    Abstract:   Effects of toxic amounts of vitamin A include skeletal effects; from acute toxic exposure to chronic high-dose intake of vitamin A, these effects have led experts to speculate that long-term consumption of diets high in vitamin A (retinol) stimulates bone resorption and inhibits bone formation, and may contribute to osteoporosis and hip fractures."]
[15056048,3,0,0,3,2004,"Bexarotene: a clinical review.","Farol",15056048,"Bexarotene: a clinical review.    Abstract:   Bexarotene (Targretin, Ligand Pharmaceuticals Inc.) is a synthetic retinoid analog with specific affinity for the retinoid X receptor and belongs to a group of compounds called rexinoids. Early clinical trials of this drug demonstrated activity in cutaneous T-cell lymphoma. Subsequent Phase II/III trials have demonstrated a greater than 50% response rate in patients with all stages of cutaneous T-cell lymphoma who were refractory or intolerant to the previous therapy. The principal toxicities of bexarotene include central hypothyroidism, xeroderma and elevation of cholesterol and triglycerides. These toxicities can be managed with dose attenuation or addition of atorvastatin (Lipitor, Pfizer) or fenofibrate (TriCor, Abbott Laboratories). Since bexarotene has little bone marrow toxicity, it is an excellent candidate for combination therapy with other modalities useful in the treatment of cutaneous T-cell lymphoma. These include ultraviolet B irradiation, psoralen and ultraviolet A photochemotherapy, interferons, denileukin diftitox (Ontak, Ligand Pharmaceuticals Inc.) and cytotoxic chemotherapy. Bexarotene has also been investigated in the treatment of breast cancer and non-small cell carcinoma of the lung with promising early results."]
[15018484,0,0,0,0,2003,"Is vitamin A consumption a risk factor for osteoporotic fracture?","Barker",15018484,"Is vitamin A consumption a risk factor for osteoporotic fracture?    Abstract:   Severe vitamin A toxicity is known to have adverse effects on skeletal health. Studies involving animal models and case reports have documented that hypervitaminosis A is associated with bone resorption, hypercalcaemia and bone abnormalities. More recently, some epidemiological studies have suggested that high habitual intake of vitamin A could contribute to low bone mineral content and fracture risk. The evidence relating to the possible deleterious role of vitamin A in bone health is of variable quality and is potentially confounded by collinearity of nutrient intake and difficulties in assessing vitamin A exposure. Furthermore, because intake of vitamin A varies between studies it is not possible to define an intake threshold associated with harm."]
[14993931,1,0,0,1,2004,"The role of cathepsin K in normal bone resorption.","Troen",14993931,"The role of cathepsin K in normal bone resorption.    Abstract:   Cathepsin K is essential for normal bone resorption; humans lacking cathepsin K exhibit pycnodysostosis, which is characterized by short stature and osteosclerosis. Cathepsin K knockout mice develop osteopetrosis and display features characteristic of pycnodysostosis, and osteoclasts isolated from these mice exhibit impaired bone resorption in vitro. Bone resorption depends upon the synthesis of cathepsin K by osteoclasts and its secretion into the extracellular compartment at the attachment site between osteoclasts and the bone surface, wherein the organic matrix is subsequently degraded by cathepsin K. Factors that directly modulate osteoclastic bone resorption, including cytokines (RANK ligand, tumor necrosis factor-alpha and interferon gamma), hormones (retinoic acid and estrogen) and nuclear transcriptional factors (c-jun and Mitf) also regulate cathepsin K gene expression. Osteoporosis is one of the leading causes of morbidity in the elderly and is characterized by a persistent excess of osteoclastic bone resorption. Therefore, cathepsin K is an attractive target for therapeutic intervention to prevent and ameliorate the significant deleterious impact of osteoporosis."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I325,I325)","v":14979475},{"$f":"(LEN($J325) - LEN(SUBSTITUTE(LOWER($J325),LOWER(B$3),\"\")))/LEN(B$3)","v":1},0,0,{"$f":"SUM(B325:D325)","v":1},2004,"Acute promyelocytic leukemia during pregnancy: report of 3 cases.","Consoli",14979475,"Acute promyelocytic leukemia during pregnancy: report of 3 cases.    Abstract:   Acute promyelocytic leukemia (APL) is characterized by onset at a young age and a life-threatening hemorrhagic diathesis, which is attributed to a disseminated intravascular coagulation (DIC)-like coagulopathy. The discovery of all-trans-retinoic acid has changed the course of APL treatment by reducing the onset of DIC and inducing a complete and durable remission in more than 90% of patients. The occurrence of APL during pregnancy is not a frequent event, but the management of these patients raises many therapeutic and ethical dilemmas and requires a careful clinical case evaluation of fetal and maternal risk, coagulation status, the parents wishes, and therapeutic options. Here we describe 3 patients with APL diagnosed during pregnancy. Clinical data and the therapeutic approaches are presented. In the discussion, we analyze clinical decisions and therapeutic options and compare our cases with those found in the literature."]
[14768094,2,0,0,2,2004,"[Basic research and clinical application of cartilage-derived retinoic acid-sensitive protein].","Liu",14768094,"[Basic research and clinical application of cartilage-derived retinoic acid-sensitive protein].    Abstract:    OBJECTIVE : To know the basic research and the clinical application of cartilage-derived retinoic acid-sensitive protein (CD-RAP) in orthopedic and in other clinical fields.  METHODS : The literature related to CD-RAP in basic research and clinical application were extensively reviewed.  RESULTS : CD-RAP, as a protein, which is cartilage-specific, could be a marker of the joint diseases. It also can be used to monitor metastasis of melanoma.  CONCLUSION : CD-RAP test provides a new way to study repair of cartilage and metastasis of melanoma."]
[14766352,1,0,0,1,2004,"Gene expression and regulation of hindbrain and spinal cord development.","Melton",14766352,"Gene expression and regulation of hindbrain and spinal cord development.    Abstract:   The formation of the central nervous system is one of the most fascinating processes in biology. Motor coordination, sensory perception and memory all depend on the complex cell connections that form with extraordinary precision between distinct nerve cell types within the central nervous system. The development of the central nervous system and its intricate connections occurs in several steps. During the first step known as neural induction, the neural plate forms as a uniform sheet of neuronal progenitors. Neural induction is followed by neurulation, the process in which the two halves of the neural plate are transformed into a hollow tube. Neurulation is accompanied by regionalisation of the neural tube anterior-posteriorly into the brain and spinal cord and dorso-ventrally into neural crest cells and numerous classes of sensory and motor neurons. The proper development of the vertebrate central nervous system requires the precise, finely balanced control of cell specification and proliferation, which is achieved through the complex interplay of multiple signaling systems. Bone morphogenetic proteins (BMPs), retinoic acid (RA) fibroblast growth factors (FGFs), Wnt and Hedgehog proteins are a few key factors that interact to pattern the developing central nervous system. In this review, we detail our current knowledge of the roles of these signaling factors in the development of the vertebrate nervous system in terms of the mechanisms underlying the formation and specification of the hindbrain and spinal cord."]
[14754643,7,0,0,7,2004,"Single-center retrospective study of long-term use of low-dose acitretin (Soriatane) for psoriasis.","Lee",14754643,"Single-center retrospective study of long-term use of low-dose acitretin (Soriatane) for psoriasis.    Abstract:    BACKGROUND : Indicated as monotherapy for severe psoriasis in adults, acitretin (Soriatane) can be used in combination therapy or as a disease-stabilizing, maintenance agent. While its efficacy for psoriasis and other disorders of keratinization is well established, its safety is often a concern for many dermatologists. The possible side effects associated with short-term treatment of oral retinoids include mucocutaneous effects, elevation in serum lipid chemistries and liver enzymes, and teratogenicity. However, the only possible long-term, cumulative side effect is skeletal and ligamentous calcification such as hyperostosis. There is a specific syndrome of hyperostosis associated with oral retinoids called DISH (diffuse idiopathic skeletal hyperostosis).  OBJECTIVE : To examine the incidence of DISH syndrome in long-term acitretin use for psoriasis and to quantify the incidence of other side effects.  METHODS : All patients seen at the UCSF Psoriasis and Skin Treatment Center who had been on acitretin for more than 1 year were identified.  RESULTS : A chart review of these patients revealed no X-ray-confirmed cases of DISH syndrome, minimal changes in coronary heart disease risk indicators, and extremely rare significant elevation of liver enzymes.  CONCLUSION : Acitretin does not appear to cause significant long-term side effects at low doses; the implications for thousands of patients are that use of this medication can be continued for long periods of time with routine monitoring."]
[14751813,1,0,0,1,2004,"The quot;CholesteRORquot; protective pathway in the vascular system.","Boukhtouche",14751813,"The quot;CholesteRORquot; protective pathway in the vascular system.    Abstract:   Retinoic acid receptor-related Orphan Receptor alpha (RORalpha) is a member of the nuclear hormone receptor superfamily. RORalpha has long been considered as a constitutive activator of transcription in the absence of exogenous ligand; however, cholesterol has recently been identified as a natural ligand of RORalpha. The spontaneous staggerer (sg/sg) mutation is a deletion in the Rora gene that prevents the translation of the ligand-binding domain (LBD), leading to the loss of RORalpha activity. The homozygous Rora(sg/sg) mutant mouse, of which the most obvious phenotype is ataxia associated with cerebellar degeneration, also displays a variety of other phenotypes, including several vascular ones; in particular, dysfunction of smooth muscle cells and enhanced susceptibility to atherosclerosis. Moreover, RORalpha appears to participate in the regulation of plasma cholesterol levels, and has been shown to positively regulate apolipoprotein (apo)A-I and apoC-III gene expression. Yet its activity is regulated by cholesterol itself, making RORalpha an intracellular cholesterol target."]
[14749265,1,0,0,1,2004,"The biology of peroxisome proliferator-activated receptors: relationship with lipid metabolism and insulin sensitivity.","Ferré",14749265,"The biology of peroxisome proliferator-activated receptors: relationship with lipid metabolism and insulin sensitivity.    Abstract:   Peroxisome proliferator-activated receptors (PPARs) are transcription factors belonging to the superfamily of nuclear receptors. Three isoforms (alpha, delta, and gamma) have been described. They act on DNA response elements as heterodimers with the nuclear retinoic acid receptor. Their natural activating ligands are fatty acids and lipid-derived substrates. PPAR-alpha is present in liver, heart, and, to a lesser extent, skeletal muscle. When activated, it promotes fatty acid oxidation, ketone body synthesis, and glucose sparing. Fibrates, which are used as hypolipidemic drugs, are ligands of PPAR-alpha. PPAR-delta is ubiquitous and could also favor fatty acid oxidation in tissues in which PPAR-alpha is absent or less expressed. PPAR-gamma is expressed in adipose tissue, lower intestine, and cells involved in immunity. Activation of PPAR-gamma induces the differentiation of preadipocytes into adipocytes and stimulates triglyceride storage. Thiazolidinediones are compounds used as hypoglycemic, muscle insulin-sensitizing agents in type 2 diabetes. Unexpectedly, they are activators of PPAR-gamma. Their action on muscle insulin sensitivity may be secondary to the lowering of circulating lipids on PPAR-gamma activation and to the secretion by adipocytes of insulin-sensitizing hormones such as adiponectin, all promoting glucose utilization. The PPARs are thus major regulators of lipid and glucose metabolism, allowing adaptation to the prevailing nutritional environment."]
[14738139,8,0,0,8,2003,"Hematopoiesis and retinoids: development and disease.","Oren",14738139,"Hematopoiesis and retinoids: development and disease.    Abstract:   Retinoids function as activating ligands for a class of nuclear receptors that control gene expression programs for a wide range of tissues and organs during embryogenesis and throughout life. Over the years, three sets of observations have spurred interest in the function of retinoids with respect to development and disease of hematopoietic cells. Since the 1920s, epidemiological studies indicated altered hematopoiesis in vitamin A-deficient (VAD) human populations. More recently, the ability of retinoids to affect various aspects of hematopoietic development has been demonstrated in vitro. Finally, it was discovered that the gene encoding a retinoid receptor is a key target for chromosomal translocations that cause acute promyelocytic leukemia (APL). More recent investigations using targeted gene disruptions, VAD animal models, and mouse models of leukemia have continued to shed light on the function of the retinoid pathway in blood cells. It is now clear that retinoids are required for normal hematopoiesis during both yolk sac and fetal liver stages of hematopoiesis, while the pathway has at least modulatory functions for bone marrow derived progenitors. Studies of normal development and APL have provided complementary insight into the molecular control of blood cell differentiation. Here we review the evidence for retinoid requirements in hematopoiesis and also summarize current ideas regarding how this pathway is subverted in leukemia."]
[14730505,1,0,0,1,2004,"Vitamin D receptor and analogs.","Dusso",14730505,"Vitamin D receptor and analogs.    Abstract:   In chronic kidney disease (CKD), high circulating levels of parathyroid hormone (PTH) cause osteitis fibrosa, bone loss, and cardiovascular complications that increase morbidity and mortality. Impaired production of 1,25-dihydroxyvitamin D (calcitriol), the hormonal form of vitamin D, is a major contributor to the generation and maintenance of parathyroid hyperplasia and increased synthesis and secretion of PTH. Calcitriol inhibits PTH gene transcription and ameliorates parathyroid hyperplasia by suppressing the expression of and growth signals from the autocrine transforming growth factor alpha (TGFalpha)/epidermal growth factor receptor (EGFR)-growth loop, a main determinant of parathyroid cell proliferation. Calcitriol reduction of parathyroid hyperplasia and serum PTH levels demands a functional vitamin D receptor (VDR). Although VDR is normal in CKD, parathyroid VDR content is reduced markedly. Furthermore, VDR function, as a transcriptional regulator of vitamin D responsive genes, is impaired by several factors including hypocalcemia, hyperphosphatemia, accumulation of uremic toxins, and reduction in cellular levels of the VDR partner, retinoid X receptor. Therapy with calcitriol analogs can overcome the antagonism on calcitriol-VDR actions induced by CKD. Although not all analog formulations are equally effective, they offer a wider therapeutic window in counteracting vitamin D resistance and survival advantage over exclusive calcitriol therapy."]
[14710892,11,0,0,11,2003,"Topical and systemic retinoid therapy for cutaneous T-cell lymphoma.","Kempf",14710892,"Topical and systemic retinoid therapy for cutaneous T-cell lymphoma.    Abstract:   Because curative therapies for CTCL are not yet available, short of TSEB in patients who have early-stage disease and allogeneic bone marrow transplantation in patients who have more advanced disease, the goal of current therapies is to prevent progression of MF and to preserve quality of life. The overall conclusion drawn from the studies reported in the literature, is that retinoids as monotherapy, or in combination with other nonaggressive treatment modalities, represent a low-risk treatment alternative that is especially suitable for controlling early stages of MF and other CTCL. A combination of therapies may be more effective in controlling CTCL as shown with IFN-alpha plus retinoids, and, recently, IFN-alpha with bexarotene and other modalities. For example, isotretinoin, followed by TSEB (for stage I to II disease) or preceded by chemotherapy (for stage II and IV disease) and bexarotene plus PUVA or photopheresis plus IFN, gave overall response rates of 82% and 69% in patients who had MF and SS, respectively. Retinoids as monotherapy may induce complete remissions, but usually these responses are of short duration and relapses are common. Clinical response is not identical to histologic clearance. Even in cases with clinically complete clearance of skin lesions, lymphoid infiltrates persisted, which are most likely the source of recurrences. The new generation of retinoids, the RXR selective agonists like bexarotene, represent a promising approach for refractory or persistent MF that is unresponsive to first-line therapies. Individual differences in response to retinoids may be due to different expression of retinoid receptors, functional polymorphisms in metabolizing retinoids, or resistance to some retinoids. In the future, pharmacogenomic studies are needed to clarify the mechanisms that underlie the differing response rates of patients who have CTCL to retinoids. In addition, new agonists of RAR and RXR, either selective or pan agonists, will become available and will enlarge the spectrum of vitamin A analogs that have antitumoral properties."]
[14659462,1,0,0,1,2003,"The molecular basis of retinoid action in tumors.","Merino",14659462,"The molecular basis of retinoid action in tumors.    Abstract:  "]
[14631893,1,0,0,1,2003,"[Population genetic correlation of vitamin D receptor polymorphisms with clinical disorders].","Gyórffy",14631893,"[Population genetic correlation of vitamin D receptor polymorphisms with clinical disorders].    Abstract:   Calcitriol, the active metabolite of Vitamin D (1,25(OH)2D3) has several major roles in the body: hormonal regulation of calcium and phosphate-homeostasis, regulation of parathormone synthesis and modulation of the immune and endocrine systems. Due to its antiproliferative effects it also plays a role in tumour development. The calcitriol can have these differential effects as it is modulating gene expression in the cell nucleus. The effects of vitamin D are mediated by the nuclear vitamin D receptor, which heterodimerizes with the retinoid X receptor and changes gene transcription. Until now 5 single nucleotide polymorphisms of the vitamin D receptor gene have been identified. This review summarizes the identified effects of vitamin D receptor polymorphisms on bone homeostasis, on the parathyroid function, on diversal tumours and on diabetes."]
[14623515,1,0,0,1,2003,"Sources of estrogen and their importance.","Simpson",14623515,"Sources of estrogen and their importance.    Abstract:   In premenopausal women, the ovaries are the principle source of estradiol, which functions as a circulating hormone to act on distal target tissues. However, in postmenopausal women when the ovaries cease to produce estrogen, and in men, this is no longer the case, because estradiol is no longer solely an endocrine factor. Instead, it is produced in a number of extragonadal sites and acts locally at these sites as a paracrine or even intracrine factor. These sites include the mesenchymal cells of adipose tissue including that of the breast, osteoblasts and chondrocytes of bone, the vascular endothelium and aortic smooth muscle cells, and numerous sites in the brain. Thus, circulating levels of estrogens in postmenopausal women and in men are not the drivers of estrogen action, they are reactive rather than proactive. This is because in these cases circulating estrogen originates in the extragonadal sites where it acts locally, and if it escapes local metabolism then it enters the circulation. Therefore, circulating levels reflect rather than direct estrogen action in postmenopausal women and in men. Tissue-specific regulation of CYP19 expression is achieved through the use of distinct promoters, each of which is regulated by different hormonal factors and second messenger signaling pathways. Thus, in the ovary, CYP19 expression is regulated by FSH which acts through cyclic AMP via the proximal promoter II, whereas in placenta the distal promoter I.1 regulates CYP19 expression in response to retinoids. In adipose tissue and bone by contrast, another distal promoter--promoter I.4--drives CYP19 expression under the control of glucocorticoids, class 1 cytokines and TNFalpha. The importance of this unique aspect of the tissue-specific regulation of aromatase expression lies in the fact that the low circulating levels of estrogens which are observed in postmenopausal women have little bearing on the concentrations of estrogen in, for example, a breast tumor, which can reach levels at least one order of magnitude greater than those present in the circulation, due to local synthesis within the breast. Thus, the estrogen which is responsible for breast cancer development, for the maintenance of bone mineralization and for the maintenance of cognitive function is not circulating estrogen but rather that which is produced locally at these specific sites within the breast, bone and brain. In breast adipose of breast cancer patients, aromatase activity and CYP19 expression are elevated. This occurs in response to tumor-derived factors such as prostaglandin E2 produced by breast tumor fibroblasts and epithelium as well as infiltrating macrophages. This increased CYP19 expression is associated with a switch in promoter usage from the normal adipose-specific promoter I.4 to the cyclic AMP responsive promoter, promoter II. Since these two promoters are regulated by different cohorts of transcription factors and coactivators, it follows that the differential regulation of CYP19 expression via alternative promoters in disease-free and cancerous breast adipose tissue may permit the development of selective aromatase modulators (SAMs) that target the aberrant overexpression of aromatase in cancerous breast, whilst sparing estrogen synthesis in other sites such as normal adipose tissue, bone and brain."]
[14619450,0,0,0,0,2003,"[Cure of adult acute myeloblastic leukemia].","Uzuka",14619450,"[Cure of adult acute myeloblastic leukemia].    Abstract:   Despite major recent advances in the understanding of the molecular biology of adult acute myeloblastic leukemia(AML), the treatment of the disease remains challenging. This review summarizes literature in the field of curative chemotherapy for adult acute myeloblastic leukemia(AML). In particular, detailed analysis of curing leukemia in patients treated with risk-oriented chemotherapy and in patients with APL was presented. In addition, results using our curative chemotherapy approach for adult AML were reported. Lastly, future directions for curing adult AML were discussed."]
[14606365,2,0,0,2,2003,"Management of mycosis fungoides: Part 2. Treatment.","Smith",14606365,"Management of mycosis fungoides: Part 2. Treatment.    Abstract:   Mycosis fungoides is a low-grade lymphoproliferative disorder of skin-homing CD4+ lymphocytes that may produce patches, plaques, tumors, erythroderma, and, ultimately, systemic dissemination. Treatment selection is generally guided by institutional experience, patient preference, and toxicity profile, as data from phase III clinical trials are limited. Effective topical treatments currently include mechlorethamine (Mustargen), carmustine (BCNU, BiCNU), corticosteroids, bexarotene (Targretin, a novel rexinoid), psoralen plus ultraviolet A, ultraviolet B, and total-skin electron-beam radiotherapy. Effective systemic treatments include interferon, retinoids, bexarotene, denileukin diftitox (Ontak), extracorporeal photopheresis, chemotherapy, and high-dose chemotherapy with allogeneic bone marrow transplant. Each of these treatments is discussed in detail, followed by specific recommendations for each stage of mycosis fungoides."]
[14561188,1,0,0,1,2002,"Peroxisome proliferator-activated receptors and the control of inflammation.","Cabrero",14561188,"Peroxisome proliferator-activated receptors and the control of inflammation.    Abstract:   Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors which form a subfamily of the nuclear receptor gene family. This subfamily consists of three isotypes, alpha (NR1C1), gamma (NR1C3), and beta/delta (NRC1C2) with a differential tissue distribution. PPARalpha is expressed primarily in tissues with a high level of fatty acid catabolism such as liver, brown fat, kidney, heart and skeletal muscle. PPARbeta is ubiquitously expressed, and PPARgamma has a restricted pattern of expression, mainly in white and brown adipose tissues, whereas other tissues such as skeletal muscle and heart contain limited amounts. Furthermore, PPARalpha and gamma isotypes are expressed in vascular cells including endothelial and smooth muscle cells and macrophages/foam cells. PPARs are activated by ligands, such as naturally occurring fatty acids, which are activators of all three PPAR isotypes. In addition to fatty acids, several synthetic compounds, such as fibrates and thiazolidinediones, bind and activate PPARalpha and PPARgamma, respectively. In order to be transcriptionally active, PPARs need to heterodimerize with the retinoid-X-receptor (RXR). Upon activation, PPAR-RXR heterodimers bind to DNA specific sequences called peroxisome proliferator-response elements (PPRE) and stimulate transcription of target genes. PPARs play a critical role in lipid and glucose homeostasis, but lately they have been implicated as regulators of inflammatory responses. The first evidence of the involvement of PPARs in the control of inflammation came from the PPARalpha null mice, which showed a prolonged inflammatory response. PPARalpha activation results in the repression of NF-kappaB signaling and inflammatory cytokine production in different cell-types. A role for PPARgamma in inflammation has also been reported in monocyte/macrophages, where ligands of this receptor inhibited the activation of macrophages and the production of inflammatory cytokines (TNFalpha, interleukin 6 and 1beta), although part of the anti-inflammatory effects of these ligands seems to be mediated by a mechanism not involving PPARgamma. All these findings suggest a role of PPARs in the control of the inflammatory response with potential therapeutic applications in inflammation-related diseases."]
[14521567,3,0,0,3,2003,"Isotretinoin treatment of acne in a patient with Apert syndrome.","Gilaberte",14521567,"Isotretinoin treatment of acne in a patient with Apert syndrome.    Abstract:   Apert syndrome is an autosomal dominant disease caused by mutations in fibroblast growth factor receptor (FGFR-2) and characterized by premature fusion of the cranial sutures and early epiphyseal closure. The development of widespread, severe, pustular acne around puberty is a characteristic feature in these patients. The FGFR-2 mutation of Apert syndrome has been described in localized nevoid acne lesions, which have been attributed to somatic mosaicism. Isotretinoin has been reported to be useful in controlling this acne. We report the successful treatment of acne with isotretinoin in a teenager with Apert syndrome and review the pathophysiology of acne in this syndrome."]
[14521561,3,1,0,4,2003,"Harlequin ichthyosis in association with hypothyroidism and juvenile rheumatoid arthritis.","Chan",14521561,"Harlequin ichthyosis in association with hypothyroidism and juvenile rheumatoid arthritis.    Abstract:   Harlequin ichthyosis is a rare and severe congenital erythrodermic ichthyosis characterized at birth by hyperkeratotic plates covering the entire body, ectropion, eclabium, poorly developed ears, and contractures of the hands and feet. Two Chinese children, a 2-year-old boy and an 11-year-old girl, presented with these classic features as well as alopecia and loss of eyebrows and eyelashes. The boy was small for his age and was found to have hypothyroidism at the age of 18 months; he is currently on thyroxine replacement therapy. At 6 years of age, the girl developed symmetrical polyarthritis associated with positive rheumatoid factor and radiologic evidence of erosive arthritis, suggestive of juvenile rheumatoid arthritis. She received prednisolone, nonsteroidal anti-inflammatory drugs (NSAIDs), and subsequently methotrexate for her arthritis, with clinical and radiologic improvement. Early therapy with oral retinoids in both children accelerated shedding of the hyperkeratotic plates as well as improved ectropion and eclabium. There was no major adverse reaction to oral retinoids. The development of juvenile rheumatoid arthritis in survivors with harlequin ichthyosis has not been previously described. The use of prednisolone and NSAIDs in the girl did not affect the skin condition, but the addition of methotrexate led to a decrease in erythema. The association with autoimmune disease is probably coincidental. The psychosocial impact of this severe lifelong disease on the two families was enormous. Early retinoid therapy may improve the disorder and help increase survival rates. A multidisciplinary approach, including psychosocial support of the affected families, is vital in the management of this lifelong disease."]
[12972706,2,0,0,2,2003,"Treatment of relapsed acute promyelocytic leukemia.","Lengfelder",12972706,"Treatment of relapsed acute promyelocytic leukemia.    Abstract:   By all-trans retinoic acid (ATRA) and chemotherapy over 70% of patients with newly diagnosed acute promyelocytic leukemia (APL) may be cured; 20-30% of patients still relapse and require salvage therapy. For relapsed or refractory APL, a standard treatment has not yet been defined. However, several effective drugs and approaches have been described. Treatment options for relapsed APL include chemotherapy regimens used in the treatment of relapsed acute myeloid leukemia usually combined with ATRA or of other differentiating agents such as liposomal ATRA or synthetic retinoids. Presently, allogeneic peripheral stem cell or bone marrow transplantation is the treatment of choice for younger patients who have a histocompatible donor, as it gives the chance of cure in second or further relapse. For patients without a donor or for those who are not suitable for allogeneic transplantation, autologous stem cell or bone marrow transplantation may offer at least the possibility of a prolongation of remission, if the harvested cells are negative in the RT-PCR of PML/RAR alpha. Arsenic compounds have a high antileukemic effectiveness on APL cells. Arsenic trioxide has recently been approved for relapsed or refractory APL. With this drug, complete hematologic remission rates of 80-92% and long-lasting molecular remissions were achieved in relapsed patients. For patients who do not qualify for these treatment options, monoclonal anti-CD33 antibodies may represent further treatment options."]
[12955859,9,0,0,9,2003,"Revisiting the role of retinoid signaling in skeletal development.","Weston",12955859,"Revisiting the role of retinoid signaling in skeletal development.    Abstract:   Several years ago, it was discovered that an imbalance of vitamin A during embryonic development has dramatic teratogenic effects. These effects have since been attributed to vitamin As most active metabolite, retinoic acid (RA), which itself profoundly influences the development of multiple organs including the skeleton. After decades of study, researchers are still uncovering the molecular basis whereby retinoids regulate skeletal development. Retinoid signaling involves several components, from the enzymes that control the synthesis and degradation of RA, to the cytoplasmic RA-binding proteins, and the nuclear receptors that modulate gene transcription. As new functions for each component continue to be discovered, their developmental roles appear increasingly complex. Interestingly, each component has been implicated in skeletal development. Moreover, retinoid signaling comes into play at distinct stages throughout the developmental sequence of skeletogenesis, highlighting a fundamental role for this pathway in forming the adult skeleton. Consistent with these roles, manipulation of the retinoid signaling pathway significantly affects the expression of the skeletogenic master regulatory factors, Sox9 and Cbfa1. In addition to the fact that we now have a greater understanding of the retinoid signaling pathway on a molecular level, much more information is now available to begin placing retinoid signaling within the context of other factors that regulate skeletogenesis. Here we review these recent advances and describe our current understanding of how retinoid signaling functions to coordinate skeletal development. We also discuss future directions and clinical implications in this field."]
[12938166,0,0,0,0,2003,"Skeletal muscle metabolism in physiology and in cancer disease.","Giordano",12938166,"Skeletal muscle metabolism in physiology and in cancer disease.    Abstract:   Skeletal muscle is a tissue of high demand and it accounts for most of daily energy consumption. The classical concept of energy metabolism in skeletal muscle has been profoundly modified on the basis of studies showing the influence of additional factors (i.e., uncoupling proteins (UCPs) and peroxisome proliferator activated receptors (PPARs)) controlling parameters, such as substrate availability, cellular enzymes, carrier proteins, and proton leak, able to affect glycolysis, nutrient oxidation, and protein degradation. This extremely balanced system is greatly altered by cancer disease that can induce muscle cachexia with significant deleterious consequences and results in muscle wasting and weakness, delaying or preventing ambulation, and rehabilitation in catabolic patients."]
[12894062,7,0,0,7,2003,"Oral retinoid therapy for dermatologic conditions in children and adolescents.","Brecher",12894062,"Oral retinoid therapy for dermatologic conditions in children and adolescents.    Abstract:   The efficacy of systemic retinoid therapy in a number of dermatologic diseases is well established; however, concerns about potential side effects limit their use, especially in children. We review the efficacy and toxicity of oral retinoids in the pediatric population. The acute mucocutaneous toxicities commonly observed are typically well tolerated, readily treatable, and reversible. Systemic toxicities include teratogenicity and effects on the musculoskeletal, neurologic, and gastrointestinal systems. Children, like adults, generally tolerate short-term retinoid therapy without major complications. Concerns regarding serious systemic side effects are greater for those on high doses of oral synthetic retinoids for longer periods of time. Close patient monitoring and patient education can minimize the occurrence of complications. (J Am Acad Dermatol 2003;49:171-82.)Learning objective At the conclusion of this learning activity, participants should be familiar with use of oral retinoids for childhood dermatologic conditions such as psoriasis, acne, and ichthyoses as well as safety and risks associated with oral retinoid use in children and adolescents."]
[12888014,1,0,0,1,2003,"Pancreas specification: a budding question.","Kumar",12888014,"Pancreas specification: a budding question.    Abstract:   Much recent investigation has been carried out into the mechanisms by which the pancreas is specified from the early endoderm. Recent advances have highlighted important roles for retinoic acid and bone morphogenetic protein signalling in patterning the endoderm at late gastrulation. Subsequently, interactions with the endothelium of the aorta in the dorsal pancreas domain and lateral plate mesoderm in the ventral pancreas domain are the source of essential pancreas-inductive signals. Additionally, the transcription factor Ptf1a has been demonstrated to have a previously unappreciated role in distinguishing pancreas from surrounding duodenal fates."]
[12880980,6,0,0,6,2003,"Retinoid therapy of high-risk neuroblastoma.","Reynolds",12880980,"Retinoid therapy of high-risk neuroblastoma.    Abstract:   Retinoids are derivatives of vitamin A that include all trans-retinoic acid (ATRA), 13-cis-retinoic acid, (13-cis-RA), and fenretinide (4-HPR). High levels of either ATRA or 13-cis-RA can cause arrest of cell growth and morphological differentiation of human neuroblastoma cell lines, and phase I trials showed that higher and more sustained drug levels were obtained with 13-cis-RA relative to ATRA. A phase III randomized trial showed that high-dose, pulse therapy with 13-cis-RA given after completion of intensive chemoradiotherapy (with or without autologous bone marrow transplantation) significantly improved event-free survival in high-risk neuroblastoma. The cytotoxic retinoid 4-HPR achieved multi-log cell kills in neuroblastoma cell lines resistant to ATRA and 13-cis-RA, and a pediatric phase I trial has shown it to be well tolerated. Cytotoxicity of 4-HPR is mediated at least in part by increasing tumor cell ceramide levels and combining 4-HPR with ceramide modulators increased anti-tumor activity in pre-clinical models. Thus, further clinical trials of 4-HPR in neuroblastoma, and of 4-HPR in combination with ceramide modulators, are warranted."]
[12858562,0,0,0,0,2002,"Regulatory networks controlling mitochondrial energy production in the developing, hypertrophied, and diabetic heart.","Finck",12858562,"Regulatory networks controlling mitochondrial energy production in the developing, hypertrophied, and diabetic heart.    Abstract:  "]
[12831362,3,0,0,3,2003,"Receptor induction and targeted drug delivery: a new antileukaemia strategy.","Ratnam",12831362,"Receptor induction and targeted drug delivery: a new antileukaemia strategy.    Abstract:   Strategic modalities of drug delivery have the potential to greatly improve the therapeutic efficacy of available drugs in acute myelogenous leukaemia (AML). Folate receptor (FR) type beta is selectively expressed on the surface of approximately 70% of AMLs. Increased FR-beta expression in these cells can be induced by all-trans retinoic acid (ATRA) and other retinoid compounds in the absence of terminal differentiation or cell growth inhibition. An apparent post-transcriptional modification prevents FR-beta in normal haematopoietic cells from binding folate, in contrast to AML cells. FR-beta may, therefore, be used as a target for the selective delivery of chemotherapeutic drugs to AML cells; this treatment modality appears to be particularly efficacious when administered in conjunction with retinoid-induction of FR-beta. FR-targeted liposomal drug delivery can also bypass the P-glycoprotein (P-gp)-mediated drug efflux pump commonly associated with multiple drug resistance in AML. The rationale and merits of this novel experimental treatment for AML and the current status of this research are provided."]
[12769477,0,0,0,0,2003,"Measurement of aggrecanase-generated interglobular domain catabolites in the medium and extracts of cartilage explants using Western blot analysis.","Hughes",12769477,"Measurement of aggrecanase-generated interglobular domain catabolites in the medium and extracts of cartilage explants using Western blot analysis.    Abstract:  "]
[12766945,1,0,0,1,2003,"About face: signals and genes controlling jaw patterning and identity in vertebrates.","Richman",12766945,"About face: signals and genes controlling jaw patterning and identity in vertebrates.    Abstract:   The embryonic vertebrate face is composed of similarly sized buds of neural crest-derived mesenchyme encased in epithelium. These buds or facial prominences grow and fuse together to give the postnatal morphology characteristic of each species. Here we review the role of neural crest cells and foregut endoderm in differentiating facial features. We relate the developing facial prominences to the skeletal structure of the face and review the signals and genes that have been shown to play an important role in facial morphogenesis. We also examine two experiments one at the genetic level and one at the signal level in which transformation of facial prominences and subsequent change of jaw identity was induced. We propose that signals such as retinoids and BMPs and downstream transcription factors such as Distal-less related genes specify jaw identity."]
[12734028,0,0,0,0,2003,"Bones and nutrition: common sense supplementation for osteoporosis.","Advani",12734028,"Bones and nutrition: common sense supplementation for osteoporosis.    Abstract:   Osteoporosis is a serious public health concern. Skeletal fragility, leading to spine and hip fractures, is a major source of morbidity and mortality. Adequate calcium intake from childhood to the end of life is critical for the formation and retention of a healthy skeleton. It is important to prevent bone loss from occurring, to identify potential risk factors, and to correct them. Many genetic and lifestyle factors influence the risk for osteoporosis. Among these, diet is believed to be one of the most important, especially the roles of calcium and vitamin D. Deficiency in other dietary factors--eg, protein, vitamin K, vitamin A, phytoestrogens, and other nutrients--might also contribute to the risk for osteoporosis. In this article, the roles of diet and nutritional supplementation in preventing and treating osteoporosis are reviewed."]
[12721355,15,0,0,15,2003,"Molecular mechanisms regulating chondroblast differentiation.","Hoffman",12721355,"Molecular mechanisms regulating chondroblast differentiation.    Abstract:    BACKGROUND : Formation of the cartilage template involves a multi-step process in which prechondrogenic mesenchymal cells form condensations prior to differentiating into matrix-producing chondroblasts. Retinoids, particularly retinoic acid, are among the numerous signaling molecules that have been implicated in this process. A proper balance of retinoids is essential for normal skeletal development in that too much or too little negatively impacts skeletogenesis. During the past few years, substantial advances have been made in our understanding of the role of retinoid signaling in these processes, which is reviewed in this report.  METHODS : To examine the function of retinoid signaling in skeletal development, transgenic mice that overexpressed a weak, constitutively active retinoic acid receptor (retinoic acid receptor-alpha) in their developing limbs were generated. The mice presented with a range of skeletal abnormalities. To examine the mechanisms responsible for these abnormalities, primary limb mesenchymal cultures from the transgenic mice were compared with cultures from wild-type mice. In addition, to address the molecular basis of retinoic acid receptor action, retinoic acid receptor activity in the primary cultures was manipulated with use of retinoic acid receptor-selective agonists and antagonists. The evaluation of the response to the manipulation of retinoic acid receptors was followed by histological studies and by the use of Northern blot analysis and reporter assays to analyze changes in the expression of chondrocytic markers and to monitor transcription factor activity, respectively.  RESULTS : The evidence reviewed here indicates that retinoids maintain cells within condensations in a prechondrogenic, mesenchymal cell state, which prevents the cells from differentiating into chondroblasts. More recent studies have demonstrated that the inhibition of receptor-mediated retinoid signaling induces the expression of Sox9, a transcription factor that is considered a quot;master switchquot; for the differentiation of chondroblasts. These effects are largely mediated by the activation of the p38 MAPK signaling cascade.  CONCLUSIONS : These findings demonstrate that retinoid receptor-mediated repression is both necessary and sufficient for chondroblast differentiation. Moreover, retinoic acid receptor repression acts downstream of BMP signaling or in a distinct pathway to activate p38 MAPK, which in turn induces chondroblast differentiation."]
[12719467,9,0,0,9,2003,"Active repression by unliganded retinoid receptors in development: less is sometimes more.","Weston",12719467,"Active repression by unliganded retinoid receptors in development: less is sometimes more.    Abstract:   The retinoid receptors have major roles throughout development, even in the absence of ligand. Here, we summarize an emerging theme whereby gene repression, mediated by unliganded retinoid receptors, can dictate cell fate. In addition to activating transcription, retinoid receptors actively repress gene transcription by recruiting cofactors that promote chromatin compaction. Two developmental processes for which gene silencing by the retinoid receptors is essential are head formation in Xenopus and skeletal development in the mouse. Inappropriate repression, by oncogenic retinoic acid (RA)**Abbreviations used in this paper: APL, acute promyelocytic leukemia; dnRARalpha, dominant-negative version of the RARalpha; E, embryonic age; HDAC, histone deacetylase; LCoR, ligand-dependent corepressor; NCoR, nuclear receptor corepressor; RA, retinoic acid; RAR, RA receptor; RARE, RXR homodimer bound to bipartite response element; RXR, retinoid X receptor; TSA, trichostatin A; CYP26, cytochrome p450, 26; TR, thyroid hormone receptor. receptor (RAR) fusion proteins, blocks myeloid differentiation leading to a rare form of leukemia. Our current understanding of the developmental role of retinoid repression and future perspectives in this field are discussed."]
[12688331,3,0,0,3,2003,"Vasculitis associated with all trans retinoic acid (ATRA) in a case with acute promyelocytic leukemia.","Paydas",12688331,"Vasculitis associated with all trans retinoic acid (ATRA) in a case with acute promyelocytic leukemia.    Abstract:   All trans retinoic acid is the drug of choice in the treatment of acute promyelocytic leukemia. But this drug has some side effects, some of which may be life-threatening. Retinoic acid syndrome is the most frequent and dangerous side effect of this differentiation inducing agent. Other side effects include Sweets syndrome, vasculitis, hypercalcemia, bone marrow necrosis and fibrosis, thromboembolic events, erythema nodosum, granulomatous proliferation and some pulmonary complications. Here, we report vasculitis in a case with APL treated with ATRA and review the literature."]
[12637589,0,0,0,0,2003,"Vitamin D: more than a quot;bone-a-fidequot; hormone.","Sutton",12637589,"Vitamin D: more than a quot;bone-a-fidequot; hormone.    Abstract:   The vitamin D endocrine system is critical for the proper development and maintenance of mineral ion homeostasis and skeletal integrity. Beyond these classical roles, recent evidence suggests that the bioactive metabolite of vitamin D, 1,25-dihydroxyvitamin D3, functions in diverse physiological processes, such as hair follicle cycling, blood pressure regulation, and mammary gland development. This minireview explores the current progress in unraveling the complexities of the vitamin D endocrine system by focusing on four main areas of research: the resolution of the vitamin D receptor crystal structure, the molecular details of 1,25-dihydroxyvitamin D3-mediated transcription, murine knockout models of key genes in the endocrine system, and alternative vitamin D receptors and ligands."]
[12636232,1,0,0,1,2003,"Pleiotropic functions of erythropoietin.","Sasaki",12636232,"Pleiotropic functions of erythropoietin.    Abstract:   Erythropoietin (EPO) produced by the fetal liver and adult kidney is an essential stimulator of erythropoiesis. EPO production is regulated through hypoxic activation of gene transcription and possibly hypoxia-induced stabilization of its mRNA. In the liver of early embryos in which EPO production poorly responds to hypoxia, retinoic acid may be an important stimulator. In this decade, new sites of EPO production have been found: central nervous system and reproductive organs. These tissues have a paracrine and/or autocrine system of EPO, which is independent of the endocrine system (kidney/bone marrow) in adult erythropoiesis. In the central nervous system, astrocytes are the main producers of EPO, while EPO receptor is expressed in neurons. EPO protects neurons from a various types of damage. The uterine EPO is likely involved in the estrogen-dependent angiogenesis of the endometrial layer. The possible functions of EPO in other tissues and tissue-characteristic regulation of EPO production are also discussed in this review."]
[12597015,5,0,0,5,2002,"Retinoic acid--a player that rules the game of life and death in neutrophils.","Mehta",12597015,"Retinoic acid--a player that rules the game of life and death in neutrophils.    Abstract:   Neutrophils are the most prevalent white blood cells in the circulation. They represent the first line of defense against invading microorganisms and have been implicated in the pathogenesis of a number of human diseases. In response to various factors, the pluripotent stem cells in bone marrow differentiate into mature neutrophils, enter the blood stream, and die within 24 hr via apoptosis. Numerous defects can occur during the process of neutrophils differentiation that can manifest in the form of a variety of clinical disorders. Retinoids (Vitamin A and analogues), in general, and all-trans retinoic acid (tRA), in particular, play a critical role during differentiation of neutrophils. tRA can directly modulate gene expression via binding to its nuclear receptors, which in turn, can activate transcription of genes that are essential for differentiation of immature cells to neutrophils. Involvement of retinoic acid receptor in pathogenesis of acute promyelocytic leukemia (APL), reflects an important role played by this receptor in differentiation of immature myeloid cells to neutrophils. This review summarizes evidence on involvement of retinoic acid-mediated events in differentiation process of neutrophils and their subsequent apoptosis."]
[12563669,1,0,0,1,2003,"Retinoids and rexinoids for the 21st century: a brave new world for arthritis.","Brinckerhoff",12563669,"Retinoids and rexinoids for the 21st century: a brave new world for arthritis.    Abstract:  "]
[12505260,2,0,0,2,2002,"Atypical t(15;17)(q13;q12) in a patient with all-trans retinoic acid refractory secondary acute promyelocytic leukemia: a case report and review of the literature.","Kurian",12505260,"Atypical t(15;17)(q13;q12) in a patient with all-trans retinoic acid refractory secondary acute promyelocytic leukemia: a case report and review of the literature.    Abstract:   A 69-year-old woman developed microgranular acute promyelocytic leukemia (APL-M3) 10 months after receiving adjuvant cyclophosphamide, doxorubicin, and paclitaxel for breast cancer. Replicate bone marrow aspirate karyotypes contained a translocation between the long arms of chromosomes 15 and 17, but not at breakpoints typical for APL. Fluorescence in situ hybridization paints and RARalpha/PML cosmid probes verified that the breakpoints on chromosomes 15 and 17 were proximal to both the PML and RARalpha genes; t(15;17)(q13;12). Although the patient received induction chemotherapy and a several month trial of all-trans retinoic acid (ATRA), there was no clinical improvement or hematological remission. We suspect that this patient developed postchemotherapy secondary APL with an atypical t(15;17), which rendered her leukemic cells unresponsive to ATRA therapy."]
[12481554,2,0,0,2,2002,"Vitamin D receptor and retinoid X receptor interactions in motion.","Barsony",12481554,"Vitamin D receptor and retinoid X receptor interactions in motion.    Abstract:   Vitamin D receptor (VDR) and retinoid X receptor (RXR) are members of the nuclear receptor superfamily and they bind target DNA sequences as heterodimers to regulate transcription. This article surveys the latest findings regarding the roles of dimerizing RXR in VDR function and emphasizes potential areas for future developments. We first highlight the importance of dimerization with RXR for both the ligand-independent (hair growth) and ligand-dependent functions of VDR (calcium homeostasis, bone development and mineralization, control of cell growth and differentiation). Emerging information regarding the regulatory control of dimerization based on biochemical, structural, and genetic studies is then presented. Finally, the main focus of this article is a new dynamic perspective of dimerization functions, based on recent research with fluorescent protein chimeras in living cells by microscopy. These studies revealed that both VDR and RXR constantly shuttle between the cytoplasm and the nucleus and between subnuclear compartments, and showed the transient nature of receptor--DNA and receptor--coregulator interactions. Because RXR dimerizes with most of the nuclear receptors, regulation of receptor dynamics by RXR has a broad significance."]
[12455623,0,0,0,0,2002,"Programmed cell death in the developing limb.","Zuzarte-Luís",12455623,"Programmed cell death in the developing limb.    Abstract:   The sculpturing of shape in the developing limb together with the regression of the tail in anuran tadpoles constitute, perhaps, the most paradigmatic processes of programmed cell death. The study of these model systems has been of fundamental importance to support the idea that cell death is a physiological behavior of cells in multicellular organisms. Furthermore, different experimental approaches, including comparative analyses of the pattern of cell death in different avian species (i.e. chick interdigits versus duck interdigital webs) and in chick mutants with different limb phenotypes, provided the first evidence for the occurrence of a genetic program underlying the control of cell death. Two well known research groups in the field of limb development, the USA group headed first by John Saunders and next by John Fallon and the group of Donald Ede and Richard Hinchliffe in the U.K. provided a remarkable contribution to this topic. In spite of the historical importance of the developing limb in establishing the concept of programmed cell death, this model system of tissue regression has been largely neglected in recent studies devoted to the analysis of the molecular control of self-induced cell death (apoptosis). However, a considerable amount of information concerning this topic has been obtained in the last few years. Here we will review current information on the control of limb programmed cell death in an attempt to stimulate further molecular studies of this process of tissue regression."]
[12452732,0,0,0,0,2002,"Minimising the long-term adverse effects of childhood leukaemia therapy.","Langebrake",12452732,"Minimising the long-term adverse effects of childhood leukaemia therapy.    Abstract:   Malignancies in childhood occur with an incidence of 13-14 per 100,000 children under the age of 15 years. Acute lymphoblastic leukaemia with an incidence of 29% is the most common paediatric malignancy, whereas acute myeloid leukaemias account for about 5%. The treatment of acute leukaemias consists of sequential therapy cycles (induction, consolidation, intensification, maintenance therapy) with different cytostatic drugs over a time period of up to 1.5-3 years. Over the last 25 years of clinical trials, a significant rise in the rate of complete remissions as well as an increase in long-term survival has been achieved. Therefore, growing attention is now focused on the long-term effects of antileukaemic treatment. Several cytostatic drugs administered in the treatment of acute leukaemia in childhood are known to cause long-term adverse effects. Anthracyclines may induce chronic cardiotoxicity, alkylating agents are likely to cause gonadal damage and secondary malignancies and the use of glucocorticoids may cause osteonecrosis. Most of the long-term adverse effects have not been analysed systematically. Approaches to minimising long-term adverse effects without jeopardising outcome have included: the design of new drugs such as a liposomal formulation of anthracyclines, the development of anthracycline-derivates with lower toxicity, the development of cardioprotective agents or, more recently, the use of targeted therapy;alternative administration schedules like continuous infusion or timed sequential therapy; and risk group stratification by the monitoring of minimal residual disease. Several attempts have been made to minimise the cardiotoxicity of anthracyclines: decreasing concentrations delivered to the myocardium by either prolonging infusion time or using liposomal formulated anthracyclines or less cardiotoxic analogues, or the additional administration of cardioprotective agents. The advantage of these approaches is still controversial, but there are ongoing clinical trials to evaluate the long-term effects. The use of new diagnostic methods, such as diagnosis of minimal residual disease, which allow reduction or optimisation of dose, offer potential advantages compared with conventional treatment in terms of reducing the risk of severe long-term adverse effects. Most options for minimising long-term adverse effects have resulted from theoretical models and in vitro studies, but only some of the modalities such as the use of dexrazoxane, the continuous infusion of anthracyclines or timed sequential therapy, have been evaluated in prospective, randomised studies in patients. Future approaches to predict severe toxicity may be based upon pharmacogenetics and gene profiling."]
[12440979,1,0,0,1,2002,"Peroxisome proliferator-activated receptors and the regulation of mammalian lipid metabolism.","Smith",12440979,"Peroxisome proliferator-activated receptors and the regulation of mammalian lipid metabolism.    Abstract:   Peroxisome proliferator-activated receptors (PPARs) are members of the superfamily of ligand-activated nuclear transcription factors. Three PPAR subtypes, PPARalpha, PPARdelta (PPARbeta) and PPARgamma, have been described in mammals. The tissue distribution of PPARs is heterogeneous: PPARalpha is highly expressed in liver and skeletal muscle, PPARgamma is preferentially expressed in adipose tissues, and PPARdelta is expressed in most cell types with relative abundance. Unlike most receptors, PPARs show low ligand specificity, being activated by many long-chain saturated and unsaturated fatty acids, or by eicosanoids. PPARs are transcriptionally active as heterodimeric complexes with the retinoid X receptor and bind to specific recognition sequences in the regulatory region of target genes. Many PPAR-regulated genes encode proteins that regulate fatty acid oxidation and storage. Elucidation of the biological functions of PPARs has been aided by the development of PPAR-null mice and the identification of humans bearing PPAR mutations, together with the discovery of synthetic small-molecule ligands that selectively activate individual PPAR subtypes. Using these genetic and pharmacological approaches, it has been shown that PPARalpha predominantly regulates pathways of fatty acid oxidation, whereas PPARgamma modifies fatty acid synthesis and storage in adipose tissues. By reducing systemic fatty acid availability, thiazolidinedione PPARgamma activators regulate glucose metabolism and are now used clinically in the treatment of Type II diabetes. In summary, PPARs play a central role in the mechanisms that balance fatty acid oxidation and storage in the face of fluctuations of dietary fat intake and energy expenditure."]
[12434275,1,0,0,1,2002,"[Myelodysplastic syndromes. Diagnosis and therapeutic strategies].","Aul",12434275,"[Myelodysplastic syndromes. Diagnosis and therapeutic strategies].    Abstract:    BACKGROUND : Myelodysplastic syndromes (MDS) are acquired hematopoietic stem cell disorders characterized by ineffective hematopoiesis, cellular dysfunction and an increased risk of transformation into acute myeloid leukemia (AML). One of the hallmarks of MDS is their prognostic heterogeneity which complicates therapeutic decisions. Therapeutic decisions are further hampered by the advanced age of most patients and the problem of attendant comorbidities. With the exception of allogeneic stem cell transplantation, no treatment modality has been proven to be of benefit over supportive care. The purpose of this review is to summarize the diagnostic work-up as well as current approaches to the treatment of MDS.  DIAGNOSIS AND RISK STRATIFICATION NlmCategory=UNASSIGNEDThe diagnosis of MDS is based on routine laboratory and peripheral blood evaluation. Bone marrow examination along with cytogenetic analyses are required for confirming und classifying MDS according to FAB or WHO proposals as well as performing a risk analysis according to the International Prognostic Scoring System (IPSS) which distinguishes four risk groups with different life expectancies and AML incidences.  THERAPEUTIC STRATEGIES NlmCategory=UNASSIGNEDSupportive treatment remains the mainstay of therapy, but does not alter the natural course of MDS. The only curative treatment of MDS is allogeneic stem cell transplantation which can be performed in high-risk patients up to an age of 60 years. The disease-free survival varies between 29% and 40% at 6-7 years after transplant. Unfavorable prognostic factors of survival in allogeneic stem cell transplantation are older age, advanced MDS stage, high-risk cytogenetics, high IPSS score and marrow fibrosis. For patients with high-risk MDS younger than 40 years, a matched unrelated donor transplant should be considered. AML-type chemotherapy is increasingly used in younger patients with high-risk MDS and yields complete remission rates between 45% and 79%. Despite high relapse rates, combination chemotherapy offers a chance of long-term remission for selected patients. For patients without HLA-matched allogeneic sibling donor, autologous stem cell transplantation may be used as consolidation therapy after successful conventional induction chemotherapy. For older patients with high-risk MDS in whom aggressive chemotherapy is contraindicated, intravenous treatment with 5-azacytidine and 5-aza-2-deoxycytidine (decitabine) or oral treatment with low-dose melphalan are promising new treatment options which yielded overall response rates of 40-63%. Based on new insights into the pathobiology of MDS, additional treatment approaches have been developed in recent years including differentiation therapy with hematopoietic growth factors and retinoids, immunosuppressive therapy with antithymocyte globulin or cyclosporine, cytokine inhibition by amifostine, pentoxifylline or soluble TNF-alpha receptor as well as angiogenesis inhibition by thalidomide.  CONCLUSION : Increased understanding of the natural course and pathophysiology of MDS has resulted in several new treatment approaches which must be further evaluated in appropriate clinical trials. In Germany, such trials are performed and coordinated by the German MDS Study Group which is part of the program quot;Kompetenznetzwerk Akute und Chronische Läukemienquot;."]
[12430923,2,0,0,2,2002,"New advances in the treatment of acute promyelocytic leukemia.","Douer",12430923,"New advances in the treatment of acute promyelocytic leukemia.    Abstract:    OBJECTIVE : Describe the treatment options of newly diagnosed and relapsed APL.  INDUCTION NlmCategory=UNASSIGNEDThe fusion PML/RAR gene provided the rationale for using all-trans retinoic acid (ATRA) as differentiation therapy. The standard approach is antracycline + ATRA and no ARA-C.  CONSOLIDATION NlmCategory=UNASSIGNEDAnthracycline based chemotherapy, no high dose ARA-C and perhaps no ARA-C. Maintenance seems to be important. Cure with ATRA + chemotherapy increased to 75% from 35% with chemotherapy alone.  POOR PROGNOSIS FACTORS NlmCategory=UNASSIGNEDWBC gt;10,000, age gt;55, platelets lt;40,000 and CD 56 expression. Achieving and maintaining a molecular remission (MCR) i.e. RT-PCR (-) for PML/RAR alpha expression, is the best predictor for cure. Conversion to PCR (+) will eventually result in relapse. PCR monitoring in the first 2 years and intervention during molecular relapse would be safer than treatment in clinical relapse. Molecular relapses have been treated successfully by ATRA plus BMT. Arsenic trioxide (ATO) or gentuzumab (mylotarg) are also being studied.  RELAPSE (INDUCTION) NlmCategory=UNASSIGNEDPatients after ATRA in first CR are less likely to respond to ATRA reinduction regardless of the time off ATRA and rarely achieve a molecular remission. Single-agent ATO induced in 52 relapsed patients CR of 87% (75% MCR) with low toxicity and no treatment related deaths (U.S. pivotal trial), confirmed in a NCI trial. Induction of relapsing patients with single agent ATO is preferable than ATRA + chemotherapy because the high molecular remission and lower toxicity.  RELAPSE (POST REMISSION) NlmCategory=UNASSIGNEDNo standard approach and the role of chemotherapy is unknown. ATO alone: in the pivotal trial, 9/21 patients had long remissions without other therapy. BMT: Not indicated in 1st MCR. In young patients auto BMT with PCR (-) harvests could be done in subsequent CR. Allo BMT has a higher death rate without overall better results. In the pivotal trial 12 patients were transplanted in CR after ATO alone (9 allo BMT) and 11 still without disease. Possibly allo BMT is safer after a less toxic ATO induction.  OTHER NlmCategory=UNASSIGNEDATO plus ATRA +/- AntiCD33 conjugated with toxin (gentuzumab) or 131I; Synthetic retinoid (Am80); histone deacetylase inhibitors; oral tetra-arsenic tetra-sulfide and various combinations."]
[12415744,1,0,0,1,2002,"Extracellular signals, cell interactions and transcription factors involved in the induction of the neural crest cells.","Aybar",12415744,"Extracellular signals, cell interactions and transcription factors involved in the induction of the neural crest cells.    Abstract:   The neural crest is induced at the border between the neural plate and the epidermis. A complex set of signals is required for the specification of the crest cells between the epidermis and the neural plate. Here we discuss evidence supporting a model for neural crest induction in which different signals contribute in a sequential order. First, a gradient of bone morphogenic proteins (BMPs) is established in the ectoderm that results in segregation into neural plate, neural folds and epidermis at increasing levels of BMP activity. Thus, the neural folds are induced at a precise threshold concentration of BMP, but this neural fold has an anterior character. In a second step, these anterior neural folds are transformed into prospective neural crest by posteriorizing signals due to fibroblast growth factor, Wnts and retinoic acid. Finally, the induced cells interact to complete neural crest induction by a process that requires Notch/Delta signaling. Once neural crest formation has been induced by this combination of extracellular and intracellular signals, a cascade of transcription factors is activated in these cells that culminates in the ultimate steps of neural crest differentiation."]
[12383393,1,0,0,1,2002,"[The epicardium and epicardial-derived cells: multiple functions in cardiac development].","Muñoz-Chápuli",12383393,"[The epicardium and epicardial-derived cells: multiple functions in cardiac development].    Abstract:   The epicardium develops from an extracardiac primordium, the proepicardium, which is constituted by a cluster of mesothelial cells located on the cephalic and ventral surface of the liver-sinus venosus limit (avian embryos) or on the pericardial side of the septum transversum (mammalian embryos). The proepicardium contacts the myocardial surface and gives rise to a mesothelium, which grows and progressively lines the myocardium. The epicardium generates, through a process of epithelial-mesenchymal transition, a population of epicardial-derived cells (EPDC). EPDC contribute to the development of cardiac connective tissue, fibroblasts, and the smooth muscle of cardiac vessels. Recent data suggest that EPDC can also differentiate into endothelial cells of the primary subepicardial vascular plexus. If this is confirmed, EPDC would show the same developmental properties that characterize the stem-cell-derived bipotential vascular progenitors recently described, whose differentiation into endothelium and smooth muscle is regulated by exposure to VEGF and PDGF-BB, respectively. Aside from their function in the development of cardiac connective and vascular tissue, EPDC also play an essential modulating role in the differentiation of the compact ventricular layer of the myocardium, a role which might be regulated by the transcription factor WT1 and the production of retinoic acid."]
[12381213,6,0,0,6,2002,"Comparative tolerability of systemic treatments for plaque-type psoriasis.","McClure",12381213,"Comparative tolerability of systemic treatments for plaque-type psoriasis.    Abstract:   Psoriasis is a chronic, debilitating skin condition that affects millions of people and is attributed to both genetic and environmental factors. Topical therapy is generally considered to be the first-line treatment of psoriasis. However, many patients do not respond to topical therapy or have disease so extensive that topical therapy is not practical. For these patients, systemic therapy is indicated. Presently, there are four available systemic treatments, psoralen with ultraviolet A (PUVA), methotrexate, oral retinoids (acitretin), and cyclosporin. Unfortunately, all of these treatments have significant potential adverse effects. PUVA may acutely cause nausea, pruritus and sunburn. More chronic and concerning is the development of PUVA lentigines, ocular complications and skin cancer. Non-melanoma skin cancer has been directly linked to PUVA; however, the association with melonoma is more elusive. Methotrexate use most notably carries the risk of hepatic fibrosis and cirrhosis, which is not always evident on liver function tests. Other more rare, but potentially life-threatening adverse effects include pancytopenia, lymphoproliferative disorders and acute pneumonitis. The addition of folic acid may help to reduce the risk of increasing liver enzymes and haematological toxicity seen in those taking methotrexate. Both methotrexate and oral retinoids are teratogenic and should never be used in pregnancy. Oral retinoids are probably the least effective available systemic medication for the treatment of plaque psoriasis. The effects are improved with the addition of other systemic therapies. Acitretin has replaced the formerly used etretinate primarily because of the significantly shorter half-life. The adverse effects are generally mild and reversible, making the drug fairly safe for long-term use. The most commonly seen adverse effects include elevated serum lipids, generalised xerosis and alopecia. Bony abnormalities, while somewhat controversial, have also been described and include diffuse idiopathic skeletal hyperostosis, skeletal calcifications and osteoporosis. Cyclosporin is the most recently approved systemic medication for plaque psoriasis. The nephrotoxicity associated with the use of cyclosporin can be minimised when used in lower doses and for a limited duration. Hypertension is usually mild and can be seen in up to about one-third of patients receiving long-term therapy. Cutaneous and internal malignancies have also been reported with cyclosporin and tend to be correlated with duration of treatment. In this review, we will examine the potential adverse effects with these US Food and Drug Administration-approved treatments in adults, with specific emphasis on the controversies that surround long-term therapy with these agents and their cumulative adverse effects."]
[12243710,6,0,0,6,2001,"Treatment of multiple miliary osteoma cutis of the face with local application of tretinoin (all-trans-retinoic acid): a case report and review of the literature.","Cohen",12243710,"Treatment of multiple miliary osteoma cutis of the face with local application of tretinoin (all-trans-retinoic acid): a case report and review of the literature.    Abstract:    BACKGROUND : Multiple miliary osteoma cutis of the face represents primary extra-skeletal bone formation that arises within the skin of the face.  METHODS : A 60-year-old woman with multiple miliary osteoma cutis of the face was treated by application of 0.05% tretinoin (all-trans-retinoic acid) cream nightly.  RESULTS : After 3 months of therapy there were fewer papules and a decrease in size of remaining lesions. In a literature search, it was found that local application of tretinoin was successful and achieved a decrease in the number of papules over the face in all patients with multiple miliary osteoma cutis of the face; however, the length of time to achieve response varied from a few weeks to 6 months.  CONCLUSION : It is suggested that local application of tretinoin cream should be considered in the therapy of multiple miliary osteoma cutis of the face, particularly when the lesions are small and superficial."]
[12214289,1,0,0,1,2002,"Myelodysplastic syndrome overview.","Kurzrock",12214289,"Myelodysplastic syndrome overview.    Abstract:   Myelodysplastic syndrome (MDS) is a heterogeneous hematopoietic stem cell disorder characterized by bone marrow dysplasia and peripheral cytopenias. Eighty percent of patients found to have MDS are older than 60 years and therefore not eligible for the only potentially curative therapy, bone marrow transplantation. Currently, there is no standard for treating MDS; therapies range from supportive care with transfusions or hematopoietic growth factors and low-intensity cytarabine therapy, to intensive anti-acute myeloid leukemia-type chemotherapy. Some of these treatments induce a limited hematologic response, but none consistently extends survival. Many are highly toxic. More than half of patients with MDS die within 3 to 4 years of infections, bleeding complications, or progression to acute leukemia. Agents in development for MDS include all-trans retinoic acid (ATRA), decitabine, and thalidomide. Farnesyltransferase inhibitors modulate many of the cancer-signaling pathways implicated in MDS initiation or progression and may therefore be well suited for treatment of these biologically diverse hematologic malignancies. Phase I and II clinical studies in our center show that the oral FTI ZARNESTRA (formerly R115777, Ortho Biotech Oncology, Raritan, NJ) has promising anti-MDS activity, suggesting that further investigation of this agent and of this class in MDS is warranted."]
[12201645,1,0,0,1,2002,"What is the optimal therapy for childhood AML?","Loeb",12201645,"What is the optimal therapy for childhood AML?    Abstract:   The use of intensive therapy overa brief period of time has produced dramatic improvements in outcome for pediatric patients with acute myelogenous leukemia (AML), as has been demonstrated in studies by the major cooperative groups in the United States and Europe. Still, despite high-intensity chemotherapy and bone marrow transplantation, only about half of the children diagnosed with AML are cured. Future improvements are unlikely to come from further increases in chemotherapy intensity. Alternative approaches, such as risk-directed therapy based on different prognostic criteria; differentiation therapy with all-trans-retinoic acid (ATRA, Vesanoid), arsenic trioxide (Trisenox), or azacytidine; and immunotherapy with monoclonal antibodies, tumor vaccines, or cytokines may lead to further advances."]
[12188026,1,0,0,1,2002,"Immunomodulatory effects of vitamin D receptor ligands in autoimmune diseases.","Adorini",12188026,"Immunomodulatory effects of vitamin D receptor ligands in autoimmune diseases.    Abstract:   The active form of vitamin D, 1,25-Dihydroxyvitamin D3 [l,25(OH)2D3], is a secosteroid hormone that binds to the vitamin D receptor (VDR), a member of the superfamily of nuclear receptors for steroid hormones, thyroid hormone, and retinoic acid. VDR ligands regulate calcium and bone metabolism, control cell proliferation and differentiation, and exert immunoregulatory activities. The immunoregulatory properties of VDR ligands are currently exploited clinically for the topical treatment of psoriasis, a Th1 cell-mediated autoimmune disease of the skin, but recent advances in understanding their functions and novel insights into the immunomodulatory mechanisms they control suggest a wider applicability in the treatment of autoimmune diseases. In addition to direct effects on T cell activation, VDR ligands modulate with different mechanisms the phenotype and function of antigen-presenting cells (APCs), and, in particular, of dendritic cells (DCs). In vitro and in vivo experiments have shown that VDR ligands induce DCs to acquire tolerogenic properties that favor the induction of regulatory rather than effector T cells. These intriguing actions of VDR ligands have been demonstrated in several experimental models and could be exploited, in principle, to treat a variety of human autoimmune diseases."]
[12097996,0,0,0,0,2002,"Contemporary therapeutic options for children with high risk neuroblastoma.","Sterba",12097996,"Contemporary therapeutic options for children with high risk neuroblastoma.    Abstract:   Despite the use of aggressive chemotherapy, stage 4 high risk neuroblastoma still has a very poor prognosis, which is estimated at 25%. Therefore, novel treatment approaches are needed. Increasing number of reports has been concerned with the use of novel treatment modalities. Literature regarding intensive induction, local therapy, myeloablative therapy and immunotherapy and biotherapy was reviewed in order to draw conclusions and recommendations for the management of children with high risk neuroblastic tumors."]
[12079836,0,0,0,0,2002,"Free fatty acid metabolism in human skeletal muscle is regulated by PPARgamma and RXR agonists.","Ciaraldi",12079836,"Free fatty acid metabolism in human skeletal muscle is regulated by PPARgamma and RXR agonists.    Abstract:   Free fatty acid (FFA) oxidation in human skeletal muscle cells can be stimulated, both independently and in a synergistic manner, by agonists for PPARgamma and RXR. Increased FFA disposal in muscle through augmented oxidation could reduce intramyocellular lipid accumulation. The abilities of such agents to improve glucose tolerance and insulin action may thus involve effects on both glucose and FFA metabolism."]
[12069675,0,0,0,0,2002,"Vitamins for chronic disease prevention in adults: scientific review.","Fairfield",12069675,"Vitamins for chronic disease prevention in adults: scientific review.    Abstract:    CONTEXT : Although vitamin deficiency is encountered infrequently in developed countries, inadequate intake of several vitamins is associated with chronic disease.  OBJECTIVE : To review the clinically important vitamins with regard to their biological effects, food sources, deficiency syndromes, potential for toxicity, and relationship to chronic disease.  DATA SOURCES AND STUDY SELECTION : We searched MEDLINE for English-language articles about vitamins in relation to chronic diseases and their references published from 1966 through January 11, 2002.  DATA EXTRACTION : We reviewed articles jointly for the most clinically important information, emphasizing randomized trials where available.  DATA SYNTHESIS : Our review of 9 vitamins showed that elderly people, vegans, alcohol-dependent individuals, and patients with malabsorption are at higher risk of inadequate intake or absorption of several vitamins. Excessive doses of vitamin A during early pregnancy and fat-soluble vitamins taken anytime may result in adverse outcomes. Inadequate folate status is associated with neural tube defect and some cancers. Folate and vitamins B(6) and B(12) are required for homocysteine metabolism and are associated with coronary heart disease risk. Vitamin E and lycopene may decrease the risk of prostate cancer. Vitamin D is associated with decreased occurrence of fractures when taken with calcium.  CONCLUSIONS : Some groups of patients are at higher risk for vitamin deficiency and suboptimal vitamin status. Many physicians may be unaware of common food sources of vitamins or unsure which vitamins they should recommend for their patients. Vitamin excess is possible with supplementation, particularly for fat-soluble vitamins. Inadequate intake of several vitamins has been linked to chronic diseases, including coronary heart disease, cancer, and osteoporosis"]
[12037503,1,0,0,1,2002,"[PPARgamma and insulin resistance].","Girard",12037503,"[PPARgamma and insulin resistance].    Abstract:   The thiazolidinediones (TZD), a new class of oral antidiabetic agent, act by improving insulin sensitivity. TZD correct hyperglycemia and hyperinsulinism in several animal models of NIDDM. Clinical studies in human have confirmed that TZD lowered postprandial and postabsorbtive glycemia and insulinemia. Glucose clamp studies have clearly shown a 30% improvement of insulin-induced glucose utilisation in skeletal muscle. TZD bind to an isoform of a nuclear receptor, the PPARgamma (Peroxisome Proliferator-Activated Receptor). PPARgamma is a transcription factor which, after heterodimerisation with the retinoid receptor (RXR), binds to specific response elements of a number of target genes, and control their transcription. How TZD, with their principal site of action being adipose tissue, can improve glucose metabolism in skeletal muscle? In human, skeletal muscles are responsible for more than 80% of glucose uptake in response to insulin and skeletal muscles contain only a limited amount of PPARgamma! This is the paradox to which we attempt to answer."]
[12012315,1,0,0,1,2002,"Arsenic trioxide: mechanisms of action.","Davison",12012315,"Arsenic trioxide: mechanisms of action.    Abstract:   The chimeric protein encoded by the PML-RAR alpha gene that is pathognomonic of acute promyelocytic leukemia (APL) causes the arrest of myeloid cell development at the promyelocyte stage, leading to an accumulation of abnormal promyelocytes in the bone marrow. Differentiation therapy with all-trans retinoic acid (ATRA) is used routinely in patients with APL, but ATRA is not the only agent in clinical use that promotes differentiation of the abnormal clone. Arsenic trioxide (ATO) has been shown to cause degradation of PML-RAR alpha, promoting differentiation. APL cells are extremely sensitive to ATO, which has shown good clinical activity at low doses in patients with relapsed APL. However, degradation of PML-RAR alpha may not be wholly responsible for the great sensitivity of APL cells to ATO, which also acts through the intracellular environment to influence apoptosis, differentiation, growth arrest, and angiogenesis. ATO can act at several points in mitochondrially induced apoptosis, including degradation of peroxides and interaction with glutathione (GSH)-related enzymes. Subclones that are resistant to ATO have been used to demonstrate that sensitivity can be restored by reducing the cellular GSH content. GSH can be reduced using agents such as buthionine sulfoximine (BSO) and ascorbic acid. The key factors that determine the ATO sensitivity of cells and control ATO-induced apoptosis have not yet been defined. It has been proposed that ATO acts through activation of Jun N-terminal kinase (JNK), activator protein-1, and inhibition of dual-specificity phosphatases, and evidence is accumulating that JNK activation is an important event in arsenic-induced apoptosis. Further research is required to determine the exact pathways through which the cytotoxic actions of ATO are mediated."]
[12001005,1,0,0,1,2002,"6-thioguanine in the treatment of psoriasis: a case report and literature review.","Sherer",12001005,"6-thioguanine in the treatment of psoriasis: a case report and literature review.    Abstract:    BACKGROUND : 6-Thioguanine is a purine analog primarily indicated for acute myelogenous leukemia. Its use in psoriasis was first investigated in the 1950s and current interest in serious treatments for psoriasis, such as cyclosporine, has renewed interest in this medication. Newer therapies, such as PUVA and retinoids, have side effects as do some older treatments, such as methotrexate, which fell into favor at the same time 6-thioguanine was being investigated. Reexamining older treatments can open up new therapeutic options in difficult cases.  OBJECTIVE : The goal of this article is to provide a comprehensive review of the literature regarding the use of 6-thioguanine in the treatment of psoriasis as well as an illustrative case report demonstrating the use and side effects of 6-thioguanine in a patient with pustular psoriasis. Topics reviewed include efficacy, side effects, laboratory monitoring, different dosing regimens, and proposed mechanisms of action.  CONCLUSIONS : 6-Thioguanine has been highly effective in treating and maintaining improvement in patients with psoriasis. A study comparing efficacies with methotrexate would be extremely useful. Because of the possibility of severe bone marrow depression, 6-thioguanine is not a first-line treatment. However, with new dosing regimens, proper laboratory monitoring, and further studies, use of 6-Thioguanine could expand in the future."]
[11978140,2,0,0,2,2002,"Treatment of cutaneous T cell lymphoma: current status and future directions.","Apisarnthanarax",11978140,"Treatment of cutaneous T cell lymphoma: current status and future directions.    Abstract:   The treatment of cutaneous T cell lymphoma (CTCL), which includes mycosis fungoides and Sezary syndrome, has been in a state of continual change over recent decades, as new therapies are constantly emerging in the search for more effective treatments for the disease. However, prognosis and survival of patients with CTCL remains dependent upon overall clinical stage (stage IA-IVB) at presentation, as well as response to therapy. Past therapies have been limited by toxicity or the lack of consistently durable responses, and few treatments have been shown to actually alter survival, especially in the late stages of disease. Even aggressive chemotherapy has not been shown to improve overall survival compared to conservative sequential therapy in advanced disease, and adds the risk of immunosuppressive complications. Over the last decade, extracorporeal photopheresis has been the only single treatment that has been shown to improve survival in patients with Sezary syndrome, although its true efficacy and place in combination therapy remain unclear. Much of the focus of current research has been on combinations of skin-directed therapies and biological response modifiers, which improve response rates. The results of various trials over the years have also brought into favor the use of post-remission maintenance therapy with topical corticosteroids, topical mechlorethamine (nitrogen mustard), interferon-alpha, or phototherapy to prevent disease relapse. Recent novel developments in CTCL therapy include oral bexarotene, a retinoid X receptor-selective retinoid that has activity in all stages of CTCL, and the topical gel formulation of bexarotene, which plays a role in treating localized lesions. US Food and Drug Administration (FDA)-approved, oral systemic bexarotene has the advantage of a 48% overall response rate at a dosage of 300 mg/m(2)/day, and avoids immunosuppression and risk of central line and catheter-related infectious complications that are associated with other systemic therapies. Monitoring of triglycerides and use of concomitant lipid-lowering agents and thyroid replacement is required in most patients. Also recently FDA-approved, denileukin diftitox is the first of a novel class of fusion toxin proteins and is selective for interleukin-2R (CD25+) T cells, targeting the malignant T cell clones in CTCL. Denileukin diftitox is associated with capillary leak syndrome in 20 to 30% of patients, which may be ameliorated by hydration and corticosteroids. Higher response rates are possible by combining bexarotene with quot;statinquot; drugs and active CTCL therapies. Studies are being conducted on combining bexarotene and denileukin diftitox with other modalities. Biological response modifier therapies that are in current or future investigational trials include topical tazarotene, pegylated interferon, interleukin-2, and interleukin-12. At the forefront of systemic chemotherapy development, pegylated liposomal doxorubicin, gemcitabine, and pentostatin appear to have the greatest potential for success in CTCL therapy. Bone marrow transplantation, which is currently limited by the risk of graft-versus-host disease, offers the greatest potential for disease cure. Further developments for CTCL may include more selective immunomodulatory agents, vaccines, and monoclonal antibodies."]
[11978137,5,0,0,5,2002,"Novel therapies for psoriasis.","Cather",11978137,"Novel therapies for psoriasis.    Abstract:   The T cell-driven immunopathogenesis of psoriasis has been well recognized since cyclosporine first revolutionized the treatment of psoriasis 20 years ago. Almost all investigative and clinical research subsequently, has concentrated on elucidating the specifics of antigen presentation, T cell interaction and the production of specific cytokines. The role of the keratinocyte, previously thought to be the primary target cell in psoriasis pathogenesis, has been relegated to a secondary role and the mechanism of action of systemic methotrexate in psoriasis has been challenged, the primary role of the T lymphocyte is now well known. While psoriasis has traditionally been treated quot;ab initioquot; with topical medications (corticosteroids, vitamin D(3), and retinoid derivatives), either singly, in combination, or with ultraviolet B (UVB) or psoralens and ultraviolet A (PUVA) therapy, the role of systemic medications has assumed greater prominence. Thus, three systemic medications currently are approved worldwide for the treatment of moderate to severe forms of psoriasis, namely cyclosporine, methotrexate and acitretin. The first two are likely to give significant clearing (greater than 75%) in the majority of cases, whereas acitretin is significantly less effective as monotherapy, but may approach methotrexate and cyclosporine in efficacy, if combined with PUVA or UVB phototherapy. The main limitations of these three drugs remain organ toxicity, especially hepatic toxicity with methotrexate, hypertension and nephrotoxicity with cyclosporine, and teratogenicity and mucocutaneous toxicity with acitretin. Thus, the need for more specific systemic therapy, targeting the T lymphocyte. This has become the major area of clinical research interest over the past 5 years, with the promise of longer-term disease control (improved remissions) and less organ toxicities. Currently, there are over 15 of these quot;biologicquot; drugs in various stages of development and clinical trials, either by the subcutaneous, intramuscular or intravenous route. The three main variables are the rapidity of onset, percentages of improvement and remission rates. Without exception, these new systemic agents appear to be remarkably free of systemic organ toxicities (liver, renal, bone-marrow, etc.), with adverse effects being limited to mild flu-like symptoms with the anticipated increase in infections (e.g., herpes simplex) being either equal to placebo or only marginally increased. Not all these agents under evaluation give clinical responses equal to methotrexate or cyclosporine (75% or greater clearing in 75% of cases). In addition, response rates may be slower with some therapies versus others. However, the need for intermittent administration even by the injectable route, longer remissions, lack of systemic organ toxicities and the potential for safer usage in females of child-bearing age, make a compelling argument for widespread acceptance by both patients and the dermatological community. Other modalities under clinical evaluation include vitamin D and retinoid drugs, topically and systemically, with effects on nuclear receptors, as well as more specific wavelengths (308 to 311 nm) of UVB phototherapy with application for more localized forms of psoriasis. For the 2 to 3% of the worldwide population of patients with psoriasis the future has never looked brighter."]
[11932986,1,0,0,1,2002,"Teratogenesis of holoprosencephaly.","Cohen",11932986,"Teratogenesis of holoprosencephaly.    Abstract:   Teratogenic causes of holoprosencephaly are critically assessed. A brief general review of holoprosencephaly is followed by four tables summarizing etiologic factors. Subjects evaluated here include: 1) maternal diabetes; 2) ethyl alcohol; 3) retinoic acid; 4) mutated genes and teratogens involving the sonic hedgehog signaling network and cholesterol biosynthesis; and 5) cholesterol trafficking, sterol adducts, target tissue response, and sterol sensing domain."]
[11921197,6,0,0,6,2002,"Selective estrogen receptor modulators (SERMs) and retinoids in breast cancer chemoprevention.","Zujewski",11921197,"Selective estrogen receptor modulators (SERMs) and retinoids in breast cancer chemoprevention.    Abstract:   Tamoxifen has been shown to decrease the risk of invasive breast cancer by 49% and noninvasive breast cancer by 50%. Tamoxifen is also associated with a threefold increased risk of endometrial cancer. Raloxifene, a second-generation selective estrogen receptor modulator (SERM), has not been associated with endometrial cancer risk, and is currently under study in a large, multi-institutional, randomized Study of Tamoxifen and Raloxifene (STAR) for breast cancer prevention in postmenopausal women. A pilot trial of raloxifene in premenopausal women to assess the safety, tolerability, effects on bone mineral density, mammographic density, and other biological endpoints is ongoing. The retinoids have been shown to decrease mammary tumors in rodent carcinogenesis models. The Italian trial of fenretinide (4-HPR) in women with stage I breast cancer randomized women to fenretinide or no intervention. This study did not show an overall effect of decreasing the risk of contralateral breast cancer. However, a protective effect was suggested in premenopausal women. It has been suggested that this effect may be related to insulin-like growth factor 1 (IGF-1), which has been shown to be modulated by fenretinide in premenopausal but not postmenopausal women. Pilot studies of SERMs alone and in combination with retinoids or other agents provide a model for testing the safety and tolerability, pharmacokinetics and pharmacodynamics, and biomarker modulation in high-risk women. These studies can provide information as to both the pathophysiology of carcinogenesis and the mechanism of action of chemopreventive agents, and help select agents and doses for testing in large randomized studies."]
[11891692,1,0,0,1,2002,"PAGOD syndrome: eighth case and comparison to animal models of congenital vitamin A deficiency.","Macayran",11891692,"PAGOD syndrome: eighth case and comparison to animal models of congenital vitamin A deficiency.    Abstract:   We observed a 46, XY infant with atrophy of the optic nerve, complex congenital heart disease including a double outlet right ventricle, hypoplasia of the right pulmonary artery and lung, eventration of the diaphragm, and ambiguous genitalia. The baby died of cardiac arrhythmias at 204 days. The pattern of malformations was compatible with pulmonary tract and pulmonary artery, agonadism, omphalocele, diaphragmatic defect, and dextrocardia (PAGOD) syndrome. The condition may resemble the malformation complex associated with developmental deficiency of vitamin A or retinoic acid, as described in animal models."]
[11862881,0,0,2,2,2001,"Candidate genes for nonsyndromic cleft lip and palate.","Vieira",11862881,"Candidate genes for nonsyndromic cleft lip and palate.    Abstract:   The confirmation of supposed genes causing susceptibility to nonsyndromic cleft lip with or without a cleft palate (CL/P) and cleft palate alone (CP) would help to understand the molecular development of the lip, the palate and the jaw, and to predict more accurately the risk of recurrence of such defects. The purpose of this article is to present a brief review of the current state of knowledge regarding the search for genes responsible for the occurrence of CL/P and CP. After ten years of research, approximately twenty candidate genes have already been suggested for CL/P and CP. Some genes or chromosomal regions seem to be frequently associated with these defects and a specific nomenclature (orofacial cleft genes--OFC) has been suggested. Everything indicates that it will still take many years of research before the genes responsible for CL/P and CP are confirmed. These efforts are justified, however, because of the possibility of being able to predict more accurately the risk of such defects occurring."]
[11850116,1,0,0,1,2002,"Age-related phenotypes in the staggerer mouse expand the RORalpha nuclear receptors role beyond the cerebellum.","Jarvis",11850116,"Age-related phenotypes in the staggerer mouse expand the RORalpha nuclear receptors role beyond the cerebellum.    Abstract:   The homozygous mutant mouse staggerer (RORa(sg)/RORa(sg)), was initially described as ataxic, due to the presence of massive neurodegeneration in the cerebellum [Science 136 (1962) 610]. The identification of the widely expressed Retinoic acid receptor-related Orphan Receptor, NR1F1 (RORalpha) gene as the site of mutation in the staggerer mouse has led to great progress in understanding the molecular basis of its phenotype in recent years [Nature 379 (1996) 736]. RORalpha is a transcription factor, belonging to the nuclear receptor superfamily, for which no natural ligand has yet been identified. Mice engineered for the disruption of the gene encoding RORalpha display the same cerebellar atrophic phenotype as the staggerer mouse [Proc. Natl. Acad. Sci. USA 95 (1998) 3960]. More recently, it has been shown that the mutation is semi-dominant, as heterozygous animals display an increased loss of Purkinje cells with age. Furthermore, a number of additional phenotypes outside the nervous system have recently been identified. These include a greater susceptibility to atherosclerosis [Circulation 15 (1998) 2738], immunodeficiencies linked to the overexpression of inflammatory cytokines [J. Neurochem. 58 (1992) 192], abnormalities in the formation and maintenance of bone tissue [Proc. Natl. Acad. Sci. USA 97 (2000) 9197] and changes in muscle differentiation [Nucleic Acids Res. 27 (1999) 411]. Thus, RORalpha has been directly linked to a number of age-related pathologies of great medical interest."]
[11836177,0,0,0,0,2002,"ATRA-induced myositis in induction therapy of acute promyelocytic leukemia.","Martínez-Chamorro",11836177,"ATRA-induced myositis in induction therapy of acute promyelocytic leukemia.    Abstract:  "]
[11825305,1,0,0,1,2001,"The pharmacological management of drug-induced rheumatic disorders.","di Fazano",11825305,"The pharmacological management of drug-induced rheumatic disorders.    Abstract:   Many drugs can induce adverse effects such as rheumatoid disorders, which we need to be aware of in order to best detect and manage them. New drugs are constantly entering the marketplace and can cause an increasing number of disorders. Through this article, we review the prevention and pharmacological management of drug-induced rheumatic disorders. These include articular and peri-articular manifestations induced by fluoroquinolones, retinoids, cyclosporin, drug-induced disorders of bone metabolism such as corticosteroid-induced osteoporosis and drug-induced osteomalacia, and multisystemic manifestations including drug-induced lupus and arthritis induced by vaccinations and cytokines."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I389,I389)","v":11818666},{"$f":"(LEN($J389) - LEN(SUBSTITUTE(LOWER($J389),LOWER(B$3),\"\")))/LEN(B$3)","v":2},0,0,{"$f":"SUM(B389:D389)","v":2},2002,"Advances in the treatment of relapsed acute promyelocytic leukemia.","Douer",11818666,"Advances in the treatment of relapsed acute promyelocytic leukemia.    Abstract:   The presence of the characteristic fusion transcript gene, promyelocytic leukemia-retinoic acid receptor-alpha (PML-RARalpha), provided hematologists with a rationale for the use of all-trans retinoic acid (ATRA) for differentiation therapy for acute promyelocytic leukemia (APL). Multiple studies have established that combination of ATRA and chemotherapy in newly diagnosed patients has increased the cure rate to 70% from 35% in patients treated with chemotherapy alone. However, still about 30% of the patients relapse and are often resistant to ATRA retreatment. Consequently, a number of novel agents that include several differentiation agents and monoclonal antibodies have been studied to provide improved outcomes for patients with APL who have relapsed. In particular, arsenic trioxide has shown great promise for the induction, consolidation, and maintenance of complete remission in relapsed patients with APL. The unique mechanisms of action by which arsenic trioxide exerts its effects are complementary to those of ATRA, potentially allowing for combination therapies with additive or even synergistic results. Within this context autologous or allogeneic bone marrow transplantations are also considered in second or subsequent relapse, especially after arsenic trioxide-induced complete remission in relapsing patients. Furthermore, molecular monitoring for the PML-RARalpha fusion protein permits prompt intervention for early molecular relapse of APL before clinical relapse, ultimately improving chances of prolonged remission."]
[11802381,0,0,0,0,2001,"[Genetic study of ossification of the posterior longitudinal ligament of the spine].","Inoue",11802381,"[Genetic study of ossification of the posterior longitudinal ligament of the spine].    Abstract:  "]
[11770391,1,0,0,1,2001,"Immunomodulating drugs in the management of psoriatic arthritis.","Jackson",11770391,"Immunomodulating drugs in the management of psoriatic arthritis.    Abstract:   Psoriatic arthritis is a chronic inflammatory arthropathy which can be distinguished from rheumatoid arthritis on the basis of differing patient demographics, genetic predisposition, histopathologic change, radiographic appearance, and clinical course. The cause of psoriatic arthritis remains unknown but appears to be autoimmune in nature as its pathogenesis is characterized by persistent synovial inflammation resulting in damage to the articular cartilage and osteolysis. Compared with rheumatoid arthritis, distinct lymphocyte subpopulations and pro-inflammatory cytokine levels appear to be present within the joint but the importance and therapeutic implications of these differences is uncertain. The clinical presentation of psoriatic arthritis is variable and overlapping patterns of joint involvement affecting both the appendicular and axial skeleton are seen. For patients with mild synovial disease and a favorable prognosis, the use of a nonsteroidal anti-inflammatory drug for symptomatic relief is often sufficient. However, the destructive potential of psoriatic arthritis is increasingly recognized and patients with more synovial disease and radiographic change at presentation appear to be at risk for greater morbidity and increased mortality. Immunomodulating therapy has the potential to suppress joint inflammation and preserve functional capacity but true disease modification has yet to be shown. The toxicity associated with presently available immunomodulatory agents makes careful patient selection and conscientious monitoring essential. The efficacy of methotrexate and sulfasalazine in patients with psoriatic arthritis is well defined while more anecdotal reports of benefit exist for other agents including the antimalarials, azathioprine, colchicine, cyclosporine, and the retinoids. For all treatment regimens, the magnitude of clinical improvement demonstrated to date has been rather small and quite subjective in character with few controlled studies of adequate size and duration having been reported. Emerging biologic therapies, such as those which target tumor necrosis factor, will hopefully provide future treatment options with greater efficacy and improved safety for patients with psoriatic arthritis."]
[11764295,2,0,0,2,2001,"Microphthalmia-associated transcription factor (MITF): multiplicity in structure, function, and regulation.","Shibahara",11764295,"Microphthalmia-associated transcription factor (MITF): multiplicity in structure, function, and regulation.    Abstract:   Microphthalmia-associated transcription factor (MITF) regulates the differentiation and development of melanocytes and retinal pigment epithelium and is also responsible for pigment cell-specific transcription of the melanogenesis enzyme genes. Heterozygous mutations in the MITF gene cause auditory-pigmentary syndromes. MITF consists of at least five isoforms, MITF-A, MITF-B, MITF-C, MITF-H, and MITF-M, differing at their N-termini and expression patterns. Here we show a remarkable similarity between the N-terminal domain of MITF-A and cytoplasmic retinoic acid-binding proteins. To date, four isoform-specific first exons have been identified in the MITF gene: exons 1A, 1H, 1B, and 1M in the 5 to 3 direction, each of which encodes the unique N-terminus of a given isoform. The 5-flanking regions of these isoform-specific exons are termed A, H, B, and M promoters, respectively. Among these promoters, the M promoter has received particular attention, because it is functional only in melanocyte-lineage cells and is upregulated by Wnt signaling via the functional LEF-1-binding site. Moreover, the M promoter is upregulated by other transcription factors, PAX3, SOX10, and CREB. The activity and degradation of MITF-M are regulated by extracellular signals via protein phosphorylation, such as c-Kit signaling. Together, multiple signals appear to converge on the M promoter as well as on MITF proteins, leading to the proper regulation of MITF-M in melanocytes and other MITF isoforms in many cell types."]
[11729636,1,0,0,1,2001,"[Mitochondrial uncoupling protein as a target of pharmacotherapy for obesity].","Saito",11729636,"[Mitochondrial uncoupling protein as a target of pharmacotherapy for obesity].    Abstract:   Uncoupling protein (UCP) is a transporter family present in the mitochondrial inner membrane, and as its name suggests, it uncouples respiration from ATP synthesis by dissipating the transmembrane proton gradient as heat. UCP is now recognized as a key molecule in metabolic thermogenesis such as cold- and diet-induced heat production, which is a significant component of energy expenditure, and its dysfunction contributes to the development of obesity. Among the UCP family, UCP-1 is expressed exclusively in brown adipose tissue (BAT), while UCP-2 is present in many organs and UCP-3 is in skeletal muscle. BAT thermogenesis by UCP-1, which has been studied most extensively, is controlled directly by sympathetic nerves principally through the beta-adrenergic action of norepinephrine. Since the beta 3-adrenoceptor is present primarily in adipose tissues, its selective agonists stimulate BAT thermogenesis and also lipid mobilization in white adipose tissue without any noticeable effect on beta 1- and beta 2-adrenoceptos. Therefore, beta 3-adrenoceptor agonists would be promising for the pharmacotherapy of obesity. UCP gene expression is up regulated by ligands for nuclear receptors such as thyroid hormone receptor, peroxisome proliferator-activated receptors (PPAR) and retinoid-X receptor. Long chain fatty acids and some of their metabolites are known to activate PPAR and thereby lead to abundant expression of UCP, which may also contribute to increase in energy expenditure and prevention of obesity. The activity of UCP is suppressed by purine nucleotides but activated by fatty acids. Thus, fatty acids increase UCP-mediated thermogenesis by direct activation of UCP and also by increased gene expression, implying some specific fatty acids or their derivatives as an effective anti-obesity tool."]
[11729635,1,0,0,1,2001,"[PPAR gamma agonist and antagonist].","Kadowaki",11729635,"[PPAR gamma agonist and antagonist].    Abstract:   Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a ligand-activated transcription factor and functions as a heterodimer with a retinoid X receptor (RXR). Supraphysiological activation of PPAR gamma by thiazolidinediones can reduce insulin resistance and hyperglycemia in type 2 diabetes, but these drugs can also cause weight gain. Quite unexpectedly, a moderate reduction of PPAR gamma activity observed in heterozygous PPAR gamma-deficient mice or the Pro 12 Ala polymorphism in human PPAR gamma has been shown to prevent insulin resistance and obesity induced by a high-fat (HF) diet. We investigated whether functional antagonism toward PPAR gamma/RXR could be used to treat obesity and type 2 diabetes. We show herein that moderate reduction of PPAR gamma with an RXR antagonist or a PPAR gamma antagonist decreases triglyceride (TG) content in white adipose tissue, skeletal muscle and liver. These inhibitors potentiate leptins effects and stimulated adiponectin levels, which increases fatty acid combustion and energy dissipation, thereby ameliorating HF diet-induced obesity and insulin resistance. Paradoxically, severe reduction of PPAR gamma by treatment of heterozygous PPAR gamma-deficient mice with an RXR antagonist or a PPAR gamma antagonist depletes white adipose tissue and markedly decreases leptin and adiponectin levels and energy dissipation, which increases TG content in skeletal muscle and the liver, thereby leading to the re-emergence of insulin resistance. Our data suggest that appropriate functional antagonism of PPAR gamma/RXR may be a logical approach to protection against obesity and related diseases such as type 2 diabetes."]
[11704845,1,0,0,1,2001,"Orchestration of multiple arrays of signal cross-talk and combinatorial interactions for maturation and cell death: another vision of t(15;17) preleukemic blast and APL-cell maturation.","Benoit",11704845,"Orchestration of multiple arrays of signal cross-talk and combinatorial interactions for maturation and cell death: another vision of t(15;17) preleukemic blast and APL-cell maturation.    Abstract:   Despite intensive molecular biology investigations over the past 10 years, and an important breakthrough on how PML-RARalpha, the fusion protein resulting from t(15;17), can alter RARalpha and PML functions, no definitive views on how leukemia is generated and by what mechanism(s) the normal phenotype is restored, are yet available. Resistances to pharmacological levels of all-trans-retinoic acid (ATRA) have been observed in experimental in vivo and in vitro models. In this review, we emphasize the key role played by signal cross-talk for both normal and neoplastic hemopoiesis. After an overview of reported experimental data on APL-cell maturation and apoptosis, we apply our current knowledge on signaling pathways to underline those which might generate signal cross-talks. The design of biological models suitable to decipher the integration of signal cross-talks at the transcriptional level should be our first priority today, to generate some realistic therapeutic approaches After Ten Years of Molecular APL, we still know very little about how the disease develops and how effective medicines work."]
[11677097,1,0,0,1,2001,"Systemic aspects of allergic disease: the role of the bone marrow.","Cyr",11677097,"Systemic aspects of allergic disease: the role of the bone marrow.    Abstract:   In recent years, there has been an increasing appreciation of the important contribution of bone-marrow-related, hemopoietic mechanisms to allergic diseases. Eosinophil/basophil-progenitor levels fluctuate in the peripheral blood during allergen exposure and the cells home to peripheral tissue, where they differentiate. It is becoming apparent that several cytokines, particularly IL-5, have multiple effects on progenitors and allergic inflammation. Within the past few years, studies of the therapeutic implications of this bone marrow contribution to atopy have been initiated; the effects of corticosteroids, leukotriene-receptor blockers, antagonism of IL-5 and modulation of differentiation by retinoic acid on progenitors will be reviewed."]
[11676281,0,0,0,0,2001,"Biologic response modifiers in pediatric cancer.","Worth",11676281,"Biologic response modifiers in pediatric cancer.    Abstract:   Biologic response modifiers are becoming an important addition to surgery, chemotherapy, and radiotherapy in the management of cancer. As this field of research grows and expands, more biologic response modifiers will be incorporated into therapeutic regimens. By stimulating the immune system to eradicate minimal residual disease, these agents may improve the disease-free and long-term survival rates of patients with a variety of malignancies. The challenge is to incorporate biologic response modifiers into the treatment armamentarium in ways that will maximize their tumorigenicity."]
[11606950,2,0,0,2,2001,"Isotretinoin effects on bone.","DiGiovanna",11606950,"Isotretinoin effects on bone.    Abstract:   Isotretinoin has demonstrated efficacy in a wide range of disorders. The beneficial effects of the drug, however, are limited by its adverse effects on the bone. Children exposed to high doses are at risk for premature epiphyseal closure, while adults on long-term therapy have an increased tendency to develop hyperstosis and other changes of the bone. The knowledge of these effects, in conjunction with continued surveillance, are necessary for expert management and can ensure many years of efficacious treatment with minimal toxicity."]
[11594672,4,0,0,4,2001,"Safety issues in isotretinoin therapy.","Hanson",11594672,"Safety issues in isotretinoin therapy.    Abstract:   Isotretinoin (Accutane, Roche Laboratories Inc, Nutley, NJ) is an important drug, not only for the treatment of severe acne, but also for other diagnoses and in chemoprevention settings. Because the use of isotretinoin is increasing, it is important for physicians to be aware of the adverse events, toxicities, and management issues related to its use. The most important issue is that of congenital defects, which has resulted in new pregnancy prevention policies and programs implemented by the manufacturer. A relatively new concern is that of depression associated with isotretinoin use, also resulting in new policies placed by the manufacturer and the FDA. The most common adverse effects observed during treatment are mucocutaneous and ocular in nature, but laboratory abnormalities and effects in the nervous, musculoskeletal, gastrointestinal, pulmonary, hematologic, and other systems are also described. Additionally, potential drug interactions, follow-up, and toxicity prevention measures are discussed."]
[11562285,0,0,0,0,2001,"Vitamin D analogs: mechanism of action and therapeutic applications.","Nagpal",11562285,"Vitamin D analogs: mechanism of action and therapeutic applications.    Abstract:   The physiological VDR ligand, 1 alpha,25-dihydroxyvitamin D3, acts upon a wide variety of tissues and cells, both related to and unrelated to calcium and phosphate homeostasis. The noncalcemic actions of natural and synthetic VDR ligands are exemplified by their potent anti-proliferative, prodifferentiative and immunomodulatory activities. As a result, a VDR ligand is an approved drug for the topical treatment of psoriasis. A plethora of actions of 1 alpha,25-dihydroxyvitamin D3 in various systems have suggested wide clinical applications of VDR ligands in such diverse disease states as inflammation (rheumatoid arthritis, psoriatic arthritis), dermatological indications (psoriasis, photoaging and skin rejuvenation), osteoporosis, cancers (breast, prostate, colon, leukemia and myelodysplastic syndrome) and autoimmune diseases (multiple sclerosis, type I diabetes and systemic lupus erythematosus). VDR ligands have shown therapeutic potential in limited human clinical trials as well as in animal models of these diseases. Some of the VDR ligands have shown not only potent preventive but also therapeutic anabolic activities in animal models of osteoporosis. However, the use of VDR in above mentioned indications as well as in oral therapy for psoriasis and even topical therapy for severe psoriasis is hampered by its associated toxicity, namely hypercalcemia. New VDR ligands have been synthesized which exhibit greater specificity by retaining desirable properties, but with reduced calcemic potential. The discovery of novel vitamin D3 analogs along with an increased understanding of the biological functions and mechanisms of action of VDR are likely to result in improved treatments for responsive indications."]
[11550795,2,0,0,2,2001,"The ROR nuclear orphan receptor subfamily: critical regulators of multiple biological processes.","Jetten",11550795,"The ROR nuclear orphan receptor subfamily: critical regulators of multiple biological processes.    Abstract:   The nuclear receptor superfamily, a group of structurally related, ligand-dependent transcription factors, includes a large number of orphan receptors for which no ligand has yet been identified. These proteins function as key regulators of many physiological processes that occur during embryonic development and in the adult. The retinoid-related orphan receptors (RORs) alpha, beta, and gamma comprise one nuclear orphan receptor gene subfamily. RORs exhibit a modular structure that is characteristic for nuclear receptors; the DNA-binding domain is highly conserved and the ligand-binding domain is moderately conserved among RORs. By a combination of alternative promoter usage and exon splicing, each ROR gene generates several isoforms that differ only in their amino terminus. RORs bind as monomers to specific ROR response elements (ROREs) consisting of the consensus core motif AGGTCA preceded by a 5-bp A/T-rich sequence. RORE-dependent transcriptional activation by RORs is cell type-specific and mediated through interactions with nuclear cofactors. RORs have been shown to interact with certain corepressors as well as coactivators, suggesting that RORs are not constitutively active but that their activity is under some regulatory control. RORs likely can assume at least two different conformations: a repressive state, which allows interaction with corepressor complexes, and an active state, which promotes binding of coactivator complexes. Whether the transition between these two states is regulated by ligand binding and/or by phosphorylation remains to be determined. Ca2+/calmodulin-dependent kinase IV (CaMKIV) can dramatically enhance ROR-mediated transcriptional activation. This stimulation involves CaMKIV-mediated phosphorylation not of RORs, but likely of specific nuclear cofactors that interact with RORs. RORalpha is widely expressed. In the cerebellum, its expression is limited to the Purkinje cells. RORalpha-/- mice and the natural RORalpha-deficient staggerer mice exhibit severe cerebellar ataxia due to a defect in Purkinje cell development. In addition, these mice have thin long bones, suggesting a role for RORalpha in bone metabolism, and develop severe atherosclerosis when placed on a high-fat diet. Expression of RORbeta is very restricted. RORbeta is highly expressed in different parts of the neurophotoendocrine system, the pineal gland, the retina, and suprachiasmatic nuclei, suggesting a role in the control of circadian rhythm. This is supported by observations showing alterations in circadian behavior in RORbeta-/- mice. RORgamma, which is most highly expressed in the thymus, plays an important role in thymopoiesis. Thymocytes from RORgamma-/- mice undergo accelerated apoptosis. The induction of apoptosis is, at least in part, due to a down-regulation of the expression of the antiapoptotic gene Bcl-XL. In addition to the thynic phenotype, RORgamma-/- mice lack lymph nodes, indicating that RORgamma is essential for lymph node organogenesis. Overexpression of RORgamma has been shown to inhibit T cell receptor-mediated apoptosis in T cell hybridomas and to repress the induction of Fas-ligand and interleukin 2. These studies demonstrate that RORs play critical roles in the regulation of a variety of physiological processes. Further characterization of the mechanisms of action of RORs will not only lead to the identification of ROR target genes and provide additional insight into their normal physiological functions, but will also determine their roles in disease."]
[11535988,1,0,0,1,2001,"The role of bone marrow transplantation in acute promyelocytic leukemia.","Nabhan",11535988,"The role of bone marrow transplantation in acute promyelocytic leukemia.    Abstract:   Acute promyelocytic leukemia (APL) is characterized by a specific gene rearrangement and the generation of the PML-RARalpha fusion transcript which results from a translocation between chromosomes 15 and 17. Targeted therapy with all-trans retinoic acid (ATRA) and anthracycline-based chemotherapy results in an apparent cure in 70-80% of patients. Both allogeneic (ALLO) and autologous (AUTO) hematopoietic stem cell transplantation (HSCT) are effective in acute myeloid leukemia (AML), but their role in APL is not clear given the excellent outcome with ATRA and chemotherapy. Several retrospective studies have analyzed the outcome of patients undergoing AUTO or ALLO-HSCT in first (CR1) or second (CR2) complete remission. Most of these studies have shown significant transplant-related mortality (TRM) with ALLO-HSCT, but a reduction in relapse rate compared with AUTO-HSCT. The high TRM with ALLO-HSCT and the excellent outcome with ATRA and chemotherapy do not justify recommending this procedure for the majority of patients in CR1. The role of AUTO-HSCT in CR1 also is unclear. A small subset of patients at high risk of relapse, possibly identifiable by a high white blood cell count at presentation may benefit from HSCT. Most patients with relapsed disease achieve CR2 with ATRA, arsenic trioxide, or combination therapy. However, it is not known if these responses are sustained or if consolidation with HSCT has a place in this setting. The outcome of AUTO-HSCT in CR2 using stem cells that are negative for PML-RARalpha is excellent. It is unclear whether ALLO-HSCT from an HLA-identical sibling is superior to AUTO-HSCT with PML-RARalpha-negative cells in CR2 since the former would be associated with graft-versus-leukemia effects and the latter with lower TRM. Alternatively, arsenic trioxide or re-treatment with ATRA, followed by intensive chemotherapy may also be effective. A randomized prospective clinical trial, or a retrospective analysis of the available data would be useful in answering this critical question."]
[11520582,1,0,0,1,2001,"Treatment of adult T-cell leukaemia/lymphoma: current strategy and future perspectives.","Bazarbachi",11520582,"Treatment of adult T-cell leukaemia/lymphoma: current strategy and future perspectives.    Abstract:   Human T-cell leukaemia virus type I (HTLV-I) associated adult T-cell leukaemia/lymphoma (ATL) carries a very poor prognosis due to an intrinsic resistance of leukaemic cells to conventional or even high doses of chemotherapy and to an associated severe immunosuppression. Therefore, the potential role of conventional chemotherapy, high dose chemotherapy with autologous or allogeneic bone marrow transplantation remains to be defined. Important progress was achieved in the treatment of ATL with the combination of zidovudine (AZT) and interferon-alpha (IFN) which produces a high response rate in ATL patients with minimal side effects. This treatment seems to prolong the survival of patients much more than intensive chemotherapy. The success of this potentially anti-retroviral approach in the treatment of ATL suggests the existence of continuous HTLV-I replication in vivo. These encouraging results may be improved by the use of higher doses of AZT and IFN combined with other anti-retroviral agents. However, since cure seems still elusive, new therapeutic approaches or new combinations are required. For example, biological mediators such as retinoid acid, which induces apoptosis of ATL cells in vitro, may reduce drug resistance and stimulates immunity to restore anti-tumour activity against ATL cells. Alternatively, immunotherapy with anti-interleukin-2 receptor monoclonal antibodies or injection of cytotoxic T-cells directed against virus antigens could be interesting approaches which may merit further investigations in the near future. Finally, the recent demonstration that the combination of arsenic trioxide (As) and IFN induces a specific degradation of the viral transactivator Tax followed by cell cycle arrest and apoptosis of HTLV-I positive cells may constitute a valuable addition to ATL treatment."]
[11452221,1,0,0,1,2001,"[Mechanisms of action of thiazolidinediones].","Girard",11452221,"[Mechanisms of action of thiazolidinediones].    Abstract:   The recent discovery and marketing of a new class of antidiabetic drug improving insulin sensitivity, the thiazolidinediones (TZD), has opened interesting therapeutic perspectives. Those molecules correct hyperglycemia and hyperinsulinemia in several animal models of NIDDM. Clinical studies in human have confirmed that TZD lowered postprandial and postabsorptive glycemia and insulinemia. Glucose clamp studies have clearly shown an improvement of insulin-induced glucose utilization (in skeletal muscle). In contrast, the inhibition of glucose production in response to insulin was much less reproducible. TZD have also been used with success to treat insulin resistance in non-diabetic obeses, in glucose-intolerant prediabetic subjects and in patients with polycystic ovary syndrome (pcos). Nevertheless, TZD appears less efficient in human than in animal models. TZD bind to an isoform of a nuclear receptor, the PPARgamma (Peroxisome Proliferator Activated Receptor). PPAR gamma is a transcription factor which, after heterodimerization with the retinoid receptor (RXR), bind to specific response elements of a number of target genes and control their transcription. There is an excellent correlation between the hypoglycemic effects of TZD in vivo and their affinity for PPARgamma in vitro, but the site of action and the molecular mechanism of TZD still remain poorly known. In human, skeletal muscles are responsible for more than 80% of glucose uptake in response to insulin. Unfortunately, skeletal muscles contain limited amounts of PPAR gamma. How TZD with the principal site of action being adipose tissue, can improve glucose metabolism in skeletal muscle? One possibility is the following Another possibility is that chronic treatment with TZD induces PPAR gamma expression in skeletal muscles. Finally, TZD could have a direct effect on skeletal muscles, independently of PPARgamma."]
[11448625,1,0,0,1,2001,"Axis formation and patterning in zebrafish.","Schier",11448625,"Axis formation and patterning in zebrafish.    Abstract:   A large collection of mutations affecting zebrafish embryogenesis was described in 1996. The cloning of the affected genes has now provided novel insights into the role and regulation of signaling by BMP, Nodal, Wnt, FGF, Hedgehog, Delta, Slit, retinoic acid and lipids. Detailed analyses have revealed a complex genetic network that patterns the early embryo."]
[11389365,0,0,0,0,2001,"Updates in pediatric nutrition.","Oken",11389365,"Updates in pediatric nutrition.    Abstract:   Ongoing research in several areas of pediatric nutrition has new practical applications for community-based pediatricians. For example, a fresh understanding of risk factors for rickets persuades pediatricians to recognize and treat this disease, which was thought to be nearly extinct in the modern industrialized world. Similarly, an expanded awareness of the antibacterial components of breast milk encourages a more complete dialogue between pediatricians and new mothers about the potential benefits of breast-feeding. For those infants with feeding intolerance, new data help to refine the indications for hypoallergenic formulas, which are increasingly recommended for children with a variety of symptoms. The past year also has seen breakthroughs in our understanding of supplemental nutrition for children. Vitamin A may provide direct benefits for the most vulnerable of children, namely premature infants at high risk for lung disease. At the other end of the pediatric spectrum, adolescent athletes seeking to enhance their performance are consuming poorly studied sports supplements that may not be beneficial and may even be toxic. Finally, a greater appreciation for the epidemic of obesity that is sweeping the United States and other countries suggests that children at high risk may represent a far more diverse population than had been recognized previously."]
[11384862,1,0,0,1,2001,"Studies of the effects of 1,25-dihydroxyvitamin D on skeletal and calcium homeostasis and on inhibition of tumor cell growth.","Goltzman",11384862,"Studies of the effects of 1,25-dihydroxyvitamin D on skeletal and calcium homeostasis and on inhibition of tumor cell growth.    Abstract:   Vitamin D, parathyroid hormone (PTH), and parathyroid hormone-related peptide (PTHrP) are major regulators of calcium metabolism and vitamin D can also reduce the growth of normal cells and tumor cells. PTHrP and PTH act via a common membrane receptor (PTHR). The mouse PTHR is regulated by a kidney-selective upstream promoter P(1) and ubiquitous downstream promoter P(2). In vitro and in vivo 1,25(OH)(2)D can inhibit PTHR expression in bone but not cartilage by downregulating transcription via P(2). Gene transcription of PTHrP per se can also be downregulated by 1,25(OH)(2)D and by low calcemic vitamin D analogs. This inhibitory effect may reduce the hypercalcemia caused by overproduction of PTHrP by tumor cells. In a malignant keratinoctye cell line, phosphorylation of the retinoid X receptor alpha occurs through the activated Ras-MAP kinase pathway and results in attenuated trans-activation by the vitamin D receptor, its heterodimeric partner. This decreases the growth-inhibitory efficacy of 1,25(OH)(2)D. Studies of the capacity of vitamin D to alter PTHrP production and action and of its anti-proliferative effects can, therefore, shed important light on basic mechanisms controlling these events, and may also have major implications for clinical medicine and therapeutics."]
[11376439,1,0,0,1,2000,"Molecular determinants of neural crest migration.","Maschhoff",11376439,"Molecular determinants of neural crest migration.    Abstract:   Normal septation of the cardiac outflow tract requires migration of neural crest cells from the posterior rhombencephalon to the branchial arches and developing conotruncal endocardial cushions. Proper migration of these cells is mediated by a variety of molecular cues. Adhesion molecules, such as integrins, are involved in the interaction of neural crest cells with the extracellular matrix, while cadherins allow neural crest cells to interact with each other during their migration. Pax3 appears to be important for proliferation of neural crest precursors, and connexin-43-mediated gap junction communication influences the rate of migration. Endothelin and its receptors are required for normal postmigratory differentiation. Platelet-derived growth factor and retinoic acid have roles in neural crest migration and differentiation as well. Finally, the similarity between the cardiovascular malformations seen in the DiGeorge and 22q11 deletion syndromes and animal models of neural crest deficiency has led to the examination of the role of genes located near or within the DiGeorge critical region in neural crest migration."]
[11338401,1,0,0,1,2001,"Xeroderma pigmentosum--bridging a gap between clinic and laboratory.","Moriwaki",11338401,"Xeroderma pigmentosum--bridging a gap between clinic and laboratory.    Abstract:   Xeroderma pigmentosum (XP) is an autosomal recessive photosensitive disorder with an extremely high incidence of UV-related skin cancers associated with impaired ability to repair UV-induced DNA damage. There are seven nucleotide excision repair (NER) complementation groups (A through G) and an NER proficient form (XP variant). XPA, B, D and G patients may also develop XP neurological disease. The laboratory diagnosis of XP can be performed by autoradiography. Recently, the isolation and characterization of the genes responsible for XP have made it possible to use molecular biological techniques to diagnose XP patients, for carrier detection and for prenatal diagnosis, especially in Japanese XPA patients. These techniques include polymerase chain reaction (PCR) and plasmid host cell reactivation assays with cloned XP genes. DNA damage is not repaired by the NER system equally throughout the genome. There are two DNA repair pathways: 1) transcription-coupled repair, and 2) global genome repair. Many factors involved in these pathways are related to the pathogenesis of XP and a related photosensitive disease, Cockayne syndrome. Clinical management consists of early diagnosis followed by a rigorous program of sun protection including avoidance of unnecessary UV exposure, wearing UV blocking clothing, and use of sunblocks on the skin. Although there is no cure for XP, the efficacy of oral retinoids for the prevention of new skin cancers, local injection of interferon, and the external use of a prokaryotic DNA repair enzyme have been reported."]
[11277079,2,0,0,2,2001,"Retinoid signalling and skeletal development.","Underhill",11277079,"Retinoid signalling and skeletal development.    Abstract:   Metabolites of vitamin A, including retinoic acid (RA), comprise a class of molecules known to be important in development and homeostasis. RA functions through a class of nuclear hormone receptors, the RA receptors (RARs), to regulate gene transcription. In the developing mammalian limb, RA affects the differentiation of many cell lineages, including those of the chondrogenic lineage. In excess, RA is a potent teratogen, causing characteristic skeletal defects in a stage- and dose-dependent manner. Genetic analysis has shown that the absence of RARs leads to severe deficiencies in cartilage formation at certain anatomical locations while promoting ectopic cartilage formation at other sites. Expression of either a dominant-negative or a weak constitutively active RAR in the developing limbs of transgenic mice adversely affects chondrogenesis leading to skeletal malformations. Together, these results show that RAR-mediated signalling plays a fundamental role in skeletogenesis. This chapter will focus on the function of RARs in regulating chondroblast differentiation and the contribution of RA signalling to appositional and longitudinal growth of the skeletal primordia."]
[11254890,1,0,0,1,2001,"Pharmacological interference with transcriptional control of osteoblasts: a possible role for leptin and fatty acids in maintaining bone strength and body lean mass.","Gordeladze",11254890,"Pharmacological interference with transcriptional control of osteoblasts: a possible role for leptin and fatty acids in maintaining bone strength and body lean mass.    Abstract:   Osteoblasts pass through a sequence of events controlled by hormones and transcriptional factors ensuring proper development of phenotype and functional properties until the osteoblast enter the osteocyte phenotype and/or undergo apoptosis. During its life cycle, the osteoblasts proliferate, deposit matrix proteins and mineralize it until they turn into osteocytes believed to constitute a mechanosensor mesh giving feed-back to the osteoblast to initiate bone modeling or remodeling necessary for the making or remaking of proper bone architecture and strength. It appears that several factors common to osteoblast and adipocyte differentiation determine their entry into different functional stages. Such factors are insulin, growth hormone (GH), insulin-like growth factor type I (IGF-I), transforming growth factor beta (TGFbeta), platelet derived growth factor (PDGF), fibroblast growth factor (FGF), cytokines (e.g. interleukins, interferon and tumor necrosis factor alpha (TNF alpha), bone morphogenetic proteins (BMPs), glucocorticoids, retinoic acid (RA), prostaglandins and cAMP-elevating hormones. The focus of this article is to review the effects of leptin on bone cells and bone turnover, the peroxisome proliferator-activated receptors (PPARs) in the regulation of bone and fat cell differentiation, hormones and fatty acids on the orchestration of osteoblast and adipocyte derived regulatory signals, and mechanostimulation of bone on the mechanisms by which the above mentioned factors modulate osteoblast and adipocyte function. The hypothesis or concept is that prescription of a certain treatment regimen to correct bone turnover, without attempting to assess how hormonal homeostasis, nutritional factors and physical exercise may interact locally, will remain far from optimal, and may even prove detrimental to the patients health condition."]
[11238791,0,0,0,0,2001,"Special nutritional needs of infants for prevention of and recovery from bronchopulmonary dysplasia.","Atkinson",11238791,"Special nutritional needs of infants for prevention of and recovery from bronchopulmonary dysplasia.    Abstract:   Extremely low birth weight infants who develop severe respiratory disease may have special nutrient requirements imposed by a combination of enhanced utilization of nutrients or the need for epithelial cell repair resulting from the disease process, as well as to support catch-up growth. Inositol, free fatty acids, vitamin E and vitamin A are proposed as nutrients for which infants at risk of chronic pulmonary insufficiency may have special requirements. Of these nutrients, only for vitamin A does suggestive evidence exist that high doses when given intramuscularly may reduce the incidence of death or chronic lung disease. Exogenous steroid therapy (dexamethasone), which is often used to improve pulmonary compliance in ventilated premature infants, may compromise vitamin A status and induce restricted somatic and bone mineral growth. Supplemental nutrition by means of enriched infant formulas has provided benefits in growth and bone mass accretion to infants recovering from bronchopulmonary dysplasia up to 3-mo corrected age. This growth advantage was not sustained over the subsequent 9 mo, suggesting that prolonged nutritional support is required until catch-up growth is complete. Further studies are required to delineate the needs for specific nutrients such as antioxidant vitamins and minerals or vitamin A that may play a role in preventing severe chronic lung disease in premature infants. As well, the role of supplemental nutrition (beyond the requirements of term infants) to support catch-up growth and maintenance during the critical stages of early development requires further investigation before evidence-based nutrient recommendations can be developed for this special population of infants."]
[11220289,0,0,0,0,1999,"The relation between insulin resistance and cardiovascular complications of the insulin resistance syndrome.","Rett",11220289,"The relation between insulin resistance and cardiovascular complications of the insulin resistance syndrome.    Abstract:   It has been known for years that cardiovascular disease frequently precedes the development of type 2 diabetes, and that atherosclerosis might not be a complication of type 2 diabetes, but rather the consequence of common genetic and environmental factors (the common soil hypothesis). The insulin resistance syndrome (IRS) is a cluster of closely associated and interdependent abnormalities, including insulin resistance, hyperinsulinaemia, android fat distribution, progressive glucose intolerance, dyslipidaemia (increased triglycerides, decreased HDL, increased small dense LDL), increased prothrombotic and antifibrinolytic factors, and hypertension. Many of these abnormalities are risk factors for type 2 diabetes, and most of them explain the predilection for atherosclerosis to occur in conjunction with IRS. Insulin resistance is a key feature of IRS, and has been suggested to be the common pathophysiological basis of atherosclerosis and type 2 diabetes. The term insulin resistance denotes resistance to insulin-mediated glucose uptake into skeletal muscle, which can be measured by the glucose clamp technique. There are, however, other less understood sites of abnormal insulin action that may also be relevant in IRS. These include liver, adipose, and kidney tissue, and systems such as muscle perfusion, antilipolysis, lipoprotein lipase activity, and cation transport. The development of clinical cardiovascular end-points in a patient with insulin resistance is complex, as it includes the degree of the defect, its associated abnormalities, its consequences, and the ability to compensate for the underlying defect. It is therefore more appropriate to consider the different facets and risk factors of IRS in aggregate, rather than seeking independent effects. Accordingly, treatment of insulin resistance per se has not yet been shown to reduce the incidence of cardiovascular complications. At the cellular level, excess insulin is involved in various elements of atherogenesis. It interacts with cytokines and growth factors in a cross talk among vascular wall cells and a variety of mediators that play a role in the establishment of atheroma. Excess insulin also plays an important role in concert with lipoproteins when they exhibit an abnormal pattern and become modified by oxidation and glycation. It is therefore currently hoped that the introduction of a new class of insulin-sensitizing agents, the thiazolidinediones, may attenuate these processes. The thiazolidinediones act through ligand activation of a nuclear transcription factor, the peroxisomal proliferator-activated receptor-gamma (PPARgamma). Although this receptor was initially linked to lipid and glucose metabolism, recent data suggest that PPARgamma is also involved in the differentiation of mononuclear phagocytes, their inflammatory reactions, and macrophage conversion to foam cells. Thus, PPARgamma ligands may also be important regulators of monocyte/ macrophage gene expression during atherogenesis."]
[11175361,1,0,0,1,2000,"Ets transcription factors and targets in osteogenesis.","Raouf",11175361,"Ets transcription factors and targets in osteogenesis.    Abstract:   Bone formation in vivo is a complex phenomenon whereby recruitment and replication of mesenchymal precursors of osteoblasts, differentiation into preosteoblasts, osteoblasts, and mature osteoblasts ultimately result in the accumulation and mineralization of the extracellular matrix. MC3T3-E1, a clonal osteoblastic cell line, was derived from mouse calvaria and undergoes an ordered and time dependent developmental sequence leading to formation of multilayered bone nodules over a 30 - 35 day period. This developmental pattern is characterized by the replication of preosteoblasts followed by growth arrest and expression of mature osteoblastic characteristics such as matrix maturation and eventual formation of multilayered nodules with a mineralized extracellular matrix. We have found that Ets1 is expressed in proliferating preosteoblastic cells whereas Ets2 is expressed by differentiating and mature osteoblasts. In addition, the expression of Ets1 can be induced in MC3T3-E1 and fetal rat calvaria cells by retinoic acid (RA) which is known to exert profound effects on skeletal growth and development, bone turnover, and induce specific cellular responses in bone cells. Thus the multiple functions of RA in bone cells are likely to be mediated in part by Ets1. Also, Ets2 transgenic mice develop multiple neurocranial, viserocranial, and cervical skeletal abnormalities. Significantly, these abnormalities are similar to the skeletal anomalies found in trisomy-16 mice and in humans with Downs syndrome, wherein the dosage of Ets2 is known to be increased. These results indicate that Ets2 has an important role in skeletal development and that Ets2 overexpression in transgenics is responsible for the genesis of the same type of skeletal abnormalities that are seen in Downs syndrome. Thus the genetic programs regulated by Ets1 and Ets2 may significantly affect the development and differentiation of osteoblasts, and in fact, Ets1 has been shown to interact with the quintessential osteoblast transcription factor CbfA1. This review will examine in detail the role and possible targets of Ets1 and Ets2 in osteoblast differentiation and bone formation."]
[11122886,5,0,0,5,2000,"Differentiating agents in pediatric malignancies: retinoids in neuroblastoma.","Reynolds",11122886,"Differentiating agents in pediatric malignancies: retinoids in neuroblastoma.    Abstract:   Retinoids are derivatives of vitamin A that include all- trans-retinoic acid (ATRA), 13-cis-retinoic acid, (13-cis-RA), and fenretinide (4-HPR). High levels of either ATRA or 13-cis-RA can cause arrest of cell growth and morphologic differentiation of human neuroblastoma cell lines. Phase I trials have shown that higher and more sustained drug levels were obtained with 13-cis-RA relative to ATRA. A phase III randomized trial showed that high-dose pulse therapy with 13-cis-RA given after completion of intensive chemoradiotherapy (with or without autologous bone marrow transplantation) significantly improves event-free survival in high-risk neuroblastoma. Because 4-HPR achieves multi-log cell kills in neuroblastoma cell lines that are resistant to ATRA and 13-cis-RA, a pediatric phase I trial is in progress to determine the maximum tolerated dose of 4-HPR, with a view toward giving 4-HPR after completion of myeloablative therapy and 13-cis-RA."]
[11084952,2,0,0,2,2000,"Neuroendocrine manifestations in Sjögrens syndrome.","Johnson",11084952,"Neuroendocrine manifestations in Sjögrens syndrome.    Abstract:   Molecular biology has had a major impact on our concepts of the immune system and its relation to neuroendocrine axes, in particular, the adrenal, gonadal, and thyroid axes. It is now well established that not only are the biosynthetic and catabolic pathways of glucocorticoids and sex hormones (estrogen, progesterone, and testosterone) closely related but that the receptors for these hormones are part of a supergene family of receptors which include (in addition to these hormone receptors) the mineralocorticoid receptor, thyroid hormone receptor, retinoic acid receptors, and vitamin D receptors. This suggests a complex network of steroid hormones and receptors for the control and integration of a multitude of physiologic functions at a systemic level. The immune system seems to be tightly integrated into this homeostatic neuroendocrine regulatory network. The neurophysiologic and biochemical events that promote successful adaptation during stressful situations are now identified for illnesses that seem to occur as a result of or are associated with dysregulation of the stress response. One difficulty in interpreting the mechanisms of HPA axis dysfunction in autoimmune-inflammatory syndromes arises from the plasticity of the hormonal systems involved. Levels of hormones produced and receptors reset rapidly with changes in the hormonal milieu (deficiency or excess) and have likely changed during the course of the chronic immune disorder. This, in turn, is further confounded by the pleomorphic natural history of most autoimmune-inflammatory diseases such as SS. The levels of sex hormones and their receptors are tightly linked to HPA axis function. It may be that significant changes in the estrogen-to-androgen ratio or the ratio of their receptors alter the activity of steroid-sensitive cells such as the individual immune cells or epithelial cells, thus providing a means for endocrine regulation of the immune response in SS. Studies in the closely related disorder RA support this hypothesis. Taken together, adrenal and gonadal steroid hormone deficiency plus elevated PRL levels probably greatly facilitate cellular immunity in SS patients. This hypothesis in SS is supported by a growing body of data indicating that RA develops as a consequence of a deficiency in adrenal and gonadal steroid hormone production. It is noteworthy that the findings in female SS patients indicated a central deficiency in all three neuroendocrine axes: adrenal, gonadal, and thyroid. At present, it is not clear if any one system plays a primary role in the expression of the disease. Rather, it is likely that the net effect involves the synergistic and antagonistic effects of multiple hormones, making the specific effects of individual hormones difficult to discern."]
[11076197,1,0,0,1,2000,"[Regulation of neural differentiation amp; neurotrophic factor responsiveness by bone morphogenetic protein and retinoic acid].","Matsuoka",11076197,"[Regulation of neural differentiation amp; neurotrophic factor responsiveness by bone morphogenetic protein and retinoic acid].    Abstract:  "]
[11066455,5,0,0,5,2000,"Acute promyelocytic leukemia (AML-M3)--Part 1: Pathophysiology, clinical diagnosis, and differentiation therapy.","Randolph",11066455,"Acute promyelocytic leukemia (AML-M3)--Part 1: Pathophysiology, clinical diagnosis, and differentiation therapy.    Abstract:    OBJECTIVES : The objectives of this review paper are to: Compare acute leukemia with chronic leukemia and other forms of cancer. Review the pathophysiology and discuss the clinical and diagnostic features of M3. Describe the variant of M3 (M3m or M3v). Compare conventional chemotherapy with all-trans retinoic acid differentiation therapy (ATRA) in the treatment of M3. Discuss the future direction of differentiation therapy.  DATA SOURCES : Current literature.  DATA SYNTHESIS : Until the late 1970s, the methods of diagnosis and treatment of AML-M3 were similar to the other forms of acute myelocytic leukemia. One notable difference between M3 and other acute myelocytic leukemias involved the common occurrence of life-threatening consumptive coagulopathies in M3 patients that dramatically affected patient outcomes. In 1977 the method of diagnosis confirmation was altered by the identification of a consistent chromosomal translocation involving the long arms of chromosomes 15 and 17. Reports in the 1970s and 1980s indicated that certain types of active metabolites of vitamin A, collectively termed retinoids, could induce differentiation in a variety of cancer derived cell lines, in vitro. It was shown in the early 1980s that 13-cis-retinoic acid (13cRA) could stimulate differentiation in bone marrow cells collected from patients with various acute leukemias, including M3. The first clinical trial of a retinoid, given as a remission induction therapeutic regimen, involved all-trans retinoic acid (ATRA) administered to M3 patients in 1988. Since then, ATRA therapy has been shown to reduce tumor burden by stimulating differentiation of the leukemic cells, induce long-term clinical remission when administered in conjunction with chemotherapy, and lower the incidence of consumptive coagulopathies in patients with AML-M3.  CONCLUSION : The diagnosis and treatment of AML-M3 has improved dramatically in the past decade, which has greatly enhanced the prognosis of patients with this disease. First remission rates have increased to greater than 85% world wide, the incidence of disseminated intravascular coagulation (DIC) has declined dramatically, and 60% to 70% of patients with AML-M3 have achieved long term survival and are potentially cured."]
[11063942,0,0,0,0,2000,"From the bottom of the heart: anteroposterior decisions in cardiac muscle differentiation.","Rosenthal",11063942,"From the bottom of the heart: anteroposterior decisions in cardiac muscle differentiation.    Abstract:   Recently, studies on specification of axes in the developing embryo have focused on the heart, which is the first functional organ to form and probably responds to common cues controlling positional information in surrounding tissues. The early differentiation of heart cells affords an opportunity to link the acquisition of regional identity with the signals underlying terminal differentiation. In the past year, a wealth of information on these signals has emerged, elucidating the general pathways controlling body axes in the context of the developing heart."]
[11061437,0,0,0,0,2000,"Integrin function and regulation in development.","Tarone",11061437,"Integrin function and regulation in development.    Abstract:   Integrins are a large family of membrane receptors, consisting of alpha and beta subunits, that play a pivotal role in the interaction of cells with the extracellular matrix. Such interaction regulates the organization of cells in organs and tissues during development as well as cell differentiation and proliferation. We have shown that unfertilized oocytes express integrins that might be important during fertilization. We also analyzed nervous system and muscle tissue development showing that integrin expression is precisely regulated during organization of these tissues. The results indicate that two distinct integrin alpha subunits mediate the outgrowth of processes in nerve and glial cells. Alpha1 integrin, a laminin receptor, is up-regulated by nerve growth factor and other differentiation stimuli and is involved in neurite extension by nerve cells. In contrast, process extension by glial cells is likely to involve the alphaV integrin. Moreover, the latter integrin subunit is also transiently expressed in muscle of the embryo body where it localizes predominantly at developing myotendinous junctions. After birth this integrin disappears and is substituted by the alpha7 subunit. At the same time, important changes also occur in the expression of the associated beta subunit. In fact, the beta1A isoform which is expressed in fetal muscles, is substituted by beta1D. These isoforms are generated by alternative splicing and differ in only a few amino acid residues at the COOH terminus of the protein. This region of the molecule is exposed at the cytoplasmic face of the plasma membrane and is connected to the actin filaments. Our results show that beta1D, which is expressed only in striated muscle tissues, binds to both cytoskeletal and extracellular matrix proteins with an affinity higher than beta1A. Thus, beta1D provides a stronger link between the cytoskeleton and extracellular matrix necessary to support mechanical tension during muscle contraction. These results indicate that cells can regulate their interactions with the extracellular matrix by changing their expression of alpha integrin subunits and thus ligand specificity, or by more subtle changes involving alternative usage of different cytoplasmic domains. The important role of both alpha and beta integrin subunit cytoplasmic domains during development is further illustrated by the analysis of targeted mutations which we have generated by homologous recombination in mice."]
[11051216,1,0,0,1,2000,"Drug-induced rheumatic disorders: incidence, prevention and management.","Vergne",11051216,"Drug-induced rheumatic disorders: incidence, prevention and management.    Abstract:   The purpose of this article is to review the causes, the clinical manifestations and the management of the more frequent drug-induced rheumatic disorders. These include: (i) articular and periarticular manifestations induced by fluoroquinolones, nonsteroidal anti-inflammatory drugs, injections of corticosteroids, and retinoids; (ii) multisystemic manifestations such as drug-induced lupus and arthritis induced by vaccination, Bacillus Calmette-Guerin therapy and cytokines; (iii) drug-induced disorders of bone metabolism (corticosteroid-induced osteoporosis, drug-induced osteomalacia and osteonecrosis); and (iv) iatrogenic complex regional pain syndromes. Disorders caused by nonpharmacological and rarely used treatments have been deliberately excluded. Knowledge of these drug-induced clinical symptoms or syndromes allows an earlier diagnosis and treatment, and earlier drug withdrawal if necessary. With the introduction of new medications such as the recombinant cytokines and antiretroviral treatments, the number of drug-induced rheumatic disorders is likely to increase."]
[11021632,1,0,0,1,2000,"Genetic and teratogenic approaches to craniofacial development.","Young",11021632,"Genetic and teratogenic approaches to craniofacial development.    Abstract:   Craniofacial malformations are the most common birth defects that occur in humans, with facial clefting representing the majority of these defects. Facial clefts can arise at any stage of development due to perturbations that alter the extracellular matrix as well as affect the patterning, migration, proliferation, and differentiation of cells. In this review, we focus on recent advances in the understanding of the developmental basis for facial clefting through the analysis of the effects of gene disruption experiments and treatments with teratogens in both chickens and mice. Specifically, we analyze the results of disruptions to genes such as Sonic hedgehog (Shh), epidermal growth factor receptor (EGFR), Distal-less (Dlx), and transforming growth factor beta 3 (TGFbeta3). We also describe the effects that teratogens such as retinoic acid, jervine, and cyclopamine have on facial clefting and discuss mechanisms for their action. In addition to providing insight into the bases for abnormal craniofacial growth, genetic and teratogenic techniques are powerful tools for understanding the normal developmental processes that generate and pattern the face."]
[11021176,2,0,0,2,2000,"[A case of intestinal Behçets disease with abnormal ossification complicated by myelodysplastic syndrome, symptoms revealed after the perforation of ileum ulcer].","Tanaka",11021176,"[A case of intestinal Behçets disease with abnormal ossification complicated by myelodysplastic syndrome, symptoms revealed after the perforation of ileum ulcer].    Abstract:   A 39-year-old man, who had been treated with Etretinate for common wart since he was 29 years old, was admitted to Taga General Hospital complaining of gradually deteriorating lumbago and bilateral hip joints pain in September, 1996. His lower vertebrae and bilateral hip joints showed abnormal ossification on X-ray. The bone scintigraphy indicated the existence of sacroiliitis. His platelet counts were fluctuating between 8 x 10(4) and 9 x 10(4)/mm3. During the follow-up in our out-patient clinic, he was suddenly suffered from severe abdominal pain in August, 1997 and admitted to our hospital. An emergency operation revealed multiple ulcers of his ileum with several perforations. Histological findings of the specimen of the ileum showed simple ulcer. After the operation, he had oral and genital ulcers. He did not have any signs or symptoms of ocular involvement. He was diagnosed as intestinal Behçets disease. Because he showed gradually pancytopenia for several months after the operation, bone marrow aspiration was performed and a diagnosis of refractory anemia, a type of myelodysplastic syndrome (MDS), with trisomy of chromosome 8 was made. Abnormal ossification of his vertebrae and hip joints were considered to be related to Behçets disease because an coexistence with sacroiliitis. On the other hand, there is no denying the effects of orally Etretinate administration. Several cases have been reported the association of MDS with Behçets disease. In this case, the existence of MDS or various symptoms in Behçets disease became apparent after the perforation of ileum ulcer. This paper discusses possible etiology of the relation between Behçets disease and MDS, or the characteristic clinical course in this case."]
[10969032,1,0,0,1,2000,"Retinoids: versatile biological response modifiers of vascular smooth muscle phenotype.","Miano",10969032,"Retinoids: versatile biological response modifiers of vascular smooth muscle phenotype.    Abstract:  "]
[10938007,1,0,0,1,2000,"Retinoids and arterial smooth muscle cells.","Neuville",10938007,"Retinoids and arterial smooth muscle cells.    Abstract:  "]
[10936415,1,0,0,1,2000,"PPARgamma: observations in the hematopoietic system.","Greene",10936415,"PPARgamma: observations in the hematopoietic system.    Abstract:   Human Peroxisome Proliferator-Activated Receptor gamma (PPARgamma) was originally cloned from a human bone marrow library. What role does this ligand activated transcription factor play in hematopoiesis and the immune system? We note that: a) PPARgamma has potential to interact/interfere or synergize with retinoid biology, b) fatty acids and a prostaglandin have been identified as ligands, and c) lymphocytes, monocytes and neutrophils use fatty acids as a major source of energy production, d) PPARgamma has been shown to oppose TNFalpha and down regulate cytokine production in monocytes. Therefore, we undertook a review of the literature and an expression survey of PPARgamma in a number of major organs and cells involved in the hematopoietic system, for the purpose of building a database towards understanding the role and function of PPARgamma gene regulation in the developing blood and immune systems. PPARgamma is expressed before mesodermal induction in tissue in and around Speymanns organizer in the xenopus blastocyst, in erythroid precursors of blood islands and in the circulation of the day 10.0 murine embryo, in human 19 week fetal liver, in some but not all murine and human bone marrow erythroid, myeloid, and monocytoid progenitors, bone marrow stromal cells and adipocytes, osteoblasts, endothelial cells, some T, and B lymphocytes, monocytes, macrophages, and other monocytic derivatives. It can be found in the cells of Peyers patches, lymphoid follicles, spleen, and thymus. It is not clear if it is ever or transiently expressed in megakaryocytes, mast cells, or neutrophils. Based on the above data and a review of the literature, PPARgamma seems to play a role during the elicitation of immune responses. We propose PPARgamma may be involved in changes in energy states required during activation and development of many cell types involved, and has additional immunologically relevant effects in erythroid, myeloid, monocytic, T and B lymphocytic, stromal, and endothelial cell function."]
[10911016,1,0,0,1,2000,"Novel approaches for designing 5-O-ester prodrugs of 3-azido-2, 3-dideoxythymidine (AZT).","Parang",10911016,"Novel approaches for designing 5-O-ester prodrugs of 3-azido-2, 3-dideoxythymidine (AZT).    Abstract:   3-Azido-2,3-dideoxythymidine (AZT, 1, zidovudine, RetrovirTM) is used to treat patients with human immunodeficiency virus (HIV) infection. AZT, after conversion to AZT-5-triphosphate (AZT-TP) by cellular enzymes, inhibits HIV-reverse transcriptase (HIV-RT). The major clinical limitations of AZT are due to clinical toxicities that include bone marrow suppression, hepatic abnormalities and myopathy, absolute dependence on host cell kinase-mediated activation which leads to low activity, limited brain uptake, a short half-life of about one hour in plasma that dictates frequent administration to maintain therapeutic drug levels, low potential for metabolic activation and/or high susceptibility to catabolism, and the rapid development of resistance by HIV-1. These limitations have prompted the development of strategies for designing prodrugs of AZT. A variety of 5-O-substituted prodrugs of AZT constitute the subject of this review. The drug-design rationale on which these approaches are based is that the ester conjugate will be converted by hydrolysis and/or enzymatic cleavage to AZT or its 5amp;prime;-monophosphate (AZT-MP). Most prodrug derivatives of AZT have been prepared by derivatization of AZT at its 5-O position to provide two prominent classes of compounds that encompass: A) 5-O-carboxylic esters derived from 1) cyclic 5-O-carboxylic acids such as steroidal 17b-carboxylic acids, 1-adamantanecarboxylic acid, bicyclam carboxylic acid derivatives, O-acetylsalicylic acid, and carbohydrate derivatives, 2) amino acids, 3) 1, 4-dihydro-1-methyl-3-pyridinylcarboxylic acid, 4) aliphatic fatty acid analogs such as myristic acid containing a heteroatom, or without a heteroatom such as stearic acid, and 5) long chain polyunsaturated fatty acid analogs such as retinoic acid, and B) masked phosphates such as 1) phosphodiesters that include monoalkyl or monoaryl phosphate, carbohydrate, ether lipid, ester lipid, and foscarnet derivatives, 2) a variety of phosphotriesters that include dialkylphosphotriesters, diarylphosphotriesters, glycolate and lactate phosphotriesters, phosphotriester approaches using simultaneous enzymatic and chemical hydrolysis of bis(4-acyloxybenzyl) esters, bis(S-acyl-2-thioethyl) (SATE) esters, cyclosaligenyl prodrugs, glycosyl phosphotriesters, and steroidal phosphotriesters, 3) phosphoramidate derivatives, 4) dinucleoside phosphate derivatives that possess a second anti-HIV moiety such as AZT-P-ddA, AZT-P-ddI, AZTP2AZT, AZTP2ACV), and 5) 5-hydrogen phosphonate and 5-methylene phosphonate derivatives of AZT. In these prodrugs, the conjugating moiety is linked to AZT via a 5-O-ester or 5-O-phosphate group. 5-O-Substituted AZT prodrugs have been designed with the objectives of improving anti-HIV activity, enhancing blood-brain barrier penetration, modifying pharmacokinetic properties to increase plasma half-life and improving drug delivery with respect to site-specific targeting or drug localization. Bypassing the first phosphorylation step, regulating transport and conferring sustained release of AZT prolong its duration of action, decrease toxicity and improve patient acceptability. The properties of these prodrugs and their anti-HIV activities are now reviewed."]
[10908464,6,0,0,6,2000,"Interventions for psoriatic arthritis.","Jones",10908464,"Interventions for psoriatic arthritis.    Abstract:    OBJECTIVES : To assess the effects of salazopyrin, auranofin, etretinate, fumaric acid, IMI gold, azathioprine, efamol marine and methotrexate, in psoriatic arthritis.  SEARCH STRATEGY : We searched Medline up to February 2000, and Excerpta Medica (June 1974-95). Search terms were psoriasis, arthritis, therapy and/or controlled trial. This was supplemented by manually searching bibliographies of previously published reviews, conference proceedings, contacting drug companies and referring to the Cochrane Clinical Trials Register. All languages were included in the initial search.  SELECTION CRITERIA : All randomized trials comparing salazopyrin, auranofin, etretinate, fumaric acid, IMI gold, azathioprine, and methotrexate, in psoriatic arthritis. Following a published a priori protocol, the main outcome measures included individual component variables derived from Outcome Measures in Rheumatology Clinical Trials (OMERACT). These include acute phase reactants, disability, pain, patient global assessment, physician global assessment, swollen joint count, tender joint count and radiographic changes of joints in any trial of one year or longer [Tugwell 1993], and the change in pooled disease index (DI). Only English trials were included in the review.  DATA COLLECTION AND ANALYSIS : Data were independently extracted from the published reports by two of the reviewers (MC, GJ). An independent blinded quality assessment was also performed.  MAIN RESULTS : Twenty randomized trials were identified of which thirteen were included in the quantitative analysis with data from 1022 subjects. Although all agents were better than placebo, parenteral high dose methotrexate (not included), salazopyrin, azathioprine and etretinate were the agents that achieved statistical significance in a global index of disease activity (although it should be noted that only one component variable was available for azathioprine and only one trial was available for etretinate suggesting some caution is necessary in interpreting these results). Analysis of response in individual disease activity markers was more variable with considerable differences between different medications and responses. In all trials the placebo group improved over baseline (pooled improvement 0.39 DI units, 95% CI 0.26-0.54). There was insufficient data to examine toxicity.  REVIEWERS CONCLUSIONS : Parenteral high dose methotrexate and salazopyrin are the only two agents with well demonstrated published efficacy in psoriatic arthritis. The magnitude of the effect seen with azathioprine, etretinate, oral low dose methotrexate and perhaps colchicine suggests that they may be effective but that further multicentre clinical trials are required to establish their efficacy. Furthermore, the magnitude of the improvement observed in the placebo group strongly suggests that uncontrolled trials should not be used to guide management decisions in this condition."]
[10898344,1,0,0,1,2000,"Prostate carcinoma: production of bioactive factors.","Deftos",10898344,"Prostate carcinoma: production of bioactive factors.    Abstract:    BACKGROUND : Many molecular mechanisms regulate prostate carcinoma pathogenesis, proliferation, and progression to bone metastases. The basic molecular mechanisms are endocrine, paracrine, autocrine, and intracrine. These mechanisms can be mediated by a variety of agents, including gonadal and adrenal steroids, retinoic acid and vitamin D derivatives, neuroendocrine factors, growth factors, cytokines, lymphokine, and bone factors. Prominent among them is parathyroid hormone-related protein (PTHrP).  METHODS : The author studied the expression and regulation of PTHrP production in prostate carcinoma cells with nucleic acid and immunochemical probes for the polypeptide. The robust expression of this oncoprotein by prostate carcinoma has been demonstrated. In the current study the author reviews his results and the studies of other investigators regarding PTHrP and the variety of bioactive factors produced by prostate cells.  RESULTS : PTHrP is expressed by most prostate carcinoma. It also is expressed by normal and hyperplastic prostate cells, and there is a gradient of expression that peaks in malignant prostate cells. PTHrP is processed by carcinoma cells into peptides that have unique biologic effects. Among them are regulation of growth and cytokine expression. It has been observed that the effect of PTHrP can be mediated by novel intracrine pathways in prostate carcinoma. These mechanisms influence transduction of growth regulatory signaling pathways, cell proliferation, immunoregulation, and angiogenesis.  CONCLUSIONS : The current study identified PTHrP among the bioactive prostate factors that appear to participate in prostate carcinoma pathogenesis and progression. This oncofetal protein is commonly expressed by prostate carcinoma, and its regulatory interactions with other bioactive prostate cell products play an important role in the pathobiology of prostate carcinoma. Understanding these regulatory interactions among prostate carcinoma, its cell products, and the skeleton continues to provide insights into the pathogenesis of this disease entity and may provide clues to clinical management."]
[10897129,1,0,0,1,2000,"Cutaneous promyelocytic sarcoma at sites of vascular access and marrow aspiration. A characteristic localization of chloromas in acute promyelocytic leukemia?","Sanz",10897129,"Cutaneous promyelocytic sarcoma at sites of vascular access and marrow aspiration. A characteristic localization of chloromas in acute promyelocytic leukemia?    Abstract:   Extramedullary disease (EMD) is a rare clinical event in acute promyelocytic leukemia (APL). Although the skin is involved in half of the reported EMD cases, the occurrence of cutaneous promyelocytic sarcoma (PS) has been described very rarely. We report here three cases of PS which have the peculiarity of appearing at sites of punctures for arterial and venous blood and marrow samples (sternal manubrium, antecubital fossa, wrist over the radial artery pulse, catheter insertion scar). At presentation, all patients had hyperleukocytosis and a morphologic diagnosis of microgranular acute promyelocytic leukemia variant confirmed at the genetic level by demonstration of the specific chromosomal translocation t(15;17). A BCR3 type PML/RARa transcript was documented in the two patients for whom diagnostic RT-PCR was available. Patients had morphologic bone marrow remission at the time the PS appeared. A predilection for the development of cutaneous PS at sites of previous vascular damage has been noted, but the pathogenesis remains largely unknown. A potential role for all-trans retinoic acid has been advocated, although one of the three patients in our series had received no ATRA. A review of the literature revealed six similar cases and hyperleukocytosis at diagnosis was a consistent finding in all of them. A careful physical examination of these particular sites in the follow-up of patients at risk, as well as cutaneous biopsy and laboratory examination of suspected lesions are strongly recommended."]
[10882175,1,0,0,1,2000,"Recent advances in the treatment of acute leukemia: 1999.","Berman",10882175,"Recent advances in the treatment of acute leukemia: 1999.    Abstract:   This review briefly summarizes literature noteworthy in the field of adult acute leukemia published during 1999. The relationship between specific cytogenetic abnormalities and response to treatment was explored within a clinical framework. In particular, detailed analyses of the abnormalities seen in acute promyelocytic leukemia were examined. Two case reports of special interest were published: one shed light on the role of histone deacetylase inhibitors in combination with all-trans retinoic acid, and the other, on the role of granulocyte colony-stimulating factor in this disease. The clinical activity of arsenic was also reported and its mechanism of action explored. In acute lymphoblastic leukemia, attention was focused on occult translocations, and the importance of minimal residual disease was again emphasized. Lastly, results of early clinical trials using an anti-CD19 antibody were reported, with provocative results."]
[10860393,0,0,0,0,2000,"Hypervitaminosis A and bone.","Binkley",10860393,"Hypervitaminosis A and bone.    Abstract:   Animal, human, and in vitro data all indicate that excess vitamin A stimulates bone resorption and inhibits bone formation. This combination would be expected to produce bone loss and to contribute to osteoporosis development and may occur with relatively low vitamin A intake. It is possible that unappreciated hypervitaminosis A contributes to osteoporosis pathogenesis."]
[10796328,6,0,0,6,2000,"Interventions for psoriatic arthritis.","Jones",10796328,"Interventions for psoriatic arthritis.    Abstract:    OBJECTIVES : To assess the effects of salazopyrin, auranofin, etretinate, fumaric acid, IMI gold, azathioprine, and methotrexate, in psoriatic arthritis.  SEARCH STRATEGY : We searched Medline up to 1995, and Excerpta Medica (June 1974-95). Search terms were psoriasis, arthritis, therapy and/or controlled trial. This was supplemented by manually searching bibliographies of previously published reviews, conference proceedings and contacting drug companies. All languages were included in the initial search.  SELECTION CRITERIA : All randomized trials comparing salazopyrin, auranofin, etretinate, fumaric acid, IMI gold, azathioprine, and methotrexate, in psoriatic arthritis. The main outcome measures included individual component variables derived from Outcome Measures in Rheumatology Clinical Trials (OMERACT). These include Acute Phase Reactants, Disability, Pain, Patient Global Assessment, Physician Global Assessment, Swollen joint count, Tender joint count and radiographic changes of joints in any trial of 1 year or longer [Tugwell 1993], and the change in pooled disease index. Only English trials were included in the review.  DATA COLLECTION AND ANALYSIS : Data were independently extracted from the published reports by two of the reviewers. An independent blinded quality assessment was also performed.  MAIN RESULTS : Nineteen randomized trials were identified of which eleven were included in the quantitative analysis with data from 777 subjects. Although all agents were better than placebo, parenteral high dose methotrexate (not included), salazopyrin, azathioprine and etretinate were the agents that achieved statistical significance in a global index of disease activity (although it should be noted that only one component variable was available for azathioprine and only one trial was available for etretinate suggesting some caution is necessary in interpreting these results). Analysis of response in individual disease activity markers was more variable with considerable differences between different medications and responses. In all trials the placebo group improved over baseline (pooled improvement 0.43 DI units, 95% CI 0. 28-0.59). There was insufficient data to examine toxicity.  REVIEWERS CONCLUSIONS : Parenteral high dose methotrexate and salazopyrin are the only two agents with well demonstrated published efficacy in psoriatic arthritis. The magnitude of the effect seen with azathioprine, etretinate, oral low dose methotrexate and perhaps colchicine suggests that they may be effective but that further multicentre clinical trials are required to establish their efficacy. Furthermore, the magnitude of the improvement observed in the placebo group strongly suggests that uncontrolled trials should not be used to guide management decisions in this condition."]
[10748547,1,0,3,4,2000,"[Environment and genetics in the etiology of cleft lip and cleft palate with reference to the role of folic acid].","Bianchi",10748547,"[Environment and genetics in the etiology of cleft lip and cleft palate with reference to the role of folic acid].    Abstract:   The combined birth prevalence of cleft palate [CP] and cleft lip with or without cleft palate [CL(P)] in Europe is approximately one in 700 with characteristic regional variations. Orofacial clefting (OC) is therefore now one of the most frequent congenital anomalies, with a higher birth prevalence that Downs Syndrome or Neural Tube defects, but still lower than cardiovascular malformation. Babies with OC require a multidisciplinary medical approach, surgery and rehabilitative treatments over time. This means an important effort in terms of social organization as well as economical costs for the health care system. In Italy, the health care costs for approximately 800 children born with orofacial clefting per year has been estimated at around 150 billion Lire (80 million Euros). The etiology of OC is complex and heterogeneous both for isolated and associated defects; causes linked to environment, genetics and gene-environment interaction are known, although there is still a lot to do, especially in clarifying the role of genetics in producing susceptibility to the environment. Four categories of genes for which there are results suggestive of a genetic susceptibility to OCs are: 1) genes expressed in a particular area of the embryo or in a particular period of the palatine arch development, such as the transforming growth factors alpha and beta (TGF alpha, TGF beta 2, TGF beta 3); 2) genes having biological activities linked to the OCs pathogenesis without direct involvement (e.g. the retinoic acid receptor (RARA), the methylenetetrahydrofolate reductase receptor (MTHFR) and the folic acid receptor (FOLR1); 3) genes or locus identified in experimental animals as the homeotic genes MSX-1 and MSX-2; 4) genes involved in the interaction with the xenobiotics metabolism as those in P-450 cytochrome system. Several environmental factors have been implicated in the OC etiology; among those, the folic acid supplementation during the periconceptional period that was found effective in the prevention of neural tube defects. In fact, folic acid deficiency may be responsible for different malformations through a common mechanism that interferes with the embryonic development, depending on the maternal or embryo genotype. Further investigation is required to study in depth how the genotype would modify the role of environmental factors like folic acid. Well-designed and conducted epidemiological studies seem to be able to give worthwhile information. Studies carried out in Europe on these issues are a few, particularly those on gene-environment interaction. Recent results obtained in molecular biology and the availability of wealth of data can allow to perform ad hoc investigations, being important not only for the basic research but also for their public health implications. For this objective a specific scientific network at the European level has been set by the European Science Foundation (ESF), whose first step will be to establish consistent case ascertainment and data collection across Europe and to develop standardized protocols and methods of analysis. It is hoped that in the longer term such multicentre collaborative research will enable combined analysis and lead to the identification of genetic susceptibility to certain environmental factors, including nutrition. Such studies would inform the current debate about the efficacy of folic acid and other nutritional factors in prevention of disease in the developing embryo. Subsequent public health measures targeted according to risk might reduce the prevalence of disorders such as orofacial clefting."]
[10728792,1,0,0,1,2000,"New aspects of hepatic fibrosis.","Brenner",10728792,"New aspects of hepatic fibrosis.    Abstract:   Hepatic stellate cells are the major source of extracellular matrix proteins in hepatic fibrosis, including Type I collagen. In response to liver injury, the hepatic stellate cells change from a quiescent to an activated phenotype. This activation process includes a phenotypic change to a myofibroblast-like cell, increased proliferation rate, loss of retinoid stores, increased production of extracellular matrix proteins, chemokines, and cytokines, and contractility. Ongoing studies are characterizing the genes that are differentially expressed in the quiescent and activated hepatic stellate cells. We have also investigated the regulation of Type I collagen expression, the cleavage of collagen propeptides, and the formation of collagen cross-links. Understanding these pathways may provide new insights into the molecular pathogenesis of hepatic fibrosis."]
[10723235,0,0,0,0,2000,"[Mechanisms of pathogenesis and differentiation-induction in acute promyelocytic leukemia].","Higuchi",10723235,"[Mechanisms of pathogenesis and differentiation-induction in acute promyelocytic leukemia].    Abstract:  "]
[10702899,1,0,0,1,2000,"Minimal residual disease in acute promyelocytic leukemia.","Weil",10702899,"Minimal residual disease in acute promyelocytic leukemia.    Abstract:   In the last decade our understanding of acute promyelocytic leukemia (APL) has advanced tremendously. The recognition of all-trans retinoic acid (ATRA) as a powerful therapeutic agent paralleled the cloning of the t(15;17) breakpoint. RtPCR for the PML-RARA hybrid mRNA has become the hallmark of molecular diagnosis and molecular monitoring in APL. Current techniques are useful in predicting complete remission and a possible cure in many patients who repeatedly test negative by PCR. Standardizing techniques and improving the sensitivity of the assay are important. Doing this in a way so that clinically relevant minimal residual disease can be distinguished from quot;indolent diseasequot; remains among the future challenges in APL."]
[10680277,0,0,0,0,2000,"Psoriasis: a clinical update on diagnosis and new therapies.","Camisa",10680277,"Psoriasis: a clinical update on diagnosis and new therapies.    Abstract:   Psoriasis varies widely in its clinical expression, from a single fingernail pit to widespread disfiguring skin lesions and disabling arthritis. Treatments are divided into five levels, providing a framework for approaching this disease according to severity and recalcitrance to previous treatment. Powerful immunosuppressive drugs are showing some success in treating severe cases."]
[10680075,2,0,0,2,2000,"Chemoprevention of breast cancer in the older patient.","Minton",10680075,"Chemoprevention of breast cancer in the older patient.    Abstract:   Age is the most important risk factor for the development of breast cancer. The risk of breast cancer continues to increase in American women until the age of 80 years. A family history of breast cancer helps identify those who possibly have the highest risk of developing breast cancer; however, most women who develop breast cancer do not have a first-degree relative with a history of breast cancer. Currently, the Gail model is a commonly used model to identify risk, and this model has now been validated in several populations of women undergoing screening for breast cancer. The first large-scale breast cancer prevention trial investigating the preventive effects of tamoxifen has demonstrated a decrease in the development of breast cancer by almost 50% in the women in the tamoxifen treatment arm as compared with those receiving placebo. The NSABP P-1 trial was the largest of the three tamoxifen breast cancer prevention trials and had the greatest power to detect a difference between the two treatment groups in breast cancer events. This trial also included the largest percentage of postmenopausal women. It is unclear why the Italian and Royal Marsden Hospital trials had negative results regarding the preventive effects of tamoxifen. These two trials were strikingly different from the NSABP P-1 trial, however, and they included a different population of women. The issues surrounding the use of HRT for treatment of hot flashes in the Italian and Royal Marsden Hospital trials adds to the controversy concerning the negative results of these trials. The new SERM, raloxifene, has shown promise in preliminary studies as a preventive agent for breast cancer. The STAR trial will open soon and will evaluate the efficacy of raloxifene in preventing breast cancer in a prospective fashion, comparing its efficacy with tamoxifen treatment. Other endpoints will evaluate side effects such as menopausal symptoms, endometrial cancer, thromboembolic events, and benefits regarding serum lipids and incidence of osteoporotic bone fractures. The development of SERMs results from an understanding of novel mechanisms of ER modulation and allows targeting for favorable effects in specific tissues. The challenge is to develop an ideal SERM that is effective in preventing breast cancer and does not increase the risk of endometrial cancer, while providing beneficial estrogenic effects on serum lipids and bone mineral density changes. Estrogen receptor-mediated intracellular processes are complex. There are at least two different types of estrogen receptors. The alpha receptors predominate in the breast and uterus, and the beta receptors predominate in the bone and blood vessels. Many proteins also interact with these receptors as co-activators or co-repressors. Transcription-activating factors modulate the effects of estrogen on its target genes. Future prevention strategies may use a combined targeted approach to inhibit ER-mediated cancer progression pathways. The retinoids are under investigation in prevention studies for a multitude of cancers, because they have been shown to inhibit cellular proliferation and to induce cellular differentiation. The retinoid 4HPR was selected for use in breast cancer prevention studies because of its low toxicity profile and prevention efficacy in preclinical studies. It is now being used in combination with tamoxifin in a phase II breast cancer prevention trial. Multiple surrogate endpoint biomarkers are being measured before and after treatment, including measurement of serum IGF-I levels. Future directions in breast cancer prevention include the development of more potent hormonal therapies that completely inhibit ER-mediated cancer progression and, ultimately, multitargeted therapies involving agents that work synergistically."]
[10657279,1,0,0,1,2000,"Steroid hormone receptor expression and action in bone.","Bland",10657279,"Steroid hormone receptor expression and action in bone.    Abstract:   The skeleton is a complex tissue, and hormonal control of bone remodelling is elaborate. The important role that steroid hormones play in bone cell development and in the maintenance of normal bone architecture is well established, but it is only relatively recently that it has become possible to describe their precise mechanism of action. This review focuses not only on the steroid hormones (oestrogens, corticosteroids, androgens and progesterone), but also on related hormones (vitamin D, thyroid hormone and the retinoids), all of which act via structurally homologous nuclear receptors that form part of the steroid/thyroid receptor superfamily. By examining the actions of all of these hormones in vivo and in vitro, this review gives a general overview of the current understanding of steroid hormone action in bone. In addition, a comprehensive review of steroid hormone receptor expression in bone cells is included. Finally, the role that future developments, such as steroid hormone receptor knockout mice, will play in our understanding of steroid hormone action in bone is considered."]
[10626120,1,0,0,1,2000,"Emerging new therapies for cutaneous T-cell lymphoma.","Duvic",10626120,"Emerging new therapies for cutaneous T-cell lymphoma.    Abstract:   Improved therapy for CTCL will depend on a better understanding of the pathogenesis of this disease at a molecular level. It is clear that the T cells in MF and CTCL do not undergo normal programmed cell death and have prolonged lifespans. Skin flora or other antigens may stimulate the initial proliferation, offering another approach to change the course of the disease. There has been tremendous interest in biological response modifiers, and the first targeted fusion toxin to activated T cells has been approved for CTCL. New retinoids with increased selectivity and decreased side effects are being tested for this disease. In summary, the treatment of CTCL should continue to improve and should be focused on strategies that preserve the immune function in these patients."]
[10608151,1,0,0,1,1999,"[Treatment of acute and chronic leukemias].","Mandelli",10608151,"[Treatment of acute and chronic leukemias].    Abstract:   In the last decade the use of new drugs (retinoic acid, interferons, purine nucleoside analogs etc.) had only minimal impact in the evolution of leukemia management. In most cases, therapeutic options have progressed because of advances in supportive therapies and optimization of old chemotherapeutic strategies. Several experiences with autologous bone marrow transplantation (BMT) have proved that in acute leukemias and in selected patients with chronic leukemias is a valid alternative to allogeneic BMT. The availability of hematopoietic stem cells from unrelated donors and from cord blood, has overcome difficulties related to the absence of a suitable HLA identical sibling donor. Modern therapeutic approaches point to tailor treatment intensity according to risk categories, defined by clinical and biological parameters at diagnosis. In this context, the prognostic role of karyotypic lesions is under investigation."]
[10540875,2,0,0,2,1999,"[Gene structure and transcriptional regulation of vitamin A, D binding proteins and nuclear receptors].","Takeyama",10540875,"[Gene structure and transcriptional regulation of vitamin A, D binding proteins and nuclear receptors].    Abstract:   Vitamin A and D play an important role in many biological processes including cell differentiation, proliferation and bone metabolism. These effects are believed to be mediated by specific nuclear receptors such as retinoic acid receptors (RARs) or vitamin D receptor (VDR), that regulate the transcription of a particular set of target genes. Hetero-dimers of RAR or VDR to retinoid X receptors (RXRs) bind target enhancer elements in their gene promoters. The target enhancer elements are referred as RA response elements (RAREs) or vitamin D response elements (VDREs), and composed of two hexamer core motife. DNA-bound RAR/VDR control transcription in a ligand-binding dependent way in co-operation with a multiprotein complex containing RNA polymerase II and a series of auxiliary factors, TFIIA, B, D, E, F and H. During process of ligand-induced transactivation by nuclear receptors, nuclear coactivators interacting with the AF-2 including ligand binding domain (LBD) seems to be involved. Several transcriptional coactivators and corepressors have been recently identified, and their function is currently under investigation."]
[10589377,0,0,0,0,1999,"Nutrition in inflammatory bowel disease.","Stein",10589377,"Nutrition in inflammatory bowel disease.    Abstract:   Clinical and basic research continues to expand our understanding of the complex pathogenesis of inflammatory bowel diseases. The potential roles played by fatty acid intake, serum leptin, and nitric oxide in the promotion of intestinal inflammation in Crohns disease and ulcerative colitis will be reviewed. In addition, important advances in the areas of bone disease, vitamin deficiency, growth failure, and home parenteral nutrition will be discussed."]
[10574173,5,0,0,5,1999,"Greater trochanter enthesopathy: an example of quot;short course retinoid enthesopathyquot;: a case report.","Stitik",10574173,"Greater trochanter enthesopathy: an example of quot;short course retinoid enthesopathyquot;: a case report.    Abstract:   Irreversible skeletal changes have been described in patients with dermatologic disorders treated with isotretinoin (Accutane), a synthetic vitamin A derivative. Although retinoids were developed to avoid toxicity associated with vitamin A, skeletal lesions and rheumatologic consequences are possible hazards of isotretinoin treatment. Enthesopathy is one of the potential musculoskeletal sequelae and is characterized by pathologic, sometimes painful changes at the insertion sites (entheses) of tendons, ligaments, and articular capsules into bone. We report a patient who was referred secondary to an extended history of bilateral hip region pain. She was subsequently found to have a greater trochanteric enthesopathy. A detailed patient history revealed past use of Accutane for cystic acne. The subsequent treatment course, including medications, corticosteroid injections, physical therapy, and activity modifications, is described and the pertinent literature is reviewed. We believe that patients who are prescribed isotretinoin should be warned about this potential pathologic condition at the initiation of treatment and that physicians who are treating patients with a history of Accutane use should be suspicious of underlying enthesopathies as the etiology behind pain of musculoskeletal origin."]
[10568485,1,0,0,1,1999,"Immunomodulators in the treatment of cutaneous lymphoma.","Rogalski",10568485,"Immunomodulators in the treatment of cutaneous lymphoma.    Abstract:    BACKGROUND : Cutaneous lymphoma involves clonal proliferation of immunocompetent cells. Immunointerventional strategies are a rational approach to the treatment of cutaneous lymphoma given the pathophysiological aspects of the disease.  OBJECTIVE : Immunomodulatory therapies in cutaneous lymphoma are reviewed, including interferons, interleukin-2, cyclosporin A, monoclonal antibodies, autologous bone marrow transplantation, fusion toxins, thymopentin and extracorporeal photopheresis as well as recently reported methods such as vaccination therapy, mycophenolate, and new retinoids.  RESULTS/CONCLUSION : Cutaneous lymphoma is sensitive to immunointerventions. This approach should be used in early stages of the disease when it is more susceptible and benefits better from immunomodulatory treatment modalities."]
[10544881,0,0,0,0,1999,"SAPHO syndrome: report of three cases and review of the literature.","Gmyrek",10544881,"SAPHO syndrome: report of three cases and review of the literature.    Abstract:   SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) is an acronym that describes a seronegative syndrome of bone and joint lesions, frequently localized to the anterior chest wall, associated with variable dermatologic manifestations. Dermatologists should be aware of this entity, as early diagnosis can prevent unnecessary surgery and avoid prolonged ineffective antibiotic therapy. We report three new cases and review the literature."]
[10521699,21,0,0,21,1999,"Interactions of retinoid binding proteins and enzymes in retinoid metabolism.","Napoli",10521699,"Interactions of retinoid binding proteins and enzymes in retinoid metabolism.    Abstract:   Naturally occurring retinoids (vitamin A or retinol and its active metabolites) are vital for vision, controlling the differentiation program of epithelial cells in the digestive tract and respiratory system, skin, bone, the nervous system, the immune system, and for hematopoiesis. Retinoids are essential for growth, reproduction (conception and embryonic development), and resistance to and recovery from infection. The functions of retinoids in the embryo begin soon after conception and continue throughout the lifespan of all vertebrates. Both naturally occurring and synthetic retinoids are used in the therapy of various skin diseases, especially acne, for augmenting the treatment of diabetes, and as cancer chemopreventive agents. Retinol metabolites serve as ligands that activate specific transcription factors in the superfamily of steroid/retinoid/thyroid/vitamin D/orphan receptors and thereby control gene expression. Additionally, retinoids may also function through non-genomic actions. Various retinoid binding proteins serve as partners in retinoid function. These binding proteins show high specificity and affinity for specific retinoids and seem to control retinoid metabolism in vivo qualitatively and quantitatively by reducing free retinoid concentrations, protecting retinoids from non-specific interactions, and chaperoning access of metabolic enzymes to retinoids. Implementation of the physiological effects of retinoids depends on the spatial-temporal expressions of binding proteins, receptors and metabolic enzymes. This review will discuss current understanding of the enzymes that catalyze retinol and retinoic acid metabolism and their unique and integral relationship to retinoid binding proteins."]
[10484977,1,0,0,1,1999,"Terminal deletion of the long arm of chromosome 9 in acute promyelocytic leukemia with a cryptic PML/RAR alpha rearrangement.","Yamamoto",10484977,"Terminal deletion of the long arm of chromosome 9 in acute promyelocytic leukemia with a cryptic PML/RAR alpha rearrangement.    Abstract:   Deletions of the long arm of chromosome 9 (9q-) are rare aberrations specifically found in acute myeloid leukemia (AML). Here we describe the first case of acute promyelocytic leukemia (APL) with a terminal 9q deletion as a sole abnormality. Chromosome analysis of the bone marrow cells showed 46,XX,del(9)(q22) in all 20 metaphases. Fluorescence in situ hybridization (FISH) analysis with painting probes of chromosomes 15, 17, and 9 revealed only two normal chromosomes 15 and 17, normal chromosome 9, and del(9)(q22). FISH with cosmid DNA probes flanking the breakpoints of t(15;17) did not show the retinoic acid receptor alpha (RAR alpha)/PML fusion signal usually generated on the der(17) t(15;17). However, rearrangement of the RAR alpha gene and expression of the PML/RAR alpha chimeric transcript were identified by Southern blot and reverse transcriptase-polymerase chain reaction analyses, respectively. These results suggested that the PML/RAR alpha fusion gene was generated by submicroscopic interstitial insertion of the RAR alpha gene into the PML gene. Therefore, 9q- was interpreted as a secondary aberration following the PML/RAR alpha rearrangement. The patient died during induction therapy because of intracerebral hemorrhage. Considering other reported cases of APL with 9q-, 9q- may be an adverse prognostic factor in APL as observed in AML with t(8;21)."]
[10459140,10,0,0,10,1999,"Acitretin in psoriasis: an overview of adverse effects.","Katz",10459140,"Acitretin in psoriasis: an overview of adverse effects.    Abstract:   Oral retinoids are among the drugs of choice for pustular and erythrodermic psoriasis. In addition, retinoids are effective in combination with other topical and systemic agents for the treatment of plaque-type psoriasis. Acitretin, the active retinoid metabolite, has replaced etretinate in retinoid therapy of psoriasis because of its more favorable pharmacokinetic profile, including a significantly shorter half-life. Retinoids, including acitretin, are potent teratogens, leading to strict requirements for pregnancy prevention during and after their use. Other retinoid side effects are generally preventable or manageable through proper patient selection, dose adjustments, and routine monitoring. Mucocutaneous side effects such as cheilitis and hair loss are the most common dose-dependent side effects, requiring dose reduction in some patients. Less common effects such as hepatotoxicity, serum lipid alterations, pancreatitis, and possible skeletal effects are also discussed."]
[10454120,1,0,0,1,1999,"Uncoupling protein-2 (UCP2): molecular and genetic studies.","Ricquier",10454120,"Uncoupling protein-2 (UCP2): molecular and genetic studies.    Abstract:   Thermogenesis is associated to oxygen consumption and cellular respiration. This process is coupled to adenosine-diphosphate (ADP) phosphorylation through the existence of a proton gradient across the inner mitochondrial membrane. It was postulated that proton leaks through this membrane would uncouple respiration from adenosine-triphosphate (ATP) synthesis and induce energy dissipation as heat. Such a mechanism was identified in thermogenic brown adipose tissue mitochondria which contain a unique proton carrier referred to as uncoupling protein (UCP). This UCP is activated by fatty acids and its synthesis is positively controlled by retinoids, thyroid hormones, catecholamines and rexinoids. In fact, in most types of cells, respiring mitochondria release heat and the coupling of substrate oxidation to ADP phosphorylation is under 100%. It suggested that the partial coupling of respiration to ADP phosphorylation was due to proton leaks possibly related to the brown fat UCP. This approach led to the identification of UCP2 and UCP3, two homologues of the brown fat UCP (renamed UCP1). UCP2 gene is widely expressed in tissues and cell types, whereas the UCP3 gene is dominantly expressed in skeletal muscles (and brown fat in mice). Recent genetic, biochemical and physiological studies suggest that these novel UCP2 contribute to resting metabolic rate, fat oxidation and may represent new targets for anti-obesity compounds."]
[10443358,1,0,0,1,1999,"Treatment of mice with retinoids in vivo and in vitro. Skeletal staining.","Morriss-Kay",10443358,"Treatment of mice with retinoids in vivo and in vitro. Skeletal staining.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I453,I453)","v":10439632},{"$f":"(LEN($J453) - LEN(SUBSTITUTE(LOWER($J453),LOWER(B$3),\"\")))/LEN(B$3)","v":3},0,0,{"$f":"SUM(B453:D453)","v":3},1999,"Excess retinol intake may explain the high incidence of osteoporosis in northern Europe.","Whiting",10439632,"Excess retinol intake may explain the high incidence of osteoporosis in northern Europe.    Abstract:   An epidemiologic study of postmenopausal women in Sweden revealed that a chronic excess of retinol intake (gt; 1.5 mg/day) decreased bone mineral density and increased hip fracture risk. These data provide one explanation for the higher incidence of osteoporosis in Sweden and Norway compared with other European countries. Retinol in fortified milk could explain also the association of high calcium intake and hip fracture incidence in northern Europe because milk is an important source of both nutrients."]
[10431270,1,0,0,1,1999,"[Drug-induced osteopathies].","Javier",10431270,"[Drug-induced osteopathies].    Abstract:   Several drugs can induce bone disorders. Steroid-induced osteoporosis is the best known of all drug-induced bone disorders. However, bone disorders have also been described in association with newer drugs (LH-RH analogs, retinoids, cyclosporine, etc.). The purpose of this revue is to familiarize radiologists with drug-induced bone disorders in order to achieve earlier diagnosis, hence, improve treatment."]
[10372835,0,0,0,0,1999,"Vitamin D and the parathyroid.","Beckerman",10372835,"Vitamin D and the parathyroid.    Abstract:   Vitamin Ds biologically active metabolite, 1,25(OH)2D3, has important effects upon the parathyroid cell that are relevant to both the physiology of mineral metabolism and the regulation of the secondary hyperparathyroidism of chronic renal failure. 1,25(OH)2D3 markedly decreases parathyroid hormone (PTH) gene transcription and thus PTH synthesis and secretion. It also acts to decrease parathyroid cell proliferation. Nonhypercalemic analogs of 1,25(OH)2D3 are being developed that may have a wider therapeutic window than 1,25(OH)2D3 itself. In the situations of chronic hypocalcemia and hypophosphatemia, there are interesting interrelationships between 1,25(OH)2D3 and the post-transcriptional regulation of the PTH gene. In nodular secondary hyperparathyroidism, there is down-regulation of the vitamin D receptor in the parathyroid. Different vitamin D receptor genotypes may be associated with higher levels of serum PTH and a predisposition to autonomous hyperplasia."]
[10356420,0,0,0,0,1999,"Vitamins and arthritis. The roles of vitamins A, C, D, and E.","Sowers",10356420,"Vitamins and arthritis. The roles of vitamins A, C, D, and E.    Abstract:   There are at least four mechanisms whereby the nutrient vitamins A, C, D, and E may be related to the processes that impede or give rise to OA. These nutrient vitamins have major roles in modulating oxidative stress, participating in immune responses, and contributing to cell differentiation. There is a substantial need to understand the contribution of these nutrients to OA, because they may provide important insight into ameliorating the initiation and progression of the disease. Simultaneously, greater understanding will add rationality to an area of potential intervention that is often based on anecdote. Investigation will be complex; there is the need to select appropriate systems. Typical animal model systems used in the study of OA are inappropriate because most animals can synthesize ascorbic acid. There is the need to disaggregate, as much as possible, the numerous subsets of OA and the plethora of processes that contribute to that heterogeneity. Certainly, there is the need to recognize the interdependency of the actions of each of these nutrients at the cellular level. Furthermore, humans rarely consume these nutrients as independent products. For example, watermelon is a primary source of both ascorbic acid and beta-carotene. Failure to address these complexities denies the scientist the opportunity to advance our understanding of health and disease processes. More importantly, failure to address these complexities denies the person with OA the opportunity to address his or her own health."]
[10200441,7,0,0,7,1998,"Retinoid-induced apoptosis in normal and neoplastic tissues.","Nagy",10200441,"Retinoid-induced apoptosis in normal and neoplastic tissues.    Abstract:   Vitamin A and its derivatives (collectively referred to as retinoids) are required for many fundamental life processes, including vision, reproduction, metabolism, cellular differentiation, hematopoesis, bone development, and pattern formation during embryogenesis. There is also considerable evidence to suggest that natural and synthetic retinoids have therapeutical effects due to their antiproliferative and apoptosis-inducing effects in human diseases such as cancer. Therefore it is not surprising that a significant amount of research was dedicated to probe the molecular and cellular mechanisms of retinoid action during the past decade. One of the cellular mechanisms retinoids have been implicated in is the initiation and modulation of apoptosis in normal development and disease. This review provides a brief overview of the molecular basis of retinoid signaling, and focuses on the retinoid-regulation of apoptotic cell death and gene expression during normal development and in pathological conditions in vivo and in various tumor cell lines in vitro."]
[10199970,1,0,0,1,1999,"From head to toe: conservation of molecular signals regulating limb and craniofacial morphogenesis.","Schneider",10199970,"From head to toe: conservation of molecular signals regulating limb and craniofacial morphogenesis.    Abstract:   Recent evidence indicates that many molecules involved in generating and patterning the limbs also play a role during craniofacial morphogenesis. On the surface, this is an unexpected finding given that these regions of the body have separate evolutionary origins, are composed of different embryonic tissues, and are quite dissimilar in their anatomy. Results from several experiments involving Sonic hedgehog and retinoic acid point to a remarkable conservation of the signaling pathways mediated by these morphogens across multiple organ systems. Moreover, mutants such as the extra-toes and doublefoot mouse, and the talpid chicken also provide insights on common developmental processes that underlie the formation of the limbs and face. The identification of highly conserved aspects of morphogenesis is important for understanding fundamental mechanisms of development, as well as for revealing the common denominator of countless birth defects and providing new strategies for their prevention and cure."]
[10190062,4,0,0,4,1999,"Tretinoin-induced sticky skin: a case report and review of the literature.","Lockridge",10190062,"Tretinoin-induced sticky skin: a case report and review of the literature.    Abstract:   Sticky skin has been reported relatively infrequently in the literature in association with etretinate and doxorubicin/ketoconazole administration. It has a poorly understood pathogenesis, and the associated histologic changes have not been described. We report a case of a patient who experienced sticky skin in areas treated with tretinoin. These reverted to normal after cessation of treatment. In comparison to a biopsy taken while the skin was not sticky, the histologic findings included a thickened, compact stratum corneum and granulosum. The basal epithelial cells showed proliferation with slight crowding and a tall, columnar shape. To our knowledge, this is the first report of sticky skin occurring in response to topical retinoid application. We suggest that the histologic changes observed could represent a modified keratin maturation profile."]
[10090920,0,0,0,0,1999,"Seed versus soil: the importance of the target cell for transgenic models of human leukemias.","Westervelt",10090920,"Seed versus soil: the importance of the target cell for transgenic models of human leukemias.    Abstract:  "]
[10048416,5,0,0,5,1999,"Retinoid-mediated signaling pathways in CD38 antigen expression in myeloid leukemia cells.","Mehta",10048416,"Retinoid-mediated signaling pathways in CD38 antigen expression in myeloid leukemia cells.    Abstract:   The lymphocyte cell surface antigen CD38, which was originally described as a differentiation marker, has emerged as an important multifunctional protein. Its most intriguing and well characterized function is its ability to catalyze the synthesis of cyclic ADP-ribose (cADPR) from NAD. cADPR serves as an important second messenger in controlling the release of intracellular calcium from ryanodine-sensitive intracellular pools. By virtue of its ability to synthesize cADPR as well as to act as an adhesion and signal transduction molecule, CD38 may play a role in such diverse physiological processes as cell growth, apoptosis, differentiation, and inflammation. Equally interesting is the pattern of CD38 expression in hematopoietic cells. In the bone marrow, early precursor cells predominantly express CD38 antigen, whereas mature circulating blood cells lack or express very low levels. The expression is also high on malignant hematopoietic cells and thus may be of prognostic relevance in certain leukemias. Presently, there is little information available on the factors that regulate the expression of CD38 antigen in hematopoietic cells. In this review, we summarize recent findings on the regulation of CD38 antigen by retinoids (vitamin A and related compounds). At least in the myeloid cell lineage, retinoids appear to be exquisitely potent and specific inducers of CD38 antigen expression, and retinoid-induced expression of CD38 is mediated via activation of the retinoic acid-alpha (RAR alpha) nuclear receptor."]
[9844917,3,0,0,3,1998,"Acute promyelocytic leukemia: a curable disease.","Lo Coco",9844917,"Acute promyelocytic leukemia: a curable disease.    Abstract:   The Second International Symposium on Acute Promyelocytic Leukemia (APL) was held in Rome in 12-14 November 1997. Clinical and basic investigators had the opportunity to discuss in this meeting the important advances in the biology and treatment of this disease achieved in the last 4 years, since the First Roman Symposium was held in 1993. The first part of the meeting was dedicated to relevant aspects of laboratory research, and included the following topics: molecular mechanisms of leukemogenesis and of response/resistance to retinoids, biologic and therapeutic effects of new agents such as arsenicals and novel synthetic retinoids; characterization of APL heterogeneity at the morphological, cytogenetic and immunophenotypic level. The updated results of large cooperative clinical trials using variable combinations of all-trans retinoic acid (ATRA) and chemotherapy were presented by the respective group chairmen, and formed the core part of the meeting. These studies, which in most cases integrated the molecular assessment of response to treatment, provided a stimulating framework for an intense debate on the most appropriate frontline treatment options to be adopted in the future. The last day was dedicated to special entities such as APL in the elderly and in the child, as well as the role of bone marrow transplantation. The prognostic value of molecular monitoring studies was also discussed in the final session of the meeting. In this article, we review the major advances and controversial issues in APL biology and treatment discussed in this symposium and emerging from very recent publications. We would like to credit the successful outcome of this meeting to the active and generous input of all invited speakers and to participants from all over the world who provided constructive and fruitful discussions."]
[9841582,6,0,0,6,1998,"Excessive dietary intake of vitamin A is associated with reduced bone mineral density and increased risk for hip fracture.","Melhus",9841582,"Excessive dietary intake of vitamin A is associated with reduced bone mineral density and increased risk for hip fracture.    Abstract:    BACKGROUND : The highest incidence of osteoporotic fractures is found in northern Europe, where dietary intake of vitamin A (retinol) is unusually high. In animals, the most common adverse effect of toxic doses of retinol is spontaneous fracture.  OBJECTIVE : To investigate whether excessive dietary intake of vitamin A is associated with decreased bone mineral density and increased risk for hip fracture.  DESIGN : A cross-sectional study and a nested case-control study.  SETTING : Two counties in central Sweden.  PARTICIPANTS : For the cross-sectional study, 175 women 28 to 74 years of age were randomly selected. For the nested case-control study, 247 women who had a first hip fracture within 2 to 64 months after enrollment and 873 age-matched controls were selected from a mammography study cohort of 66,651 women 40 to 76 years of age.  MEASUREMENTS : Retinol intake was estimated from dietary records and a food-frequency questionnaire. Bone mineral density was measured with dual-energy x-ray absorptiometry. Hip fracture was identified by using hospital discharge records and was confirmed by record review.  RESULTS : In multivariate analysis, retinol intake was negatively associated with bone mineral density. For every 1-mg increase in daily intake of retinol, risk for hip fracture increased by 68% (95% CI, 18% to 140%; P for trend, 0.006). For intake greater than 1.5 mg/d compared with intake less than 0.5 mg/d, bone mineral density was reduced by 10% at the femoral neck (P = 0.05), 14% at the lumbar spine (P = 0.001), and 6% for the total body (P = 0.009) and risk for hip fracture was doubled (odds ratio, 2.1 [CI, 1.1 to 4.0]).  CONCLUSION : High dietary intake of retinol seems to be associated with osteoporosis."]
[9823001,4,0,0,4,1998,"Retinoids and their receptors in skeletal development.","Underhill",9823001,"Retinoids and their receptors in skeletal development.    Abstract:   The embryonic vertebrate limb serves as an excellent experimental model system in which to study mechanisms that regulate morphogenesis of the skeleton. The appendicular skeleton arises through the process of endochondral ossification, whereby a cartilage template is initially formed and subsequently replaced by bone. One molecule that has a dramatic effect on these processes is the vitamin-A metabolite, retinoic acid (RA). RA functions through a class of nuclear hormone receptors, the retinoic acid receptors (RARs) and retinoid-X-receptors (RXRs), to regulate gene transcription. Experimental evidence from RA teratogenesis suggests that the presence of ligand-activated RARs and/or inappropriate expression of RARs inhibits chondrogenesis. Conversely, genetic analysis has shown that the absence of the receptors can lead to deficiencies in cartilage formation while also promoting chondrogenesis at ectopic sites. Taken together, these studies suggest that the RARs play a fundamental role in the early stages of skeletal development, specifically those involved in the formation of prechondrogenic condensations and their subsequent differentiation into chondroblasts."]
[9796408,2,0,0,2,1998,"[Extramedullary relapse in the external auditory canal in a patient with acute promyelocytic leukemia treated with all-trans retinoic acid and autologous peripheral blood stem cell transplantation].","Yagita",9796408,"[Extramedullary relapse in the external auditory canal in a patient with acute promyelocytic leukemia treated with all-trans retinoic acid and autologous peripheral blood stem cell transplantation].    Abstract:   A 41-year-old man was given a diagnosis with of acute promyelocytic leukemia (APL) in August 1994. A chromosome analysis showed 46, XY, t(15; 17) and 47, XY, idem, +8 at that time. Because initial induction chemotherapy (BHAC-DMP) has not been successful, the patient was given 45 mg/m2 of all-trans retinoic acid (ATRA) and achieved complete remission (CR) after 26 days on this regimen. Following intensified chemotherapy, he received an autologous peripheral blood stem cell transplant (PBSCT) with high-dose busulfan and cyclophosphamide in April 1995. Competitive RT-PCR for PML-RAR alpha mRNA did not find any of APL cells in the collected stem-cell fraction. Although the patient remained in CR without therapy, a myeloblastoma was found in his left external auditory canal in August 1996. Recurrence in bone marrow, moreover, was discovered the following month. A chromosome analysis of bone marrow cells showed 47, XY, t(15; 17), +8 at this time. Thus, the extramedullary relapse developed after autologous PBSCT. This case provides information linking ATRA to the development of extramedullary relapse in patients with APL."]
[9755806,0,0,0,0,1998,"A review of breast cancer chemoprevention.","Chang",9755806,"A review of breast cancer chemoprevention.    Abstract:   Breast cancer remains a major cause of mortality and morbidity, and may be amenable to chemoprevention as estrogen stimulation is believed to be responsible for the promotion of this disease. Tamoxifen is the most widely studied compound for chemoprevention and clinical trials involving over 20,000 women world-wide are currently underway. This drug is well-tolerated with low acute toxicity and high compliance, and has a favorable profile in both decreasing serum cholesterol and increasing bone mineral density in postmenopausal women. However, there are fears of its potential carcinogenicity, especially an increased risk of endometrial cancers, which may jeopardize further recruitment and compliance of women in these chemoprevention studies. Meta-analyses of these studies are expected to be conducted in the year 2000 to address the efficacy of tamoxifen in women with an increased familial predisposition and in those with known germline BRCA mutations."]
[9706339,1,0,2,3,1998,"Orofacial cleft defects: inference from nature and nurture.","Houdayer",9706339,"Orofacial cleft defects: inference from nature and nurture.    Abstract:   Cleft lip with or without cleft palate (CL/P), and cleft palate (CP) are most common congenital malformation conditions. Prognosis mainly rests on the possibility of associated symptoms, since more than a hundred recognised Mendelian disorders involve this orofacial defect (thereby defining syndromic CL/P, or CP). Multiplex non-syndromic CL/P, or CP families indicate that genetic factors are likely involved in causation. Inheritance is generally regarded as multigenic, allelic variation at different loci (TGF alpha, TGF beta 3, RARA) determining a fraction of the genetic risk, as demonstrated by association or transmission/disequilibrium non-parametric tests. Some pedigrees are however clearly monogenic, consistent with either autosomal dominant or recessive inheritance. X-linked recessive CP (with or without ankyloglossia) is an additional possibility. Significant linkage to 6p23 (EDN1) or 19q13 (BCL3) could be achieved using parametric models with reduced penetrance. Environmental exposures were also demonstrated to interfere with lip and/or palatal formation when present during the first trimester of pregnancy. Whereas ethanol, retinoids or folate antagonists are clearly teratogenic, indictment of more common exposures such as caffeine is merely tentative. The development of animal models allowed to confirm the genetic bases of CL/P, or CP, exemplify the role of teratogens, and study the interaction of nature and nurture."]
[9702042,1,0,0,1,1998,"[Structure of the retinoic acid receptor and its functional analysis using a mutated receptor].","Kakizuka",9702042,"[Structure of the retinoic acid receptor and its functional analysis using a mutated receptor].    Abstract:   RA shows a variety of actions including the teratogenicity at pharmacological doses, but its physiological roles remain unclear. Recently, receptors for RA, RARs, have been identified and shown to belong to the nuclear receptor superfamily. We introduced a mutation, which was originally identified in the thyroid hormone receptor gene, causing dominantly inherited thyroid hormone resistance, to the equivalent position in RAR, and showed that the mutated RAR demonstrated a dominant-negative phenotypes. We next expressed the mutated RAR specifically in chondrogenic cells in mice. From the analysis of mice phenotypes, we unveiled the chondrogenic cells as a novel vital RA target in skeletal development. The results simultaneously indicated that RA specifies cervical identities through the regulation of homeobox genes."]
[9682036,1,0,0,1,1998,"Transcriptional activation through the vitamin D receptor in osteoblasts.","Kraichely",9682036,"Transcriptional activation through the vitamin D receptor in osteoblasts.    Abstract:   Osteoblasts are bone-forming cells that play an essential role in the development and maintenance of a mineralized bone extracellular matrix and they are target cells for vitamin D. Osteoblasts express vitamin D receptors (VDR) and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] regulates the expression of osteoblastic-specific genes such as osteocalcin and osteopontin. VDR is a ligand-inducible transcription factor which heterodimerizes with retinoid X receptor (RXR) and binds as a heterodimer to vitamin D-responsive elements (VDREs) in the promoter region of vitamin-D responsive genes, ultimately leading to their increased transcription. Important structural aspects of the VDR and the role that each functional domain plays in mediating VDR action in the context of the osteoblast are discussed. A summary of the potential molecular mechanisms involved in VDR-activated transcription highlighting the importance of interactions between the VDR and general transcription factors (GTFs), TBP-associated factors (TAFIIs), and nuclear receptor coactivator and corepressor proteins are reviewed. These interactions have a role in linking the VDR-RXR heterodimer to the transcriptional pre-initiation complex (PIC) and in regulating the transcription of vitamin D-dependent genes. In addition, recent findings suggest that these interactions are important for regulating the accessibility to promoters by modifying the acetylation state of histones. The complex interplay that occurs between VDR and these various factors to determine the overall transcriptional activity of vitamin D-responsive genes will be summarized."]
[9563695,1,0,0,1,1998,"Maternal exposure to prescription and non-prescription pharmaceuticals or drugs of abuse and risk of craniosynostosis.","Gardner",9563695,"Maternal exposure to prescription and non-prescription pharmaceuticals or drugs of abuse and risk of craniosynostosis.    Abstract:    BACKGROUND : The pre- and peri-natal drug exposures reported by women participating in a case-control study of children in Colorado were examined for association with infant craniosynostosis.  METHODS : Mothers of case and control children underwent a standardized telephone interview and obstetric and newborn medical record review. The interview included questions on the use of prescription and non-prescription drugs, nutritional supplements, recreational and drugs of abuse. The mothers obstetric record was abstracted for information about pharmacologic agents taken before and during the antepartum period.  RESULTS : There were no statistically significant risk ratios associating craniosynostosis with prenatal exposure to hydantoin, valproic acid, or cocaine. Mothers of four case children and one control child reported specific exposure to retinoic acid. There were no statistically significant increases in the odds ratio (OR) for any suture type among children exposed to hypoxigenic agents, sympathomimetic or parasympatholytic agents, or metal-containing agents. The OR was 1.87 (lower bound of the two-sided 95% test-based confidence interval (CI): 1.08) among children with sagittal/lambdoid suture synostosis who were exposed to nitrosatable drugs chlorpheniramine, chlordiazepoxide, and nitrofurantoin compared to controls.  CONCLUSIONS : Certain nitrosatable drugs may be associated with increased risk of infant sagittal/lambdoid craniosynostosis. A possible mechanism related to ischaemia/reperfusion injury is suggested."]
[9545093,1,0,0,1,1998,"Correlated heart/limb anomalies in Mendelian syndromes provide evidence for a cardiomelic developmental field.","Wilson",9545093,"Correlated heart/limb anomalies in Mendelian syndromes provide evidence for a cardiomelic developmental field.    Abstract:   Coordinated development of heart and limbs is suggested by a review of human abortus, chromosomal, and teratogenic syndromes, and characterized by an analysis of Mendelian disorders that affect the limbs, heart, or both (672, 202, or 107, respectively). Mendelian syndromes with altered limb patterns often include cardiac anomalies, as shown by limb duplications (34%), deficiencies (30%), hypoplasias (23%), or dysplasias (9.3%). Syndromes with particular cardiac anomalies, illustrated by VSD (85%) or ASD (90%), frequently include limb defects. Positional correlations of anterior (preaxial/conotruncal), posterior (postaxial/atrial), or lateral (mirror hand/atrial isometry) heart/limb anomalies are consistent with the existence of a cardiomelic developmental field. Vertebrate comparisons suggest an early D-V limb-heart gradient, influenced by the neural crest, with distal limb segments (80% of syndromic defects) at its dorsal extreme. The proposed cardiomelic field relates the genetic heterogeneity of disorders such as Holt-Oram syndrome to a cascade of molecules, including the brachyury, sonic hedgehog, bone morphogenetic protein, retinoic acid receptor, and transforming growth factor-beta families."]
[9524574,2,0,0,2,1998,"Teratocarcinomas and human embryology: pluripotent human EC cell lines. Review article.","Andrews",9524574,"Teratocarcinomas and human embryology: pluripotent human EC cell lines. Review article.    Abstract:   The histogenesis of germ cell tumours (GCT) reflects the normal processes of gametogenesis, fertilisation and subsequent embryonic cell differentiation. Understanding the mechanisms that control the differentiation of embryonal carcinoma (EC) cells into a variety of embryonic and extraembryonic cell types is pertinent to understanding the progression of GCT. EC cells also provide a tool for analysing the mechanisms that control differentiation during embryonic development, and particularly the mechanisms that control differentiation along alternative cell line, NTERA2, into neurones and other cell types in response to agents such as retinoic acid, HMBA and the bone morphogenetic proteins. We have also compared the pluripotent NTERA2 EC cells with other human EC cell lines that exhibit a much reduced capacity for cell differentiation. A variety of genes are activated during NTERA2 differentiation. In particular we have identified a novel human member of the wnt family. This wnt gene is activated following retinoic acid induction of differentiation but is later down-regulated as the cells mature into neurones and other cell types. We have also observed expression of genes belonging to the Frizzled family, which is likely to include genes encoding receptors for the wnt gene products. Thus in the NTERA2 system, genes pertinent to regulating cell differentiation during embryonic development are activated and appear to play a role in modulating how these pluripotent human EC cells differentiate."]
[9492819,0,0,0,0,1998,"[Current situation and perspective for treatment of acute myelogenous leukemia in adults].","Fukushima",9492819,"[Current situation and perspective for treatment of acute myelogenous leukemia in adults].    Abstract:   The current situation and perspectives for the treatment of acute myelogenous leukemia in adults were summarized. Due to the recent progress of chemotherapy, the complete remission (CR) rate is close to 80% in adults with newly diagnosed acute myelogenous leukemia in Japan. On the other hand, the long-term disease-free survival rate is 30-40% in CR cases. The allogeneic bone marrow transplantation (allo BMT) during the first CR has a low relapse rate compared with that of chemo therapy. However, the therapy-related mortality is not inconsiderable, so, the time of allo BMT is controversial. Idarubicin has a superior CR rate as well as long-term disease-free survival in comparison with daunorubicin, and it is becoming the first line treatment for acute myelogenous leukemia in adults."]
[9434862,1,0,0,1,1997,"Craniofacial abnormalities induced by the ectopic expression of homeobox genes.","Whiting",9434862,"Craniofacial abnormalities induced by the ectopic expression of homeobox genes.    Abstract:   In this paper I have tried to bring together work that highlights the role of homeobox genes in generating craniofacial form. I review both normal and disrupted embryogenesis and ask whether mis-expression of the homeobox genes outside their normal domains could be contributing to congenital facial abnormalities arising from either genetic or teratogenic actions. Experimentally generated transgenic mice carrying loss- or gain-of-function mutations in homeobox genes, in combination with their normal expression patterns, have allowed us to compile and test models of embryonic specification based around a Hox/homeobox code. These models form the basis on which the functional questions are considered. There are four major sections covering different experimental approaches designed to ectopically induce homeobox genes in the head. Transgenic mice, where heterologous promoters drive a given Hox gene in the head, have shown that the more posteriorly expressed Hox genes tend to have a significant effect only on the skull bones of mesodermal origin whereas those normally expressed more anteriorly, in the hindbrain and branchial arches, can affect more anterior branchial arch and neural crest-derived structures. Manipulation experiments which can induce homeobox genes in small, localised regions of the facial precursors show clear and dramatic effects of this expression on facial development. Null mutations in predicted repressors of Hox gene expression, however, do not appear to give rise to substantial craniofacial abnormalities. Retinoic acid, on the other hand, is well known for its teratogenic actions and its ability to induce Hox gene expression. Evidence is now accumulating that at least some of its teratogenic actions may be mediated by its regulation of the Hox and other homeobox genes in the head."]
[9426975,1,0,0,1,1997,"Production of activin A and its roles in inflammation and hematopoiesis.","Yu",9426975,"Production of activin A and its roles in inflammation and hematopoiesis.    Abstract:   Activin A, a member of the transforming growth factor beta (TGF-beta) superfamily, is a protein consisting of two homodimeric beta A subunits. It was originally isolated from follicular fluid as a factor stimulating the release of follicle-stimulating hormone from the pituitary gland. Increasing evidence suggests that activin A is broadly distributed and regulates multiple functions in various biological systems by autocrine/paracrine mechanisms. In this review, we discuss the effects of activin A on hematopoiesis, especially the enhancement of erythropoiesis, and the production of activin A within the bone marrow microenvironment and in peripheral blood monocytes. The regulatory control of activin A expression by its 5 promoter region is also discussed. Furthermore, we consider that the expression of activin A is modulated by different agents, including proinflammatory cytokines, glucocorticoids and retinoic acid, suggesting new roles for activin A in inflammation reactions. Recently, this role in inflammation was further strengthened by the findings that activin A expression is elevated in inflammatory arthropathies, is regulated by inflammation-associated cytokines in synoviocyte and articular chondrocyte cultures, and is able to counteract many of the interleukin-6 (IL-6)-induced biological activities. Therefore it is likely that activin A may also act as a paracrine/autocrine moderator in diverse functions, including host defenses."]
[9373192,0,0,0,0,1997,"Modulation of interleukin-6/interleukin-6 receptor cytokine loop in the treatment of multiple myeloma.","Chen",9373192,"Modulation of interleukin-6/interleukin-6 receptor cytokine loop in the treatment of multiple myeloma.    Abstract:   Interluekin-6 (IL-6)/IL-6 receptor (IL-6R) play a major role in autocrine/paracrine growth regulation of myeloma cells and are the central mediators for bone destruction and other systemic manifestations of multiple myeloma. Modulation of the IL-6/IL-6R cytokine loop thus represents a rational therapeutic approach. We updated and reviewed the studies on the agents that targeted IL-6/IL-6R modulation and the results of selected clinical trials. Extensive in vitro studies with human myeloma cell lines or primary myeloma explants have shown that components of this cytokine loop could be modulated by various agents, and such modulation is associated with inhibition of myeloma cell growth. The purported mechanisms of action of these agents, down-regulation or neutralization of IL-6 and/or IL-6R and the interruption of IL-6 binding to IL-6R or gp 130 signal transducer, with possible exception for glucocorticoids and specific antibodies, remain to be formally proven. Clinical trials showed largely limited benefits of these agents. Given tumor cell heterogeneity and the complexity of inter-connected cytokine network in vivo, the future emphasis should be on the strategy of combination treatment that would modulate this cytokine loop at multiple sites. Further advances in delineating IL-6 and related cytokine signal transduction pathways should also suggest other targets for therapeutic intervention."]
[9365539,2,0,0,2,1997,"Gene rearrangements in the molecular pathogenesis of acute promyelocytic leukemia.","Kalantry",9365539,"Gene rearrangements in the molecular pathogenesis of acute promyelocytic leukemia.    Abstract:   Acute Promyelocytic Leukemia (APL) is a distinct subtype of myeloid leukemia that in the USA alone affects more than 3,000 individuals every year. APL is characterized by three distinct and unique features: i) the accumulation in the bone marrow of tumor cells with promyelocytic features; ii) the invariable association with specific translocations which always involve chromosome 17 and the Retinoic Acid Receptor alpha (RAR alpha) locus; iii) the exquisite sensitivity of APL blasts to the differentiating action of Retinoic Acid (RA). These features have led APL to become the paradigm for therapeutic approaches utilizing differentiating agents. The last 5 years have provided crucial insights into the molecular basis of APL. RAR alpha translocates in 99% of cases to a gene located on chromosome 15 that we initially named myl and subsequently has been called PML. In a few cases, RAR alpha variably translocates to chromosome 11 where it fuses to the PLZF gene or to a newly described partner, NuMA. In addition, RAR alpha is also found translocated to chromosome 5 where it fuses to the NPM gene. The cloning of variant translocations in APL and the comparative analysis of their associated products is crucial for the understanding of the molecular etiopathogenesis of the disease. The generation of animal models, i.e., transgenic mice expressing the fusion genes, will be instrumental in determining the precise contribution of these fusion genes to leukemogenesis. In fact, mice harboring a PML/RAR alpha transgene whose expression is specifically targeted to the myeloid-promyelocytic lineage develop acute myeloid leukemia with promyelocytic features. Moreover, the functional analysis of the various fusion proteins, as well as RAR alpha partners, is revealing striking common features beneath a misleading structural heterogeneity which unravels a possible unifying molecular mechanism towards APL leukemogenesis."]
[9379138,2,0,0,2,1997,"The vitamin D hormone and its nuclear receptor: molecular actions and disease states.","Haussler",9379138,"The vitamin D hormone and its nuclear receptor: molecular actions and disease states.    Abstract:   Vitamin D plays a major role in bone mineral homeostasis by promoting the transport of calcium and phosphate to ensure that the blood levels of these ions are sufficient for the normal mineralization of type I collagen matrix in the skeleton. In contrast to classic vitamin D-deficiency rickets, a number of vitamin D-resistant rachitic syndromes are caused by acquired and hereditary defects in the metabolic activation of the vitamin to its hormonal form, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), or in the subsequent functions of the hormone in target cells. The actions of 1,25(OH)2D3 are mediated by the nuclear vitamin D receptor (VDR), a phosphoprotein which binds the hormone with-high affinity and regulates the expression of genes via zinc finger-mediated DNA binding and protein-protein interactions. In hereditary hypocalcemic vitamin D-resistant rickets (HVDRR), natural mutations in human VDR that confer patients with tissue insensitivity to 1,25(OH)2D3 are particularly instructive in revealing VDR structure function relationships. These mutations fall into three categories: (i) DNA binding/nuclear localization, (ii) hormone binding and (iii) heterodimerization with retinoid X receptors (RXRs). That all three classes of VDR mutations generate the HVDRR phenotype is consistent with a basic model of the active receptor as a DNA-bound, 1,25(OH)2D3-liganded heterodimer of VDR and RXR. Vitamin D responsive elements (VDREs) consisting of direct hexanucleotide repeats with a spacer of three nucleotides have been identified in the promoter regions of positively controlled genes expressed in bone, such as osteocalcin, osteopontin, beta 3-integrin and vitamin D 24-OHase. The 1,25(OH)2D3 ligand promotes VDR-RXR heterodimerization and specific, high affinity VDRE binding, whereas the ligand for RXR, 9-cis retinoic acid (9-cis RA), is capable of suppressing 1,25(OH)2D3-stimulated transcription by diverting RXR to form homodimers. However, initial 1,25(OH)2D3 liganding of a VDR monomer renders it competent not only to recruit RXR into a heterodimer but also to conformationally silence the ability of its RXR partner to bind 9-cis RA and dissociate the heterodimer. Additional probing of protein-protein interactions has revealed that VDR also binds to basal transcription factor IIB (TFIIB) and, in the presence of 1,25(OH)2D3, an RXR-VDR-TFIIB ternary complex can be created in solution. Moreover, for transcriptional activation by 1,25(OH)2D3, both VDR and RXR require an intact short amphipathic alpha-helix, known as AF-2, positioned at their extreme C-termini. Because the AF-2 domains participate neither in VDR-RXR heterodimerization nor in TFIIB association, it is hypothesized that they contact, in a ligand-dependent fashion, transcriptional coactivators such as those of the steroid receptor coactivator family, constituting yet a third protein-protein interaction for VDR. Therefore, in VDR-mediated transcriptional activation, 1,25(OH)2D3 binding to VDR alters the conformation of the ligand binding domain such that it: (i) engages in strong heterodimerization with RXR to facilitate VDRE binding, (ii) influences the RXR ligand binding domain such that it is resistant to the binding of 9-cis RA but active in recruiting coactivator to its AF-2 and (iii) presents the AF-2 region in VDR for coactivator association. The above events, including bridging by coactivators to the TATA binding protein and associated factors, may position VDR such that it is able to attract TFIIB and the balance of the RNA polymerase II transcription machinery, culminating in repeated transcriptional initiation of VDRE-containing, vitamin D target genes. Such a model would explain the action of 1,25(OH)2D3 to elicit bone remodeling by stimulating osteoblast and osteoclast precursor gene expression, while concomitantly triggering the termination of its hormonal signal by inducing the 24-OHase catabolizing enzyme."]
[9297571,1,0,0,1,1997,"Transcription factors AP-1 and NF-kappa B: where steroids meet the gold standard of anti-rheumatic drugs.","Handel",9297571,"Transcription factors AP-1 and NF-kappa B: where steroids meet the gold standard of anti-rheumatic drugs.    Abstract:   The disease modifying anti-rheumatic drugs belong to a chemically heterogeneous group that includes inorganic salts (e.g. gold thiolates), plant derived products (e.g. chloroquine) and a drug metabolite (e.g. D-penicillamine). Understanding their mechanisms of action has long been clouded by numerous and conflicting theories. A wide variety of unpredictable adverse effects, extremely long half lives and lack of dose-response and concentration-response relationships have added to the confusion. Although they have no known high affinity receptors that might provide a clue to their mechanisms of action, the observation that gold(I) salts and penicillamine are reactive with thiols has suggested that there might be a mechanism in common between these two drugs. Recent advances in the function and chemistry of proteins involved in gene expression have indicated that thiol groups in the quot;pro-inflammatoryquot; transcription factors AP-1 and NF-kappa B are targets for at least some of the therapeutic effects of disease modifying anti-rheumatic drugs. Developments in understanding the transcriptional effects of glucocorticoid and retinoid receptors indicate that they too act, at least in part, via inhibition of AP-1 and/or NF-kappa B activities. It is possible to develop a unifying hypothesis for the actions of this seemingly diverse group of drugs and make testable predictions for the development of more specific, and less toxic anti-inflammatory therapies."]
[9239156,1,0,0,1,1997,"[Progress in the treatment of adult acute myeloid leukemia].","Ohno",9239156,"[Progress in the treatment of adult acute myeloid leukemia].    Abstract:   Due to advances in chemotherapy, differentiation therapy and bone marrow transplantation (BMT), adult acute myeloid leukemia (AML) has become a curable disease, and we are making further efforts to heighten the cure rate. The JALSG AML 89 study resulted in a 77% complete remission (CR) rate in 326 adults with AML, and a 38% 4.5-year disease-free survival (DFS) in CR cases. The JALSG AML92 study for APL with all-trans retinoic acid resulted in a 89% CR rate in 196 and 64% 4-year DFS in CR cases."]
[9220656,3,0,0,3,1997,"Rare but important adverse effects of all-trans retinoic acid in acute promyelocytic leukemia and their management.","Hatake",9220656,"Rare but important adverse effects of all-trans retinoic acid in acute promyelocytic leukemia and their management.    Abstract:   Several adverse effects have been reported to occur after clinical application of all-trans retinoic acid (RA) in acute promyelocytic leukemia (APL). Except for severe side effects including retinoic acid syndrome, the mechanism of action of RA on adverse effects remains unclear. Here we describe some rare adverse effects and their management. We reviewed the English literature, and we added our cases of endocrine and metabolic adverse effects, such as hypercalcemia, male infertility, bone marrow necrosis, fibrosis and acute pancreatitis. We also described our cases of thromboembolic events, RA-dependent growth of pathologic cells including Sweets syndrome, erythema nodosum, hyperhistaminemia, granulomatous proliferation, and mild cases of pulmonary complications. In addition, we reviewed the efficacy of RA administration for other types of leukemia or myelodysplastic syndrome. RA and chemotherapeutic agents might induce complete remission, but we obtained a response in only one case of M2 in the third relapse. During RA administration the patient should be monitored for these adverse effects, and early diagnosis and appropriate treatment are important."]
[9380984,0,0,0,0,1997,"[Myelodysplastic syndromes].","Raza",9380984,"[Myelodysplastic syndromes].    Abstract:  "]
[9262807,0,0,0,0,1997,"Preservation of permanent teeth in a patient with Papillon-Lefèvre syndrome by professional tooth-cleaning.","Kim",9262807,"Preservation of permanent teeth in a patient with Papillon-Lefèvre syndrome by professional tooth-cleaning.    Abstract:  "]
[9082990,1,0,0,1,1997,"Amphibian limb regeneration: rebuilding a complex structure.","Brockes",9082990,"Amphibian limb regeneration: rebuilding a complex structure.    Abstract:   The ability to regenerate complex structures is widespread in metazoan phylogeny, but among vertebrates the urodele amphibians are exceptional. Adult urodeles can regenerate their limbs by local formation of a mesenchymal growth zone or blastema. The generation of blastemal cells depends not only on the local extracellular environment after amputation or wounding but also on the ability to reenter the cell cycle from the differentiated state. The blastema replaces structures appropriate to its proximodistal position. Axial identity is probably encoded as a graded property that controls cellular growth and movement through local cell interactions. The molecular basis is not understood, but proximodistal identity in newt blastemal cells may be respecified by signaling through a retinoic acid receptor isoform. The possibility of inducing a blastema on a mammalian limb cannot be discounted, although the molecular constraints are becoming clearer as we understand more about the mechanisms of urodele regeneration."]
[9168299,1,0,0,1,1997,"Chronic myelomonocytic leukemia: from biology to therapy.","Cambier",9168299,"Chronic myelomonocytic leukemia: from biology to therapy.    Abstract:   Chronic myelomonocytic leukemia represents a distinct myelodysplastic syndrome in which an excess of monocytes is observed both in the blood and bone marrow of the patients. Whereas diagnosis is relatively easy, therapeutic design and efficacy is difficult and no treatment has to date provided complete or significant partial response. In vitro data suggest that the growth and differentiation of myelomonocytic progenitors may be altered inasmuch as monocytic or granulo-macrophagic colonies show spontaneous growth. Different entities may be observed: the childhood form, Juvenile Chronic Myelomonocytic Leukemia (JCML) shows in vitro a typical pattern with constitutive growth of only macrophagic colonies and hypersensitivity to GM-CSF; in the adult form at least two patterns may be observed one close to the JCML form and one more heterogeneous with absence of GM-CSF sensitivity and spontaneous growth of both CFU-GM and CFU-M colonies. Chemotherapy reduces all myeloid colonies in vitro whereas retinoic acid has a selective effect on monocytic colonies with a concomitant increase of CFU-G colonies forwarding an explanation for the correction of pancytopenia observed in some patients. Recent analysis of altered molecular pathways in this disease suggest a common disruption of intracellular signalling pathways namely the Ras pathway and targetting for drugs with may selectively control or inhibit a constitutive activation may forward novel therapeutic perspectives."]
[9073437,1,0,0,1,1997,"Ectodermal patterning in vertebrate embryos.","Sasai",9073437,"Ectodermal patterning in vertebrate embryos.    Abstract:   Recent molecular insights on how the ectodermal layer is patterned in vertebrates are reviewed. Studies on the induction of the central nervous system (CNS) by Spemanns Organizer led to the isolation of noggin and chordin. These secretory proteins function by binding to, and inhibiting, ventral BMPs, in particular BMP-4. Neural induction can be considered as the dorsalization of ectoderm, in which low levels of BMP-signaling result in CNS formation. At high levels of BMP signaling the ectoderm adopts a ventral fate and skin is formed. In Xenopus the forming neural plate already has extensive dorsal-ventral (D-V) patterning, and neural induction and D-V patterning may share common molecular mechanisms. At later stages sonic hedgehog (shh) plays a principal role in D-V patterning, particularly in the neural tube of the amniote embryo. A great many transcription factor markers are available and mouse knockouts provide evidence of their involvement in the regional specification of the neural tube. Recent evidence indicating that differentiation of posterior CNS is promoted by FGF, Wnt-3a, and retinoic acid is reviewed from the point of view of the classical experiments of Nieuwkoop that defined an activation and a transformation step during neural induction."]
[9591187,6,0,0,6,1997,"Research and development of cancer chemopreventive agents in China.","Rui",9591187,"Research and development of cancer chemopreventive agents in China.    Abstract:   Since the late 1970s, a comprehensive search for cancer chemopreventive agents has been established in our Institute. A series of new retinoids have been synthesized and screened on the basis of established methodologies of experimental chemoprevention in vitro as well as in vivo. Pharmacological studies demonstrated that N-4-(carboxyphenyl)retinamide (RII) induces cell differentiation of HL-60 cells and inhibits dimethylnitrosamine-induced carcinogenesis of the forestomach in mice, 7,12-dimethylbenz[a]anthracene (DMBA)-induced papilloma in mouse skin, and DMBA-induced carcinogenesis of the buccal pouch in Syrian golden hamsters. It significantly promoted lymphoblastic transformation and activated macrophages. In further studies, RII significantly inhibited ornithine decarboxylase activity. After 6 months of chronic toxicological studies in rats and dogs, RII was recommended for clinical trial. Phase II studies found that RII is effective in treating oral and vulvar leukoplakia. It is also effective in treating myelodysplastic syndrome and dysplasia of uterine cervix. The chalcone retinoidal compounds were discovered when the search for new retinoids with less toxicity and higher potency led to third-generation retinoids, which were synthesized and screened. Structure-activity relationship studies found that 3,5-di-tert-butyl-4-methoxy-4-carboxyl chalcone (R9158) is the most active inhibitor of a variety of cancer cells. It has no effect on the Colony Forming Unit-Granulocyte/Macrophage (CFU-GM) of bone marrow in mice. In in vivo studies, R9158 showed a remarkable inhibition of chondrosarcoma in rats. It had no cross-resistance to vincristine, but was cross-resistant to all-trans retinoic acid. Red ginseng, a processed Panax ginseng, is considered a typical tonic in traditional Chinese medicine. Our studies demonstrated that red ginseng extract inhibited DMBA-induced skin papilloma significantly. Experiments showed that glycyrrhetinic acid inhibited croton oil-induced ear edema in mice. It also inhibited epidermal ornithine decarboxylase as well as the rapid DNA damage induced by the carcinogen benzo[a]pyrene (B[a]P). Our pharmacological studies demonstrated that Chinese gallotannin inhibited the malignant transformation of B[a]P-induced V79 cells in vitro and B[a]P-induced pulmonary adenoma in A/J mice in vivo significantly."]
[9433514,1,0,0,1,1997,"Modulation of cardiac hypertrophy by estrogens.","Pelzer",9433514,"Modulation of cardiac hypertrophy by estrogens.    Abstract:   Gender-specific differences in heart disease have long been known but it has only been since the advent of molecular biology that it has become possible to investigate the molecular mechanisms. Most biochemical work in the last 50 years has focused on the characterization of the steroid hormones involved in gender specificity. More recently, the cloning of the steroid receptors and characterization of the signaling pathways through these proteins has given new insights into the mechanisms underlying the mode of action of steroid hormones. It has also become clear that the steroid receptors can be classified into families (receptors for thyroid hormone, glucocorticoids, estrogens, androgens, retinoic acid, and so called orphan receptors of mostly unknown function). The structures of these receptors show very close resemblance and all are DNA-binding proteins acting as transcription factors. Some (if not all) act as repressors of transcription of some genes in the native state and are converted to activators (or perhaps repressors of other genes) upon binding of the cognate hormone. Naturally, classical target tissues for estrogens and androgens have been studied first and only in very recent years has it been recognized that estrogens and androgens act on a much wider spectrum of tissues. In the cardiovascular field, the beneficial effect of estrogen replacement therapy in postmenopausal women which reduces the incidence of cardiovascular disease by some 40% and the lower incidence of cardiovascular disease in premenopausal women have mostly been explained by the beneficial action of estrogens on the lipid profile (increase in HDL and decrease in LDL cholesterol). Recently, functional estrogen receptors have also been shown in vascular smooth muscle cells and in the endothelium. Our own group has characterized the presence of estrogen receptors in the myocardium and in cardiac fibroblasts. We have also shown that these receptors are transcriptionally active because they are able to drive a minigene composed of a triple estrogen responsive DNA regulatory element (promoter) coupled to the firefly luciferase gene which serves as a reporter by way of its ability to drive a light-emitting reaction. We are in the process of characterizing the target genes for estrogen in the myocardium. A specific series of immediate-early genes is induced by estradiol (the major premenopausal estrogen) and we have also characterized a number of tissue-specific genes whose expression is driven by estrogens in the myocardium. The ultimate goal of these investigations is to explore the use of estrogens in the treatment of cardiac hypertrophy (and failure) by way of their properties to counteract (at least some of) the pathological switches in gene expression in these disease entities."]
[9238853,1,0,0,1,1997,"Aromatase expression in health and disease.","Simpson",9238853,"Aromatase expression in health and disease.    Abstract:   Family 19 of the P450 superfamily is responsible for the conversion of C19 androgenic steroids to the corresponding estrogens, a reaction known as aromatization, since it involves conversion of the delta 4-3-one A-ring of the androgens to the corresponding phenolic A-ring characteristic of estrogens. Its members occur throughout the entire vertebrate phylum. The reaction mechanism of aromatase is very interesting from a chemical point of view and has been studied extensively; however, a detailed examination of structure-function relationships has not been possible due to lack of a crystal structure. Recent attempts to model the three-dimensional structure of aromatase have permitted a model that accounts for the reaction mechanism and predicts the location of aromatase inhibitors. The gene encoding human aromatase has been cloned and characterized and shown to be unusual compared to genes encoding other P450 enzymes, since there are a number of untranslated first exons that occur in aromatase transcripts in a tissue-specific fashion, due to differential splicing as a consequence of the use of tissue-specific promoters. Thus, expression in ovary utilizes a proximal promoter that is regulated primarily by cAMP. On the other hand, expression in placenta utilizes a distal promoter that is located at least 40 kb upstream of the start of transcription and that is regulated by retinoids. Other promoters are employed in brain and adipose tissue. In the latter case, class I cytokines such as IL-6 and IL-11 as well as TNF alpha are important regulatory factors. PGE2 is also an important regulator of aromatase expression in adipose mesenchymal cells via cAMP and PGE2 appears to be a major factor produced by breast tumors that stimulates estrogen biosynthesis in local mesenchymal sites. In all of the splicing events involved in the use of these various promoters, a common 3-splice junction is employed that is located upstream of the start of translation; thus, the coding regions of the transcripts- and hence the protein-are identical regardless of the tissue site of expression; what differ in a tissue-specific fashion are the 5-ends of the transcripts. This pattern of expression has great significance both from a phylogenetic and ontogenetic standpoint as well as for the physiology and pathophysiology of estrogen formation. Recently, a number of mutations of the aromatase gene have been described, which give rise to complete estrogen deficiency. In females this results in virilization in utero and primary amenorrhea with hypergonadotropic hypogonadism at the time of puberty. In men the most striking feature is continued linear bone growth beyond the time of puberty, delayed bone age, and failure of epiphyseal closure, thus indicating an important role of estrogens in bone metabolism in men. In both sexes the symptoms can be alleviated by estrogen administration."]
[9210910,1,0,0,1,1997,"Characteristics of a cell line established from a case of acute megakaryoblastic leukemia.","Skinnider",9210910,"Characteristics of a cell line established from a case of acute megakaryoblastic leukemia.    Abstract:   Acute megakaryoblastic leukemia is uncommon and comprises about 5% of acute nonlymphoid leukemias in the French-American-British classification. Cell lines from such leukemias are relatively rare with only about 8 reported in the literature. We established a cell line from a case of acute megakaryoblastic leukemia arising in a 2-year-old child. Surface marker studies of the cells confirmed their megakaryoblastic nature, with 54% of the cells being CD61 positive and peroxidase and esterase negative. The cells had a doubling time of 72 h. Emperipolesis (a phenomenon in which a cell, usually a lymphocyte or neutrophil, enters another cell, moves about and leaves without undergoing phagocytosis) of one blast into another, larger one, was occasionally seen, and a review of the original bone marrow specimen also showed emperipolesis of neutrophils into the megakaryoblasts. The cells responded to interleukin 3 and were inhibited with all-trans-retinoic acid. The karyotype of the cells was the 46,XX,-16 with a marker chromosome. The marker chromosome is possibly chromosome 16 with a small segment of a chromosome translocated to the terminal portion of chromosome 16."]
[9156652,0,0,0,0,1997,"Bcl-2 expression in acute myeloblastic leukaemia: relationship with autonomous growth and CD34 antigen expression.","Bradbury",9156652,"Bcl-2 expression in acute myeloblastic leukaemia: relationship with autonomous growth and CD34 antigen expression.    Abstract:   The bcl-2 gene encodes a mitochondrial protein that inhibits the onset of apoptosis induced by growth factor withdrawal or cytotoxic agents. Using quantitative flow cytometry and expressing bcl-2 levels as the number of molecules of equivalent soluble fluorochrome (MESF) per cell, we have shown that bcl-2 protein expression in the blast cells from patients with acute myeloblastic leukaemia (AML) is heterogeneous, but not related to FAB type. The blast cells from AML patients with the capacity to grow and survive autonomously in vitro were found to have higher bcl-2 MESF values than those that were dependent upon exogenous growth factors. We have previously reported that the blast cells from 70% of AML patients exhibit autonomous growth and autocrine growth factor production in vitro and that this has been shown to be an important indicator of poor prognosis in AML. High bcl-2 expression has also been associated with a low complete remission rate and poor survival in AML. In the patients whose blast cells exhibited autonomous growth, neutralisation of endogenous GM-CSF resulted in down-regulation of bcl-2 protein, whereas in blast cells from patients whose cells proliferated only in the presence of added growth factors, incorporation of recombinant human (rh) GM-CSF in the culture media resulted in up-regulation of bcl-2. Because CD34 positivity has been reported as another indicator of poor prognosis in AML, we compared bcl-2 expression in cases of CD34 positive AML, CD34 negative AML and CD34 positive normal bone marrow cells. Bcl-2 was found to be strongly expressed on the CD34+ normal bone marrow cells. The blast cells from CD34+ AML patients expressed significantly higher bcl-2 levels than CD34- AML patients. In five cases of CD34+ AML, the bcl-2 levels were determined on purified CD34+ and CD34- blast cell populations. The CD34+ blast cells were found to express significantly higher bcl-2 levels compared with the CD34-blast cells. Our data would suggest that quantification of bcl-2 in AML blast cell may be useful as a prognostic indicator in AML."]
[9090490,1,0,0,1,1997,"Treatment of adult acute leukemia.","Büchner",9090490,"Treatment of adult acute leukemia.    Abstract:   In 1996 progress has been made toward a better understanding of acute leukemias, their biology, the effects of different intensity or subtype-specific chemotherapy, and the contribution of bone marrow transplantation. In acute lymphoblastic leukemia, high-dose cytarabine in induction and in postremission treatment improves the cure rate, whereas dose reduction of daunorubicin in older patients worsens response and increases mortality. After acute promyelocytic leukemia has been successfully treated by retinoids, another subtype-specific chemotherapy containing high-dose methotrexate has overcome the primarily poor prognosis of B-cell acute lymphoblastic leukemia. The leukemic stem cell of acute myeloid leukemia representing minimal residual disease, producing disease progression in the patients, and initiating long-term growth in cultures or immunodeficient mice appears as a primitive multipotent cell. Leukemic transformation is reflected either by the specific balanced chromosome translocations or by chromosome deletions or losses. They are associated with histories of cytotoxic drugs such as epipodophylotoxins and anthracyclines or alkylating agents. Alternatively, both kinds of aberrations develop spontaneously with ethnic differences in special subtypes. Cytogenetics also determine favorable and unfavorable prognosis both for chemotherapy and bone marrow transplantation. In acute lymphoblastic leukemia high-risk and nonstandard-risk patients seem to benefit from allogeneic transplantation, whereas in acute myeloid leukemia there is no adequate basis for risk-adapted stratification between treatment modalities. New prospects lie in a more successful use of the effects of treatment intensification possibly supported by autologous blood stem cell transplantation. On the basis of standardized treatment, future clinical research can address the role of biologic features of the individual leukemia such as specific chromosome aberrations, fusion genes, expression of oncogenes, and monitoring of minimal residual disease."]
[8952559,1,0,0,1,1996,"Extramedullary acute promyelocytic leukemia.","Wiernik",8952559,"Extramedullary acute promyelocytic leukemia.    Abstract:    BACKGROUND : Extramedullary acute promyelocytic leukemia (APL) is rare, and said to be more common after treatment with all-trans retinoic acid (ATRA) than after any other treatment.  METHODS : The case of a child with extramedullary relapse of APL after initial treatment with ATRA and that of an adult whose initial treatment was chemotherapy are presented, and the literature on extramedullary relapse of APL is reviewed.  RESULTS : Twenty-six patients were identified, including the 2 current patients. Ethnicity could be determined in 23 patients, 17 of whom were of other than Northern European extraction. The most common sites of extramedullary disease were the skin (15 patients), central nervous system (5 patients), mediastinum (3 patients), and, curiously, gingiva (3 patients). Extramedullary leukemia developed in 19 patients: after treatment with ATRA (6 patients), cytotoxic chemotherapy (12 patients), or both (1 patient), and developed in 7 others before any treatment for leukemia was given.  CONCLUSIONS : These data suggest but do not prove that extramedullary APL may occur more frequently after ATRA than other therapy, since ATRA has been available for a relatively short period of time. However, it is clear from the literature that extramedullary APL may occur after chemotherapy or before any treatment."]
[9152974,1,0,0,1,1996,"Acute promyelocytic leukaemia in the all trans retinoic acid era.","DeLoughery",9152974,"Acute promyelocytic leukaemia in the all trans retinoic acid era.    Abstract:   Bleeding diathesis is a common complication of acute promyelocyctic leukaemia (APL). Multiple haemostatic defects are found in most patients with APL, which often worsen following cytoreductive chemotherapy. Besides thrombocytopenia, most patients develop disseminated intravascular coagulation, systemic fibrinolysis or both. A major aim in treating haemostatic defects of APL is to prevent death or disability from bleeding until chemotherapy clears the malignant promyelocytes from the blood and bone marrow. The therapeutic options are discussed in this review and practical guidelines for treatment are outlined."]
[9031080,1,0,0,1,1996,"Leukocyte alkaline phosphatase a specific marker for the post-mitotic neutrophilic granulocyte: regulation in acute promyelocytic leukemia.","Garattini",9031080,"Leukocyte alkaline phosphatase a specific marker for the post-mitotic neutrophilic granulocyte: regulation in acute promyelocytic leukemia.    Abstract:   Leukocyte alkaline phosphatase (LAP) is the product of the gene coding for the liver/bone/kidney-type alkaline phosphatase. In the normal hematopoietic system, the only cell type expressing LAP in basal conditions is the post-mitotic neutrophilic granulocyte. Thus LAP represents a specific and restrictive marker for the terminal maturation of the neutrophilic granulocyte. The study of the factors and the molecular mechanisms responsible for the expression of LAP in cells undergoing granulocytic maturation may shed light on this complex biological process. Acute promyelocytic leukemia (APL) represents a unique biological model in which it is possible to investigate neutrophilic differentiation. APL blasts undergo rapid and irreversible maturation towards cells morphologically and biochemically resembling normal mature granulocytes upon in vivo and in vitro challenge with all-trans retinoic acid (ATRA). In this cellular context, we studied the endogenous factors involved in the expression of LAP. The phosphatase is not synthesized in undifferentiated APL blasts and it is expressed only upon treatment with combinations between ATRA and a second cyto-differentiating signal. The second signal may be given by G-CSF, cAMP analogs, IL-6 and to a lesser extent by IL-1 beta. The molecular mechanisms underlying the induction of LAP by combinations of ATRA and G-CSF or cAMP analogs were studied in detail and are the object of this review."]
[9035704,14,0,0,14,1996,"Oral retinoids--efficacy and toxicity in psoriasis.","Gollnick",9035704,"Oral retinoids--efficacy and toxicity in psoriasis.    Abstract:   Psoriasis is a disease of unknown aetiology, affecting approximately 1-3% of the population. In most cases involving relatively localized disease, patients are best managed with either topical therapy alone or topical therapy in combination with UV-phototherapy. However, approximately 35% of patients do not respond well to these conventional treatments or have moderate-to-severe disease requiring more aggressive forms of therapy. The second-generation retinoids, etretinate and its metabolite acitretin, are important additions to the armamentarium of agents used to treat these recalcitrant or severe forms of the disease. Generalized pustular psoriasis generally responds well to high-dose (0.7-1 mg/kg/day) oral retinoid monotherapy. In contrast, increasing small doses of the retinoid are recommended initially in erythrodermic psoriasis in order not to provoke the disease. Long-term clinical experience favours a combination treatment of the retinoid with either topical and/or UV irradiation in chronic plaque-like psoriasis. Both oral retinoids have comparable efficacy and tolerability profiles, and the relapse rates for both drugs are similar. The toxicities associated with both short- and long-term treatment with oral retinoids are significant and include mucocutaneous effects, adverse modulation of serum lipid chemistries, elevation of liver enzymes, and after long-term chronic dosing, skeletal and ligamentous calcification, and hyperostosis. Both etretinate and acitretin, like all retinoids, are known teratogens in animal models, and documented evidence exists for teratogenic activity in humans as well. Consequently, women of childbearing age are strongly advised to avoid pregnancy during treatment and up to 5 years following cessation of therapy with both etretinate and the carboxylic acid metabolite acitretin."]
[8885715,0,0,0,0,1996,"Craniofacial defects in AP-2 null mutant mice.","Morriss-Kay",8885715,"Craniofacial defects in AP-2 null mutant mice.    Abstract:   AP-2 is a recent significant addition to the list of transcription factors that have been demonstrated by targeted gene disruption to be essential for normal development. Two recent reports of AP-2 null mutant mice indicate that AP-2 holds a key position in the network of genes and proteins controlling developmental pattern and morphogenesis, and that it is particularly important for development of the cranial region and for midline fusions."]
[9081766,1,0,0,1,1996,"Molecular basis of familial cleft lip and palate.","Hibbert",9081766,"Molecular basis of familial cleft lip and palate.    Abstract:   Cleft lip and palate (CLP) is one of the commonest congenital malformations and although the aetiology is still very unclear, a familial genetic component is considered to be an important factor in certain individuals. Molecular biology techniques are being used to identify the genes involved and this paper reviews current knowledge and the advances that have already been made. Recent evidence suggests a potential major gene on 6p, and a modifying role for transforming growth factor alpha (TGFA). Moreover retinoic acid receptor alpha (RARA) (17q), MSXI (4p), 4q and BCL3 (19q) could all be implicated in certain CLP families. In addition, the potential modifying role of various genes with the environment are considered to be important areas of research in the future. The identification of a genetic locus associated with this disease would be an important advance in CLP genetic counselling and lead to a better understanding of the genetic basis of CLP."]
[8952164,2,0,0,2,1996,"PML, PLZF and NPM genes in the molecular pathogenesis of acute promyelocytic leukemia.","Pandolfi",8952164,"PML, PLZF and NPM genes in the molecular pathogenesis of acute promyelocytic leukemia.    Abstract:   Acute promyelocytic leukemia (APL) is a distinct subtype of myeloid leukemia that in the USA and Italy alone affects more than 3,000 individuals every year. APL is characterized by three distinct and unique features: i) accumulation in the bone marrow of tumor cells with promyelocytic features; ii) invariable association with specific translocations which always involve chromosome 17 and the retinoic acid receptor alpha (RAR alpha) locus; iii) exquisite sensitivity of APL blasts to the differentiating action of retinoic acid (RA). From this point of view APL has become the paradigm for therapeutic approaches utilizing differentiating agents. The last five years have been crucial for the understanding of the molecular basis of APL. RAR alpha translocates in 99% of cases to a gene located on chromosome 15 that we initially named myl and is now known as PML. In a few cases RAR alpha variably translocates to chromosome 11, where it fuses to the PLZF gene or to a gene, also on 11, which has not yet been characterized. In addition, RAR alpha is also found translocated to chromosome 5, where it fuses to the NPM gene. The cloning of variant translocations in APL and comparative analysis of their associated products is crucial for the understanding of the molecular etiopathogenesis of the disease. Functional analysis of the various fusion proteins as well as RAR alpha partners is revealing strikingly common features beneath a misleading structural heterogeneity which unravels a possible unifying molecular mechanism towards APL leukemogenesis."]
[9159226,1,0,0,1,1996,"New mechanisms of regulation of the genomic actions of vitamin D in bone cells: interaction of the vitamin D receptor with non-classical response elements and with the multifunctional protein, calreticulin.","St-Arnaud",9159226,"New mechanisms of regulation of the genomic actions of vitamin D in bone cells: interaction of the vitamin D receptor with non-classical response elements and with the multifunctional protein, calreticulin.    Abstract:   Vitamin D exerts its genomic effects following binding to a specific receptor which is a member of the steroid hormone receptor superfamily. The vitamin D receptor (VDR) forms heterodimers with retinoid X receptors (RXRs) and the dimer then interacts with its cognate binding site, termed vitamin D response element (VDRE), to affect the transcription of target genes. Recent studies have identified novel sequence motifs for VDREs as well as novel protein-protein interactions involving the VDR. These will be reviewed with particular emphasis on the complex VDRE from the c-fos proto-oncogene promoter region and the inhibition of the vitamin D signal transduction pathway by the multifunctional protein, calreticulin. Thus research on the control of gene transcription by vitamin D reveals examples of molecular interplay between transcriptional regulatory pathways and provides new insight into the molecular mechanism of action of vitamin D."]
[8877454,0,0,0,0,1996,"Re-examining jaw regeneration in urodeles: what have we learnt?","Ferretti",8877454,"Re-examining jaw regeneration in urodeles: what have we learnt?    Abstract:   Urodele amphibians can regenerate not only their limbs and tails, but also their upper and lower jaws rather faithfully. However, relatively few studies of jaw regeneration in amphibians have been carried out, especially in recent years. It is therefore important to reexamine thoroughly this regenerating system, since the advent of sophisticated morphological techniques and the development of molecular approaches offer the promise of renewed and rapid progress in our understanding of complex developmental problems such as this. This paper briefly reviews some of the early research on jaw regeneration, some of the fundamental questions which have been asked and have yet to be answered, and the work we have carried out in order to understand the molecular mechanisms underlying jaw regeneration in the newt, Notophthalmus viridescens. In addition, some aspects of jaw regeneration will be discussed in relation to regeneration of the adult limb."]
[8974789,1,0,0,1,1996,"Apoptosis in blood diseases. Review new data.","Binet",8974789,"Apoptosis in blood diseases. Review new data.    Abstract:   In this report we reviewed the recent data regarding the involvement of apoptosis or programmed cell death in hematological diseases. We summarized new features of apoptosis including high molecular weight DNA fragmentation and programmed cell death of enucleated cells. We described the recent contributions about the three oncogenes bcl-2, p53 and c-myc. New inducers and inhibitors of apoptosis have been reported, particularly the role of stromal environment, thrombopoietin, erythropoïetin and flt-3 ligand has been mentioned. Apoptosis has been studied in red cell pathology: polycythemia, thalassemia and deficiency in folates, vitamin B12, iron and G6PD. Recently, the involvement of programmed cell death has been documented in bone marrow failure and myelodysplasia. In Acute Leukemia, the therapeutic action of numerous drugs has been proven by their in vitro apoptotic effect. The resistance of malignant cells to apoptosis, in Chronic Myeloïd Leukemia, due to bcr-abl oncogene, has been partially explained by conformational changes in p53 expression and is reversed by retinoic acid. Numerous reports in Chronic Lymphocytic Leukemia have documented the major role of apoptosis in this disease, especially in therapeutic efficacy of Chlorambucil, Fludarabine and Methylxanthine derivatives. At least, in Myeloma, it has been shown that apoptosis is induced by dexamethasone and HMBA, and inhibited by interleukine 6 that prevents activation of SAP Kinases."]
[8836870,1,0,0,1,1996,"Expression of bone-specific genes by hypertrophic chondrocytes: implication of the complex functions of the hypertrophic chondrocyte during endochondral bone development.","Gerstenfeld",8836870,"Expression of bone-specific genes by hypertrophic chondrocytes: implication of the complex functions of the hypertrophic chondrocyte during endochondral bone development.    Abstract:   Endochondral bone formation is one of the most extensively examined developmental sequences within vertebrates. This process involves the coordinated temporal/spatial differentiation of three separate tissues (cartilage, bone, and the vasculature) into a variety of complex structures. The differentiation of chondrocytes during this process is characterized by a progressive morphological change associated with the eventual hypertrophy of these cells. These cellular morphological changes are coordinated with proliferation, a columnar orientation of the cells, and the expression of unique phenotypic properties including type X collagen, high levels of bone, liver, and kidney alkaline phosphatase, and mineralization of the cartilage matrix. Several studies indicate that hypertrophic chondrocytes also express osteocalcin, osteopontin, and bone sialoprotein, three proteins which until very recently were widely believed to be restricted in their expression to osteoblasts. Recent studies suggest that the hypertrophic chondrocytes are regulated by the calcitropic hormones, morphogenic steroids, and local tissue factors. These considerations are based on the regulation by 1,25 (OH)2D3 and retinoids of the cartilage specific genes as well as osteopontin and osteocalcin expression in hypertrophic chondrocytes. They are also based on the effects on growth plate development caused by 1) transgenic ablation of autocrine/paracrine regulators such as PTHrP and of the transcriptional regulator c-fos and 2) naturally occurring genetic mutations of the FGF receptor. These studies further suggest that specific transcriptional factors mediate exogenous regulatory signals in a coordinated manner with the development of bone. While it has been widely demonstrated that the majority of hypertrophic chondrocytes undergo apoptosis during terminal stages of the developmental sequence, their response to specific exogenous regulatory signals and their expression of bone-specific proteins give rise to questions about whether all growth chondrocytes have the same developmental fates and have identical functions. Furthermore, specific questions arise as to whether there are similar mechanisms of regulation for commonly expressed genes found in both cartilage and bone or whether these genes have unique regulatory mechanisms in these different tissues. These recent findings suggest that hypertrophic chondrocytes are functionally coupled during endochondral bone formation to the recruitment of osteoblasts, vascular cells, and osteoclasts."]
[8791518,0,0,0,0,1996,"Transcription factors in disease.","Engelkamp",8791518,"Transcription factors in disease.    Abstract:   Mutations affecting several predominantly tissue-specific transcriptional regulators have recently been associated with disease phenotypes. Although the mutational spectrum is variable, many of the reported cases involve clear loss-of-function mutations-such as Waardenburg syndrome type 1, aniridia and Rubinstein-Taybi syndrome-suggesting that the genetic mechanism involved in disease is haplo-insufficiency. The high degree of dosage sensitivity often appears to affect only a subset of the tissues that express the gene. Position effects with cytogenetic rearrangements well outside the coding region have been implicated for four of the genes discussed: POU3F4, SOX9, PAX6, and GL13."]
[8724548,0,0,0,0,1996,"Granulocytic sarcoma in acute promyelocytic leukemia.","Benekli",8724548,"Granulocytic sarcoma in acute promyelocytic leukemia.    Abstract:  "]
[8796989,1,0,0,1,1996,"Miscellaneous metabolic diseases.","Van Linthoudt",8796989,"Miscellaneous metabolic diseases.    Abstract:   Musculoskeletal manifestations are commonly observed in metabolic disorders. Here we review the recent literature on several metabolic arthropathies. Hemochromatosis should be suspected in patients with the sign of the quot;iron salutequot;. Screening for this disorder by routine measurement of transferrin saturation appears to be a cost-effective procedure in white men aged 30 years or older. In dialysis arthropathy, radiologic lesions of the hand joints increased in size and frequency with the duration of dialysis. However, destructive arthropathy of the fingers is not necessarily related to amyloid deposition. In patients with dialysis-related beta 2-microglobulin amyloid deposition, renal transplantation improved clinical rheumatologic manifestations but did not prevent progression of destructive arthropathies nor dissolution of amyloid deposits. In ochronotic arthropathy, spinal changes may resemble those seen in ankylosing spondylitis and can lead to cord compression. The presence of brownish-blackish rods in the synovial fluid is an unusual but useful diagnostic tool. Metabolic factors are likely to play a role in the pathogenesis of diffuse idiopathic skeletal hyperostosis, and recent studies have demonstrated elevated insulin and growth hormone but normal insulin-like growth factor-1 levels in these patients. Other metabolites that may play a role in this condition include retinoids and bone morphogenetic protein-2."]
[9026350,1,0,0,1,1996,"Transcription factors and the cardiac gene programme.","Doevendans",9026350,"Transcription factors and the cardiac gene programme.    Abstract:   During the past decade, major advances have been made in uncovering the mechanisms that switch genes on and off. Gene methylation and histones play an important role in gene (in)activation. Following gene activation, the initiation of transcription by RNA polymerase requires the assembly of multiple protein complexes on the promoter region of a gene. How a cell type-specific gene expression pattern can be induced is a key question in cardiovascular biology today. Members of the helix-loop-helix-family of the transcription factors play a dominant role in skeletal muscle formation. In cardiac muscle the situation is less obvious. Recent studies identified muscle transcription factors like MEF-2, TEF-1 and MNF, which are common to both the skeletal and cardiac muscle lineages. A few transcription factors, among which Nkx 2.5 and GATA-4, are expressed predominantly in the heart. The absence of master regulators in the heart points to the importance of interaction between ubiquitous factors and tissue restricted factors to initiate the cardiac gene programme and to lock these cells in their differentiated state. The recent development of murine transgenic and gene-targeting technology provides tools to study the role of mammalian transcription factors in vivo. Interesting cardiac phenotypes are found in gene targeted mice, indicating a crucial role for retinoic acid and homeobox genes in murine cardiogenesis."]
[8676045,0,0,0,0,1996,"Age-related endocrine deficiencies and fractures of the proximal femur. II implications of vitamin D deficiency in the elderly.","Boonen",8676045,"Age-related endocrine deficiencies and fractures of the proximal femur. II implications of vitamin D deficiency in the elderly.    Abstract:   In the United Kingdom, as many as 60% of institutionalized people who are not taking vitamin D supplements may be deficient. Both impaired mineralization and a hyperparathyroidism-related increase in bone turnover have been identified in the presence of vitamin D deficiency. Recent interventional data have confirmed the role of vitamin D deficiency in the pathogenesis of senile osteoporosis and indicated the need to maintain serum cholecalciferol levels within the normal range in elderly people."]
[8882470,1,0,0,1,1996,"Modulation of elastin expression and cell proliferation in vascular smooth muscle cells in vitro.","Tajima",8882470,"Modulation of elastin expression and cell proliferation in vascular smooth muscle cells in vitro.    Abstract:   Elastin expression in cultured vascular smooth muscle cell (VSMC) was found to be enhanced by potent inhibitors of VSMC proliferation including minoxidil, heparin and retinoic acid. By contrast, elastin expression was declined by potent stimulators of VSMC proliferation like epidermal growth factor, high K+, angiotension II and phorbol ester. To elucidate the relationship between elastin expression and cell proliferation, the elastin expression in the different cell growth states brought by cell-synchronizing culture or suspension culture, a culture system independent of potent modulators of VSMC proliferation. Elastin was found to be expressed maximally at G0 and minimally at G2/M phases, suggesting that cell growth state regulates elastin expression in VSMC culture. Synthetic elastin peptide VPGVG or its polymeric form (VPGVG)n enhanced VSMC proliferation, which resulted in the reduction of elastin expression. The results suggests that elastin fragment regulates VSMC proliferation. These correlation between elastin expression and cell growth state may play an essential role in elastin metabolism under the normal and diseased conditions."]
[8850563,2,0,0,2,1996,"A sticky problem: the Xenopus cement gland as a paradigm for anteroposterior patterning.","Sive",8850563,"A sticky problem: the Xenopus cement gland as a paradigm for anteroposterior patterning.    Abstract:   The cement gland is a mucus-secreting organ found at the extreme anterior of frog embryos. It attaches the embryo to a solid support before swimming and feeding begin, and also serves a related sensory function that stops the embryo from moving once it is attached. Cement gland is an extremely useful anterior marker, whose study continues to yield fundamental information concerning vertebrate axial patterning. Cement gland arises from the outer layer of the embryonic ectoderm and, in Xenopus, forms a cone of columnar epithelium. It is the first ectodermal organ to differentiate, beginning to do so by late gastrula. A battery of genes expressed in the developing and mature cement gland serve as useful markers. Cement gland development can be influenced by both stimulatory and inhibitory cell interactions. Stimulatory signals arise from the anterior neural plate, head endoderm, and the dorsal mesoderm. Inhibitory signals are present in the posterior dorsal mesoderm and in ventral ectoderm and mesoderm. Further, signalling between the ectodermal layers may restrict cement gland differentiation to the outer ectodermal cells. Several secreted molecules are able to induce or repress cement gland formation: these include noggin, follistatin, hedgehog, chordin, retinoic acid, embryonic fibroblast growth factor (eFGF), Bone Morphogenetic Protein-4 (BMP-4), and Xwnt-8. Several of these factors alter expression of the homeodomain gene Xotx2, which may be a transcriptional activator of cement gland differentiation genes. The significance of the cell interactions and factors described in positioning cement gland at the front of the embryo is explored."]
[8882305,1,0,0,1,1996,"The regulation and regulatory role of collagenase in bone.","Partridge",8882305,"The regulation and regulatory role of collagenase in bone.    Abstract:   Interstitial collagenase plays an important role in both the normal and pathological remodeling of collagenous extracellular matrices, including skeletal tissues. The enzyme is a member of the family of matrix metalloproteinases. Only one rodent interstitial collagenase has been found but there are two human enzymes, human collagenase-1 and -3, the latter being the homologue of the rat enzyme. In developing rat and mouse bone, collagenase is expressed by hypertrophic chondrocytes, osteoblasts, and osteocytes, a situation that is replicated in a fracture callus. Cultured osteoblasts derived from neonatal rat calvariae show greater amounts of collagenase transcripts late in differentiation. These levels can be regulated by parathyroid hormone (PTH), retinoic acid, and insulin-like growth factors, as well as the degree of matrix mineralization. Much of the work on collagenase in bone has been derived from studies on the rat osteosarcoma cell line, UMR 106-01. All bone-resorbing agents stimulate these cells to produce collagenase mRNA and protein, with PTH being the most potent stimulator. Determination of secreted levels of collagenase has been difficult because UMR cells, normal rat osteoblasts, and rat fibroblasts possess a scavenger receptor that removes the enzyme from the extracellular space, internalizes and degrades it, thus imposing another level of control. PTH can also regulate the abundance of the receptor as well as the expression and synthesis of the enzyme. Regulation of the collagenase gene by PTH appears to involve the cAMP pathway as well as a primary response gene, possibly Fos, which then contributes to induction of the collagenase gene. The rat collagenase gene contains an activator protein-1 sequence that is necessary for basal expression, but other promoter regions may also participate in PTH regulation. Thus, there are many levels of regulation of collagenase in bone perhaps constraining what would otherwise be a rampant enzyme."]
[8868093,1,0,0,1,1996,"Biology and treatment of acute promyelocytic leukemia.","Fenaux",8868093,"Biology and treatment of acute promyelocytic leukemia.    Abstract:   Recent progresses made in the biology of acute promyelocytic leukemia and therapeutic improvements obtained in acute promyelocytic leukemia since the advent of all-trans retinoic acid have continued to generate a large number of publications on this disease in the past 12 months, which concern both its biological and therapeutic aspects."]
[8850437,0,0,0,0,1996,"Nutrition and prostate cancer.","Kolonel",8850437,"Nutrition and prostate cancer.    Abstract:   Epidemiologic evidence on the relation between nutrition and prostate cancer is reviewed. Little is known about the etiology of prostate cancer, despite its prominence as the leading cancer among men in the United States. Rational mechanisms for dietary influences on prostate carcinogenesis, including effects on production or metabolism of androgenic hormones, have been proposed, but because few suitable animal models have been developed, the laboratory literature on diet and prostate cancer is sparse. Despite strong ecologic data and largely consistent case-control and cohort data on dietary fat and prostate cancer, the role of this nutrient remains unclear. Few studies, to date, have adjusted the results for caloric intake, and no particular fat component has been consistently implicated. A notable finding is a strong positive association with intake of animal products, especially red meats, but this in itself does not specifically implicate fat. Epidemiologic investigations on vitamin A and carotenoids are divided almost equally between studies showing positive and inverse associations. The evidence from these studies for a protective effect of fruits and vegetables on prostate cancer, unlike many other cancer sites, is not convincing. The data on other dietary components that have been examined with regard to prostate cancer etiology (cadmium, zinc, vitamins C and D, beverages, and legumes) are too incomplete at this time to draw any inferences as to their importance. The evidence for anthropometric associations with prostate cancer is weak. Whereas a clear association with obesity has not been shown, a positive relationship to muscle mass, though not yet established conclusively, further suggests the importance of androgens in this cancer."]
[8745889,10,0,0,10,1996,"Prolonged treatment with oral retinoids in adults: no influence on the frequency and severity of spinal abnormalities.","Van Dooren-Greebe",8745889,"Prolonged treatment with oral retinoids in adults: no influence on the frequency and severity of spinal abnormalities.    Abstract:   It is generally accepted that the spine is the site of predilection for retinoid-induced skeletal abnormalities. However, the reported prevalence of skeletal problems varies widely. To investigate the frequency and severity of retinoid-induced spinal abnormalities, all records of patients who underwent spinal radiographs at the request of the department of dermatology between 1983 and 1993 were reviewed. This group of 135 patients comprised the total population of retinoid-treated patients and those patients who were investigated for possible future retinoid treatment. The mean treatment period in the total group was 30 months and the mean cumulative dose of retinoid was 31 g. In 50 patients the treatment period was gt; or = 24 months with 30 patients being treated for more than 48 months. Baseline radiographs were available from 26 patients and these were compared with the most recent X-rays during treatment. The mean treatment period in this prospective group was 25 months and the mean cumulative dose of retinoid was 25 g. The prevalence of diffuse idiopathic skeletal hyperostosis (DISH), degenerative changes and osteoporosis in the total group was respectively 16%, 53% and 29%. There was no statistically significant relation between the duration of treatment or the cumulative dose and the prevalence or severity of DISH, degenerative changes and osteoporosis. Only the age of the patients was significantly related to the frequency and severity of skeletal abnormalities. In the prospective group, again, no important changes were observed between the radiographs at baseline and during treatment. In this study no relation whatsoever between spinal abnormalities and prolonged oral retinoid treatment could be established. The performance of annual routine spinal radiographs during retinoid treatment is not necessary in our opinion. Additional controlled and prospective studies on spinal and extraspinal skeletal abnormalities are required to develop definitive screening guidelines for patients submitted to long-term retinoid treatment."]
[8603034,3,0,0,3,1996,"P450-dependent enzymes as targets for prostate cancer therapy.","De Coster",8603034,"P450-dependent enzymes as targets for prostate cancer therapy.    Abstract:   Metastatic prostate adenocarcinoma is a leading cause of cancer-related deaths among men. First line treatment is primarily aimed at blocking the synthesis and action of androgens. As primary endocrine treatment, androgen deprivation is usually achieved by orchidectomy or LHRH analogues, frequently combined with androgen receptor antagonists in order to block the residual adrenal androgens. However, nearly all the patients will eventually relapse. Available or potential second line therapies include, among others, alternative endocrine manipulations and chemotherapy. Cytochrome P450-dependent enzymes are involved in the synthesis and/or degradation of many endogenous compounds, such as steroids and retinoic acid. Some of these enzymes represent suitable targets for the treatment of prostate cancer. In first line therapy, inhibitors of the P450-dependent 17,20-lyase may achieve a maximal androgen ablation with a single drug treatment. Ketoconazole at high dose blocks both testicular and adrenal androgen biosynthesis but its side-effects, mainly gastric discomfort, limit its widespread use. A series of newly synthesized, more selective, steroidal 17,20-lyase inhibitors related to 17-(3-pyridyl)androsta-5,16-dien-3beta-ol, may open new perspectives in this field. In prostate cancer patients who relapse after surgical or medical castration, therapies aiming at suppressing the remaining adrenal androgen biosynthesis (ketoconazole) or producing a medical adrenalectomy (aminoglutethimide+hydrocortisone) have been used, but are becoming obsolete with the generalization of maximal androgen blockade in first line treatment. The role of inhibition of aromatase in prostate cancer therapy, which was postulated for aminoglutethimide, could not be confirmed by the use of more selective aromatase inhibitors, such as formestane. An alternative approach is represented by liarozole fumarate (LIA), a compound that blocks the P450-dependent catabolism of retinoic acid (RA). In vitro, it enhances the antiproliferative and differentiation effects of RA in cell lines that express RA metabolism, such as F9 teratocarcinoma and MCF-7 breast carcinoma cells. In vivo, monotherapy with LIA increases RA plasma levels and, to a greater extent, endogenous tissue RA levels leading to retinoid-mimetic effects. In the rat Dunning prostate cancer models, it inhibits the growth of androgen-independent as well as androgen-dependent carcinomas relapsing after castration. Concurrently, changes in the pattern of cytokeratins characteristic of increased differentiation were observed. Early clinical trials show that LIA, in second or third line therapy in metastatic prostate cancer, induces PSA responses in about 30% of unselected patients. In some patients regression of soft tissue metastasis ha been observed. In a subgroup of patients, an important relief of metastatic bone pain was also noted."]
[8845574,1,0,0,1,1995,"The role of biotherapies (interleukins, interferons and erythropoietin) in multiple myeloma.","Avvisati",8845574,"The role of biotherapies (interleukins, interferons and erythropoietin) in multiple myeloma.    Abstract:   During the last decade, the availability of large numbers of cytokines and growth factors has greatly favoured the use of biotherapies in several haematological disease. For MM, the majority of clinical studies have dealt with the use of IFN-alpha. From these studies it appears that IFN-alpha has a definite role in the treatment of MM especially in the setting of minimal residual disease, as maintenance therapy after response to conventional therapies or HDC followed by BMT procedures or PBSCI. Data on the use of EPO have consistently demonstrated the role of this growth factor in ameliorating the grade of anaemia as well as the quality of life of those MM patients whose disease is complicated by the presence of a severe or moderate anemia. Despite the large amount of experimental data indicating a role for IL-2 and IL-6 in controlling tumour growth, there are only a few clinical studies dealing with their use in MM. From these, it appears that IL-2 and anti-IL-6 antibodies should be further investigated as therapeutic tools useful in maintaining responses, because results show that they arrest tumour progression rather than aid, tumour regression. Finally, in the next years, there will be a wider diffusion of biotherapies in MM that should take into account the roles that IL-1 beta and TNF alpha play in myeloma cell proliferation and bone destruction and the finding that retinoic acid is capable of inhibiting the growth of human myeloma cells in vitro through modulation of IL-6 and its receptor."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I517,I517)","v":8573421},{"$f":"(LEN($J517) - LEN(SUBSTITUTE(LOWER($J517),LOWER(B$3),\"\")))/LEN(B$3)","v":1},0,0,{"$f":"SUM(B517:D517)","v":1},1995,"Tiludronate: bone pharmacology and safety.","Bonjour",8573421,"Tiludronate: bone pharmacology and safety.    Abstract:   The pharmacological properties of tiludronate (4-chlorophenyl)thiomethylene bisphosphonate), a sulfured bisphosphonate, have been characterized in a series of preclinical in vivo and in vitro studies. In vivo, tiludronate exerts a dose-dependent inhibitory activity on bone resorption. This property was demonstrated in several animal models, including rats, ewes, and dogs, when bone resorption was induced by administration of retinoid acid or parathyroid hormone, or by immobilization, ovariectomy or orchidectomy. By uncoupling bone resorption from bone formation, tiludronate can induce a positive calcium and phosphate balance. When administered either continuously or intermittently to ovariectomized osteoporotic rats, tiludronate promotes a significant increase in bone mass. This positive effect is associated with an increase in mechanical resistance. Bone tolerance studies indicate that tiludronate is a safe compound with an appreciable therapeutic margin since it can effectively inhibit bone resorption without reducing bone mineralization and strength. In vitro, tiludronate added to bone tissue culture inhibits calcium release, lysosomal enzyme secretion and collagen matrix degradation when induced by various stimulators of bone resorption. At the cellular level, tiludronate does not appear to exert its inhibitory effect on bone resorption by impairing either the recruitment, the migration or the fusion of osteoclast precursors. Tiludronate could act on mature osteoclasts by reducing their capacity to secrete proton into the resorption space and also by favoring their detachment from the bone matrix. The available preclinical data indicate that tiludronate should be an efficacious bisphosphonate in the management of clinical conditions characterized by excessive bone resorption."]
[7637474,0,0,0,0,1995,"Adult leukaemia in 1995: new directions.","Scheinberg",7637474,"Adult leukaemia in 1995: new directions.    Abstract:  "]
[8579895,3,0,0,3,1995,"New understanding of the molecular mechanism of receptor-mediated genomic actions of the vitamin D hormone.","Haussler",8579895,"New understanding of the molecular mechanism of receptor-mediated genomic actions of the vitamin D hormone.    Abstract:   The nuclear vitamin D receptor (VDR) binds the 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]hormone with high affinity and elicits its actions to regulate gene expression in target cells by binding to vitamin D-responsive elements (VDREs). VDREs in positively controlled genes such as osteocalcin, osteopontin, beta 3-integrin, and vitamin D-24-OHase are direct hexanucleotide repeats with a spacer of three nucleotides. The VDR associates with these VDREs with the greatest affinity as a heterodimer with one of the family of retinoid X receptors (RXRs). VDR consists of an N-terminal zinc finger domain that determines DNA binding, a quot;hingequot; segment and a C-terminal hormone binding domain which also contains two conserved regions that engage in heterodimerization with an RXR on the VDRE. The role of the 1,25(OH)2D3 ligand in transcriptional activation by the VDR-RXR heterodimer is to alter the conformation of the hormone-binding domain of VDR to facilitate strong dimerization with RXR, which results in ligand-enhanced association with the VDRE. Thus RXR is recruited into a heterocomplex by liganded VDR. The natural ligand for the RXR coreceptor, 9-cis retinoic acid, suppresses both VDR-RXR binding to the VDRE and 1,25(OH)2D3-stimulated transcription, indicating that 9-cis retinoic acid diverts RXR away from being the silent partner of VDR to instead form RXR homodimers. Recent data reveal that after binding RXR, a subsequent target for VDR in the vitamin D signal transduction cascade is basal transcription factor IIB (TFIIB).(ABSTRACT TRUNCATED AT 250 WORDS)"]
[7614708,0,0,0,0,1995,"Diversification of cardiomyogenic cell lineages during early heart development.","Yutzey",7614708,"Diversification of cardiomyogenic cell lineages during early heart development.    Abstract:  "]
[7489147,0,0,0,0,1995,"The role of bone marrow transplantation in the treatment of myelodysplastic syndromes.","Schultz",7489147,"The role of bone marrow transplantation in the treatment of myelodysplastic syndromes.    Abstract:  "]
[7624746,1,0,0,1,1995,"[Current aspects of therapy in chronic and acute leukemias].","Seipelt",7624746,"[Current aspects of therapy in chronic and acute leukemias].    Abstract:   A significant fraction of patients with chronic myelogenous leukemia (CML) in the chronic phase have durable hematologic remissions following treatment with interferon-alpha. Some clinical trials are beginning to show a modest overall survival advantage with interferon compared to hydroxyurea. The only curative therapy for CML is allogeneic bone marrow transplantation. In chronic lymphocytic leukemia (CLL), stable early stage disease requires no treatment. Recent trials have confirmed that several new purine analogues are effective in CLL. In acute myeloid leukemias there appears to be a dose-dependent effect on remission and intensified treatment may increase the percentage of disease free survivors. Hemopoietic growth factors may reduce treatment-related morbidity and mortality. Enhancement of cytotoxicity by prestimulation with GM-CSF is still controversial. All-trans retinoic acid induces remissions in 80% of patients with acute promyelocytic leukemia by forcing the leukemic promyelocytes to maturation. Allogeneic bone marrow transplantation is effective in high risk patients with Philadelphia chromosome positive acute lymphocytic leukemia (ALL), in patients with relapse or resistant acute myelogenous leukemia (AML) or ALL. In patients with ALL a risk-adapted therapy including allogeneic and autologous bone marrow transplantation and the use of hemopoietic growth factors to improve supportive therapy may result in more cures."]
[8535190,4,0,0,4,1995,"Induction of retinoid resistance by all-trans retinoic acid in acute promyelocytic leukemia after remission.","Cornic",8535190,"Induction of retinoid resistance by all-trans retinoic acid in acute promyelocytic leukemia after remission.    Abstract:   Acute promyelocytic leukemia (APL) results from a malignant process that leads to the accumulation in the blood and the bone marrow of myeloid precursor cells characterized by an abnormal behavior and a differentiation arrest. It aroused considerable interest well beyond the hematologic field during the last five years since APL has two unique features i) the remission of the disease obtained with all-trans retinoic acid (ATRA) treatment ii) the presence in APL blasts of an abnormal protein, the promyelocytic myeloid leukemia/retinoic acid receptor (PML/RAR alpha) protein. APL is characterized cytogenetically by a t(15;17) translocation which involves both the PML gene on chromosome 15 and the RAR alpha gene on chromosome 17 and gives rise to the PML/RAR alpha fusion protein."]
[7762914,1,0,0,1,1995,"Systemic lupus erythematosus: emerging concepts. Part 2: Dermatologic and joint disease, the antiphospholipid antibody syndrome, pregnancy and hormonal therapy, morbidity and mortality, and pathogenesis.","Boumpas",7762914,"Systemic lupus erythematosus: emerging concepts. Part 2: Dermatologic and joint disease, the antiphospholipid antibody syndrome, pregnancy and hormonal therapy, morbidity and mortality, and pathogenesis.    Abstract:    PURPOSE : To review 1) advances in the pathogenesis, diagnosis, and management of dermatologic and joint disease and the antiphospholipid antibody syndrome in patients with systemic lupus erythematosus; 2) controversies related to pregnancy and hormonal therapy and to morbidity and mortality in these patients; and 3) current views on the pathogenesis of systemic lupus erythematosus.  DATA SOURCES AND STUDY SELECTION : Review of the English-language medical literature with emphasis on articles published within the last 5 years. More than 400 articles were reviewed.  DATA SYNTHESIS : Despite considerable overlap, cutaneous lesions specific to lupus erythematosus may be divided into subsets with distinct clinical, histologic, and immunofluorescent features. A recent short-term, prospective, uncontrolled trial found hydroxychloroquine and retinoids to be of similar efficacy in the treatment of cutaneous lupus erythematosus. Optimal treatment for patients with lupus and the anticardiolipin antibody syndrome remains to be defined; uncontrolled, retrospective, and treatment-withdrawal studies suggest that warfarin may be more protective than aspirin. Whether pregnancy induces lupus flares has not yet been established; existing data suggest both that it does and that it does not. Oral contraceptive use and postmenopausal estrogen replacement therapy appear not to cause clinical deterioration in patients with lupus. Recent studies have documented a substantial improvement in the survival of patients with systemic lupus erythematosus; they found 5-year survival rates of 90% or more and 10-year survival rates of more than 80%. Most data suggest that systemic lupus erythematosus results from the activation of self-reactive T cells and B cells by genetic or environmental factors.  CONCLUSIONS : The optimal treatment for dermatologic disease and the antiphospholipid antibody syndrome in patients with systemic lupus erythematosus remains unknown. Although mortality has decreased substantially, the morbidity related to the disease itself and to complications of therapy is still considerable. More studies are needed to further elucidate the effects of pregnancy on this condition and the pathogenetic mechanisms responsible for the development of this disease."]
[7782928,1,0,0,1,1995,"Genomic actions of 1,25-dihydroxyvitamin D3.","Whitfield",7782928,"Genomic actions of 1,25-dihydroxyvitamin D3.    Abstract:   Recent studies have identified a heterodimer of the vitamin D receptor (VDR) and the retinoid X receptor (RXR) as the active complex for mediating positive transcriptional effects of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], the active hormonal form of vitamin D. The VDR-RXR heterodimer has been shown to bind to direct repeat vitamin D-responsive elements (VDREs) upstream of positively controlled genes in the target tissues for vitamin D, including bone (osteocalcin, osteopontin, and beta 3 integrin), kidney (24-hydroxylase) and intestine (calbindin). Residues that participate in heterodimer formation have been identified in the C-terminal hormone-binding domain by analysis of VDR mutants. The role of the 1,25(OH)2D3 ligand in transcriptional activation by the VDR-RXR heterodimer is not entirely clear, but studies of two natural VDR mutants suggest that the binding of both hormone and RXR are required to induce a receptor conformation that is competent to activate transcription. A final level of complexity is added by recent observations that VDR is modified by phosphorylation. Thus, the VDR-mediated action of 1,25(OH)2D3 is now known to involve multiple factors that may provide a conceptual basis for future understanding of the tissue-specific genomic effects of 1,25(OH)2D3."]
[7626498,4,0,0,4,1995,"Developmental roles of the retinoic acid receptors.","Lohnes",7626498,"Developmental roles of the retinoic acid receptors.    Abstract:   Retinoic acid, one of the principle active metabolites of vitamin A (retinol), is believed to be essential for numerous developmental and physiological processes. Vitamin A deprivation (VAD) during development leads to numerous congenital defects. Previous studies of retinoic acid receptor (RAR) deficient mice failed to reveal any of these VAD-induced defects. This finding suggested that either the RARs are functionally redundant or that they are not critically required during development. In order to address these possibilities, we derived a number of RAR compound mutants. Unlike RAR single mutants, these compound null mutants died either in utero or shortly following birth. Histological analysis revealed essentially all of the defects characteristic of fetal VAD. A number of additional malformations, not described in previous VAD studies, were also observed. These included defects of the ocular and salivary glands and their ducts, the skeletal elements of the fore- and hindlimbs, and the cervical region of the axial skeleton. In addition, with the exception of derivatives forming within the first pharyngeal arch, most of the elements derived from mesectoderm emanating from cranial and hindbrain levels were affected. A number of these mutants also exhibited supernumerary cranial skeletal elements characteristics of the reptilian skull. A summary of the defects found in these RAR double mutants is presented."]
[7742522,1,0,0,1,1995,"All-trans-retinoic acid as a differentiating agent in the treatment of acute promyelocytic leukemia.","Degos",7742522,"All-trans-retinoic acid as a differentiating agent in the treatment of acute promyelocytic leukemia.    Abstract:  "]
[7783341,1,0,0,1,1995,"[Recent progress in the treatment of adult acute leukemia].","Ohno",7783341,"[Recent progress in the treatment of adult acute leukemia].    Abstract:   Due to the advance of chemotherapy and bone marrow transplantation, adult acute leukemia has become a curable disease. In acute myeloid leukemia, the JALSG AML89 study resulted in 77% complete remission (CR) rate in 326 adults and 38% 4.5-year disease-free survival (DFS) in CR cases. However, the result of acute lymphoblastic leukemia in the JALSG ALL87 study is not satisfactory; 84% CR in 116 adults and only 24% 6-year DFS. For acute promyelocytic leukemia (APL), all-trans retinoic acid works remarkably, and the JALSG AML92 study for newly diagnosed APL resulted in 89% CR in 109 adults and 81% 2.5-year DFS."]
[7628783,0,0,0,0,1995,"[Pharmacological study of tooth formation and mineralization using a tooth germ cultivation system].","Matsumoto",7628783,"[Pharmacological study of tooth formation and mineralization using a tooth germ cultivation system].    Abstract:   In this study, we introduce a cultivation method for mandibular first molars from mouse embryos. We also investigate the in vitro effects of several drugs on tooth formation. Histological observations demonstrated that the tooth germ dissected from 17-day-old embryonic mice and cultivated for 7 days under the conditions described here showed clear mineralization in the dentin and enamel. Alkaline phosphatase (ALP) activity and calcium content in the tooth germ increased developmentally during 7-day cultivation. The increase of calcium was preceded by that of ALP in the germ. The removal of ALP attached covalently to the external surface of plasma membranes by phosphatidylinositol specific phospholipase C disturbed in vitro mineralization in the tooth germ, suggesting that ALP functioning as an ectoenzyme is involved in the physiological process of tooth formation. To elucidate the effects of calcium regulating hormones and several drugs on tooth mineralization, ALP and calcium content were measured and also the tooth germ was observed histologically. The results obtained from the present study suggest that this in vitro system provides a useful tool for investigating both the direct action of drugs on tooth formation and the mechanisms of drug action."]
[7755274,0,0,0,0,1995,"Stimulation of proliferative events in the adult amphibian cardiac myocyte.","Oberpriller",7755274,"Stimulation of proliferative events in the adult amphibian cardiac myocyte.    Abstract:  "]
[7787753,2,0,0,2,1995,"Treatment of newly diagnosed acute promyelocytic leukemia (APL) by all transretinoic acid (ATRA) combined with chemotherapy: The European experience. European APL Group.","Oberpriller",7787753,"Treatment of newly diagnosed acute promyelocytic leukemia (APL) by all transretinoic acid (ATRA) combined with chemotherapy: The European experience. European APL Group.    Abstract:   All transretinoic acid (ATRA) gives complete remission (CR) rates of 80 to 90% in newly diagnosed acute promyelocytic leukemia (APL). However, it has two major drawbacks (1) a rapid rise in WBC in some patients, with potentially fatal ATRA syndrome (2) rapid relapse with maintenance therapy using ATRA alone or low dose chemotherapy. The French APL group therefore designed a treatment approach with ATRA followed by intensive chemotherapy. The latter was administered after CR achievement with ATRA, or was rapidly added to ATRA in case of rapid rise in leukocyte counts. This combined approach, in a pilot study and in a randomized trial, proved superior to intensive chemotherapy alone, by slightly increasing the CR rate but more importantly by reducing the relapse rate. These results were confirmed by the Chinese, Japanese and New York groups. Our group (and other European groups) are now testing in a new randomized trial the better timing of ATRA and chemotherapy administration (ATRA followed by chemotherapy or ATRA plus chemotherapy) and the role (after an intensive consolidation) of maintenance treatment with intermittent ATRA, continuous low dose chemotherapy or both."]
[7740309,4,0,0,4,1995,"Rheumatologic complications of vitamin A and retinoids.","Nesher",7740309,"Rheumatologic complications of vitamin A and retinoids.    Abstract:   Retinoids are synthetic derivatives of vitamin A. They are administered primarily for dermatological conditions, such as psoriasis, acne, and disorders of keratinization. Toxicity has proven a significant problem with long-term administration of the retinoids. Bone abnormalities mimicking seronegative spondyloarthropathy or diffuse idiopathic skeletal hyperostosis have been described in many cases, as well as other rheumatologic manifestations such as arthritis, myopathy, and vasculitis. These retinoid-related adverse effects are reviewed."]
[7626396,3,0,0,3,1995,"Roles of retinoic acid receptors and of Hox genes in the patterning of the teeth and of the jaw skeleton.","Mark",7626396,"Roles of retinoic acid receptors and of Hox genes in the patterning of the teeth and of the jaw skeleton.    Abstract:   Retinoic acid receptors and transcriptional factors encoded by Hox genes play key roles in vertebrate development and belong to an integrated functional network. To investigate the actual functions of these molecules during ontogenesis and in particular in the patterning of the cranial neural crest cells giving rise to the teeth and to the jaw bones, we have generated null mutant mice lacking functional retinoic acid receptors or Hox genes by gene targeting in embryonic stem cells."]
[8664424,3,0,0,3,1995,"Prenatal craniofacial development: new insights on normal and abnormal mechanisms.","Johnston",8664424,"Prenatal craniofacial development: new insights on normal and abnormal mechanisms.    Abstract:   Technical advances are radically altering our concepts of normal prenatal craniofacial development. These include concepts of germ layer formation, the establishment of the initial head plan in the neural plate, and the manner in which head segmentation is controlled by regulatory (homeobox) gene activity in neuromeres and their derived neural crest cells. There is also a much better appreciation of ways in which new cell associations are established. For example, the associations are achieved by neural crest cells primarily through cell migration and subsequent cell interactions that regulate induction, growth, programmed cell death, etc. These interactions are mediated primarily by two groups of regulatory molecules: quot;growth factorsquot; (e.g., FGF and TGF alpha) and the so-called steroid/thyroid/retinoic acid superfamily. Considerable advances have been made with respect to our understanding of the mechanisms involved in primary and secondary palate formation, such as growth, morphogenetic movements, and the fusion/merging phenomenon. Much progress has been made on the mechanisms involved in the final differentiation of skeletal tissues. Molecular genetics and animal models for human malformations are providing many insights into abnormal development. A mouse model for the fetal alcohol syndrome (FAS), a mild form of holoprosencephaly, demonstrates a mid-line anterior neural plate deficiency which leads to olfactory placodes being positioned too close to the mid-line, and other secondary changes. Work on animal models for the retinoic acid syndrome (RAS) shows that there is major involvement of neural crest cells. There is also major crest cell involvement in similar syndromes, apparently including hemifacial microsomia. Later administration of retinoic acid prematurely and excessively kills ganglionic placodal cells and leads to a malformation complex virtually identical to the Treacher Collins syndrome. Most clefts of the lip and/or palate appear to have a multifactorial etiology. Genetic variations in TGF alpha s, RAR alpha s, NADH dehydrogenase, an enzyme involved in oxidative metabolism, and cytochrome P-450, a detoxifying enzyme, have been implicated as contributing genetic factors. Cigarette smoking, with the attendant hypoxia, is a probable contributing environmental factor. It seems likely that few clefts involve single major genes. In most cases, the pathogenesis appears to involve inadequate contact and/or fusion of the facial prominences or palatal shelves. Specific mutations in genes for different FGF receptor molecules have been identified for achondroplasia and Crouzons syndrome, and in a regulatory gene (Msx2) for one type of craniosynostosis. Poorly co-ordinated control of form and size of structures, or groups of structures (e.g., teeth and jaws), by regulatory genes should do much to explain the very frequent quot;mismatchesquot; found in malocclusions and other dentofacial quot;deformitiesquot;. Future directions for research, including possibilities for prevention, are discussed."]
[8571734,1,0,0,1,1995,"[Current approaches of treatment for myelodysplastic syndrome (MDS)].","Lewandowski",8571734,"[Current approaches of treatment for myelodysplastic syndrome (MDS)].    Abstract:   The number of treatment modalities for patients with myelodysplastic syndromes (MDS) has increased, but curative options are still limited. For the majority of patients with low risk there is no standard therapy other than appropriate supportive care. In selected patients anabolic steroids, differentiation inducers such as cis-retinoic acid (RA), interferon alpha or gamma have been claimed to be active. Application of growth factors such as granulocyte-macrophage colony stimulating factor (GM-CSF), granulocyte colony stimulating factor (G-CSF), and interleukin 3 (IL-3) improves neutrophil count and diminishes frequency of infectious complications, but responses are incomplete and of short duration. Preliminary results of erythropoietin (Epo) applied in therapeutical doses are disappointing, giving an improvement in 15-20% patients. Epo in large doses produces greater and sustained responses, but this treatment is too expensive. Low-dose cytosine arabinoside (Ara-C) induces a response rate in 25-30% patients, however, no survival advantage has been obtained. Addition of RA or GM-CSF produces response rates comparable to Ara-C alone, but also with no prolongation in survival. Bone marrow transplantation (BMT) offers a good chance of long-term disease-free survival if is performed in an early stage of the disease or in complete remission, however, it is limited to patients below 55 years with an HLA-identical donor. Relatively young, high risk patients not eligible for allogeneic BMT should be considered for treatment with intensive polychemotherapy."]
[7737795,1,0,0,1,1995,"Chondrocyte differentiation.","Cancedda",7737795,"Chondrocyte differentiation.    Abstract:   Data obtained while investigating growth plate chondrocyte differentiation during endochondral bone formation both in vivo and in vitro indicate that initial chondrogenesis depends on positional signaling mediated by selected homeobox-containing genes and soluble mediators. Continuation of the process strongly relies on interactions of the differentiating cells with the microenvironment, that is, other cells and extracellular matrix. Production of and response to different hormones and growth factors are observed at all times and autocrine and paracrine cell stimulations are key elements of the process. Particularly relevant is the role of the TGF-beta superfamily, and more specifically of the BMP subfamily. Other factors include retinoids, FGFs, GH, and IGFs, and perhaps transferrin. The influence of local microenvironment might also offer an acceptable settlement to the debate about whether hypertrophic chondrocytes convert to bone cells and live, or remain chondrocytes and die. We suggest that the ultimate fate of hypertrophic chondrocytes may be different at different microanatomical sites."]
[7721539,0,0,1,1,1995,"Molecular genetic approaches to the study of human craniofacial dysmorphologies.","Moore",7721539,"Molecular genetic approaches to the study of human craniofacial dysmorphologies.    Abstract:   Craniofacial dysmorphologies are common, ranging from simple facial disfigurement to complex malformations involving the whole head. With the advent of gene mapping and cloning techniques, the genetic element of both simple and complex human craniofacial dysmorphologies can be investigated. For many of the dysmorphic syndromes, it is possible to find families that display a particular phenotype in either an autosomal dominant, recessive, or X-linked manner. This article focuses on a subgroup of craniofacial dysmorphologies, covering these three main inheritance patterns, that are being studied using molecular biology techniques: DiGeorge syndrome, Treacher Collins syndrome, Greig cephalopolysyndactyly syndrome, acrocallosal syndrome, amelogenesis imperfecta, and X-linked cleft palate with ankyloglossia. Once the mutated or deleted gene or genes for each syndrome have been cloned, patterns of normal and abnormal craniofacial development should be elucidated. This should enhance both diagnosis and treatment of these common and disfiguring disorders."]
[7696360,1,0,0,1,1995,"Developments in the treatment of acute leukemia in adults.","Volm",7696360,"Developments in the treatment of acute leukemia in adults.    Abstract:   Since 1977, when it was first demonstrated that a small number of patients with refractory leukemia could be cured by bone marrow transplantation, there has been an international effort to increase the proportion of patients cured. This article reviews recent developments in the treatment of adult leukemia with particular emphasis on reports published during the past year. Several new preparative regimens for transplantation are discussed. New chemotherapeutic strategies reported during the past year have included modulating the activity of cytarabine, the most active agent in autologous myelogenous leukemia, using other agents such as etoposide, mitoxantrone, and carboplatin, and attempting to overcome the multidrug resistance phenomenon. There has been further experience in the use of autologous marrow for transplantation, with several centers reporting excellent results for patients so treated. Biologic-based strategies are an exciting area of exploration. The implications of the landmark discovery of all-trans retinoic acid as a treatment for acute promyelocytic leukemia continue to be investigated. Reports of the use of targeted monoclonal antibodies, cytokines, and other immunotherapies have generated the hope that these strategies might prove to be non-cross-resistant therapies and thus effective against residual disease following conventional chemotherapy."]
[7632866,3,0,0,3,1995,"Prenatal craniofacial development: new insights on normal and abnormal mechanisms.","Johnston",7632866,"Prenatal craniofacial development: new insights on normal and abnormal mechanisms.    Abstract:   Technical advances are radically altering our concepts of normal prenatal craniofacial development. These include concepts of germ layer formation, the establishment of the initial head plan in the neural plate, and the manner in which head segmentation is controlled by regulatory (homeobox) gene activity in neuromeres and their derived neural crest cells. There is also a much better appreciation of ways in which new cell associations are established. For example, the associations are achieved by neural crest cells primarily through cell migration and subsequent cell interactions that regulate induction, growth, programmed cell death, etc. These interactions are mediated primarily by two groups of regulatory molecules: quot;growth factorsquot; (e.g., FGF and TGFalpha) and the so-called steroid/thyroid/retinoic acid superfamily. Considerable advances have been made with respect to our understanding of mechanisms involved in primary and secondary palate formation, such as growth, morphogenetic movements, and the fusion/merging phenomenon. Much progress has been made on the mechanisms involved in the final differentiation of skeletal tissues. Molecular genetics and animal models for human malformations are providing many insights into abnormal development. A mouse model for the fetal alcohol syndrome(FAS), a mild form of holoprosencephaly, demonstrates a mid-line anterior neural plate deficiency which leads to olfactory placodes being positioned too close to the mid-line, and other secondary changes. Work on animal models for the retinoic acid syndrome (RAS) shows that there is major involvement of neural crest cells. There is also major crest cell involvement in similar syndromes, apparently including hemifacial microsomia. Later administration of retinoic acid prematurely and excessively kills ganglionic placodal cells and leads to a malformation complex virtually identical to the Treacher Collins syndrome. Most clefts of the lip and/or palate appear to have a multifactorial etiology. Genetic variations in TGF alpha s, RAR alpha s, NADH dehydrogenase, an enzyme involved in oxidative metabolism, and cytochrome P-450, a detoxifying enzyme, have been implicated as contributing genetic factors. Cigarette smoking, with the attendant hypoxia, is a probable contributing environmental factor. It seems likely that few clefts involve single major genes. In most cases, the pathogenesis appears to involve inadequate contact and/or fusion of the facial prominences or palatal shelves. Specific mutations in genes for different FGF receptor molecules have been identified for achondroplasia and Crouzons syndrome, and in a regulatory gene (Msx2) for one type of craniosynostosis.(ABSTRACT TRUNCATED AT 400 WORDS)"]
[7565448,0,0,0,0,1995,"Cellular and molecular mechanisms of bone resorption.","Teitelbaum",7565448,"Cellular and molecular mechanisms of bone resorption.    Abstract:  "]
[7554921,1,5,0,6,1995,"Molecular biology experimental strategies for craniofacial-oral-dental dysmorphology.","Slavkin",7554921,"Molecular biology experimental strategies for craniofacial-oral-dental dysmorphology.    Abstract:   This paper is a minireview of molecular biology experimental strategies for problems within craniofacial-oral-dental biology. Many of these strategies have already made remarkable contributions towards understanding the complex developmental processes associated with craniofacial biology. For example, the utilization of these strategies has resulted in the successful mapping of approximately 70 genes related to craniofacial anomalies (e.g., Pax, retinoic acid receptors, cadhedrins, aggrecan, cell adhesion molecules, substrate adhesion molecules, etc.), 30 genes related to dental tissue disorders (e.g., BMPs, bone morphogenetic proteins; dentin phosphoproteins, dentin sialoglycoproteins, enamelins, amelogenins), 20 genes related to facial clefting defects (e.g., Hox genes, transforming growth factor alpha), and 3 genes related to craniosynostosis (e.g., Msx-2). This minireview highlights selected examples of scientific progress derived from the following experimental strategies: (i) molecular approaches to the organization of the mouse and human chromosomes, with the mapping of specific gene sequences linked to human diseases (e.g., amelogenesis imperfecta, Boston type craniosynostosis, Riegers syndrome, Treacher Collins syndrome); (ii) reverse genetic approaches for studies of gene function; (iii) homologous recombinations and the advances from quot;knock-outquot; transgenic mouse models for human craniofacial-oral-dental diseases; (iv) mutational analyses of congenital craniofacial-oral-dental dysmorphogenesis; (v) structural biology studies using computer-assisted molecular modeling for protein-protein, protein-nucleic acid and protein-inorganic interactions; (vi) computer modeling of genetic paradigms; and (vii) a cluster of newer methodologies including computer-assisted morphometry, new microinjection techniques, new cell membrane and intracellular dyes, and a number of new RNA and DNA viral constructs for the delivery of genes to enhance the resolution of cell fate maps, cell lineage studies and gene therapy approaches to human diseases."]
[7486827,0,0,0,0,1995,"DiGeorge syndrome and related syndromes associated with 22q11.2 deletions. A review.","Demczuk",7486827,"DiGeorge syndrome and related syndromes associated with 22q11.2 deletions. A review.    Abstract:   DiGeorge syndrome (DGS) is a developmental defect which associates hypo- or aplasia of the thymus and parathyroids, facial dysmorphism and conotruncal cardiac malformations. The etiological factor in a great majority of DGS patients is monosomy for the 22q11.2 chromosomal region either through a large interstitial deletion of that region (inherited or de novo) or through an unbalanced translocation involving chromosome 22. In one instance, a balanced translocation of chromosome 22 was associated with a DGS phenotype. Extensive analyses of this region of chromosome 22 has led to the obtention of precise physical maps of the corresponding genomic region, to the cloning of the balanced translocation breakpoint and to the isolation of different genes from the minimal critical deleted region."]
[7887491,12,0,0,12,1994,"Retinoic acid in limb-bud outgrowth: review and hypothesis.","Paulsen",7887491,"Retinoic acid in limb-bud outgrowth: review and hypothesis.    Abstract:   Limb outgrowth is arguably the most fundamental aspect of limb development. It begins with the emergence of buds from the embryos lateral body wall. More rapid growth along each buds proximodistal axis than along its anteroposterior or dorsoventral axes yields the limbs basic elongated shape. Many processes that generate refinements of this basic limb form are now being explored at the molecular level. Yet, there remain gaps in our understanding of basic limb outgrowth itself. This review examines the pivotal role of the apical ectodermal ridge in promoting and maintaining limb-bud outgrowth. It discusses the interplay between the apical ectodermal ridge and the subridge limb mesenchyme. It examines evidence that the pattern of limb anomalies in the offspring of mothers exposed to exogenous retinoids such as retinoic acid strongly suggests interference with apical ectodermal ridge function. It covers evidence that cellular retinoic acid-binding protein in the cytoplasm of the cells under the apical ectodermal ridge limits the effects of retinoic acid, a potent retinoid and teratogen, on retinoic acid-driven gene transcription. It explains that retinoic acid generally enhances differentiation in a variety of cell types. On the basis of the information presented, it is suggested that the limb ectoderm promotes cellular retinoic acid-binding protein expression in the subridge mesenchyme and thereby limits the access of retinoic acid to its nuclear receptors in these cells. Cellular-retinoic-acid-binding-protein-mediated, local sequestration or inactivation of free retinoic acid is suggested as a prerequisite not only for the continued responsiveness of the distal mesenchyme to growth promotion by the apical ectodermal ridge, but to the maintenance of the apical ectodermal ridge itself by the subridge mesenchyme."]
[7825969,9,0,0,9,1994,"Retinoids and differentiation treatment: a strategy for treatment in cancer.","Cornic",7825969,"Retinoids and differentiation treatment: a strategy for treatment in cancer.    Abstract:   The retinoids are a large group of compounds structurally related to vitamin A. Retinoids elicit specific biological responses by binding to and activating nuclear receptors. Information about the metabolism and storage of vitamin A and retinoids, their plasma transport and uptake and the retinoid dose efficient on target cell had to be established because retinoic acid (RA), the natural acidic derivative of vitamin A (retinol), is likely to be a key factor during specific phases of embryonic development and maintenance of normal differentiated phenotypes in adult, so vitamin A is involved in the normal morphological differentiation of the visual system. RA appears an important agent since it induces in vitro leukemic cells from acute promyelocytic leukemia (APL) to differentiate into mature functional granulocytes which lose their self-renewal ability and die spontaneously. In vivo, APL patients treated with oral all-trans retinoic acid (all-trans RA) alone achieve complete remission in 80% of the cases. APL results from a malignant process that leads to the accumulation in the blood and in the bone marrow of myeloid precursor cells characterized by an abnormal behavior and a differentiation arrest. APL is characterized cytogenetically by a t(15;17) translocation which involves both the PML gene on chromosome 15 and the RARa gene on chromosome 17 and gives rise to the PML/RARa fusion protein. The high sensitivity of the promyelocytic blasts to all-trans RA should be related to the presence in APL blast of an abnormal protein, the PML/RAR alpha. The antineoplastic effects of retinoids suggest that these drugs could be used therapeutically for the chemoprevention of cancer."]
[7977023,0,0,0,0,1994,"Oxygen free radicals and antioxidants: a review.","Barber",7977023,"Oxygen free radicals and antioxidants: a review.    Abstract:   In 1989, nearly 43% of deaths in the United States were due to some form of cardiovascular disease, and 23% were caused by cancer. Thus, two of every three people in this country die from either cardiovascular disease or cancer. Based on both experimental and epidemiological evidence, investigators believe that free radicals play a critical role in the development of both diseases. Low levels of antioxidants, which increases free radical activity, are clearly associated with an increased risk of these diseases. This link has led to the conclusion that use of antioxidant vitamin supplements to scavenge free radicals could potentially decrease the risks of cancer and cardiovascular disease. Results from numerous studies to date have been very promising, although a true protective or preventive causal relationship has not yet been established. Numerous primary and secondary intervention trials currently underway should more definitively assess the role of antioxidants in disease prevention. In the interim, many people feel the evidence is now strong enough to begin supplementation on their own. The pharmacist is in a position to advise patients on the safe and moderate use of antioxidants. The antioxidants discussed in this article are relatively non-toxic, with the exception of vitamin A. The possible benefits of vitamin A are better achieved with the use of beta-carotene. Megadose antioxidant supplementation does not appear to provide any additional benefit beyond what a more moderate supplement can provide and should therefore be discouraged. Taking a trace mineral with antioxidant potential is generally a waste of money, provided the patient is not initially deficient in the element.(ABSTRACT TRUNCATED AT 250 WORDS)"]
[7994245,1,0,0,1,1994,"European survey of bone marrow transplantation in acute promyelocytic leukemia (M3). Working Party on Acute Leukemia of the European Cooperative Group for Bone Marrow Transplantation (EMBT).","Barber",7994245,"European survey of bone marrow transplantation in acute promyelocytic leukemia (M3). Working Party on Acute Leukemia of the European Cooperative Group for Bone Marrow Transplantation (EMBT).    Abstract:   Acute promyelocytic leukemia (M3) is a distinct subtype of AML considered to have better response to chemotherapy and a higher cure rate than other subtypes. We analyzed the outcome for 362 M3 patients transplanted in Europe from November 1979 to December 1992 and reported to the acute leukemia registry of the European Cooperative Group for Bone Marrow Transplantation (EMBT). Of these 362 patients, 187 received an autograft, 129 in first remission (CR1) and 58 in second remission (CR2), and 175 an allograft, 142 in CR1 and 33 in CR2. Patients autografted in CR1 had at 7 years a leukemia-free survival (LFS) of 48 +/- 5%, a relapse rate (RR) of 41 +/- 5% and a probability of transplant-related mortality (TRM) of 18 +/- 6%. Patients allografted in CR1 had a LFS of 42 +/- 6%, a RR of 28 +/- 5% and a TRM probability of 42 +/- 8%. For patients transplanted in CR2, the respective figures after auto and allotransplantation were: LFS: 31 +/- 7% and 22 +/- 8%, RR: 54 +/- 8% and 64 +/- 11%, TRM: 23 +/- 9% and 40 +/- 9%. These data, which do not permit comparison between autologous and allogeneic BMT, indicate that roughly 45% of M3 patients achieving CR1 may be cured by a marrow transplant. Since the recent use of transretinoic acid-containing induction regimens has increased early control for patients with AML M3, it will be important to find out how these results affect outcome following allogeneic or autologous BMT."]
[7964584,5,0,0,5,1994,"Retinoids. A window into vertebrate development.","Rogers",7964584,"Retinoids. A window into vertebrate development.    Abstract:   Vitamin A is required for maintaining healthy epithelial tissues, e.g., skin and gut, normal reproductive capacity, and vision. Vitamin A deficiency also causes premalignant changes in epithelial tissues. These observations led to the use of retinoids (vitamin A-related compounds) in treating various skin diseases and more recently to inhibit cancer growth. Retinoids are extremely teratogenic to developing vertebrate embryos, a fact which limits their clinical usefulness. In particular, specific malformations of skeletal structures are often observed; for instance, retinoic acid induces craniofacial and limb deformities in avian and mammalian embryos. Recent technological advances have increased our understanding of how retinoids affect vertebrate development. Some newly discovered mechanisms underlying these actions are reviewed."]
[9371290,1,0,0,1,1994,"Acute leukemia.","Ganser",9371290,"Acute leukemia.    Abstract:   Within the past year substantial progress has been made in understanding the molecular changes underlying the development of acute leukemia. Development of molecular probes allowed substantial improvements in the detection of minimal residual disease. Pilot studies underlined the correlation between the expression of the multidrug resistance gene and the likelihood of response to chemotherapy. The expression of mdr-1 apparently correlates with the expression of certain surface antigens like CD34 and CD7, which by themselves are associated with the expression of bcl-2 and poor treatment response. The value of hematopoietic growth factors to overcome drug resistance has not yet been clearly demonstrated in clinical trials, but they seem to reduce early mortality in elderly patients with acute myeloid leukemia when given after chemotherapy. Substantial progress has been made in the understanding of molecular changes in acute promyelocytic leukemia. Combination of all-trans retinoic acid and chemotherapy is the treatment of choice in acute promyelocytic leukemia. Allogeneic bone marrow transplantation proved to be superior in certain high-risk groups of patients with acute leukemia, including those with acute lymphoblastic leukemia with the bcr-abl configuration. The value of allogeneic bone marrow transplantation from related and unrelated donors, as well as the value of autologous bone marrow transplantation, is increasingly defined in randomized trials."]
[8090139,0,0,0,0,1994,"Gorlin syndrome: a report on a family.","Zmak",8090139,"Gorlin syndrome: a report on a family.    Abstract:   We describe a 9 year old boy with skin changes, minor facial signs, jaw cysts and cryptorchism, compatible with Gorlin syndrome. His 7 year old sister has similar skin changes, while their father has radiographic signs of the syndrome. Gorlin syndrome is rarely described in childhood when it occurs without major manifestations or associated neoplasia. The monitoring for prevention of complications is the greatest problem at this age."]
[8076399,1,0,0,1,1994,"Treatment of psoriatic arthritis.","Cuéllar",8076399,"Treatment of psoriatic arthritis.    Abstract:   The treatment of psoriatic arthritis has acquired relevance in the past few years because of advances and better understanding of the pathogenetic mechanisms implicated in the disease, and also because of recognition that this disorder is not a benign disease as was previously thought. The general principles of management for any inflammatory arthritis, including pharmacological, surgical and rehabilitative treatment, are to be used, with concomitant therapeutic management of skin involvement. Non-steroidal anti-inflammatory drugs constitute the mainstay of pharmacological therapy for most patients, with a good clinical response observed in 75-85%. Early use of remittive agents, especially methotrexate, is indicated in patients with a poor response to NSAIDs or those with polyarticular and progressive joint involvement. Patients who are refractory to conventional therapy should be considered for newer and potentially more toxic therapeutic modalities such as cyclosporin A and retinoids."]
[8141124,2,0,0,2,1994,"Treatment of refractory undifferentiated acute myelogenous leukemia with all-trans-retinoic acid.","Griggs",8141124,"Treatment of refractory undifferentiated acute myelogenous leukemia with all-trans-retinoic acid.    Abstract:   A patient is described with undifferentiated acute myeloblastic leukemia refractory to two courses of daunorubicin and cytosine arabinoside. Because some the myeloblasts developed morphologic features of promyelocytes, the patient was treated with all-trans-retinoic acid (ATRA) in an attempt to promote maturation. Cytogenetic studies and sensitive molecular analysis did not reveal any abnormality classically associated with acute promyelocytic leukemia. Serial bone marrow biopsies demonstrated myeloid maturation, and the patient uneventfully went into a sustained complete remission. A review of the literature confirms this to be an apparently hitherto undescribed response to ATRA that may have therapeutic implications in similar patients."]
[8031675,0,0,0,0,1994,"Miscellaneous neurologic, cardiac, pulmonary, and metabolic disorders with rheumatic manifestations.","Larkin",8031675,"Miscellaneous neurologic, cardiac, pulmonary, and metabolic disorders with rheumatic manifestations.    Abstract:   The First International Workshop on Hypertrophic Osteoarthropathy crystallized the current knowledge of this puzzling syndrome. Cytokine release by large thrombocytes in the periphery is the favored etiology, although specific therapy remains unavailable. An article on the rheumatologic consequences of alcohol is reviewed, along with a number of case reports of joint problems in rare skin and metabolic diseases. Understanding the mechanisms of rarities, including rheumatic fever, interleukin-2-induced arthritis, and a unique quot;menstrual arthritisquot; might give insight into the etiology of more common arthropathies."]
[7979022,2,0,0,2,1994,"[Cutis verticis gyrata and pachydermoperiostosis. Several cases in a same family. Initial results of the treatment of pachyderma with isotretinoin].","Beauregard",7979022,"[Cutis verticis gyrata and pachydermoperiostosis. Several cases in a same family. Initial results of the treatment of pachyderma with isotretinoin].    Abstract:   This is a case report of four patients of the same family with pachyderma. Their clinical findings are discussed in regard of a review of the literature. Also, because there are few data on effective treatment, their dramatic improvement with isotretinoin is of significant interest."]
[7888174,0,0,0,0,1994,"Vertebrate limb development.","Tickle",7888174,"Vertebrate limb development.    Abstract:  "]
[7808024,9,0,0,9,1994,"The arotinoids: early clinical experience and discussion of future development.","Arnold",7808024,"The arotinoids: early clinical experience and discussion of future development.    Abstract:   There has been great interest in the use of drugs attempting to modify the properties of malignant cells without necessarily destroying them. The family of compounds known as the retinoids have shown particular promise in this area. Current interest is directed towards established retinoids such as ATRA and 13-CRA. Newer synthetic retinoids such as fenretinide, the arotinoid Ro 40-8757, and 9-cis retinoic acid have been entering clinical trials. Ro 40-8757 is a particularly interesting new arotinoid with properties quite distinct from the other retinoids. It has different binding proteins and appears to regulate different genes than the classical retinoids such as ATRA or 13-CRA. Furthermore, it appears active against a different spectrum of malignancies. It also appears to have a relatively favourable side-effect profile. In addition to its anti-proliferative effects, this arotinoid may play a role in protection of bone marrow function after use of cytotoxic drugs. Development of Ro 40-8757 was halted before the compound had entered phase II testing due to lack of resources. Future developmental programmes for retinoids should move rapidly to explore the potential of interesting combinations identified in preclinical models. Retinoids should be considered primarily as drugs which modulate and enhance the effects of other active anticancer agents. Their development should not be prevented because they are unlikely to be active as single agents against common solid tumours."]
[7632008,1,0,0,1,1994,"[Multifocal epithelioid hemangioendothelioma with partial remission after interferon alfa-2a treatment].","Roudier-Pujol",7632008,"[Multifocal epithelioid hemangioendothelioma with partial remission after interferon alfa-2a treatment].    Abstract:    INTRODUCTION : Epithelioid hemangioendothelioma (EHE) is a rare vascular tumour of the soft tissue having an intermediate malignancy. Cutaneous presentations have exceptionally been reported.  OBSERVATION : A young woman, initially affected by an EHE with cutaneous and bone involvement, then with pulmonary and hepatic localizations, was in partial remission after one year of treatment with alpha 2a interferon.  DISCUSSION : In a critical review of the literature, we describe the main features of this tumour and the difficulties to classify this entity in the vascular tumors spectrum. Histologically, epithelioid hemangioendothelioma has a very characteristic appearance and is clearly different from other vascular tumors as angiolymphoid hyperplasia with eosinophilia and Kimuras disease. The assumption of a multicentric or a metastatic origin when multiple tumor deposits are found, is still not elucidated. Different therapeutic approaches are proposed: surgery, interferon, interleukin-2, retinoids. Randomized studies would be necessary to confirm our results with alpha 2a interferon but are probably difficult to realize because of the lack of cases."]
[8285119,2,0,0,2,1993,"[Acute promyelocytic leukemia. The therapeutic advances].","de Lacerda",8285119,"[Acute promyelocytic leukemia. The therapeutic advances].    Abstract:   Acute promyelocytic leukemia (APL) is a rare subtype of acute myelogenous leukemia. It is frequently associated with a life-threatening hemorrhagic diathesis, often aggravated by induction cytotoxic chemotherapy. Patients with APL have bone marrow infiltration by abnormal promyelocytes, usually with prominent cytoplasmic granulation. These patients have a unique cytogenetic abnormality, a balanced reciprocal translocation between the long arms of chromosomes 15 and 17. The nuclear retinoic acid receptor alpha gene, on chromosome 17, is translocated to the PML gene region, on chromosome 15, resulting in the synthesis of two fusion messenger ribonucleic acids, PML/RAR-alpha and RAR-alpha/PML, easily detected by the reverse transcriptase polymerase chain reaction. This assay is extremely useful in the diagnosis and detection of minimal residual disease in APL patients. All trans-retinoic acid (ATR) differentiates the malignant cell clone and corrects the coagulopathy associated with this disease. The most important adverse effect is a respiratory distress syndrome, treatable with steroids, if detected at its onset. ATR yields durable remissions in patients with APL, after consolidation with cytotoxic chemotherapy."]
[8259456,1,0,0,1,1993,"[Clonal myelodysplasia: prognostic stratification and therapeutic possibilities].","Sánchez Fayos",8259456,"[Clonal myelodysplasia: prognostic stratification and therapeutic possibilities].    Abstract:   Myelodysplastic syndromes represent an entire group of clonal panmyelopathies with very distinct evolutionary pathways. Their common denominator, however, is a self-maintained functional failure of the myeloid hemopoiesis which tends to evolve into severe non-lymphoid leukemia (SNLL) in 20-30% of the cases. First, the prognostic value of each the following is reviewed: the morphological classification F.A.B., the stratification system for quot;Bournemouth groupquot;, the abnormal placement of immature myeloid precursors (ALIP) in bone marrow, and cytogenetic changes. Second, the therapeutic potential for each of the following is assessed: vitamin and support treatments; suprarenal steroids; conventional androgens and danazol; agents of cellular differentiation (cytosine arabinoside in low doses, retinoid acids, vitamin D3, etc.). Finally, the role of aggressive chemotherapies (in succession or unrelated to marrow transplant) in the eradication of myelodysplastic clone or post-myelodysplasia SNLL is examined."]
[8234212,6,0,0,6,1993,"Retinoids or carotenoids: is there another choice?","Greenberg",8234212,"Retinoids or carotenoids: is there another choice?    Abstract:   Both retinoids and carotenoids decrease cancer occurrence in selected animal models of carcinogenesis, but the retinoids appear to have more potent activity against a wider variety of tumors. Further use of retinoids for cancer prevention will be limited, however, because of their toxic effects on bone and skin (among other organs). In contrast to retinoids, carotenoids seem to be free of important toxicity and this fact makes them more promising for use in the general adult population. However, the idea that carotenoids have a cancer-preventive effect in humans is based almost entirely on epidemiological studies of diet and serum which could simply reflect the effects of some other dietary constituents. In the search to explain the profoundly lower risk of death associated with eating a diet high in fruits, vegetables, and grains, there is a place for clinical trials testing one specific nutrient, such as beta-carotene, against one disease, such as lung cancer, but we should not rely exclusively on these narrowly focused studies. In addition, careful analyses of cohort studies may reveal broad patterns of diet that are associated with lower mortality. These diets can then be tested in clinical trials for their efficacy against a variety of causes of death and disability. For now, the most rational and prudent choice would be to consume a diet high in fruits, vegetables, and grains and not to take either supplemental antioxidants or retinoids until there is clear evidence of their effectiveness and safety."]
[7902975,0,0,0,0,1993,"[The dermal dendrocyte].","Hoyo",7902975,"[The dermal dendrocyte].    Abstract:   Dermal dendrocytes represent a population of resident cells of the dermis identified recently by virtue of the immunohistochemical expression of the coagulation factor XIIIa (fXIIIa). These dendritic cells of bone-marrow origin bear particular histoenzymatic and immunohistochemical features, some of which are shared with antigen-presenting cells; however, they are clearly distinct from epidermal Langerhans cells. Dermal dendrocytes could act as macrophages, antigen-presenting cells or participate in the homeostasis of macromolecules of the dermis. These cells give rise to some cutaneous tumours and seem involved in inflammatory dermatoses where they act by means of cytokine production; they could even represent targets of HIV infection. Future functional studies will hopefully lead to a better understanding of their precise role in normal and diseased skin, which remains presently partly speculative."]
[8371229,4,0,0,4,1993,"Arthritis precipitated by isotretinoin treatment for acne vulgaris.","Hughes",8371229,"Arthritis precipitated by isotretinoin treatment for acne vulgaris.    Abstract:   We describe the case of a 21-year-old woman who developed biopsy proven seronegative oligoarthritis in association with isotretinoin treatment for acne vulgaris. Elevated levels of antinuclear antibody accompanied joint disease and resolution occurred over a 6-month period. Isotretinoin, an orally active derivative of vitamin A, has been associated with reported arthritis, arthralgia, myalgia, vasculitis and skeletal and soft tissue calcification. We review the literature and discuss the possible association between isotretinoin and immune dysfunction. The etiology of arthritis associated with vitamin A analog treatment remains obscure."]
[8518195,1,0,0,1,1993,"Embryonic induction.","Slack",8518195,"Embryonic induction.    Abstract:   The current understanding of the mechanism of embryonic induction is reviewed. The embryological data which are necessary to establish the existence of an inductive process are described and the criteria for the identification of inducing factors are discussed. These criteria comprise: a demonstration that the factor has the appropriate biological activity, that it is expressed in biologically available form at the correct time and place in the embryo, and that when it is inhibited in vivo, the interaction should fail. Current understanding of the molecular basis of competence and threshold responses is discussed. Four case studies are examined in further detail: the dorsoventral patterning in Drosophila is controlled by a gradient of the decapentaplegic gene product, a member of the TGF beta superfamily. Mesoderm induction in Xenopus embryos is thought to be controlled by several factors acting in concert: activins, fibroblast growth factors (FGFs), Wnt proteins and bone morphogenetic proteins (BMPs). The formation of the kidney in higher vertebrates involves a permissive interaction and some molecules are known to be necessary for the process but the identity of the primary inducing signal remains elusive. The anteroposterior pattern in the chick limb is controlled by a morphogen gradient emitted by the zone of polarising activity (ZPA). Although closely mimicked by retinoic acid (RA), this substance is probably not itself the morphogen. In general, the technical advances of recent years have enabled dramatic progress to be made in understanding the molecular basis of embryonic induction. Although much remains to be done, the methods of investigation are now well established."]
[8377392,2,0,0,2,1993,"[Oncology 1992. Association with ophthalmology and brief status evaluation].","Lohri",8377392,"[Oncology 1992. Association with ophthalmology and brief status evaluation].    Abstract:   Several clinical situations require the cooperation of ophthalmologist and medical oncologist. Systemic metastasis spreading from an ocular primary tumor may rarely pose a problem. Liver metastasis from an ocular melanoma can be treated with intrahepatic chemoembolization and local palliation can be achieved. Disseminated tumors such as breast cancer or leukemias may spread to the eye and require local therapy. Per continuitatem orbital infiltrations of i.e. nasopharyngeal carcinomas need a cooperative management. Ocular side effects from chemo/radiotherapy may be especially severe in high dose therapies such as preparative regimes for allogeneic bone marrow transplants (BMT). A Sjögren-type sicca syndrome, cataracts and a microvasculopathy with cotton wool spots are associated with total body irradiation and the immunosuppression needed in BMT. Cancer research over the past ten years was increasingly influenced by molecular biology which has added to our understanding of tumor biology. The retinoblastoma gene is a typical example of a tumor suppressor gene. It regulates cell growth in its normal physiological state. Deletions may occur, that lead to tumor formation. The detection of oncogenes helps in the diagnosis of leukemias or lymphomas. Growth factors such as the Granulocyte Colony Stimulating Factor (G-CSF) were introduced recently. The differentiation therapy with retinoids has brought a new dimension into the field of cancer treatment and probably also of cancer prophylaxis. Taxol, an alkaloid from the yew tree is a novel cytostatic compound with very promising activity in tumors such as refractory ovarian or breast cancer. High dose therapy with BMT today is an established treatment for certain leukemias.(ABSTRACT TRUNCATED AT 250 WORDS)"]
[8483269,1,0,0,1,1993,"[Vitamin D].","Miyaura",8483269,"[Vitamin D].    Abstract:   1 alpha,25-Dihydroxyvitamin D3 [1 alpha,25(OH)2D3], the active form of vitamin D3, stimulates intestinal calcium absorption and osteoclastic bone resorption, resulting in the elevation of plasma calcium. Recent studies have revealed that 1 alpha,25(OH)2D3 also promotes differentiation of various cells such as myeloid leukemia cells, lymphocytes, macrophages and skin keratinocytes. The target cells of 1 alpha,25(OH)2D3 possess 1 alpha,25(OH)2D3 receptors (VDR) which belong to the steroid thyroid retinoic acid receptor gene family. The complex of VDR and 1 alpha,25(OH)2D3 binds to vitamin D3-responsive elements (VDRE) present in the promoter region of target genes of 1 alpha,25(OH)2D3. In bone, osteoblasts possess VDR and synthesize several proteins, such as BGP, osteopontin and the third component of complement (C3), in response to 1 alpha, 25(OH)2D3. 1 alpha, 25(OH)2D3 is involved in the differentiation of osteoclast progenitors into mature osteoclasts directly and also by an indirect mechanism involving some proteins produced by osteoblasts. In this review article, we show the mode of action and the biological function of 1 alpha, 25(OH)2D3."]
[7710454,1,0,0,1,1993,"Basophilic differentiation in acute promyelocytic leukemia.","Tallman",7710454,"Basophilic differentiation in acute promyelocytic leukemia.    Abstract:   A rare variant of acute promyelocytic leukemia (APL) is associated with basophilic differentiation. Such a patient presented with basophilia, headaches, and diffuse engorgement of superficial blood vessels, attributable to hyperhistaminemia. Karyotype analysis showed a clonal rearrangement of chromosome 12p13 in addition to the t(15;17). During treatment with all-trans-retinoic acid (TRA), the absolute basophil count rose steadily during the first week, then declined. By one month, the basophilia resolved, an abrupt rise occurred in both the platelet and absolute neutrophil count, and the bone core biopsy showed complete maturation of all cell lines. Abnormalities of chromosome 12p13 in acute myelogenous leukemia have been associated with basophilia. Since every cell in our patient with t(12p13;?) also had the t(15;17), we speculate that the basophilia was due to clonal evolution with acquisition of the t(12p13;?). In two out of five other reported cases, abnormalities of chromosomes known to be associated with basophilia were present in addition to t(15;17). It is possible that the basophilia in this variant is reactive; however, since TRA induces differentiation of leukemic promyelocytes into mature neutrophils, we speculate that the leukemic promyelocytes in our patient differentiated into basophils. Future studies employing either fluorescent in situ hybridization or polymerase chain reaction using a probe to the breakpoint on t(15;17) may establish whether or not the basophils derive from the leukemic clone."]
[8507558,1,0,0,1,1993,"P19 embryonal carcinoma cells.","McBurney",8507558,"P19 embryonal carcinoma cells.    Abstract:   P19 cells are a line of pluripotent embryonal carcinoma able to grow continuously in serum-supplemented media. The differentiation of these cells can be controlled by nontoxic drugs. Retinoic acid effectively induces the development of neurons, astroglia and microglia--cell types normally derived from the neuroectoderm. Aggregates of P19 cells exposed to dimethyl sulfoxide differentiate into endodermal and mesodermal derivatives including cardiac and skeletal muscle. P19 cells can be effectively transfected with DNA encoding recombinant genes and stable lines expressing these genes can be readily isolated. These manipulations make P19 cells suitable material for investigating the molecular mechanisms governing developmental decision made by differentiating pluripotent cells."]
[8465097,1,0,0,1,1993,"[Differentiating agents in myelodysplastic syndromes. Analysis of personal cases].","Olivieri",8465097,"[Differentiating agents in myelodysplastic syndromes. Analysis of personal cases].    Abstract:   The Myelo-Dysplastic Syndromes are a heterogeneous group of diseases which includes patients with different prognosis. There is no agreement about the management and the therapeutic strategy must be based on many individual parameters, particularly the age of the patients and their performance status. The therapeutic options range from no cytotoxic therapy for low-risk patients up to more aggressive treatment for high-risk patients, with disappointing results except for the very few cases eligible for allogenic bone marrow transplantation. The leukaemic cell can be induced to differentiate, so losing its self-maintenance potential; different drugs such as Interferon, vitamin D3, retinoids and arabinosyl-cytosine (low doses) have shown a differentiating action on myeloid blasts in quot;vitroquot;. We summarize the general strategy in the treatment of myelo-dysplastic syndromes based on literature data, and on our results about the efficacy and tolerance of a combination of the above mentioned differentiating drugs, in a group of 27 elderly patients affected by myelodysplastic syndrome with poor prognosis. We obtained 14 objective responses (52%), and the median overall survival of these patients have been compared with that of 25 patients with severe myelodysplastic syndrome treated with a conventional regimen. In the 27 patients receiving the differentiating combination the median survival was found to be 14.7 months, versus 8.4 months for the control group. The results obtained are encouraging about the tolerance and the efficacy of this combination in elderly patients with a poor MDS prognosis. Further randomized studies are necessary to establish whether this treatment can really improve the survival in this group of patients."]
[8439701,3,0,0,3,1993,"Use of trans-retinoic acid in the treatment of acute promyelocytic leukemia.","Dulaney",8439701,"Use of trans-retinoic acid in the treatment of acute promyelocytic leukemia.    Abstract:    OBJECTIVE : To discuss acute promyelocytic leukemia (APL) and review the literature concerning differentiation treatment of APL with trans-retinoic acid (t-RA).  DATA SOURCES : English-language articles concerning APL or its treatment with t-RA were identified with a MEDLINE search.  STUDY SELECTION : All studies available at the time of article preparation, which addressed t-RA treatment in APL, were selected.  DATA EXTRACTION : Data extraction and assessment were performed subjectively by the authors. An extensive discussion of specific study details is included in the article.  DATA SYNTHESIS : APL is a unique subset of acute myelogenous leukemia and is typified by an accumulation of malignant promyelocytes in the bone marrow. Within the granulocyte cell cycle of a patient with APL, differentiation has been halted at the level of the promyelocyte, preventing formation of mature granulocytes. Upon treatment with traditional cytotoxic chemotherapy, complete remission rates of approximately 70 percent, with a five-year survival ranging from 25 to 40 percent have been achieved. In most patients with APL, a characteristic chromosomal t(15q+;17q-) translocation has been found, which may be responsible for the production of an aberrant retinoic acid receptor-alpha. Therefore, t-RA induction therapy has been investigated and has produced promising results. Administration of t-RA in dosages of 45-100 mg/m2/d has induced complete remissions. The apparent mechanism of t-RA is the induction of promyelocyte differentiation and maturation. The most common adverse effects noted have been dry skin, cheilitis, and headaches.  CONCLUSIONS : Upon consideration of the initial trials, t-RA appears to be a promising and unique treatment for APL."]
[8286848,1,0,0,1,1993,"Signaling pathways for vitamin D-induced differentiation: implications for therapy of proliferative and neoplastic diseases.","Studzinski",8286848,"Signaling pathways for vitamin D-induced differentiation: implications for therapy of proliferative and neoplastic diseases.    Abstract:   The physiological form of vitamin D, 1 alpha,25-dihydroxyvitamin D3 (1,25D3) is not only a powerful regulator of calcium homeostasis but also a hormone with important roles in cell growth and differentiation. The differentiating effects of 1,25D3 have been studied extensively in a large number of in vitro systems but primarily using cultured leukemia cells, keratinocytes, and bone cells. In spite of this attention, the understanding of the mechanisms that lead to the diverse forms of cell differentiation by 1,25D3 is fragmentary. It seems likely, however, that the effects of 1,25D3 on calcium homeostasis and on cell differentiation are both signaled by direct effects on the cell membrane and by the transduction of the signal to the genome. The direct effect may be mediated by a hypothetical membrane recognition element, the G proteins, phosphoinositide metabolism, and protein kinase C (PKC). Signals to the nucleus may include PKC, the Ca2+ gradient, and protein phosphorylation cascades, but the protein receptor (VDR) plays a principal role in this form of signal transduction. The VDR interacts with the promoter elements of a number of nuclear genes, either as a homodimer or a heterodimer with a retinoid or orphan receptors. The key nuclear responses include the increased expression of phenotype-specifying proteins and the appearance of G1/S and G2+M cell cycle blocks, which result in cessation of cell proliferation. The attempts to improve control of neoplastic cell proliferation will depend on a selective exploitation of these properties of 1,25D3 to design novel analogs of 1,25D3 with low hypercalcemic but high differentiation-inducing properties. It is anticipated that a better understanding of the multiple pathways that transduce the signals from 1,25D3 to the nucleus and to the cell membrane, a consideration of the structure-function relationships of the derivatives of 1,25D3, and the use of synergistic combinations of 1,25D3 with other biological response modifiers or cytotoxic drugs will lead to improved therapy of several hyperproliferative and malignant diseases."]
[8280500,1,0,0,1,1993,"Retinoid receptors and acute promyelocytic leukaemia.","Trayner",8280500,"Retinoid receptors and acute promyelocytic leukaemia.    Abstract:   While a great deal has been learned about APL over the last few years, many important questions remain unanswered. It has become clear that the PML/RAR-alpha fusion protein is expressed in most cases of APL, and this protein presumably contributes to leukaemia initiation and/or progression. PML/RAR-alpha appears to specifically block the further differentiation of myeloid progenitor cells, although the mechanism of its action is not known. It may inhibit the transcription of RAR- or PML-regulated genes, in which case expression must be restored in the presence of therapeutic RA concentrations. However, the possibility remains that PML/RAR-alpha may have a novel function. In order to elucidate the molecular pathogenesis of APL, several important questions remain to be answered. These include whether PML is a transcription factor; the identification of its target genes and response elements, and the role of PML/RAR-alpha and RA in their regulation. Also whether the expression of PML/RAR-alpha in bone marrow cells (either by itself or in combination with other oncogenes) alters their tumourigenicity or differentiation potential. It is also important to determine the function(s) of PLZF and PLZF/RAR-alpha, and determine whether other APL patients with mutations involving PML or RAR-alpha (but not both) respond to therapy with all-trans-RA. Finally, it is important both for the understanding of the molecular biology of APL and its therapy, to determine the effects of other regulatory factors involved in the control of myeloid cell differentiation such as granulocyte colony stimulation factor (G-CSF) and granulocyte macrophage colony stimulating factor (GM-CSF) on APL cells in vitro and in vivo, both at presentation and in the RA-resistant patients in relapse."]
[8239386,0,0,0,0,1993,"[Skin diseases and enthesiopathies].","Péré",8239386,"[Skin diseases and enthesiopathies].    Abstract:  "]
[8124230,2,0,0,2,1993,"What is the best treatment for acute promyelocytic leukemia?","Avvisati",8124230,"What is the best treatment for acute promyelocytic leukemia?    Abstract:   The modern treatment of acute myelogenous leukemia (AML), consists of a polychemotherapeutic induction treatment followed by a post-remission therapy of variable intensity and duration and acute promyelocytic leukemia (APL) does not differ from this behavior. However, differently from the other AML subtypes, APL shows a high response rate to induction monochemotherapies with anthracycline drugs. This high response rate to anthracycline monochemotherapies is very peculiar of APL. Moreover, it has been suggested that maintenance treatment regimens incorporating the drugs Methotrexate and 6-Mercaptopurine, two drugs generally not utilized in the post-remission treatment of other AML subtypes, may be effective in prolonging the leukemia-free survival of APL. Furthermore, the results firstly obtained by a Chinese group in 1988 by using the vitamin A derivative all-trans retinoic acid (ATRA) have been successively confirmed by several other groups in the world. Therefore, at present the all-trans retinoic acid appears to be the best CR inducer in APL. However, these CRs are short lasting when maintained with ATRA alone and eventually all patients relapse. As a consequence, patients achieving CR with ATRA still require intensive post-remission chemotherapy to maintain the CR. As for bone marrow transplantation procedures, it is our opinion that they do not represent the treatment of choice of APL in first CR considering the very good results obtained with standard pharmacological approaches. In conclusion, only future randomized prospective trials will clarify which, among the several proposed therapeutic approaches, should be preferred in this very peculiar subtype of AML."]
[7915184,2,0,0,2,1993,"Syndactylies and polydactylies: embryological overview and suggested classification.","Winter",7915184,"Syndactylies and polydactylies: embryological overview and suggested classification.    Abstract:   In 1978, Temtamy and McKusick classified isolated, non-syndromic polydactyly and syndactyly, using a logical anatomical approach, into five distinct types for each group. Since then, there have been considerable advances in the molecular embryology of the developing limb bud. These include the proposal that retinoic acid and/or related retinoids are the morphogens responsible for the morphogenetic gradient giving rise to anterior-posterior pattern formation of the limb bud, the suggestion that the HOX4 complex and other homeotic genes may also be involved in patterning, and a greater understanding of other mechanisms such as programmed cell death in the shaping of the final hand and foot. This paper briefly reviews the molecular embryology of limb development and outlines the end-organ responsiveness of the limbs to a variety of single-gene mutations. An alternative classification of syndactylies and polydactylies is suggested. It is still too early to match specific defects to individual genes with precision, and it is obvious that many important developmental genes remain to be identified; nevertheless, it is envisaged that clues from molecular embryological studies will become increasingly more useful."]
[7905645,0,0,0,0,1993,"Why does a limb look like a limb?","Newman",7905645,"Why does a limb look like a limb?    Abstract:  "]
[1465023,1,0,0,1,1992,"Strategies in the treatment of acute myelogenous leukemia.","Vogler",1465023,"Strategies in the treatment of acute myelogenous leukemia.    Abstract:   The current treatment of acute myelogenous leukemia is far from satisfactory despite some recent advances. This review focuses on current strategies designed to improve treatment outcome. With advances in molecular biology, the definition of a complete remission should be redefined as a molecular remission where any abnormal gene rearrangement has disappeared or a clonal remission with morphologic characteristics of a complete remission, but with detectable genetics or molecular abnormalities. Abnormal gene rearrangements permit the detection of minimal residual disease, the significance of which remains to be determined. New drug development remains an important area of research and several new drugs are active in acute myelogenous leukemia. These include etoposide, idarubicin, mitoxantrone and carboplatin. Various combinations are undergoing clinical trials. Prognostic factors which predict for outcome include phenotyping, cytogenetics, cytokinetics, drug resistance and age. Proto-oncogene expression as a predictor of response is under investigation. Post-induction therapy remains controversial and approaches have included allogeneic bone marrow transplantation, autologous bone marrow transplantation with or without purging, intensive consolidation and maintenance programs. The superiority of one approach over the other has not been firmly established. Differentiating agents such as all-trans retinoic acid, and growth factors, the latter for supportive care, or recruitment of leukemic cells into the cycle are being investigated. Understanding the mechanisms of drug resistance should lead to the development of new approaches. Thus, with knowledge generated in many areas, the future should bring increasing success in treating AML."]
[1460122,8,0,0,8,1992,"Long-term safety of retinoid therapy.","Vahlquist",1460122,"Long-term safety of retinoid therapy.    Abstract:   The concern about long-term toxicity of oral synthetic retinoids has developed because many patients, especially those with genodermatoses, require lifelong therapy. Several organ systems are at risk, especially the hepatic, skeletal, and cardiovascular systems. Although acute hepatotoxicity is a rare side effect of etretinate and acitretin therapy, prospective studies have not demonstrated chronic liver toxicity. The frequency of bone changes induced by retinoids is difficult to estimate, because this adverse effect is usually asymptomatic and requires x-ray or scintigraphic examination for detection. Atherosclerosis develops in many patients who receive long-term retinoid therapy, but the extent to which the process is aggravated by drug-induced hyperlipidemia is not known. Many patients have now been treated with either etretinate or isotretinoin continuously for as many as 15 years and have not developed any signs of severe chronic toxicity. However, continued intense surveillance is recommended for patients expected to require lifelong therapy."]
[1361890,1,0,0,1,1992,"Retinoids and the molecular basis of limb patterning.","Brown",1361890,"Retinoids and the molecular basis of limb patterning.    Abstract:  "]
[1301490,0,0,1,1,1992,"[A current update on the etiopathogenesis of palatoschisis].","Pierleoni",1301490,"[A current update on the etiopathogenesis of palatoschisis].    Abstract:   By means of a review of the most recent literature, the authors report on quot;state of the artquot; about etiology and pathogenesis of cleft palate. Epithelial-mesenchymal interactions regulating growth and orientation of palatal shelves, as well as teratogenic effects on such ultrastructural development control by endogenous and exogenous substances, are described."]
[1290955,2,0,0,2,1992,"The present status in all-trans retinoic acid (ATRA) treatment for acute promyelocytic leukemia patients: further understanding and comprehensive strategy are required in the future.","Chen",1290955,"The present status in all-trans retinoic acid (ATRA) treatment for acute promyelocytic leukemia patients: further understanding and comprehensive strategy are required in the future.    Abstract:   All-trans retinoic acid (ATRA) has recently been recognized as the first line therapeutic agent in the treatment of patients with acute promyelocytic leukemia (APL). The extraordinary high remission rate achieved by ATRA in comparison with other chemotherapeutic agents suggested that ATRA differentiation induction therapy seemed superior to conventional chemotherapy for APL patients. However, after the great excitement aroused after the initial successes, we have to take stock and examine in detail several problems which have emerged preventing us from improving the clinical outcome in APL. Maintenance in order to prolong remission and prevention of or retreatment for the relapse are the major subjects of concern at present. Efforts should be made either to keep ATRA effective for APL patients or to resensitize the relapsing patients for repeated ATRA therapy. The administration of ATRA should be carefully adapted in accordance with the individual patients condition. From both conceptual and practical points of view, ATRA differentiation therapy should be combined with chemotherapy, bone marrow transplantation and biomodifier treatment. Thus, a more comprehensive strategy must be planned and developed in the near future. Using molecular biological techniques, the diagnosis of APL can be more precisely made and the course of the disease more closely monitored. The central dogma, still to be revealed, is the relationship between APL pathogenesis, the chromosome translocation present with the relevant molecular alterations and the response to ATRA treatment. Current studies in all these above fields have provided us with a deeper understanding of the pathogenesis of APL and the physiological function and curative action of ATRA.(ABSTRACT TRUNCATED AT 250 WORDS)"]
[1419509,0,0,0,0,1992,"Musculoskeletal signs of metabolic and systemic diseases in childhood.","Miller",1419509,"Musculoskeletal signs of metabolic and systemic diseases in childhood.    Abstract:   Many metabolic and systemic disorders affect the musculoskeletal system in growing children. This review surveys some of the recent literature in several diverse areas, including new radiologic methods to determine bone mineralization and their use in children with juvenile arthritis and other systemic diseases, bone disorders in childhood, and the association of endocrinopathies and musculoskeletal symptoms."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I581,I581)","v":9511604},{"$f":"(LEN($J581) - LEN(SUBSTITUTE(LOWER($J581),LOWER(B$3),\"\")))/LEN(B$3)","v":0},0,0,{"$f":"SUM(B581:D581)","v":0},1992,"The effect of vitamin A on the development of the craniofacial complex--an update for practitioners.","Lefkowitz",9511604,"The effect of vitamin A on the development of the craniofacial complex--an update for practitioners.    Abstract:  "]
[1525510,1,0,0,1,1992,"Vertebrate craniofacial development: novel approaches and new dilemmas.","Noden",1525510,"Vertebrate craniofacial development: novel approaches and new dilemmas.    Abstract:   Unexpected patterns of neuroblast, angioblast and myoblast movement and tissue organization have been defined using lineage tracing and transplantation methods. The most novel and enigmatic new data derive from analyses of genes in the Hox- and Pax-gene families. In addition to the characterization of expression patterns, the effects of Hox-gene knock-out and retinoic acid treatment have been assessed. These basic studies are complemented by the identification of correlations between inherited craniofacial anomalies, for example Waardenburgs syndrome, and the function of specific genes."]
[1626958,4,0,0,4,1992,"Skeletal hyperostosis in patients receiving chronic, very-low-dose isotretinoin.","Tangrea",1626958,"Skeletal hyperostosis in patients receiving chronic, very-low-dose isotretinoin.    Abstract:    BACKGROUND AND DESIGN : We conducted a prospective roentgenographic survey of patients participating in a randomized, placebo-controlled, multicenter clinical trial that evaluated the effectiveness of chronic, very-low-dose (approximately 0.14 mg/kg per day for 3 years) isotretinoin in preventing the subsequent occurrences of new basal cell carcinoma in patients with previous basal cell carcinoma. To assess potential skeletal changes, a sample of 269 patients from among a total of 981 enrollees were randomly selected for comparative roentgenographic review. Baseline and 36-month roentgenograms of the cervical and thoracic spine of each patient were read side by side by a radiologist, masked to treatment group, who noted both the presence and extent of abnormalities at each vertebral level at baseline and the progression of existing or occurrence of new abnormalities at previously unaffected levels at 36 months.  RESULTS : In comparison with the placebo group, significantly more patients in the isotretinoin group exhibited progression of existing hyperostotic abnormalities (40% vs 18%; P less than .001) and new hyperostotic involvement at previously unaffected vertebral levels (8% vs 1%; P = .015).  CONCLUSION : Our findings indicate that chronic, very-low-dose isotretinoin can induce hyperostotic axial skeletal changes similar to those reported in patients taking higher doses."]
[1510240,1,0,0,1,1992,"The membranous skeleton: the role of cell condensations in vertebrate skeletogenesis.","Hall",1510240,"The membranous skeleton: the role of cell condensations in vertebrate skeletogenesis.    Abstract:   Elements of the vertebrate skeleton are initiated as cell condensations, collectively termed the membranous skeleton whether cartilages or bones by Grüneberg (1963). Condensations, which were identified as the basic cellular units in a recent model of morphological change in development and evolution (Atchley and Hall 1991) are reviewed in this paper. Condensations are initiated either by increased mitotic activity or by aggregation of cells towards a centre. Prechondrogenic (limb bud) and preosteogenic (scleral ossicle) condensations are discussed and contrasted. Both types of skeletogenic condensations arise following epithelial-mesenchymal interactions; condensations are identified as the first cellular product of such tissue interactions. Molecular characteristics of condensations are discussed, including peanut agglutinin lectin, which is used to visualize prechondrogenic condensations, and hyaluronan, hyaladherins, heparan sulphate proteoglycan, chondroitin sulphate proteoglycan, versican, tenascin, syndecan, N-CAM, alkaline phosphatase, retinoic acid and homeo-box-containing genes. The importance for the initiation of chondrogenesis or osteogenesis of upper and lower limits to condensation size and the numbers of cells in a condensation are discussed, as illustrated by in vitro studies and by mutant embryos, including Talpid3 in the chick and Brachypod, Congenital hydrocephalus and Phocomelia in the mouse. Evidence that genes specific to the skeletal type are selectively activated at condensation is discussed, as is a recent model involving TGF-beta and fibronectin in condensation formation. Condensations emerge as a pivotal stage in initiation of the vertebrate skeleton in embryonic development and in the modification of skeletal morphology during evolution."]
[1626281,1,0,0,1,1992,"Treatment of psoriatic arthropathy.","Goupille",1626281,"Treatment of psoriatic arthropathy.    Abstract:   Psoriatic arthritis develops in 5% of patients with cutaneous psoriasis. Management is similar to that of other chronic inflammatory joint diseases, and the characteristic features of psoriatic arthritis should be considered: the disease is usually mild, with unpredictable flares and remissions, and skin disease is a concomitant feature. Nonsteroidal antiinflammatory agents are the mainstay of therapy and usually provide adequate control. Among long-term treatments, parenteral gold salts, methotrexate, and azathioprine have been shown to be effective. Retinoids are often used in patients with extensive skin lesions. Other treatments are currently being evaluated (auranofin, colchicine, D-penicillamine, sulfasalazine, cyclosporine, and gamma-interferon). Antimalarials are difficult to handle and may cause progression of skin lesions. Topical treatments are indicated in every case. Indications depend on the specific features of psoriatic arthritis, the clinical pattern, and the severity of the condition."]
[1495761,1,0,0,1,1992,"Update of sporadic microphthalmos and coloboma. Non-inherited anomalies.","Warburg",1495761,"Update of sporadic microphthalmos and coloboma. Non-inherited anomalies.    Abstract:   The majority of patients with microphthalmos and colobomas have genetic disorders. This is a survey of non-inherited, sporadic microphthalmos. Such cases may occur in the Goldenhar, CHARGE and VATER associations; it may also be due to teratological agents, for instance maternal ingestion of drugs, maternal infection, fever or irradiation. In these cases it is possible that neural crest cell development is abnormal. Some drugs, for instance retinoic acid are regulators of Hox genes which control an ordered sequence of differentiation; coloboma or microphthalmos may appear if deregulation occurs. Large choristomas of the anterior segment of the eye may be associated with microphthalmos or anophthalmos. Encephaloceles or orbital tumours may deform the growing eye and are another cause of non-inherited microphthalmos."]
[1617504,1,0,0,1,1992,"The role of morphogens in endochondral ossification.","Campbell",1617504,"The role of morphogens in endochondral ossification.    Abstract:   The formation of bone occurs normally by one of two developmental processes: intramembranous or endochondral ossification. Endochondral ossification occurs in the morphogenesis of the limb buds and growth plates, and in the regeneration of bone following injury (fracture callus). Two classes of diffusible morphogen-like molecules (MLMs) involved in limb development are the bone morphogenetic proteins (BMPs) and retinoic acid (RA). These MLMs are associated, respectively, with the apical ectodermal ridge (AER) and the zone of polarizing activity (ZPA) of the primitive limb bud. They function as potent regulators of pattern formation and are involved in tissue proliferation and differentiation. The presence of endochondral ossification in fracture callus suggests a role for MLMs in that process as well. To date, virtually nothing is known about the role of morphogens in the regeneration of bone (fracture healing). In this article, we review the current knowledge of MLMs in bone formation and propose a theory on their role in fracture healing. We hypothesize that MLMs involved in fracture healing may also express spatial and temporal information. A more complete understanding of the role of morphogens in both limb development and fracture healing is of major importance to practicing orthopedists and their patients."]
[1349798,0,0,0,0,1992,"Anticancer role of dendritic cells (DC) in human and experimental cancers--a review.","Becker",1349798,"Anticancer role of dendritic cells (DC) in human and experimental cancers--a review.    Abstract:   The bone marrow-derived dendritic cells (DL/LC) are antigen-presenting accessory cells functioning as part of the immune system. In addition, DC/LC in epithelial tissues may have the capacity to be involved in cellular interactions which may have regulatory functions. Such properties can also be noted when LC/DC interact with cancer cells in tumors. The present review summarizes reports which suggest that the outcome of a primary tumor in patients depends on the presence or absence of DC/LC in the tumor. The evidence showing that the presence of DC/LC in primary tumors indicates that a good prognosis may be reached are presented and discussed. Based on these observations and the ability of immunomodulators to enhance the activity of DC/LC and the ability of these cells to enter into tumors, it is suggested that the molecular basis of DC/LC activity against primary tumors cells should be investigated. It is possible that activation of DC/LC, thereby enhancing their ability to enter primary tumors, and the abrogation of the ability of DC/LC-resistant tumors to destroy or prevent DC/LC from entering the tumor, could be developed as an effective anti-cancer approach."]
[1379818,0,0,0,0,1992,"Myelodysplastic syndromes. Pathogenesis, diagnosis and treatment.","Noël",1379818,"Myelodysplastic syndromes. Pathogenesis, diagnosis and treatment.    Abstract:   Our understanding of the biology of leukemia and myelodysplasia is still only partial. The diagnosis of myelodysplasia is often based on quantitative and qualitative findings in the peripheral blood and bone marrow. These findings are often shared by other disorders. There is a need for sensitive and inexpensive laboratory tests to determine clonality and karyotypic abnormalities in this disorder. Future classifications of these syndromes will need to be based on morphologic and biologic markers that are closely linked to disease progression, response to treatment, and survival. Our limited understanding of the pathogenesis of MDS decreases the specificity and effectiveness of our therapeutic interventions. Agents that are minimally toxic such as CRA, danazol, 1,25-dihydroxyvitamin D3, androgens, and pyridoxine are seldom useful. Antileukemic therapy and allogeneic bone marrow transplantation have a major role to play in patients younger than 45 years of age; in older patients these treatment modalities remain controversial because of their toxicity. Hematopoietic growth factors, used alone or in combination, may improve the quality of life and improve survival of patients with MDS. Growth factors may also decrease treatment-related mortality associated with chemotherapy and bone marrow transplantation and render these treatment modalities available for a higher percentage of patients. The development of more specific differentiating agents may permit hematopoietic differentiation while minimizing side effects."]
[1480060,1,0,0,1,1992,"Matrix metalloproteinases in periodontal tissue remodelling.","Sodek",1480060,"Matrix metalloproteinases in periodontal tissue remodelling.    Abstract:   Inflammation of the periodontium leads to connective tissue degradation and eventual tooth loss. The regulation of matrix metalloproteinases (MMPs) has been studied to determine their role in these processes and also during tissue remodelling. Analysis of gingival crevicular fluid has revealed the presence of collagenase and gelatinase that, in the acute stages of periodontal disease, are derived predominantly from polymorphonuclear leukocytes. These MMPs appear to be intimately associated with tissue destruction since the levels of the active forms of these enzymes obtained from either crevicular fluid or mouthrinse samples correlate with tissue destruction and, therefore, provide a sensitive means of demonstrating disease activity. Transforming growth factor-beta, an important regulator of connective tissue remodelling, has been implicated in the rapid remodelling of periodontal tissues. TGF-beta promotes tissue matrix formation by stimulating both the synthesis of matrix proteins (collagen, fibronectin and SPARC) and proteinase inhibitors (TIMP, PAI-1) and by decreasing the synthesis of MMPs, but not the 72 kDa-gelatinase. Nuclear run-on analyses have shown that TGF-beta reduces collagenase and stromelysin synthesis by suppressing gene transcription without altering mRNA stabilities. In contrast, the transcription of the gelatinase and TIMP genes was increased by TGF-beta, which also increased gelatinase mRNA stability. Remodelling of alveolar bone involves interaction between osteoblasts and osteoclasts. Osteoblasts, under the influence of osteotropic hormones (vit D3, PTH and retinoic acid), produce MMPs which appear to function in the removal of soft tissue that precludes access of osteoclasts to the mineralized tissue surface. Rat osteoblastic cells produce MMPs with activity on native collagen, native collagen 3/4-fragments and gelatin and, in addition, two forms of TIMP activity. The 3/4-collagen endopeptidase, purified to apparent homogeneity, also has significant collagenase and gelatinase activities and an amino terminal sequence almost identical to human 72 kDa-gelatinase. The production of this enzyme was stimulated by TGF-beta, which suppresses bone resorption, and by osteotropic hormones which stimulate bone resorption, supporting a bifunctional role for the gelatinase in connective tissue remodelling. Although there is strong evidence for the involvement of MMPs in the resorption of bone and in the inflammation-mediated destruction of periodontal tissues, the role of MMPs in the remodelling of mature soft connective tissues remains equivocal."]
[1425010,1,0,0,1,1992,"Leukaemia inhibitory factor and bone cell function.","Martin",1425010,"Leukaemia inhibitory factor and bone cell function.    Abstract:   A bone-resorbing product of mouse spleen cells found to have differentiation-inducing activity was most probably leukaemia inhibitory factor (LIF). This revealed that LIF is a cytokine active on bone, in addition to its several other sites of action. In organ culture of newborn mouse bone, recombinant LIF promoted bone resorption by a prostaglandin-dependent process. Resorption by isolated rat osteoclasts was also promoted by LIF through an initial action on osteoblasts which was receptor-mediated. Incorporation of [3H]thymidine into DNA was increased by LIF in cells (most probably osteoblasts) of the newborn mouse bones. Osteoblasts have been shown to produce LIF, and the amount is increased by treatment with retinoic acid or TNF-alpha. LIF also acts directly on osteoblasts to inhibit plasminogen activator activity, by stimulating the synthesis of plasminogen activator inhibitor 1 mRNA and protein. The latter actions are very similar to those of TGF-beta. Again like TGF-beta, LIF was ineffective in promoting bone resorption in vitro in fetal rat long bones. These results, together with the in vivo data showing that high circulating levels of LIF in the mouse are accompanied by a substantial increase in trabecular bone mass, indicate that LIF is another cytokine with potent actions on bone and potentially important interactions with other osteotrophic factors."]
[1337425,1,0,0,1,1992,"Vitamin D3 and skin diseases.","Kragballe",1337425,"Vitamin D3 and skin diseases.    Abstract:   The physiologically active metabolite of vitamin D3, 1 alpha,25-dihydroxycolicalciferol [1,25(OH)2D3, calcitriol] has achieved the status of a hormone. It is believed to mediate its effects by binding to a specific receptor which belongs to the family of nuclear receptors for glucocorticoids, estrogens, thyroxine, and retinoid acid. It has been discovered that 1,25(OH)2D3 has the ability to regulate growth and differentiation in many cell types, including cancer cells, epidermal keratinocytes, and activated lymphocytes. This has set the stage for the development of a new class of compounds with potential usefulness in hyperproliferative and immune-mediated diseases. Ideally, such agents should possess potent effects as regulators of cell proliferation and differentiation at concentrations well below those that may induce side effects related to the classical vitamin D activity on calcium absorption and bone mineralization. In addition to 1,25(OH)2D3, the synthetic vitamin D3 analogues 1 alpha-OH-D3, 1,24(OH)2D3, and calcipotriol have undergone clinical evaluation. Calcipotriol has been studied most extensively. Compared with 1,25(OH)2D3, calcipotriol is about 200 times less potent in its effect on calcium metabolism although similar in receptor affinity. In double-blind, placebo-controlled multicenter studies, topical calcipotriol has been shown to be both efficacious and safe for the short- and long-term treatment of plaque-type psoriasis. Because some of the novel vitamin D analogues are potent regulators of cell growth and immune responses, they may be of potential interest in the treatment of ichthyoses, cancer, and autoimmune diseases."]
[1334741,19,0,0,19,1992,"[Mechanism of action of retinoids in a new therapeutic approach to acute promyelocytic leukemia].","Cornic",1334741,"[Mechanism of action of retinoids in a new therapeutic approach to acute promyelocytic leukemia].    Abstract:   Vitamin A (retinol) and retinoic acid, its natural derivative, play an important role in the growth, differentiation and development of known normal tissues. Retinoids have recently become of interest to research in areas as diverse as dermatology, embryonal development and cancer research. Retinol is the major retinoid transported in the blood and tissues by its specific carrier retinol binding protein (RBP). The normal level of retinol in plasma is regulated very precisely by retinol homeostasis. RBP-retinol circulation supplies target cells, which then activate retinol into retinoic acid (RA) if they possess the NAD-dependent enzymatic oxidation system. RA, which is one of the most active metabolites of retinol, is also present in low concentration in the blood and the RA rate formation varies from tissues depending on specific need of the cell. The cellular transport and biological activity of retinoids may be mediated by their specific cytoplasmic binding proteins cellular retinol binding protein (CRBP) and the cellular retinoic acid binding protein (CRABP) which may function as shuttles targetting RA to nucleosol fraction and/or as regulator of cellular concentration of RA. The nuclear proteins RARs (retinoic acid receptors), which are members of the nuclear receptor superfamily are likely to be the final transducers of the RA signal at the gene expression. All-trans retinoic acid (ATRA) is able to specifically differentiate the malignant cells from leukemic patients with APL in short-term culture. For this reason, APL patients were successfully treated with ATRA (Chinese and French results). Acute promyelocytic leukemia M3 (French-American-British FAB classification) is a rare disease (10% of AML), characterized by a reciprocal chromosome 15-17 translocation. It has been shown that the chromosome 17 breakpoint of the translocation is localized within the RAR alpha gene. Due to the t(15;17) RAR alpha gene translocated to a gene PML on chromosome 15 resulting in synthesis of PML/RAR alpha fusion messenger RNA. Detection of PML/RAR alpha transcript is now a molecular marker of the disease. The abnormal PML/RAR alpha protein exhibits altered transcription activation properties when compared with RAR alpha. Clinical trials have demonstrated that ATRA is extremely efficient in inducing complete remission in APL patients. The morphologic finding of maturing elements in the bone marrow and peripheral blood during retinoic acid treatment indicates that the remission is obtained without hypoplasia and suggests that a differentiating mechanism is involved.(ABSTRACT TRUNCATED AT 400 WORDS)"]
[1333827,7,0,0,7,1992,"The role of retinoids in normal and abnormal embryonic craniofacial morphogenesis.","Richman",1333827,"The role of retinoids in normal and abnormal embryonic craniofacial morphogenesis.    Abstract:   The objective of this article is to evaluate the role of retinoids in the developing head and face. This article covers two lines of evidence that strongly support a role for retinoids in craniofacial development. First, the specific effects of exogenous retinoids on the head and face are covered and mechanisms for the specificity discussed. Second, the function of endogenous retinoids in facial development is discussed in relation to the distribution of retinoid-binding substances in the face. Finally, the interaction of retinoids with other genes known to be expressed in the face as well as other factors required for facial growth is discussed."]
[1324500,4,0,0,4,1992,"Patterned distributions of chondroitin sulfate isoforms, retinoic acid receptor gamma and cellular retinoic acid binding proteins in the embryonic mouse incisor.","Mark",1324500,"Patterned distributions of chondroitin sulfate isoforms, retinoic acid receptor gamma and cellular retinoic acid binding proteins in the embryonic mouse incisor.    Abstract:   Odontogenesis is an example of developmental process whereby pluripotential embryonic ectodermal and ectomesenchymal cells give rise to specific, highly ordered, spatial arrangements of overtly differentiated tissues. This process implies the sequential and coordinated expression of several molecules of defined biological activities. The data presented here demonstrate the occurrence, in the embryonic mouse incisor, of a striking correspondence between gradients of mitoses, chondroitin 6-sulfate distribution, retinoic acid receptor gamma and cellular retinoic acid binding protein I transcripts. Although purely phenomenological, these observations provide an important guide to the design of experiments for understanding the mechanisms of pattern formation during tooth development."]
[1310127,0,0,0,0,1992,"Therapeutic aspects of myelodysplastic syndromes in chronic phase.","Hast",1310127,"Therapeutic aspects of myelodysplastic syndromes in chronic phase.    Abstract:   Myelodysplastic syndromes (MDS) include hemopoietic cytopenias of different origin, which are usually refractory to treatment. Therefore MDS patients should generally be treated conservatively. Transfusions of packed red cells (given in a strict regimen to minimize the risk for secondary hemochromatosis) may be sufficient to maintain a good quality of life. Indications for cytotoxic treatment include signs of progression of the disease. In patients with symptomatic cytopenias low-dose cytarabine (ara-C) should be tried. It is essential then to monitor each patient individually and to avoid fixed treatment schedules. Standard (high-dose) chemotherapy in MDS, is associated with a high mortality and a low response rate, and should be considered only in younger patients with advanced MDS. Allogeneic bone marrow transplantation (BMT) may be offered to younger MDS patients, when a suitable donor is available. Treatment with differentiation inducers has not met with expectations and should not be used outside clinical trials at the present. The use of recombinant hemopoietic growth factors (GF) seems promising. GF, like GM-CSF, G-CSF, IL-3, and erythropoietin, can be used either alone or in combinations, to support failing peripheral blood values, and decrease the risk for lethal complications. GF can also be given together with chemotherapy, in an effort to make the leukemic clonogenic cells more susceptible to cytotoxic drugs. Other treatments for MDS include: IFN-alpha and etoposide, with responses primarily in chronic myelomonocytic leukemia; hem arginate, whose role is still not clear; and corticosteroids, but only in carefully selected cases."]
[1667579,5,0,0,5,1991,"Retinoids and their targets in vertebrate development.","Ragsdale",1667579,"Retinoids and their targets in vertebrate development.    Abstract:   The elaboration of the effect of retinoic acid on limb morphogenesis has prompted renewed investigation into the teratology of retinoic acid treatment, with the hope that such analysis might give insight into mechanisms of vertebrate patterning. Retinoids, their nuclear receptors and their cytoplasmic binding proteins are now known to be deployed throughout development, but the extent to which they are natural agents of morphogenesis remains obscure. The study of retinoic acid receptors may offer molecular insight into gene regulation underlying vertebrate pattern formation."]
[1684842,4,0,0,4,1991,"[How to choose a basic drug for psoriatic arthritis?].","Koó",1684842,"[How to choose a basic drug for psoriatic arthritis?].    Abstract:   On the basis of an earlier retrospective study in 270 psoriatic arthritis (PA) patients and according to the data of the literature 1. aurotherapy for the patients having mild skin changes and active joint involvement (mainly polyarticular type), 2. sulfasalazine for the patients having moderate skin changes and moderate articular activity, 3. etretinate for the patients having widespread skin involvement and mild articular activity, 4. methotrexate for the patients having both severe skin and severe articular involvement were introduced by the authors. The experiences of prospective study of 52 patients treated with disease modifying antirheumatic drugs (DMARDs) during 3-6 months are reported (21: aurothiomalate, 13: sulfasalazine, 4: methotrexate, 14: etretinate). Morning stiffness (MS), visual analog scale (VAS), number of swollen joints (No), psoriasis area and severity index (PASI) and erythrocyte sedimentation rate (ESR) were monitored. The methotrexate proved to be the most effective in every parameters, except the ESR. Regarding PASI the etretinate was the second most effective. Among the monitored parameters ESR and VAS showed significant improvement at every drugs. Withdrawal was necessary in 7 cases during aurotherapy (7/21), in 4 cases during sulfasalazine (4/13), in 4 cases during etretinate (4/14), meanwhile there was not withdrawal during methotrexate therapy. Low frequency of skin exacerbation (4/52) doesnt contraindicate the introduction of these drugs. If the choice and monitoring of psoriatic arthritis patients is correct we can detect really good results with DMARDs in PA."]
[1779464,1,0,0,1,1991,"[New trends in the treatment of leukemia].","Harada",1779464,"[New trends in the treatment of leukemia].    Abstract:   More than 50% cure can be obtained with allogeneic bone marrow transplantation (BMT) when patients are transplanted in first remission of AML and ALL or chronic phase of CML. On the other hand, considerable progress has been made recently in treating acute leukemia with chemotherapy. Recent studies of intensive chemotherapy in adults with AML report approximately 40-50% 3-year disease-free survival (DFS). Accordingly, several prospective randomized clinical trials have been conducted on the use of BMT versus intensive chemotherapy in the treatment of AML. Significant differences in DFS were found only in a few studies though the results of BMT appear to be comparable or superior to chemotherapy. Therefore, the overall advantage of BMT in first remission AML is smaller than expected. We should know not whether to transplant or to perform chemotherapy, but rather whether to transplant in first remission or to perform chemotherapy first and reserve transplantation as salvage therapy. Recently acute promyelocytic leukemia has been successfully treated with differentiation therapy using all-trans retinoic acid. Low-dose aclarubicin has also been reported to be effective as differentiation therapy in some patients with myelodysplastic syndrome and atypical AML. With the advance of molecular biology of cytokines, several of them are now available for clinical use. G-CSF, GM-CSF and M-CSF are potent stimulators for the granulocyte-macrophage production; they are very effective for accelerating hematologic recovery after chemotherapy-induced myelosuppression or BMT. Interferon-alpha (IFN-alpha) has been used in the several studies. Furthermore, Ph chromosome positivity can be reduced with long-term administration of IFN-alpha; Ph-positive clone can be undetectable in some patients. Thus, IFN-alpha will be the choice of treatment for CML even if BMT is planned."]
[1812134,0,0,0,0,1991,"Expression and structure of cartilage proteins.","Yamada",1812134,"Expression and structure of cartilage proteins.    Abstract:   Cartilage has unique physical characteristics attributable to the presence of an unusually high content of proteoglycan embedded in the network of collagen fibrils. Advances in understanding the structure of these components and how their synthesis is regulated have been greatly assisted by the application of molecular biology. For example, an immortalized rat chondrocyte cell line was obtained by infection with a recombinant retrovirus encoding the myc gene product. Several positive and negative DNA regulatory elements of the collagen II gene have been identified that appear to be important in the regulation of this gene in chondrocytes. The complete primary structure of the cartilage proteoglycan (aggrecan) core protein deduced from cDNA sequence displays a complex multidomain structure including numerous repeats of Ser-Gly sequences and sequence homologies with link protein and animal lectins. Such studies advance our understanding of normal morphogenetic events and lay the groundwork for determining the basis of molecular and genetic defects."]
[1812133,10,0,0,10,1991,"Effects of retinoids on chick face development.","Wedden",1812133,"Effects of retinoids on chick face development.    Abstract:   Local application of retinoic acid to chick embryos produces severe bilateral clefting of the primary palate but does not affect the lower beak. This paper reviews what is known about the basis and specificity of this retinoid-induced defect by examining three major developmental processes: morphogenesis, cell differentiation, and pattern formation. The conclusion reached is that neither cytotoxicity nor cartilage inhibition is the basis of the specific retinoid-induced defect. Retinoid treatment interferes with reciprocal epithelial-mesenchymal interactions in the upper beak. These interactions are involved in linking pattern formation--the spatial ordering of cell differentiation--to morphogenesis and outgrowth. These results suggest that retinoids are interfering with the process of pattern formation in the upper beak, a conclusion that is supported by the similarities between retinoid effects on face and limb development. Thus, it appears that retinoids may be acting as general signaling molecules throughout the developing embryo. In the lower beak, pattern-forming cues may occur earlier in development. Alternatively, the cells may be unresponsive to retinoids. The molecular basis for the specificity of the facial defect--as well as for the action of retinoids on developing systems--is discussed with reference to recent advances in molecular biology."]
[1812131,4,0,0,4,1991,"Teratogenic effects of alcohol and isotretinoin on craniofacial development: an analysis of animal models.","Webster",1812131,"Teratogenic effects of alcohol and isotretinoin on craniofacial development: an analysis of animal models.    Abstract:   The teratogens alcohol and isotretinoin cause different patterns of facial dysmorphogenesis in the human. For isotretinoin the pattern is consistent with interference with the normal development of the cranial neural crest, particularly that destined for the second visceral arch. In vitro studies in the rat indicate that, at threshold levels of exposure to isotretinoin, the development of the second arch crest represents the most sensitive process of organogenic development. For alcohol, the facial abnormalities result from exposure very early in development, during the gastrulation process. There is no evidence that this is a peculiarly sensitive stage of development with respect to alcohol; animal studies indicate that other processes in the organogenic period are equally or more vulnerable. The emphasis given to the abnormal facial features in the fetal alcohol syndrome is considered a phenomenon associated with the exclusivity of syndromes."]
[1812129,3,0,0,3,1991,"Animal models for human craniofacial malformations.","Johnston",1812129,"Animal models for human craniofacial malformations.    Abstract:   Holoprosencephaly malformations, of which the fetal alcohol syndrome appears to be a mild form, can result from medial anterior neural plate deficiencies as demonstrated in an ethanol treated animal model. These malformations are associated with more medial positioning of the nasal placodes and resulting underdevelopment or absence of the medial nasal prominences (MNPs) and their derivatives. Malformations seen in the human retinoic acid syndrome (RAS) can be produced by administration of the drug 13-cis-retinoic acid in animals. Primary effects on neural crest cells account for most of these RAS malformations. Many of the malformations seen in the RAS are similar to those of hemifacial microsomia, suggesting similar neural crest involvement. Excessive cell death, apparently limited to trigeminal ganglion neuroblasts of placodal origin, follows 13-cis retinoic acid administration at the time of ganglion formation and leads to malformations virtually identical to those of the Treacher Collins syndrome (TCS). Secondary effects on neural crest cells in the area of the ganglion appear to be responsible for the TCS malformations. Malformations of the DiGeorge Syndrome are similar to those of the RAS and can be produced in mice by ethanol administration or by quot;knocking outquot; a homeobox gene (box 1.5). Human and animal studies indicate that cleft lips of multifactorial etiology may be generically susceptible because of small MNP)s or other MNP developmental alterations, such as those found in A/J mice, that make prominence contact more difficult. Experimental maternal hypoxia in mice indicates that cigarette smoking may increase the incidence of cleft lip by interfering with morphogenetic movements. Other human cleft lips may result from the action of a single major gene coding for TGF-alpha variants. A study with mouse palatal shelves in culture and other information suggest that a fusion problem may be involved."]
[1749528,1,0,0,1,1991,"The osteocalcin gene promoter: stimulated by vitamins A and D, inhibited by cell-growth factors Jun-Fos.","Johnston",1749528,"The osteocalcin gene promoter: stimulated by vitamins A and D, inhibited by cell-growth factors Jun-Fos.    Abstract:   The gene of the bone protein osteocalcin has a promoter region recognized by the receptors for 1,25-dihydroxyvitamin D3 and retinoic acid, both of which stimulate transcription. Unexpectedly, this same gene element interacts with the cell-proliferation factors Jun-Fos, which inhibit osteocalcin gene transcription."]
[1667403,7,0,0,7,1991,"Retinoid-binding proteins in craniofacial development.","Dencker",1667403,"Retinoid-binding proteins in craniofacial development.    Abstract:   Cephalic neural crest cells are known to form the frontonasal mesenchyme and contribute to the mesenchyme of the visceral arches. Retinoids affect neural crest cells and their derivatives during development, and thus cause craniofacial, thymus, and conotruncal heart malformations. In addition, retinoids induce malformations of the central nervous system (CNS). Retinoic acid (RA) and its congeners accumulate in a saturable manner in neural crest and neural crest-derived cells, in the hindbrain, and the spinal cord of mouse embryos. Cellular retinoic acid-binding protein (CRABP) was localized by immunohistochemistry in the same areas as were the labelled RA congeners. Thus, CRABP and RA congeners were found in the transitional zone between surface ectoderm and neuropeithelium, from where neural crest cells are known to emanate (day 8 1/2). Later, specific labelling was found in the frontonasal mesenchyme and in the visceral arches. Also in the trunk, neural crest cells were labelled. In CNS, strong staining was seen in the rhombomeres (especially numbers 4-6) of the hindbrain and in the spinal cord. Retinol and cellular retinol-binding protein (CRBP) were more evenly distributed, with exception of surface ectoderm, epithelium of gut, and myocardium, where CRBP was specifically expressed. These findings are discussed in relation to the differential expression of nuclear RA receptors and homeobox genes in the craniofacial region and in the hindbrain. It is possible that RA is important for the normal pattern formation in these regions and acts as a morphogen as previously proposed in limb development."]
[1948768,1,0,0,1,1991,"Review of drug-induced limb defects in mammals.","Sanders",1948768,"Review of drug-induced limb defects in mammals.    Abstract:   The objective of this paper was to illustrate the spectrum of possible limb malformations in mammals resulting from drug exposure. A bibliography of 171 papers from 20 journals was generated from which pertinent data (drug used, limb defects reported, predominant defect location) were tabulated. These data should provide a basis for predictions about types of defects that might be expected in further studies and for judging postulated drug-induced human limb defects. However, direct extrapolation to humans is inappropriate. The following trends were observed: 1) Distal limb defects (autopod) are almost twice as common as proximal limb defects (stylopod and zygopod). 2) Ectrodactyly is the single most common type of limb defect, accounting for over half of the autopod defects. 3) Ectrodactyly is almost twice as common in the hindlimb as in the forelimb. 4) Postaxial ectrodactyly is over twice as common as preaxial ectrodactyly in the forelimb, but preaxial ectrodactyly is four times more common in the hindlimbs. 5) Polydactyly occurs with approximately equal frequency in forelimbs and hindlimbs, and preaxial polydactyly is most common in both fore and hindlimbs. 6) Polymelia (supernumerary limbs) occurred in one case, and may have been a spurious result. 7) Either transverse hemimelia is greatly underreported in teratology studies or it essentially does not occur. We have concluded that, at least in some cases, acetazolamide, adenine, 1,7-dimethylxanthine, and xanthine derivative aminophylline, retinoic acid, acetoxy-methyl-methylnitrosamine, aspirin, and cadmium can all cause unilateral defects."]
[1918486,1,1,0,2,1991,"Skin and bones. II.","Orlow",1918486,"Skin and bones. II.    Abstract:   Skin disorders in which a radiograph may detect associated bony changes or abnormalities of calcification are discussed. They are grouped into eight categories: (1) inherited diseases (e.g., alkaptonuria, neurofibromatosis); (2) congenital disorders (e.g., Sturge-Weber and Proteus syndromes); (3) inflammatory conditions (e.g., dermatomyositis, sarcoidosis); (4) infections (e.g., dental sinus, syphilis); (5) neoplasias (e.g., histiocytosis, mastocytosis); (6) drug- and environment-induced (e.g., acroosteolysis, retinoid toxicity); (7) calcinosis cutis; and (8) osteoma cutis. The first part of this review, published in the August 1991 issue of this JOURNAL, dealt with the first two categories; part II discusses categories 3 through 8."]
[1918456,1,1,0,2,1991,"Skin and bones. I.","Orlow",1918456,"Skin and bones. I.    Abstract:   Skin disorders in which a radiograph may detect associated bony changes or abnormalities of calcification are discussed. They are grouped into eight categories: (1) inherited diseases (e.g., alkaptonuria, neurofibromatosis); (2) congenital disorders (e.g., Sturge-Weber and Proteus syndromes); (3) inflammatory conditions (e.g., dermatomyositis, sarcoidosis); (4) infections (e.g., dental sinus, syphilis); (5) neoplasias (e.g., histiocytosis, mastocytosis); (6) drug- and environment-induced (e.g., acroosteolysis, retinoid toxicity); (7) calcinosis cutis; and (8) osteoma cutis. Part I of our review discusses the first two categories."]
[1821298,1,0,0,1,1991,"Etiopathogenesis of craniosynostosis.","Cohen",1821298,"Etiopathogenesis of craniosynostosis.    Abstract:   Craniosynostosis is both etiologically and pathogenetically heterogeneous. Known causes include monogenic and chromosomal disorders, fetal head constraint, teratogens (aminopterin, diphenylhydantoin, retinoic acid, valproic acid), metabolic diseases (hyperthyroidism, rickets, mucopolysaccharidoses, mucolipidoses), hematologic disorders (thalassemias, sickle cell anemia, congenital hemolytic icterus, polycythemia vera), and malformations (microcephaly, encephalocele, shunted hydrocephaly, holoprosencephaly)."]
[2058682,1,0,0,1,1991,"Growth and differentiation factors in tracheobronchial epithelium.","Jetten",2058682,"Growth and differentiation factors in tracheobronchial epithelium.    Abstract:   The normal tracheobronchial epithelium is continuously renewing itself: cells are lost and replaced by the proliferation and differentiation of stem cells. The proliferation and differentiation of these cells have to be tightly controlled in order to maintain the normal structure of the epithelium. A variety of biological and biochemical processes are involved in controlling the proliferation and differentiation of the tracheobronchial epithelium. Since the trachea and bronchus are comprised of a heterogeneous cell population, interactions between the different cell types are of crucial importance not only in controlling the normal maintenance of this tissue but also in the regulation of repair processes following injury and morphogenesis during lung development. A variety of factors, including several polypeptide growth factors and cytokines, have been identified that regulate positively or negatively the growth and differentiation of tracheobronchial epithelial cells by autocrine or paracrine mechanisms. Retinoids are another group of regulatory factors that appear to play a crucial role in controlling cell proliferation and differentiation in the tracheobronchial epithelium. Recently, many advances have been made in understanding the action of these agents in these cells. Alterations in the balance between growth and differentiation regulatory factors appear to play an important role in several pathophysiological changes such as hyperplasia, fibrosis, and neoplasia."]
[2050852,3,0,0,3,1991,"Improvement of scleromyxedema associated with isotretinoin therapy.","Hisler",2050852,"Improvement of scleromyxedema associated with isotretinoin therapy.    Abstract:   The treatment of scleromyxedema has been largely ineffective. We report improvement of scleromyxedema with myopathy after treatment with isotretinoin, 40 mg twice a day. We review other therapeutic modalities used for this disorder and discuss properties of isotretinoin that may have contributed to the favorable response."]
[2070429,9,0,0,9,1991,"Rheumatological symptoms due to retinoids.","Kaplan",2070429,"Rheumatological symptoms due to retinoids.    Abstract:   Isotretinoin and etretinate are synthetic derivatives of vitamin A widely used in the treatment of dermatological diseases, mainly those affecting keratinization. They have numerous side-effects, among which the rheumatic symptoms are not the most common or the most severe. The main skeletal adverse reaction of retinoids is hyperostosis. It mainly occurs with protracted treatments and high dosages, and its incidence may exceed 80% after a few years of administration. Hyperostosis is axial, located in the cervical and thoracic spine, and may be responsible for limitation of movement; in the appendicular bone, enthesopathies occur at the foot, pelvis, hip, and less commonly the shoulder and elbow. They are usually mild and asymptomatic. The radiological appearance is very similar to diffuse idiopathic skeletal hyperostosis. Isotretinoin tends to be responsible for axial involvement, etretinate for peripheral locations. The other skeletal side-effects are uncommon and include periosteal proliferation, calcification of the interosseous membrane of the forearm and diffuse radiological bone hyperlucency. In children, premature epiphyseal closure is very rare. About 20% of patients complain of musculoskeletal pain and arthralgias. A few cases of true arthritis have been reported. Retinoids may be responsible for muscular damage and an abnormality of muscular tone resembling the stiff-man syndrome. Some cases of necrotizing vasculitis and three cases of Wegeners granulomatosis have been observed in patients treated with retinoids. Except for these latter arguable cases, rheumatoid syndromes due to retinoids are rather benign, and should not be an obstacle to the future development of their therapeutic utilization."]
[2068576,3,0,0,3,1991,"Gout and vitamin A intoxication: is there a connection?","Mawson",2068576,"Gout and vitamin A intoxication: is there a connection?    Abstract:   Several lines of indirect evidence implicate vitamin A intoxication, associated mainly with impaired renal function, in the etiopathogenesis of gouty arthritis. The enzyme xanthine oxidase is involved not only in the conversion of xanthine to uric acid but also in that of retinol to its more toxic metabolite, retinoic acid. Retinoic acid should therefore be present in high concentration in hyperuricemic states."]
[1709576,1,0,0,1,1991,"Treatment of myelodysplastic syndromes.","Greenberg",1709576,"Treatment of myelodysplastic syndromes.    Abstract:   Therapeutic options have been rapidly evolving for management of patients with the indolent myeloid clonal hemopathies termed myelodysplastic syndromes (MDS). Heterogeneity of MDS has been demonstrated on the basis of marrow morphology and biologic features and has been useful for prognostication into high and low risk groups for transformation to acute leukemia. Such stratification has been important for evaluating responses to various treatments. These therapeutic options include the differentiation-inducing vitamins retinoic acid and vitamin D, and cytokines such as alpha and gamma interferon, to which there has been a generally low response. The use of intensive or low dose chemotherapy has been associated with relatively low response rates, few durable responses and a high degree of hemopoietic toxicity. Allogeneic bone marrow transplantation (BMT) has shown durable responses for a subset of MDS patients, particularly those who are young and who are in the low risk subgroups. however, due to the elderly nature of the majority of MDS patients, and the toxicity associated with BMT, this option has limited utility for most of these patients. Major focus has been on the recent therapeutic use of recombinant human hemopoietic growth factors, particularly G-CSF, GM-CSF and IL3. These agents have been well-tolerated and generally produce a high incidence of sustained improvements in neutrophil counts and marrow morphology, although hemoglobin and platelet counts have generally not been altered. More extensive clinical trials evaluating the impact of these hemopoietic growth factors on the natural history of MDS are ongoing."]
[2043697,1,0,0,1,1991,"Therapy for acute leukemias in children.","Kalwinsky",2043697,"Therapy for acute leukemias in children.    Abstract:   Improvement in therapies for childhood acute lymphocytic leukemia has resulted in cure for the majority of young people with this disease. Recent therapeutic advances have focused on testing more extensive treatments for cases with adverse clinical/biologic features, or pharmacologic studies to maximize dose intensity. The latter includes a trial of alternating high-dose intravenous methotrexate with high-dose intravenous 6-mercaptopurine given for the first year postremission in an attempt to circumvent the patients natural variability of absorption and metabolism of these drugs. Patients with acute myeloid leukemia continue to fare much worse and only one in three are long-term survivors. Acute myeloid leukemia therapies emphasize the use of intensive toxic courses of cytarabine, etoposide, and an anthracycline to cytoreduce the leukemic clone. Acute progranulocytic leukemia, however, now appears to be responsive in vitro to the differentiation agent all-trans retinoic acid. For this disease, complex responses are now obtained without the use of conventional antineoplastics."]
[1946205,0,0,0,0,1991,"[Current concepts of odontogenesis].","Rojano Pérez",1946205,"[Current concepts of odontogenesis].    Abstract:   Tooth growth and development involve complex biochemical and physiological processes. Some vitamins are required as coenzymes, but these molecules are also needed to synthesize specific proteins with structural or transport functions. Collagen synthesis is carried out by ascorbic acid interaction. Vitamin A induces calbindin synthesis. Collagen and calbindins are both involved in the mineralization and development of hard tissues. The formation, eruption and growth of teeth are also mediated by the interaction of several hormones."]
[1828308,4,0,0,4,1991,"Musculoskeletal syndromes associated with acne.","Knitzer",1828308,"Musculoskeletal syndromes associated with acne.    Abstract:   The acne conglobata (AC)-, acne fulminans (AF)-, and isotretinoin-associated musculoskeletal syndromes are three distinct clinical entities. The AC-associated musculoskeletal syndrome occurs primarily in black men over the age of 22, who develop sacroilitis with or without a peripheral arthropathy. In contrast, the AF-associated musculoskeletal syndrome is found almost exclusively in white male teenagers. Fever, weight loss, and arthralgias are prominent components of this syndrome. A unique feature of the AF-associated musculoskeletal syndrome is osteolytic lesions that occur most frequently in the clavicle, sternum, long bones, and ilium. The isotretinoin-associated musculoskeletal syndrome occurs with equal frequency in male and female acne patients. Mild, transient myalgias and arthralgias are very common and do not require discontinuation of isotretinoin therapy. Asymptomatic, small, hyperostotic lesions of the spine occur in approximately 10% of acne patients with the isotretinoin-associated musculoskeletal syndrome."]
[1710505,1,0,0,1,1991,"Recent advances in biology and treatment of myelodysplasia.","Heyman",1710505,"Recent advances in biology and treatment of myelodysplasia.    Abstract:   The myelodysplastic syndromes are clonal hematopoietic stem cell disorders characterized by varying degrees of pancytopenia and often a progression to acute myeloid leukemia. Recent evidence has linked myelodysplastic syndromes to environmental and occupational genotoxic exposure. Specific cytogenetic abnormalities are well described in myelodysplastic syndromes and have been demonstrated to be useful diagnostic and prognostic tools. Activation of protooncogenes such as ras and fms have also been noted in myelodysplastic syndromes; however, their contribution to the pathogenesis of the syndrome remains to be determined. Aggressive leukemia-like induction therapy, differentiating agents (low-dose cytarabine, 13-cis-retinoic acid) have had little impact on overall survival in myelodysplastic syndromes. The recombinant hematopoietic growth factors (granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor) may be of significant benefit to patients with myelodysplastic syndromes, although it remains to be determined whether they will have a substantial impact on survival. Allogeneic bone marrow transplantation is the only potentially curable treatment of myelodysplastic syndromes. The advanced age of these patients as well as the lack of histocompatible donors restricts this modality to only a small proportion of patients."]
[2003103,0,0,0,0,1991,"Myelodysplastic syndromes: a review for nurses.","Cain",2003103,"Myelodysplastic syndromes: a review for nurses.    Abstract:   The Myelodysplastic Syndromes (MDS) are a group of hematologic disorders that resemble hematologic malignancies but are often treated much differently. These syndromes result from a clonal disorder of certain stem cells in the bone marrow. Treatment can range from simple supportive care to new and innovative approaches such as immunotherapy. In general, treatment is dictated by the severity of the presenting disease. Oncology nurses, because of their familiarity with the manifestations of cancer, are particularly qualified to intervene for the patient and family experiencing MDS. Nursing interventions, based on a firm understanding of the underlying disease, include patients and family education. In addition, emotional support and symptom management are important nursing roles."]
[1917382,0,0,0,0,1991,"Cellular mechanisms of pattern formation in the developing limb.","Maini",1917382,"Cellular mechanisms of pattern formation in the developing limb.    Abstract:  "]
[1822394,3,0,0,3,1991,"[Biological parameters of the efficiency of retinoic acid in acute leukemia].","Chomienne",1822394,"[Biological parameters of the efficiency of retinoic acid in acute leukemia].    Abstract:   We have previously shown that all-trans retinoic acid therapy is an alternative therapy for acute promyelocytic leukemia (AML3) via differentiation of the leukemic cells. The t(15;17) translocation is specifically found in this leukemia. We and others have shown that through this translocation the RAR alpha gene is rearranged and its expression altered in AML3 cells. The gene is truncated and fused to a novel gene (PLM). This results in a fusion protein whose transactivating properties may be implicated in the leukemogenesis of this disease. Retinoic acid cytoplasmic binding proteins (CRABP and CRBP) are not detected by PAGE chromatography in normal or malignant hematopoietic cells. During all-trans RA therapy, a) all-trans RA plasma concentrations are within in vitro differentiating concentration (med. 0.4 microgram/ml); b) increased expression of the normal remaining RAR alpha allele is rapidly observed and may explain the paradoxical induction of RA differentiation in these cells; c) CRABPII is induced in the bone marrow cells of AML3 patients and remains detectable 1 month after withdrawal of RA. AML3 in relapse after RA therapy is always less sensitive to RA in vitro and in vivo. Our data suggest that modification of the metabolisation pathways of RA may be one of parameters linked to this resistance. It appears that the efficacy of all-trans RA is the resultant of multiple parameters (RA concentration, ratio of PML/RAR alpha transcripts to normal RAR alpha, CRABP) which need to be defined to efficiently monitor all-trans RA therapy in APL."]
[1781599,1,0,0,1,1991,"[Bones and retinoids].","Zabarino",1781599,"[Bones and retinoids].    Abstract:  "]
[1364730,0,0,0,0,1991,"[The effects of glucocorticoids on connective tissue].","Oikarinen",1364730,"[The effects of glucocorticoids on connective tissue].    Abstract:  "]
[2099815,0,0,0,0,1990,"Transcriptional control and the integration of cell-autonomous and environmental cues during development.","Karin",2099815,"Transcriptional control and the integration of cell-autonomous and environmental cues during development.    Abstract:  "]
[2230879,1,0,0,1,1990,"The unique aspects of acute promyelocytic leukemia.","Stone",2230879,"The unique aspects of acute promyelocytic leukemia.    Abstract:   Acute promyelocytic leukemia (APL) accounts for approximately 10% of cases of acute myeloid leukemia (AML). Distinctive features of this disorder at the time of diagnosis include leukopenia coexisting with a marrow replaced with granulated dysplastic promyelocytes, disseminated intravascular coagulopathy, lack of Ia (HLA-DR) antigen expression, and translocation between the long arms of chromosomes 15 and 17 (t[15;17]). Heparin is widely but not universally used to interfere with the coagulopathy during the initial phases of treatment. Serial bone marrow examinations during the induction period demonstrate the achievement of remission despite the persistence of malignant-appearing promyelocytes. Patients with APL are generally younger than those with other subtypes of AML, have a 70% to 80% likelihood of entering remission, and are thought to have a more favorable prognosis than other individuals with AML. Remission may be achieved with a conventional anthracycline-cytarabine combination, anthracycline alone, or, apparently, all-trans retinoic acid. Genes potentially important in myeloid differentiation such as granulocyte colony-stimulating factor (G-CSF) and myeloperoxidase are located close to the breakpoint in the t(15;17) but have not been conclusively shown to be rearranged in the translocation. A better understanding of the unique aspects of APL may well shed light on the pathogenetic processes of AML."]
[2258296,13,0,0,13,1990,"[Retinoid-induced changes of the bones and ligaments].","Zelger",2258296,"[Retinoid-induced changes of the bones and ligaments].    Abstract:   Bone and ligament lesions induced by systemic retinoids (premature epiphyseal closure, osteophytes, calcification of ligaments, osteoporosis, etc.) are radiologically nonspecific. We assessed the incidence of quot;possibly retinoid-induced bone and ligament lesionsquot; (MRKBV) in 46 patients (aged 24-82 years) who had been treated with various systemic retinoids for a variety of chronic dermatoses for an average of 4.5 years and compared the data with observations in a similarly structured group of control patients. All types of MRKBV were found more frequently in the retinoid group (41.3% vs 30.2%) and were more severe. Differences were only slight, however, being statistically significant only for moderate and severe MRKBV and for calcification of ligaments. Within the retinoid group, MRKBV were strikingly correlated with age, whereas no correlation was found with duration of treatment, mean daily and cumulative retinoid dose, underlying dermatosis, type of retinoid used or presence of other retinoid side-effects. Within the control group, MRKBV were also correlated with age, although to a lesser degree. We conclude that retinoids amplify and accelerate physiological and pathophysiological remodelling of the bones, thereby producing a varied range of lesions, which are characteristic for the age and the individual constitution of the patient treated. Retinoid-induced bone and ligament lesions, as a rule, do not cause subjective symptoms and are not associated with predictive or accompanying laboratory values. Also, MRKBV are not paralleled by other retinoid-induced side-effects (hyperlipidaemia, elevation of liver transaminases). In 16 cases in which bone X-ray had been performed prior to retinoid treatment, no indication of reversibility of MRKBV was found.(ABSTRACT TRUNCATED AT 250 WORDS)"]
[2226349,1,0,0,1,1990,"Metabolism and effects of epidermal growth factor and related growth factors in mammals.","Fisher",2226349,"Metabolism and effects of epidermal growth factor and related growth factors in mammals.    Abstract:   The initial observations of Stanley Cohen in the 1960s established that EGF induced in vivo effects such as precocious eyelid opening and tooth eruption. Subsequently the actions of EGF have been extensively explored in cell culture systems. The receptor for EGF was characterized as a prototype model for other growth factors and the now extensive in vitro data indicate multiple functions for EGF. Moreover, EGF and EGF receptors have been characterized in many tissues, and EGF has been identified in most body fluids of several mammalian species. Interestingly, neither EGF antibody administration to newborn animals nor passive immunization of pregnant rodents against EGF has caused major deleterious effects (except the delay in epidermal maturation events), as might be expected from the in vitro studies. This is in contrast to the effects of nerve growth factor antiserum in developing rodents. Also, to date, no pathological EGF deficiency disorder has been characterized. However, the EGF family of growth factors appears to be important in mammalian development and function, although the precise roles and significance are not yet clear. Members of the family may have a role in embryogenesis and fetal growth since receptors have been identified in fetal tissues. Available evidence suggests that TGF alpha subserves the growth factor family roles in fetal development. In the developing postnatal animal pro-EGF mRNA, immunoreactive EGF, immunoreactive TGF alpha, and EGF receptors are present in many tissues. EGF also is produced and secreted by the maternal mammary gland, and mammary derived EGF appears to be important in gut development in the neonatal rodent. There is now extensive data to indicate important hormone-EGF interactions. In the postnatal period, thyroid and steroid hormones including retinoic acid have been shown to modulate EGF and/or EGF receptors in several tissues. GH increases EGF binding in liver and increases urine EGF concentrations. Moreover, EGF stimulates secretion of several hypothalamic and pituitary hormones, increases placental production of hCG and human chorionic somatomammotropin, increases adrenal cortisol production, and inhibits testicular, ovarian, and thyroid hormone secretions. As summarized in this review EGF has been implicated in a number of developmental events including palate and skin differentiation, growth of hair follicles, eye opening and tooth eruption, lung maturation, gut and liver growth, and differentiation of neurons. These EGF actions probably are mediated via autocrine, paracrine, and endocrine routes. A role for salivary and urine EGF in the maintenance of adult stomal, gut, and urinary epithelial surface integrity seems likely, although not yet proven.(ABSTRACT TRUNCATED AT 400 WORDS)"]
[2142437,6,0,0,6,1990,"Risk: benefit ratio in the treatment of psoriasis with systemic retinoids.","Halioua",2142437,"Risk: benefit ratio in the treatment of psoriasis with systemic retinoids.    Abstract:   This is a review of the efficacy of etretinate/acitretin in the treatment of psoriasis and of the currently reported side-effects. The data indicate that retinoids bring significant improvement (if not total clearing) with frequent low-morbidity but rarely serious side-effects. The most serious side-effect of etretinate/acitretin is teratogenicity."]
[1696325,0,0,0,0,1990,"[Management of myelodysplastic syndromes].","Hotta",1696325,"[Management of myelodysplastic syndromes].    Abstract:  "]
[2406831,1,0,0,1,1990,"Myelodysplastic syndromes.","Yeomans",2406831,"Myelodysplastic syndromes.    Abstract:   A cure for MDS has yet to be found. The aim of therapy is to attempt to restore normal hematopoiesis and prevent evolution to acute leukemia. The major trend is supportive care. Blood counts and bone marrow aspirations are taken to evaluate the disease, and transfusions of blood products and antibiotics are given when necessary. A new encouraging modality of therapy is the use of hematopoietic growth factors to reverse cytopenias. As there is no curative treatment for MDS, the patient is likely to be offered investigational drugs either singly or in combination. Future trends in the treatment of MDS will be combinations of agents including biological agents with retinoic acid or vitamin D, low-dose Ara-C, the interferons, and colony-stimulating factors."]
[2404492,1,0,0,1,1990,"Similar regulation of chondrocyte functions by cellular stimulants of unknown mechanism. Retinoids, cytokines, and bacterial lipopolysaccharide.","Benton",2404492,"Similar regulation of chondrocyte functions by cellular stimulants of unknown mechanism. Retinoids, cytokines, and bacterial lipopolysaccharide.    Abstract:  "]
[2686630,3,0,0,3,1989,"Morphogens in chick limb development.","Brickell",2686630,"Morphogens in chick limb development.    Abstract:   Retinoic acid is a good candidate for a morphogen in chick limb bud development. The challenge now is to determine how retinoic acid interacts with limb bud cells and how the retinoic acid signal is integrated with other signals to mould and pattern the developing limb."]
[2688058,1,0,0,1,1989,"[A new case of hyperostosis induced by a retinoid].","Martin",2688058,"[A new case of hyperostosis induced by a retinoid].    Abstract:  "]
[2671546,0,0,0,0,1989,"Cutaneous reactions to drugs used for rheumatologic disorders.","Roth",2671546,"Cutaneous reactions to drugs used for rheumatologic disorders.    Abstract:   Cutaneous reactions to medications probably represent the most common manifestation of drug reactions. The diversity of cutaneous eruptions produced by drugs provide a challenge in searching for the mechanisms producing the reaction. Many eruptions are due to a form of allergic hypersensitivity, while others may be idiosyncratic, due to a metabolic abnormality, or represent a cumulative phenomenon. This article discusses the diagnosis of drug-induced cutaneous reactions by reviewing specific drugs commonly used in rheumatologic therapy."]
[2659580,8,1,0,9,1989,"The use of retinoids as probes for analyzing morphogenesis of glands from epithelial tissues.","Hardy",2659580,"The use of retinoids as probes for analyzing morphogenesis of glands from epithelial tissues.    Abstract:   Thirty-five years ago Honor Fell and Edward Mellanby were studying effects of high doses of vitamin A on skeletal development in chick embryos when they noticed that a piece of epidermis, accidentally included in an organ culture, had undergone mucous metaplasia. Further studies by Fell and others eventually led to an understanding of the important role of vitamin A in modulating epithelia in vivo. Fifteen years later another organ culture experiment showed me that excess vitamin A could also initiate the morphogenesis of branching and mucus-secreting glands from developing vibrissa follicles in upper lip skin of embryonic mice. Since then our group has shown that induction of this novel structure by naturally occurring retinoids resembles a normal embryonic induction in that it is stage-dependent, time-dependent, and irreversible. Tissue separation and recombination studies showed that isolated upper lip epidermis can form these glands when combined with retinoid-treated upper lip dermis. Untreated mouse epidermis can form similar glands after combination with chick dermis containing higher retinoid levels. The hamster cheek pouch, normally devoid of glandular structures, can also form mucous glands when treated with a retinoid, either in vivo or in vitro. Recombination studies in organ culture have now shown that mesenchyme exposed to retinoid is essential for gland morphogenesis from pouch epithelium. Evidence is accumulating that retinoic acid may even be the active morphogen in some normally developing systems."]
[2523875,8,0,0,8,1989,"[Retinoids: the new status. Maintenance therapy, disorders of resorption in quot;non-respondersquot;, interactions and interferences with drugs, treatment of children and bone toxicity, acitetin and 13-cis-acitretin].","Orfanos",2523875,"[Retinoids: the new status. Maintenance therapy, disorders of resorption in quot;non-respondersquot;, interactions and interferences with drugs, treatment of children and bone toxicity, acitetin and 13-cis-acitretin].    Abstract:   Oral retinoids are now well-established drugs for the systemic treatment of skin diseases. For etretinate to be effective on a long-term basis it is recommended that maintenance therapy should be continued for 3-6 months after clinical signs of the disease have disappeared. In quot;non-respondersquot; with psoriasis the blood levels of etretinate may be low and increasing the dose to 1.5 mg/kg body weight per day will be necessary and helpful in some cases. The interaction of drugs should also be considered carefully in non-responding individuals. Children usually respond well to treatment, but they also often require higher dose levels. Bone toxicity with premature epiphyseal closure and hyperostoses may be seen during isotretinoin administration and, more rarely, in patients receiving etretinate, but the risk is relatively low. Teratogenicity is a major concern in young females being treated for acne with isotretinoin, since 70 embryopathies have been recorded worldwide."]
[2660711,8,0,0,8,1989,"[Rheumatologic effects of etretinate].","Cuny",2660711,"[Rheumatologic effects of etretinate].    Abstract:   The effects of chronic hypervitaminosis A and long-term isotretinoin treatment on bone include cortical hyperostosis, ligament calcification and premature epiphyseal closure. Similar effects have now been reported in patients under maintenance treatment with etretinate in high doses. Etretinate, an oral, aromatic, synthetic vitamin A derivative, is widely used in Europe for disorders of keratinization. We report the cases of two patients--one with lamellar ichthyosis, the other with pachyonychia congenita--who developed such bone diseases during treatment with etretinate over 2 and 6 years respectively. The doses ranged from 0.5 to 1 mg/kg/day. Two years after starting treatment (total dose 25 g), the patient with lamellar ichthyosis complained of mechanical pain in the lumbar region and hips. Radiography showed calcification of the extraspinal tendons and ligaments and hyperostosis of the calcaneus bone at the insertion of the plantar ligament. After six years of etretinate treatment (total dose 50 g), the patient with pachyonychia congenita presented with scoliosis and limb length discrepancy. The musculoskeletal abnormalities resembled chronic hypervitaminosis A, with such osseous changes as demineralization, thinning and increased curvature of long bones with osteopenia, and premature closure of the epiphyses. Acroosteolysis was also present. Etretinate has been implicated in the formation of spinal hyperostoses and calcification of extraspinal ligaments in patients who had taken the drug for many years. The occurrence of premature epiphyseal closure in children certainly is a consequence of therapy with relatively high doses of etretinate for six years. But premature epiphyseal closure may also result from trauma to a fragile bone.(ABSTRACT TRUNCATED AT 250 WORDS)"]
[2660707,1,0,0,1,1989,"[Ossification of the antibrachial interosseous membrane caused by etretinate].","Zabarino",2660707,"[Ossification of the antibrachial interosseous membrane caused by etretinate].    Abstract:  "]
[2653491,0,0,0,0,1989,"Myelodysplasia: clinical and morphological aspects and treatment.","Geary",2653491,"Myelodysplasia: clinical and morphological aspects and treatment.    Abstract:  "]
[2645589,1,0,0,1,1989,"Retinoids: toxicology and teratogenicity to date.","Teelmann",2645589,"Retinoids: toxicology and teratogenicity to date.    Abstract:  "]
[2645586,1,0,0,1,1989,"Bone changes associated with oral retinoid therapy.","White",2645586,"Bone changes associated with oral retinoid therapy.    Abstract:  "]
[3054577,1,0,0,1,1988,"[Skeletal abnormalities caused by etretinate].","de Groot",3054577,"[Skeletal abnormalities caused by etretinate].    Abstract:  "]
[2976328,4,0,0,4,1988,"New retinoids for dermatologic diseases. Uses and toxicity.","Lowe",2976328,"New retinoids for dermatologic diseases. Uses and toxicity.    Abstract:   Systemic administration of retinoids is frequently associated with mucocutaneous side effects, liver toxicity, and abnormalities of the serum lipid profile. Currently, the main factors limiting more common use of retinoids are their teratogenicity and chronic bone toxicity. Treatment with retinoids requires appropriate selection of patients, careful periodic monitoring of the clinical response, and appropriate laboratory tests. Careful therapeutic management is necessary in order to prevent or minimize side effects."]
[3050774,0,0,0,0,1988,"[The effect of vitamin A therapy on the immune function and lipid peroxidation in patients with Sjögren syndrome].","Szöcsik",3050774,"[The effect of vitamin A therapy on the immune function and lipid peroxidation in patients with Sjögren syndrome].    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I645,I645)","v":2971690},{"$f":"(LEN($J645) - LEN(SUBSTITUTE(LOWER($J645),LOWER(B$3),\"\")))/LEN(B$3)","v":1},0,0,{"$f":"SUM(B645:D645)","v":1},1988,"Use of oral and topical agents for acne in pregnancy.","Rothman",2971690,"Use of oral and topical agents for acne in pregnancy.    Abstract:   Dermatologists frequently are consulted by a pregnant patient or a woman of childbearing age who desires acne therapy. Because there are no published studies in which women took acne medications throughout pregnancy, information about safety must be obtained indirectly from studies in which the agents were taken for another indication during some portion of pregnancy. Oral tetracycline is associated with maternal liver toxicity and deciduous tooth staining in the infant, and tetracycline occasionally has been associated with other congenital anomalies. Maternal isotretinoin ingestion is associated with major craniofacial and cardiac deformities, as well as other congenital anomalies. Erythromycin, however, appears to be safe. Topical acne medications never have been implicated as a cause of fetal deformities in human beings. Dermatologists should be aware of potential toxic and teratogenic effects of acne medicines before prescribing them to women of childbearing age. Prompt reporting of adverse effects is encouraged."]
[3054426,12,0,0,12,1988,"Adverse effects of retinoids.","David",3054426,"Adverse effects of retinoids.    Abstract:   Oral retinoids, synthetic derivatives of vitamin A, have been used in the treatment of various dermatoses over the last decade. The most useful drugs have been isotretinoin (13-cis-retinoic acid) for nodulocystic acne and etretinate for psoriasis vulgaris. Retinoids are also effective in the treatment of papulosquamous dermatoses other than psoriasis (i.e. inherited disorders of keratinisation), cutaneous T-cell lymphoma and in chemotherapy and chemoprevention of cancer. However, systemic administration of these compounds is frequently associated with mucocutaneous side effects, liver toxicity and abnormalities of serum lipid profiles, which might be related to an increased risk of coronary heart disease. Of particular concern is the teratogenic effect of all retinoids, which limits their use in women of child-bearing potential. Chronic toxicities from long term therapy with retinoids may result in skeletal abnormalities, usually mimicking diffuse idiopathic hyperostosis syndrome. Furthermore, the chronic use of retinoids in children may inhibit their growth due to premature epiphyseal closure. In contrast to other side effects of retinoids which are dose dependent and reversible upon withdrawal of the drug, it seems unlikely that bone abnormalities will resolve after discontinuation of the medication. In view of the wide spectrum of toxicities, treatment with retinoids requires appropriate selection of patients, careful consideration of the benefit to risk ratio for each individual, periodic monitoring of clinical response and laboratory tests. Clinicians should use special management techniques in order to prevent or minimize slide effects. Extensive investigations are currently being conducted in an attempt to develop new retinoids which will improve the therapeutic efficacy and reduce unwanted reactions."]
[3045876,6,0,0,6,1988,"[Skeletal changes following long-term treatment with retinoids].","Montag",3045876,"[Skeletal changes following long-term treatment with retinoids].    Abstract:   The synthetic retinoids, the vitamin-D-derivatives etretinate and isotretinoin, have substantially enlarged the therapeutic arsenal in dermatology. They are primarily used in severe cases of acne and cornification disorders. In the majority of cases, long-term treatment is necessary. Certain side effects in the skeletal system can occur, e.g., osteoporosis, premature epiphyseal closure, and changes similar to DISH (diffuse idiopathic skeletal hyperostosis). We discuss the reports in the literature and our own observations in 31 patients treated at the Westphalian Wilhelms University in Muenster, as well as at the Technical University in Munich. In 3 out of 31 patients treated by retinoids on a long-term basis, skeletal changes were found radiologically as a result of the retinoid medication."]
[3280622,4,0,0,4,1988,"Adverse reactions to isotretinoin. A report from the Adverse Drug Reaction Reporting System.","Bigby",3280622,"Adverse reactions to isotretinoin. A report from the Adverse Drug Reaction Reporting System.    Abstract:   Between October 1982 and June 1985 the Adverse Drug Reaction Reporting System received reports of 104 suspected adverse reactions occurring in 93 patients who took isotretinoin. Adverse reactions involving the skin and mucous membranes (29 reports), central nervous system (23), musculoskeletal system (12), pregnancy (11), and eyes (8) were most commonly reported. Severe headache was the most frequently reported adverse reaction (15 reports). In four cases headaches were attributed to pseudotumor cerebri. Some of the reported reactions, for example, a disulfiram (Antabuse)-like reaction and oculogyric crisis, have not been described previously in the literature. Other reports, such as congenital malformations, serve to emphasize some of the serious reactions that are known to occur. These spontaneous reports of adverse reactions associated with isotretinoin use, together with the literature we review, may help alert physicians to the diverse spectrum of adverse reactions that may develop in patients taking isotretinoin."]
[3074910,2,0,0,2,1988,"Teratogens and craniofacial malformations: relationships to cell death.","Sulik",3074910,"Teratogens and craniofacial malformations: relationships to cell death.    Abstract:   Environmental agents including ethanol, 13-cis retinoic acid (RA, Accutane), the antimetabolite methotrexate, periods of hypoxia, ionizing radiation or hyperthermic stress, when administered acutely to pregnant experimental animals, induce stage-dependent craniofacial malformations comparable to those in corresponding human teratogen syndromes. Acute treatment regimens have allowed analysis of cell populations initially affected and subsequent dysmorphogenetic sequences as well as speculation relative to mechanisms of teratogenesis. In rodent models, ethanol and RA appear to affect similar cell populations and comparable malformations can be induced by both agents. When administered during gastrulation they cause a major insult to the anterior neural plate which results in characteristic ocular, brain and facial malformations comparable to those seen in the fetal alcohol syndrome. Exposure to these drugs at a time just prior to and during neural crest cell migration into the craniofacial and cervical regions results in malformations comparable to those seen in the Di-George sequence and/or retinoic acid embryopathy. Slightly later, at the time that the epibranchial placodes are active, insult results in mandibulofacial dysostosis-like syndromes. We propose that the pattern of these malformations is related to the particular vulnerability of cells in the vicinity of normal programmed cell death. Cell death is also associated with ionizing radiation and hyperthermia-induced malformations. Both of these teratogens are particularly damaging to the early development of the eye and central nervous system. Teratogenic temperature elevations result in arrest of mitotic activity and death of cells in mitosis. Hypoxia is also associated with cell death in specific regions and subsequent malformation. For example, death of cells in the invaginating olfactory placode has recently been associated with cleft lip formation. The relationship of hypoxia-induced cell death to energy requirements is being explored. Acute treatment with methotrexate results in frontonasal dysplasia (median facial clefts). Combined effects of fluid imbalance, lack of proliferation or death of frontonasal mesenchyme appear to be involved. Although the mechanisms of craniofacial malformation are complex, a common feature for many is excessive cell death for which the embryo may be unable to compensate. Excessive cell death in regions of programmed cell death represents an important, yet little appreciated, mechanism of teratogenesis."]
[3053038,0,0,0,0,1988,"Factors modifying the secretion and action of parathyroid hormone in renal failure.","Cundy",3053038,"Factors modifying the secretion and action of parathyroid hormone in renal failure.    Abstract:  "]
[3429723,1,0,0,1,1987,"Mycophenolic acid for psoriasis. A review of pharmacology, long-term efficacy, and safety.","Epinette",3429723,"Mycophenolic acid for psoriasis. A review of pharmacology, long-term efficacy, and safety.    Abstract:   In previous studies of up to 2 years duration, mycophenolic acid has been shown to be an effective psoriasis suppressant. As the result of questions raised regarding the possible immunosuppressive and carcinogenic potentials of the drug, in addition to its apparent acute gastrointestinal side effects, widespread clinical trials were discontinued in 1977. We were given the unique opportunity of continuing to administer the drug on a compassionate-use basis to 85 patients for up to 13 years. In this review we report continued efficacy without dose escalation. Gastrointestinal side effects, prominent in the early years of the study, became infrequent. Although 11.6% of the patients developed uncomplicated zoster, no clinical evidence of immunosuppression was noted. The seven malignant neoplasms that arose in six of the patients were not unusual considering the age of the study population. Six patients died of conditions believed to be unrelated to drug therapy. We continue to believe that mycophenolic acid is an effective drug for the treatment of moderate to severe psoriasis and that the risks of its long-term administration are acceptable. With appropriate clinical and laboratory monitoring it can be given safely to patients who cannot take methotrexate and who may not be candidates for PUVA, retinoids, or other systemic chemotherapy."]
[2827313,0,0,0,0,1987,"Management of the myelodysplastic syndromes.","Tricot",2827313,"Management of the myelodysplastic syndromes.    Abstract:   It is important to make the correct diagnosis of MDS and to exclude very carefully all other disorders that may induce dysplastic features in the bone marrow. In patients without excess of bone marrow blasts, cytogenetics and in vitro bone marrow cultures may aid in making the correct diagnosis. MDS patients without excess of bone marrow blasts or symptomatic cytopenia or cytogenetic abnormalities associated with poor prognosis should be followed on a regular basis with sequential examinations of blood counts and bone marrow specimens. In the absence of obvious disease progression, ie, increasing cytopenia or increasing percentage of marrow blasts, patients should only receive supportive care. An increase in RBC requirements alone is insufficient reason to start cytotoxic therapy. Once progression of the disease has been well documented, cytotoxic treatment is indicated. There is no reason to delay treatment until these patients have progressed to overt AML. In patients over the age of 50, the best available therapy is low-dose cytarabine with a 30% probability of a good response; this therapy requires careful supervision and the availability of intensive supportive care. In patients under 50 years with progressive disease, or with clear evidence of a poor prognosis, allogeneic BMT is the therapy of choice if a HLA-identical sibling can be identified. In those patients who lack a HLA-identical sibling, intensive combination therapy is the treatment of choice and should preferably include high-dose cytarabine. Intensive consolidation therapy will be necessary for a durable remission. Trials with inducers of differentiation remain experimental. Results to date have been disappointing."]
[3310911,7,0,0,7,1987,"Side effects and long-term toxicity of synthetic retinoids.","Yob",3310911,"Side effects and long-term toxicity of synthetic retinoids.    Abstract:   The observation that vitamin A (retinol) has antikeratinizing properties has led to the development of synthetic retinol derivatives (retinoids) for the treatment of a variety of skin disorders characterized by abnormal keratinization. The goal of research in this area is the synthesis of retinoids that would have a more favorable therapeutic: toxic ratio than retinol itself. A limiting factor in the use of any vitamin A analogue is that, even with a more favorable therapeutic: toxic ratio, large pharmacologic doses are required that produce side effects related to the drugs action in most individuals. With few exceptions, all of the side effects are those seen from mega-vitamin A ingestion, primarily affecting the mucocutaneous, skeletal, and central nervous systems. Most of the side effects from excess vitamin A are reversible, with notable exceptions being those involving hepatic and osseous tissues. In terms of reversibility from synthetic retinoids, the experience to date has been incomplete, so there remains imprecise information as to the incidence and the persistence of toxic effects after drug withdrawal."]
[3547011,2,0,0,2,1987,"Nevoid basal-cell carcinoma syndrome.","Gorlin",3547011,"Nevoid basal-cell carcinoma syndrome.    Abstract:   The nevoid basal-cell carcinoma syndrome is characterized by major manifestations, such as multiple basal-cell carcinomata, cysts of the jaws, and skeletal--specifically, rib--abnormalities. Findings in 53 patients and a review of the literature document both major and lesser-known manifestations of the disorder. The odontogenic keratocyst, which usually appears during adolescence, has a marked tendency to recur. In addition to the skin tumors, milia, epidermoid cysts, chalazia, comedones, and palmar and plantar pits are frequent. The skin tumors, originally thought to be independent of sun exposure, are more common in sun-exposed areas and are far less frequent and occur at a much later age in blacks than in whites. There is some evidence that radiation of the skin promotes the appearance of skin cancers in this disorder. Unilateral linear nevoid basal-cell carcinomas with comedones may represent postzygotic somatic mutation. A proclivity to other forms of neoplasia exists. Patients with this syndrome have had medulloblastoma, meningioma, ovarian fibroma, ovarian fibrosarcoma, fibrosarcoma of the jaws, cardiac fibroma, fetal rhabdomyoma, and lymphatic or chylous cysts of the mesentery. In addition to the usual modalities of treatment, topical immunotherapy and topical 5-fluorouracil have been used with success. Oral synthetic retinoids, such as 13-cis-retinoic acid, have been used to prevent new lesions from appearing and to arrest the growth of older lesions by inducing differentiation. The independent observations of increased prostaglandin levels associated both with odontogenic keratocyst expansion and aggression of basal cell cancers merit further investigation both as a fundamental cellular mechanism and as a possible basis for treatment (e.g., with antiprostaglandins). The key to pre- and early postnatal diagnosis of the disorder--as well as to an understanding of the basic abnormality--lies in molecular genetics. Prime attention should be given to finding the site of the gene through the use of DNA and other markers."]
[3322144,5,0,0,5,1987,"[Sjogren-Larsson syndrome. Apropos of a case].","Bonafé",3322144,"[Sjogren-Larsson syndrome. Apropos of a case].    Abstract:   Sjögren-Larsson syndrome is a rare genodermatosis described by Sjögren and Larsson in 1957 (28) and characterized by ichthyosis, spastic di- or tetraplegia and oligophrenia. In the case reported here a female child, born to consanguineous parents, presented at birth as a quot;collodion babyquot;. Progressively, she developed an ichthyosiform and erythrodermic state and at the same time, after an episode of seizures, spasticity of the lower limbs set in. From then on, her acquisitions were very slow. Symptomatic treatment with retinoids (etretinate, 13-cisretinoid, etretinate again) was attempted repeatedly, but it only resulted in temporary improvement of the ichthyosiform state. Overall evaluation at the age of 6 years showed: i) persistence of the ichthyosiform and erythrodermic state; ii) growth retardation (-2 in stature); iii) spasticity of the lower limbs with difficulty in walking, and beginning of speech. Routine examinations gave normal results. Serum linoleic acid level was within normal limits. Electroencephalography displayed immaturity tracings without signs of epilepsy. Radiography of the skull was normal, and in particular there was no thickening of the sphenoid bone. Histological examination of the skin, outside or during treatment with retinoids, showed ortho- and parakeratosic hyperkeratosis, absence of granular layer, moderate hyperacanthosis, vacuolization of numerous acanthocytes in the uppermost layers and inflammatory infiltrates in the superficial dermis. All these abnormalities were confirmed by electron microscopy. Previously published series are reviewed. In most cases the patient is a quot;collodion babyquot; at birth and progressively develops ichthyosis, spasticity, psychomotor and growth retardation.(ABSTRACT TRUNCATED AT 250 WORDS)"]
[3319725,12,0,0,12,1987,"New indications and new retinoids.","Gollnick",3319725,"New indications and new retinoids.    Abstract:   In addition to well-accepted indications, etretinate has a beneficial effect in a variety of other dermatoses such as the hyperkeratotic eczema of the palms and soles, prurigo nodularis, and other nonpsoriatic, sterile, pustular eruptions. Due to its influence on dermal inflammatory processes and immunomodulation of the tissue response, etretinate is effective in cutaneous lupus erythematosus, certain bullous disorders like pemphigus herpetiformis, the persistent variant of Grovers disease, dermatitis herpetiformis, and bullous pemphigoid. Isotretinoin is reported to be effective in cutaneous sarcoidosis, disseminated granuloma annulare, systemic sclerosis and tumors of the cutaneous appendages. New synthetic retinoids have been developed. Etretin, the main metabolite of etretinate, was shown to be effective and to have a short elimination half-life of approximately equal to 50 h. Arotinoid ethyl ester and arotinoid-free carboxylic acid are effective in minimal doses 500-fold lower than etretinate. Arotinoid ethyl ester was shown not to increase serum lipids. Arotinoid ethyl sulfone is the first retinoid without bone toxicity in animal experiments. Motretinide is the ethylamide of tretinoin and is reported to be effective in the local treatment of acne. Some of the new polyaromatic retinoids appear to have sebosuppressive, antikeratinizing and/or anti--inflammatory effects via topical application."]
[3319724,5,0,0,5,1987,"Mucocutaneous and systemic toxicity of retinoids: monitoring and management.","Shalita",3319724,"Mucocutaneous and systemic toxicity of retinoids: monitoring and management.    Abstract:   Oral retinoid therapy is associated with significant mucocutaneous and systemic toxicity similar to that found in hypervitaminosis A. Beside the well-known mucocutaneous adverse effects like cheilitis, xerosis, desquamation, dryness of mucous membranes, more troublesome findings are ocular effects, hair loss or hypergranulation tissue. The most unwanted systemic side effects under both retinoids (isotretinoin and etretinate) are teratogenicity, bone toxicity and serum lipid increments. Careful patient counselling and monitoring will enable the physician to modulate these effects and reduce their impact on patient compliance."]
[3303134,11,0,0,11,1987,"Vitamin A in human nutrition.","Sklan",3303134,"Vitamin A in human nutrition.    Abstract:   Vitamin A, an unsaturated 20 carbon cyclic alcohol, has a variety of physiological functions including a role in vision, reproduction, growth and maintenance of epithelial and bone structures. The main sources of vitamin A are from preformed vitamin A in animal foods or from -carotene in green plants. Carotene is cleaved in the intestinal mucosa to retinol, which is transported in chylomicrons mainly to the liver which is the major storage site of vitamin A, where stores are mainly of retinyl palmitate. Utilization of vitamin A appears to be a highly regulated process; retinol is transported in the serum bound to a specific binding protein. There also may be some control of the level of retinol in cells possibly through membrane receptors or of excretion from the cell. Intracellular cytosolic retinol binding proteins transport retinol to the nucleus where specific receptors for retinol have been found. Intracellular binding proteins for retinoic acid and retinal, metabolites of retinol have also been found, and an interstitial protein transporting retinol is present in the eye. Vitamin A deficiency causes cessation of growth, night blindness, and renders the organism more susceptible to infection, and vitamin A supplementation has been shown to enhance immune response. Epidemiological studies have shown low vitamin A and carotene to be correlated with incidence of cancer. Excess vitamin A intake results in hypervitaminosis with severe detrimental effects. Vitamin A requirements appear to be met in most developed countries although in the populations at greatest risk, newborns and pregnant and nursing women, cases of deficiency are observed. However, in large areas of the world vitamin A deficiency is endemic, causing widespread blindness and mortality."]
[2961628,10,0,0,10,1987,"Retinoids in disorders of keratinization: their use in adults.","Happle",2961628,"Retinoids in disorders of keratinization: their use in adults.    Abstract:   Hereditary disorders of keratinization may be a considerable handicap. Oral treatment with retinoids has been shown to be effective in many of these diseases. In the group of ichthyoses, the best results can be obtained in the various types of nonbullous congenital ichthyosis (erythrodermic autosomal recessive lamellar ichthyosis, nonerythrodermic autosomal recessive lamellar ichthyosis, autosomal dominant lamellar ichthyosis). It should be borne in mind, however, that retinoid therapy alone cannot lead to a complete response of these forms of ichthyosis and that this treatment cannot replace an appropriate topical treatment. During continuous treatment with etretinate a reduction of the dosis to 0.5 mg/kg is often necessary. Etretinate treatment of bullous congenital ichthyosiform erythroderma is more difficult, and it is advisable to begin with a low dosis of 0.25-0.5 mg/kg. The epidermolytic form of palmoplantar keratoderma is in our opinion no indication for retinoid treatment which seems to result inevitably in large erosions. Good or excellent results have been seen in other forms of palmoplantar keratoderma including mal de Meleda, Papillon-Lefèvre syndrome, erythrokeratodermia variabilis, verrucous epidermal nevi, Darier disease and pityriasis rubra pilaris. In patients with Darier disease it is wise to begin with a relatively low dosage of 0.5 mg/kg and to adjust the dosage to the further course of the disease. The same is true for the ichthyosis seen in the Netherton syndrome, which may be either a diffuse hyperkeratosis or ichthyosis linearis circumflexa. In view of the fact that any inherited keratinization disorder requires long-term treatment, the risk of bone toxicity should be carefully weighed against the benefit of this therapy. The results so far obtained indicate that the effect of etretin is comparable to that of etretinate in the treatment of inherited keratinization disorders. Intermittent therapy should be tried whenever possible. A combination therapy seems reasonable in pityriasis rubra pilaris of the adult type. We have seen good results by combination with PUVA treatment. Autosomal dominant ichthyosis vulgaris and X-linked recessive ichthyosis are inappropriate to treat with oral retinoid therapy because these diseases are too mild. Papillomatous epidermal nevi should also be excluded because they do not respond to the drug. Hailey-Hailey disease may even be worsened by this treatment. According to our experience, oral retinoid therapy has no effect in monilethrix."]
[3535154,1,0,0,1,1986,"[Etretinate and the prevention of skin cancers].","Verret",3535154,"[Etretinate and the prevention of skin cancers].    Abstract:  "]
[3524212,1,0,0,1,1986,"Management of myelodysplastic syndromes.","Buzaid",3524212,"Management of myelodysplastic syndromes.    Abstract:   The treatment of myelodysplastic syndromes is reviewed, with emphasis on recently published clinical trials. Pyridoxine is rarely effective, but a trial in patients with refractory anemia with ringed sideroblasts is justifiable. Corticosteroids do not appear indicated unless in vitro data suggest response. Androgens are generally not beneficial, although danazol merits further evaluation. Both 13-cis-retinoic acid and low-dose cytosine arabinoside have considerable toxicity and yield short-lived partial responses that may not have a significant impact on survival. Combination chemotherapy may be considered in selected patients with refractory anemia with excess of blasts, refractory anemia with excess of blasts in transformation, and chronic myelomonocytic leukemia; however, in general, its toxicity outweighs potential benefit. For unusual patients under 30 years old, bone marrow transplantation should be considered as first-line therapy. Until more effective and less toxic agents are available, supportive care may still be the most appropriate therapy for many of these generally elderly patients."]
[3543954,0,0,0,0,1986,"The mechanism of chemically-induced differentiation of a mouse embryonal carcinoma cell line.","McBurney",3543954,"The mechanism of chemically-induced differentiation of a mouse embryonal carcinoma cell line.    Abstract:  "]
[3541761,1,0,0,1,1986,"[Side-effects of retinoids].","Auffret",3541761,"[Side-effects of retinoids].    Abstract:  "]
[3515516,0,0,0,0,1986,"Treatment of patients with myelodysplastic syndromes: a review.","Tricot",3515516,"Treatment of patients with myelodysplastic syndromes: a review.    Abstract:  "]
[3146293,1,0,0,1,1986,"Fibular a/hypoplasia: review and documentation of the fibular developmental field.","Lewin",3146293,"Fibular a/hypoplasia: review and documentation of the fibular developmental field.    Abstract:   Fibular aplasia and/or hypoplasia is documented as a developmental field defect and the extent of the fibular developmental field is delineated. The term fibular a/hypoplasia denotes the clinical spectrum of fibular deficiency in different patients and also implies that aplasia can be present in one limb and hypoplasia in the other. Causal heterogeneity of fibular a/hypoplasia is demonstrated, thereby defining it as a developmental field defect. Most cases of fibular a/hypoplasia are isolated, sporadic events. An autosomal dominant form of isolated fibular a/hypoplasia with ankle joint anomaly is reviewed. Fibular a/hypoplasia may be part of more complex sporadic dysostoses; sporadic syndromes, an aneuploidy syndrome; several autosomal dominant and autosomal recessive conditions. Fibular a/hypoplasia is also postulated to occur as a result of disruption or teratogenic insult; in animals, fibular development can be disturbed by radiation, busulfan, and retinoic acid. Clinical data allow evaluation of the extent of the fibular developmental field of the lower limb. This appears to include the pubic portion of the pelvis, proximal femur (distal half being apparent tibial developmental territory), patella, anterior cruciate ligament, and lateral and/or axial foot rays (but quot;neverquot; the hallux and almost never associated with polydactyly). The rare cases of fibuloulnar dimelia allow confirmation of the well known homology of mesomelic limb segments responsible for concordant ulnar and fibular (and radial and tibial) defect, if both upper and lower limbs are involved in a given condition. Because fibular a/hypoplasia is the commonest of the mesomelic paraxial hemimelias, is usually nonsyndromal, and in most cases is apparently nongenetic (ie, with negligible recurrence risk), we propose that in humans, as in several other tetrapods, the fibula is undergoing regressive evolution and hence is developmentally especially labile."]
[2999194,0,0,0,0,1985,"Myelodysplastic syndromes: pathogenesis, functional abnormalities, and clinical implications.","Jacobs",2999194,"Myelodysplastic syndromes: pathogenesis, functional abnormalities, and clinical implications.    Abstract:   The myelodysplastic syndromes represent a preleukaemic state in which a clonal abnormality of haemopoietic stem cell is characterised by a variety of phenotypic manifestations with varying degrees of ineffective haemopoiesis. This state probably develops as a sequence of events in which the earliest stages may be difficult to detect by conventional pathological techniques. The process is characterised by genetic changes leading to abnormal control of cell proliferation and differentiation. Expansion of an abnormal clone may be related to independence from normal growth factors, insensitivity to normal inhibitory factors, suppression of normal clonal growth, or changes in the immunological or nutritional condition of the host. The haematological picture is of peripheral blood cytopenias: a cellular bone marrow, and functional abnormalities of erythroid, myeloid, and megakaryocytic cells. In most cases marrow cells have an abnormal DNA content, often with disturbances of the cell cycle: an abnormal karyotype is common in premalignant clones. Growth abnormalities of erythroid or granulocyte-macrophage progenitors are common in marrow cultures, and lineage specific surface membrane markers indicate aberrations of differentiation. Progression of the disorder may occur through clonal expansion or through clonal evolution with a greater degree of malignancy. Current attempts to influence abnormal growth and differentiation have had only limited success. Clinical recognition of the syndrome depends on an acute awareness of the signs combined with the identification of clonal and functional abnormalities."]
[2419928,0,0,0,0,1985,"[Progress in the field of drug development. 18].","Délenk-Heydenreich",2419928,"[Progress in the field of drug development. 18].    Abstract:  "]
[2408489,0,0,0,0,1985,"Regulation of gap junctional conductance.","Spray",2408489,"Regulation of gap junctional conductance.    Abstract:   Gap junctional conductance is regulated by the number of channels between coupled cells (the balance between formation and loss of these channels) and by the fraction of these channels that are open (gating mechanisms). A variety of treatments are known to affect junction formation. Adenosine 3,5-cyclic monophosphate (cAMP) is involved in some cases, and protein synthesis may be required but precursor molecules can also exist. Junction removal occurs both by dispersion of particles and by internalization of junctional membrane. Factors promoting removal are not well understood. A variety of gating mechanisms exist. Coupling may be controlled by changes in conductance of nonjunctional membranes. Several kinds of voltage dependence of junctional conductance are known, but rat ventricular junctions at least are electrically linear. Cytoplasmic acidification decreases conductance of most gap junctions. Sensitivity in rat ventricular myocytes allows modulation of coupling by moderate changes near normal internal pH. Increasing intracellular Ca also decreases junctional conductance, but in the better studied cases sensitivity is much lower to Ca than H. A few data support low sensitivity to Ca in cardiac cells, but quantitative studies are lacking. Higher alcohols such as octanol block junctional conductance in a wide range of tissues including rat ventricular myocytes. An antibody to liver gap junctions blocks junctions between rat ventricular myocytes. Cross reactivity indicates at least partial homology between many gap junctions. Although differences among gap junctions are known, a general physiology is being developed, which may have considerable relevance to normal cardiac function and also to conduction disorders of that tissue."]
[3158386,7,0,0,7,1985,"Synthetic retinoids in dermatology.","Heller",3158386,"Synthetic retinoids in dermatology.    Abstract:   The potential of vitamin A, or retinol, in the treatment of a variety of skin diseases has long been recognized, but because of serious toxic effects this substance generally could not be used. The recent development and marketing of two relatively non-toxic synthetic analogues, which are known as retinoids, has made it possible to treat some of the diseases that are resistant to standard forms of therapy. Isotretinoin is very effective in cystic and conglobate acne, while etretinate is especially useful in the more severe forms of psoriasis. Good results have also been obtained in other disorders of keratinization. Vitamin A and its derivatives apparently have an antineoplastic effect as well and may come to be used in both the prevention and the treatment of epithelial cancer. In many of these diseases the retinoids act by enhancing the normal differentiation and proliferation of epidermal tissues, but the exact mechanisms are not well understood. Their influence on the intracellular polyamines that control the synthesis of nucleic acids and proteins may be an important factor. Although the retinoids have few serious systemic effects, they are teratogenic, and because they persist in the body their use in women of childbearing potential is limited."]
[2581632,0,0,0,0,1985,"Chronic myelogenous leukemia: recent advances.","Champlin",2581632,"Chronic myelogenous leukemia: recent advances.    Abstract:  "]
[3904327,0,0,0,0,1985,"The nutritional state and nutrition.","Dodge",3904327,"The nutritional state and nutrition.    Abstract:   Cystic fibrosis children tend to have a low birth weight and their mean height and weight during childhood is below that for the general population. They also tend to have a delayed bone age and puberty. The degree of underweight correlates more closely with the respiratory condition than with the degree of malabsorption. There is evidence that their nutritional requirements are increased, perhaps up to 150% of the recommended daily allowance, but in later childhood their food intake is frequently low and maybe the major reasons for their poor growth and development. Specific deficiencies of vitamins, minerals and essential fatty acids occasionally present as clinical problems. New approaches to nutrition include increasing dietary fat, which was traditionally low because of malabsorption, and this change has been made possible with the development of modern pancreatic supplements. Supplementary nutrition with elemental diets or intravenous hyperalimentation have given promising results in some studies and might be expected to improve the patients resistance to infection as well as his nutritional state. The place of oral essential fatty acid supplements is still being evaluated, but intravenous infusions of fat emulsion are not justifiable in themselves."]
[3896698,8,0,0,8,1985,"Retinoids and the control of pattern in regenerating limbs.","Maden",3896698,"Retinoids and the control of pattern in regenerating limbs.    Abstract:   It has recently been discovered that, as well as having effects on cell division and differentiation, retinoids induce dramatic changes in the development of pattern in limbs. Local application of retinoic acid to the anterior side of chick limb buds causes anteroposterior mirror-imaging such that the limb has six digits instead of three. In Rana limb buds retinoids induce changes in both the anteroposterior and proximodistal axes. In regenerating axolotl limbs their effect is primarily on the proximodistal axis. These proximodistal effects result in the regeneration of a complete limb from distal amputation levels. Concentration effects, time effects and the relative efficacy of various retinoids have been established. Cellular changes observed include a stimulation of epidermal mucopolysaccharide production, inhibition of cell division, induction of cartilage matrix breakdown and a stimulation of fibronectin production by mesodermal cells. The relevance of each of these changes to pattern effects has been determined. Initial experiments on the cellular location of radiolabelled retinoic acid are described. It thus seems that retinoids can change the determination of developing cells, and once we know the molecular basis of retinoid action then we should also know how developing cells become specified to form particular cell types."]
[3157194,4,0,0,4,1985,"Skeletal morphogenesis: comparative effects of a mutant gene and a teratogen.","Kochhar",3157194,"Skeletal morphogenesis: comparative effects of a mutant gene and a teratogen.    Abstract:   As a teratogenic agent retinoic acid (RA) produces severe limb reduction defects if administered at a certain stage of embryonic development. In vitro, RA is able to prevent chondrogenesis and this inhibitory effect is accompanied by the absence of cartilage specific proteoglycans in treated cultures. Such an effect is ruled out as a direct causative factor in teratogenesis for two reasons. First, the limbs of treated embryos show extensive chondrogenesis and this cartilage is normal as far as the expression of biochemical markers of differentiation are concerned. Second, the morphogenetic effects of a mutant gene, cmd, where there is a functional deficit of the proteoglycan core protein are very different from those associated with RA-induced teratogenesis. The differences between the two are not wholly reconciled by the fact that the effects of the mutant gene are cumulative and progressive while those of the RA insult are transitory. There are a number of developmental events which are, however, altered by RA in the mesenchymal cells of the early limb bud such as cell proliferation, cell death, and hyaluronic acid metabolism. Not only any one or more of these factors may secondarily inhibit chondrogenesis but, more importantly, may also have a number of other consequences in the developing embryo. Since a number of cell types besides mesenchymal cells respond to RA by altering their pattern of differentiation, it is conceivable that some fundamental molecular step in the process of differentiation provides a target for its action. In a recent review, Sporn and Roberts (1983) have suggested that to be compatible with the wide ranging effects of retinoids documented so far, any hypothesis put forward for its molecular mechanism of action must include a role in gene expression. No experimental work has yet directly addressed how retinoids might modify gene expression. We believe that along with teratocarcinoma stem cell lines, the use of retinoids as selective teratogens may open up another avenue in search of molecular mechanisms of cell differentiation."]
[2580708,5,0,0,5,1985,"Etretinate therapy in children with severe keratinization defects.","Traupe",2580708,"Etretinate therapy in children with severe keratinization defects.    Abstract:   Keratinization defects can be very severe and disfiguring diseases. The development of retinoids such as etretinate has provided us with an effective symptomatic form of oral therapy for these skin conditions. Based on our own experience, we briefly outline the therapeutic potential of etretinate in various keratinization defects (lamellar ichthyosis, Netherton syndrome, Sjögren-Larsson syndrome, mal de Meleda and juvenile pityriasis rubra pilaris). The toxicology of etretinate is reviewed with special regard to the treatment of children. Bone changes such as premature closure of the growth line or other unacceptable side-effects have so far not been observed. Guidelines for patient selection and for the safe treatment of children are given."]
[2412243,1,0,0,1,1985,"Effects of interferon on differentiation of normal and tumor cells.","Fisher",2412243,"Effects of interferon on differentiation of normal and tumor cells.    Abstract:   As described in this review, both partially purified and recombinant interferons are potent modulators of differentiation in diverse cell culture systems (Table 2). Depending on the target cell, interferon exerts either an inhibitory or an inductive effect on cell differentiation. In certain myeloid leukemic cells, such as HL-60, interferon by itself is growth suppressive but does not induce cell maturation, whereas in combination with inducers of differentiation, such as DMSO, TPA or retinoic acid, interferon potentiates their ability to stimulate differentiation in both sensitive and resistant cell populations (Grant et al., 1982, 1983; Tomida et al., 1982). Interferon also interacts synergistically with phorbol ester tumor promoters in inhibiting melanogenesis in murine B-16 cells (Fisher et al., 1981a, 1984a) and adipocyte formation in 3T3 cells (Cioe et al., 1980), whereas the combination is synergistic in inducing differentiation in human melanoma cells (Fisher et al., 1984b,c). In contrast, interferon and TPA display antagonistic effects on differentiation in human skeletal muscle cultures, i.e. interferon induces and TPA inhibits myogenesis (Fisher et al., 1982, 1983). Recent studies have demonstrated the presence of high affinity saturable cell membrane receptors for mouse and human interferons (Aguet, 1980; Branca and Baglioni, 1981, 1982; Mogensen et al., 1981; Branca et al., 1982; Anderson et al., 1982; Joshi et al., 1982; Faltynek et al., 1983; Yonehara et al., 1983; Langer and Pestka, in preparation). Similarly, specific membrane receptors have been identified for phorbol esters and mezerein (Driedger and Blumberg, 1980; Shoyab and Todaro, 1980; Horowitz et al., 1981; Fisher et al., 1981b). These findings suggest that the plasma membrane may be a primary target for mediating the biochemical effects induced by both interferon and phorbol esters. Although the mechanism by which interferon and phorbol esters transmit the necessary membrane signal(s) required for altering differentiation are not known, a possible component of this transmembrane signaling process may involve changes in the physical dynamics of the plasma membrane. It is therefore of interest that both interferon and TPA induce early changes in the fluidity of the plasma membrane (Fisher et al., 1979, 1981b, 1984d; Castagna et al., 1979; Kuhry et al., 1983).(ABSTRACT TRUNCATED AT 400 WORDS)"]
[6098078,0,0,0,0,1984,"A review of the aetiology and pathogenesis of hypercalcaemia.","Choo-Kang",6098078,"A review of the aetiology and pathogenesis of hypercalcaemia.    Abstract:  "]
[6237133,0,0,0,0,1984,"Porokeratosis plantaris palmaris et disseminata.","Shaw",6237133,"Porokeratosis plantaris palmaris et disseminata.    Abstract:   Porokeratosis plantaris palmaris et disseminata (PPPD) is a rare variant of porokeratosis. We report a second kinship with PPPD that typically appears first on the palms and soles and then gradually progresses to the extremities and trunk. We discuss clinical, histologic, pathogenetic, and therapeutic aspects of PPPD and review the literature concerning the histogenesis of cornoid lamella formation."]
[6397187,0,0,0,0,1984,"Whats new in paediatric dermatology.","Rasmussen",6397187,"Whats new in paediatric dermatology.    Abstract:  "]
[6235105,15,0,0,15,1984,"Isotretinoin. A review of its pharmacological properties and therapeutic efficacy in acne and other skin disorders.","Ward",6235105,"Isotretinoin. A review of its pharmacological properties and therapeutic efficacy in acne and other skin disorders.    Abstract:   Isotretinoin is a new orally active retinoic acid derivative for the treatment of severe refractory nodulocystic acne. The pharmacological profile of isotretinoin suggests that it acts primarily by reducing sebaceous gland size and sebum production, and as a result alters skin surface lipid composition. Bacterial skin microflora is reduced, probably as a result of altered sebaceous factors. Isotretinoin 1 to 2 mg/kg/day for 3 to 4 months produces 60 to 95% clearance of inflammatory lesions in patients with severe, recalcitrant nodulocystic acne, with evidence of continued healing and prolonged remissions in many patients after treatment withdrawal. Doses as low as 0.1 mg/kg/day have also proven successful in the clearance of lesions; however, with such low doses the duration of remission after discontinuation of therapy is usually shorter. Encouraging results have also been seen in small numbers of patients with rosacea, Gram-negative folliculitis, Dariers disease, ichthyosis and pityriasis rubra pilaris, the response in keratinising disorders resembling that with the related drug etretinate. While long term follow-up studies in these patients have not been reported, prolonged remission after withdrawal of isotretinoin in disorders of keratinisation is unlikely, as with other drugs used in these conditions. Isotretinoin is only partially effective in psoriasis, in contrast to etretinate which is very effective in psoriasis but ineffective in severe acne. Some encouraging results have also been reported with isotretinoin in patients with squamous and basal cell carcinomas, but isotretinoin has proven unsuccessful in non-squamous cell epithelial and non-epithelial cancer. Side effects affecting the mucocutaneous system occur in nearly all patients receiving isotretinoin, but rarely lead to drug withdrawal. Raised serum triglyceride levels are also commonly reported. The possibility of long term spinal or skeletal bone toxicity may restrict the use of isotretinoin in severe disorders of keratinisation requiring prolonged administration. Isotretinoin is strictly contraindicated in women of childbearing potential due to its severe teratogenic properties, unless an effective form of contraception is used. Thus, isotretinoin offers an effective advance on the treatment options available in a difficult therapeutic area - those patients with severe, nodulocystic acne not responding to traditional therapy."]
[6233342,5,0,0,5,1984,"Isotretinoin and pregnancy.","Stern",6233342,"Isotretinoin and pregnancy.    Abstract:   Approximately 120,000 women of childbearing age used isotretinoin in the first 16 months after its release for the treatment of cystic acne. In September, 1983, the American Academy of Dermatology requested its members to relate the outcome of pregnancies of women inadvertently exposed to isotretinoin ( Accutane ) during pregnancy to its Adverse Drug Reaction Reporting System ( ADRRS ). Of nine pregnancies reported, seven ended in spontaneous abortion or the birth of an infant with birth defects. Of thirty-five pregnancies with isotretinoin exposure reported to the ADRRS or the U.S. Food and Drug Administration, twenty-nine (83%) resulted in spontaneous abortion or infants with birth defects. The most frequently reported severe birth defects involved the central nervous system (microcephaly or hydrocephalus) and the cardiovascular system (anomalies of the great vessels). Microtia or absence of external ears were also noted in a majority of cases. These findings illustrate the usefulness of specialty-based reporting of adverse drug effects and emphasize the teratogenic risk of isotretinoin in humans. Physicians need to fully and carefully inform women of childbearing age of these risks."]
[6230219,0,0,0,0,1984,"Vitamin therapy in the absence of obvious deficiency. What is the evidence?","Ovesen",6230219,"Vitamin therapy in the absence of obvious deficiency. What is the evidence?    Abstract:   Vitamins are a group of organic compounds occurring naturally in food and are necessary for good health. Lack of a vitamin may lead to a specific deficiency syndrome, which may be primary (due to inadequate diet) or secondary (due to malabsorption or to increased metabolic need), and it is rational to use high-dose vitamin supplementation in situations where these clinical conditions exist. However, pharmacological doses of vitamins are claimed to be of value in a wide variety of conditions which have no, or only a superficial, resemblance to the classic vitamin deficiency syndromes. The enormous literature on which these claims are based consists mainly of uncontrolled clinical trials or anecdotal reports. Only a few studies have made use of the techniques of randomisation and double-blinding. Evidence from such studies reveals a beneficial therapeutic effect of vitamin E in intermittent claudication and fibrocystic breast disease and of vitamin C in pressure sores, but the use of vitamin A in acne vulgaris, vitamin E in angina pectoris, hyperlipidaemia and enhancement of athletic capacity, of vitamin C in advanced cancer, and niacin in schizophrenia has been rejected. Evidence is conflicting or inconclusive as to the use of vitamin C in the common cold, asthma and enhancement of athletic capacity, of pantothenic acid in osteoarthritis, and folic acid (folacin) in neural tube defects. Most of the vitamins have been reported to cause adverse effects when ingested in excessive doses. It is therefore worthwhile to consider the risk-benefit ratio before embarking upon the use of high-dose vitamin supplementation for disorders were proof of efficacy is lacking."]
[6385136,4,0,0,4,1984,"Vitamin A and carotene in animal nutrition.","Bondi",6385136,"Vitamin A and carotene in animal nutrition.    Abstract:   Vitamin A, an unsaturated 20 carbon cyclic alcohol, subserves a number of important physiological functions. However, the biochemical basis of these roles is not well understood. The main sources of retinol are liver, egg yolk and milk fat. Several carotenoids show vitamin A activity. The conversion of beta-carotene to retinol is affected by copper-containing dioxygenase and zinc-containing retinene reductase. The efficiency of conversion varies in different species. The latter is defined in units as the daily dose required to produce a weight gain of 3 g/week in young rats between the 4th and 8th week. Retinol is unstable on exposure to light or heat, particularly in the presence of heavy metal ions and water. Much recent work has focused on the absorption, metabolism and excretion of vitamin A. It is now recognized that plasma vitamin A levels do not reflect the nutritional status except in severe hypo- and hypervitaminosis A. Also, many dietary factors may influence vitamin A metabolism. These basic and applied aspects of vitamin A are reviewed."]
[6356909,1,0,0,1,1983,"Evaluation of pathophysiology and drug effects on rheumatoid arthritis.","Harris",6356909,"Evaluation of pathophysiology and drug effects on rheumatoid arthritis.    Abstract:   The treatment of rheumatoid arthritis has been divided into symptomatic or anti-inflammatory drug therapy, and disease-modifying or remission-inducing drug therapy. A more useful classification may be one that correlates the therapy with the component of the disease process that it affects. In general, nonsteroidal drugs do not affect cells as much as they do some of the mediators that cells produce. The effects of gold and D-penicillamine, although used later in the disease because of their toxicity, probably act early in the cascade of development of the disease by affecting the macrophages and lymphocytes. Prednisone may be effective in inhibiting synthesis by macrophages and fibroblasts of proteinases as well as arachidonic acid metabolites. Retinoids may be prototypes of drugs that selectively inhibit collagenase/proteinase production but do not affect production of normal connective tissue components."]
[6226726,3,0,0,3,1983,"Isotretinoin treatment of acne and related disorders: an update.","Shalita",6226726,"Isotretinoin treatment of acne and related disorders: an update.    Abstract:   In the one year since isotretinoin has been available in the United States for the treatment of severe, recalcitrant, nodulocystic acne, there has been extensive clinical verification of the reports of its dramatic efficacy in the treatment of this troublesome disease. Proper selection of patients, as well as treatment with adequate doses of drug for 3 to 5 months, will most often result in significant clinical improvement or total clearing. Although dosages of less than 1 mg/kg/day may produce a nearly equivalent degree of improvement with somewhat fewer or less severe side effects, the recommended daily dose remains 1 mg/kg/day because lower dosages are associated with more frequent relapses. In severe cases, the daily dosage may be increased to 2 mg/kg/day. Teratogenicity, elevation of serum triglycerides, liver function abnormalities, pancreatitis, and pseudotumor cerebri may all be associated with isotretinoin therapy and require close monitoring of the patient."]
[6364354,1,0,0,1,1983,"Adverse effects of large doses of vitamin A and retinoids.","Olson",6364354,"Adverse effects of large doses of vitamin A and retinoids.    Abstract:  "]
[6238291,5,0,0,5,1983,"Oral synthetic retinoid treatment in children.","DiGiovanna",6238291,"Oral synthetic retinoid treatment in children.    Abstract:   The synthetic retinoids are a new class of drugs which are highly effective in the treatment of a broad spectrum of dermatologic disease. In this report 15 patients with chronic disorders of keratinization and one patient with severe cystic acne were treated with oral isotretinoin. The degree of clinical response and duration of post-treatment remission varied with the different disorders. Acute side effects were predominantly limited to the skin and mucous membranes and were reversible after discontinuation of treatment in these patients. Acute retinoid toxicity and the potential for developing chronic toxicity are reviewed. In an attempt to facilitate the monitoring of dermatologic patients treated with oral synthetic retinoids, we present our current guidelines for the use of these agents."]
[6217852,0,0,0,0,1983,"Current status of the biology and treatment of acute non-lymphocytic leukemia in children (report from the ANLL strategy group of the Childrens Cancer Study Group.","Lampkin",6217852,"Current status of the biology and treatment of acute non-lymphocytic leukemia in children (report from the ANLL strategy group of the Childrens Cancer Study Group.    Abstract:   Major advances have been made in the past 10 yr in both the understanding of the biologic characteristics of acute nonlymphocytic leukemia and in the treatment of patients with this disease. Advances in the biologic characteristics include: a better understanding of the nature of leukemic cell proliferation and differentiation; a clearer description of the morphological, histochemical, and ultrastructural characteristics of leukemic cells; a recognition that a high percentage of patients may have specific cytogenetic abnormalities; and a recognition that biochemical differences exist between acute nonlymphocytic leukemia (ANLL) and acute lymphoblastic leukemia (ALL). Today, over 70% of children with ANLL can be induced into a complete remission and over 25% are remaining in a continuous remission for over 2 yr. In spite of these improved results, the best method of extending remissions is unknown. It is unlikely that better results of therapy will be achieved in the future by tailoring the treatment according to the biologic characteristics of the patient, since it appears that ANLL is a heterogeneous group of diseases."]
[6192964,15,0,0,15,1983,"Isotretinoin: new therapy for severe acne.","Perry",6192964,"Isotretinoin: new therapy for severe acne.    Abstract:   The chemistry, pharmacology, pharmacokinetics, clinical use, adverse effects, dosage and administration, and FDA-approved indications of isotretinoin, a new agent used for treating acne, are reviewed. Isotretinoin is a synthetic retinoid compound with pharmacologic actions similar to those of other retinoids. Isotretinoins effects on nodulocystic acne lesions apparently result from its reduction of the size of sebaceous glands, inhibition of sebum production, and inhibition of follicular keratinization. Isotretinoin is administered orally; peak serum drug concentrations occur approximately three hours after ingestion. The drug is widely distributed throughout body tissues and metabolized by the liver by oxidation and glucuronidation; both parent drug and metabolites are excreted in the urine and feces. Clinical trials of isotretinoin have shown the drug to be effective in treating cystic or conglobate acne that is unresponsive to therapy with oral or topical antibiotics, topical tretinoin, or topical benzoyl peroxide. Isotretinoin is unique in that acne remission continues after discontinuance of therapy. The most frequent adverse effects involve mucocutaneous tissues and include cheilitis, xerosis, xerostomia, dry nose, epistaxis, and pruritus. Other adverse effects--including some serious ones--have been found rarely in humans or animals receiving isotretinoin. The usual oral dosage of isotretinoin for patients with cystic acne is 1-2 mg/kg/day in two divided doses; administration should continue for 15-20 weeks. Isotretinoin is currently more expensive than other acne treatments. Isotretinoin is an effective agent for treating cystic acne; pending accumulation of further data, its use should be limited to patients with severe conditions that do not respond to older therapies because of isotretinoins cost and sometimes serious adverse effects."]
[6184615,0,0,0,0,1982,"Immunoregulation and natural killer cells.","Herberman",6184615,"Immunoregulation and natural killer cells.    Abstract:  "]
[7029637,0,0,0,0,1981,"[Role of polyamines in expression of the differentiated phenotype of chondrocytes in culture (authors transl)].","Takano",7029637,"[Role of polyamines in expression of the differentiated phenotype of chondrocytes in culture (authors transl)].    Abstract:  "]
[389569,0,0,1,1,1979,"Hypervitaminosis A induced teratogenesis.","Geelen",389569,"Hypervitaminosis A induced teratogenesis.    Abstract:   In the past decade, the toxicology of reproduction has become increasingly important. This branch of toxicology focuses on mutagenic and embryotoxic effects. The study of embryotoxicity requires an extensive knowledge of the interaction of drugs and embryonic tissues, normal and abnormal developmental processes, and the susceptible stages during prenatal development. Hypervitaminosis A is one of the most extensively studied teratogens. It produces defects in almost all organ systems. Therefore, this article will first of all review the vitamin A-induced malformations in several organ systems. Moreover, it will discuss their morphogenesis and the susceptible developmental stages. Thus, the first ten chapters will cover the following subjects: malformations of the nervous system, ocular malformations, malformations of the ear, craniofacial malformations, cleft palate, defects of the circulatory system, defects of the respiratory systems, defects of the digestive tract, urogenital defects, skeletal malformations, and abnormal postnatal development. Since in general little is known about the mechanisms involved in the induction of congenital defects, we think it is of great value to review the knowledge and experience that have been gathered by the experimental work with hypervitaminosis A. Therefore, the next chapters will discuss the following subjects: teratogenic effects in different species, minimum effective dose, interaction with other agents, influence of chemical form, solvent, and route of administration, pathophysiology of vitamin A embryotoxicity, and hypervitaminosis A and human pregnancy."]
[463921,0,0,0,0,1979,"Hypertrophic hepatic osteoarthropathy. Clinical, roentgenologic, biochemical, hormonal and cardiorespiratory studies, and review of the literature.","Epstein",463921,"Hypertrophic hepatic osteoarthropathy. Clinical, roentgenologic, biochemical, hormonal and cardiorespiratory studies, and review of the literature.    Abstract:   Twenty patients with biopsy proved liver disease, and roentgenologic features of hypertrophic osteoarthropathy have been studied, and the literature has been reviewed. The syndrome is a rare association of many chronic liver diseases, including primary biliary cirrhosis, bile duct carcinoma, benign bile duct stricture, chronic active hepatitis, posthepatitic cirrhosis and alcoholic cirrhosis. Patients may be asymptomatic, although bone pain, arthralgia or arthritis may be presenting symptoms. Ninety per cent of the patients are clinical jaundiced at the time of diagnosis, and 95 per cent have digital clubbing. The distal tibia and fibula are the first bones to become involved, although wrist, foot bones, femurs, hand bones and humeri may be affected in order of frequency. There is no correlation between the presence of esophageal varices or surgical portacaval shunts and the extent of the syndrome, neither is there a correlation with the degree of liver function impairment. Serum calcium and phosphate levels are normal, as is urinary hydroxyproline and estrogen excretion. There was no evidence to implicate elevated levels of growth hormone or overdosage of vitamin A. Although the majority of patients tested had mild arterial hypoxemia, increased cardiac output and evidence of right to left shunting, these were also present in disease-matched control subjects without osteoarthropathy. For screening purposes, patients with chronic liver disease and clubbing should have roentgenologic studies of the lower tibias and fibulas, to select those patients suitable for a more extensive skeletal survey."]
[104446,0,0,0,0,1978,"Biochemical functions of zinc in animals.","Chesters",104446,"Biochemical functions of zinc in animals.    Abstract:  "]
[329348,0,0,0,0,1977,"Application of the radiological sciences to advance clinical and fundamental knowledge of the animal kingdom. New Horizons for Radiologists Lecture.","James",329348,"Application of the radiological sciences to advance clinical and fundamental knowledge of the animal kingdom. New Horizons for Radiologists Lecture.    Abstract:   Many radiological techniques are useful in fundamental research. Selected clinical problems in animals as well as certain basic research projects are utilized to emphasize the potential of radiological imaging. The author describes the use of several radiological methods in studies of how birds breathe."]
[322746,0,0,0,0,1977,"Considerations on the problem of critical period during the development of limb skeleton.","Merker",322746,"Considerations on the problem of critical period during the development of limb skeleton.    Abstract:  "]
[775753,0,0,0,0,1976,"Nutrition and bone disease in the dog and cat.","Bennett",775753,"Nutrition and bone disease in the dog and cat.    Abstract:   The most commonly encountered nutritional bone disease is nutritional secondary hyperparathyroidism. This is primarily of importance in the dog but is occasionally seen in kittens, particularly of the Siamese breed, and is often associated with the feeding of owner compiled, meat-rich diets. Classic rickets is now a rare clinical entity. Hypertrophic osteodystrophy is regularly seen in the larger breeds of dog and the aetiology remains obscure. Hypervitaminosis A associated with liver-rich diets is often encountered in the cat. Hypovitaminosis A has been described but its true clinical significance is unknown."]
[1107280,0,0,0,0,1976,"Nutrition and bone development in horses.","Hintz",1107280,"Nutrition and bone development in horses.    Abstract:  "]
[798150,0,0,0,0,1976,"Significance of vitamins in cancer.","Basu",798150,"Significance of vitamins in cancer.    Abstract:   The relationship of vitamins to cancer is very complex. Three types of interactions are possible: the effect of vitamins on tumor growth, the effect of tumors on vitamin metabolism, and the effect of vitamins on chemical carcinogens and anti-tumor chemotherapeutic agents. The significance of vitamins with particular references to vitamins A,B-complex and C, in cancer has been reviewed."]
[1102220,0,0,0,0,1975,"Vitamins and minerals in pregnancy.","Pitkin",1102220,"Vitamins and minerals in pregnancy.    Abstract:  "]
[812958,0,1,0,1,1975,"[A case of Goldenhar syndrome: acute vitamin A intoxication in the mother during pregnancy].","Mounoud",812958,"[A case of Goldenhar syndrome: acute vitamin A intoxication in the mother during pregnancy].    Abstract:   The authors describe the case of a boy aged 2 1/2, who showed at birth a bilateral epibulbar dermoid, preauricular appendices on the left side and other malformations suggesting Goldenhars syndrome. The history disclosed that in the second month of pregnancy the mother had accidentally swallowed 10 ml of an oily solution of Vitamin A during a laboratory manipulation. In their discussion, the autonrs analyse the teratogenic action of Vitamin A during embryonic development and review the aetiologies found in cases of Goldenhars syndrome."]
[806181,0,0,0,0,1975,"Bone pathology in experimental malnutrition.","Stewart",806181,"Bone pathology in experimental malnutrition.    Abstract:  "]
[4612941,0,0,0,0,1974,"Roentgen signs of the spine.","Lewis",4612941,"Roentgen signs of the spine.    Abstract:  "]
[4586199,0,0,0,0,1973,"Phytate and rickets.","Lewis",4586199,"Phytate and rickets.    Abstract:  "]
[4267671,0,0,0,0,1972,"[Review of recent data on the physiopathology of articular cartilage. IV. Cartilage and arthrosis. Characteristics of arthrosic cartilage].","Peyron",4267671,"[Review of recent data on the physiopathology of articular cartilage. IV. Cartilage and arthrosis. Characteristics of arthrosic cartilage].    Abstract:  "]
[4552382,0,0,0,0,1972,"Analogies between the defects characteristic of osteogenesis imperfecta and aberrations in vitamin A metabolism. A collective review.","Bovill",4552382,"Analogies between the defects characteristic of osteogenesis imperfecta and aberrations in vitamin A metabolism. A collective review.    Abstract:  "]
[4339020,0,0,0,0,1972,"Effect of hormones on bone development.","Raisz",4339020,"Effect of hormones on bone development.    Abstract:  "]
[4261784,0,0,0,0,1972,"Drugs toxic to bone.","Au",4261784,"Drugs toxic to bone.    Abstract:  "]
[4941080,0,0,0,0,1971,"Hypervitaminosis A: a review.","Clark",4941080,"Hypervitaminosis A: a review.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I709,I709)","v":4330879},{"$f":"(LEN($J709) - LEN(SUBSTITUTE(LOWER($J709),LOWER(B$3),\"\")))/LEN(B$3)","v":0},0,0,{"$f":"SUM(B709:D709)","v":0},1971,"Effect of calcitonin on bone resorption induced by excess vitamins A and D.","Clark",4330879,"Effect of calcitonin on bone resorption induced by excess vitamins A and D.    Abstract:  "]
[4932663,0,0,0,0,1971,"[Gastrointestinal symptoms and pathophysiology of Basedows disease].","Nagata",4932663,"[Gastrointestinal symptoms and pathophysiology of Basedows disease].    Abstract:  "]
[4928238,0,0,0,0,1971,"Some oral lesions in the cat.","Prescott",4928238,"Some oral lesions in the cat.    Abstract:  "]
[4330580,0,0,0,0,1971,"Metabolic role of vitamins A and D.","Wasserman",4330580,"Metabolic role of vitamins A and D.    Abstract:  "]
[4319586,0,0,0,0,1970,"[Mucopolysaccharides of bone and cartilage tissue in normal and pathological conditions].","Kasavina",4319586,"[Mucopolysaccharides of bone and cartilage tissue in normal and pathological conditions].    Abstract:  "]
[4945766,0,0,0,0,1970,"The proteinpolysaccharides of cartilage.","Rosenberg",4945766,"The proteinpolysaccharides of cartilage.    Abstract:  "]
[4922143,0,0,0,0,1970,"Hypervitaminosis A of the cat.","Seawright",4922143,"Hypervitaminosis A of the cat.    Abstract:  "]
[4913200,0,0,0,0,1970,"[The epithelium of the mouth cavity and its keratinization].","Tolo",4913200,"[The epithelium of the mouth cavity and its keratinization].    Abstract:  "]
[4316909,0,0,0,0,1970,"Degradation processes in bone and cartilage.","Reynolds",4316909,"Degradation processes in bone and cartilage.    Abstract:  "]
[4895716,0,2,0,2,1969,"[Nutrition and diet in dental health--especially, in relation to dental caries].","Iizuka",4895716,"[Nutrition and diet in dental health--especially, in relation to dental caries].    Abstract:  "]
[4890804,0,0,0,0,1969,"Role of biological membranes in some skeletal reactions.","Fell",4890804,"Role of biological membranes in some skeletal reactions.    Abstract:  "]
[4898213,0,0,0,0,1969,"The effect of environment on skeletal tissue in culture.","Fell",4898213,"The effect of environment on skeletal tissue in culture.    Abstract:  "]
[4882346,0,0,0,0,1967,"[Physiology of vitamin A].","Raoul",4882346,"[Physiology of vitamin A].    Abstract:  "]
[4331872,0,0,0,0,1967,"Differentiation of connective tissues.","Thorp",4331872,"Differentiation of connective tissues.    Abstract:  "]
[14191790,0,0,0,0,1964,"[ACTION OF HORMONES AND VITAMINS ON GROWTH AND DIFFERENTIATION OF BONE CULTIVATED IN VITRO].","LEDOUARIN",14191790,"[ACTION OF HORMONES AND VITAMINS ON GROWTH AND DIFFERENTIATION OF BONE CULTIVATED IN VITRO].    Abstract:  "]
[14238547,0,0,0,0,1964,"[THE VITAMIN CONTROL OF CALCIUM METABOLISM].","RAOUL",14238547,"[THE VITAMIN CONTROL OF CALCIUM METABOLISM].    Abstract:  "]
[14057441,0,0,0,0,1963,"[ON THE THERAPY OF PAGETS OSTEITIS DEFORMANS].","HIRSCH",14057441,"[ON THE THERAPY OF PAGETS OSTEITIS DEFORMANS].    Abstract:  "]
[14281755,0,0,0,0,1963,"VITAMIN A, VITAMIN D, CARTILAGE, BONES, AND TEETH.","MCLEAN",14281755,"VITAMIN A, VITAMIN D, CARTILAGE, BONES, AND TEETH.    Abstract:  "]
[13354851,0,0,0,0,1956,"Infantile cortical hyperostosis; report of two cases with review of points of differential diagnosis from hypervitaminosis A.","ALLEN",13354851,"Infantile cortical hyperostosis; report of two cases with review of points of differential diagnosis from hypervitaminosis A.    Abstract:  "]
[13068115,0,0,0,0,1953,"[Nutrition and the tooth system; general review with special reference to vitamins].","KOLLATH",13068115,"[Nutrition and the tooth system; general review with special reference to vitamins].    Abstract:  "]

{"sheet":"Abstract","index":1,"n_rows":5,"n_cols":4,"rows_kept":5,"cut":false,"hidden":false,"merged":[[0,0,0,1]]}
["Abstract with highlights"]
["Article:",{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & C2,C2)","v":22595346},22595346,"Pub Yr: 2012"]
[]
["Title:","The neural crest in cardiac congenital anomalies.",null,"Fauthor: Keyte"]
["Title and Abstract:","The neural crest in cardiac congenital anomalies.    Abstract:   This review discusses the function of neural crest as they relate to cardiovascular defects. The cardiac neural crest cells are a subpopulation of cranial neural crest discovered nearly 30 years ago by ablation of premigratory neural crest. The cardiac neural crest cells are necessary for normal cardiovascular development. We begin with a description of the crest cells in normal development, including their function in remodeling the pharyngeal arch arteries, outflow tract septation, valvulogenesis, and development of the cardiac conduction system. The cells are also responsible for modulating signaling in the caudal pharynx, including the second heart field. Many of the molecular pathways that are known to influence specification, migration, patterning and final targeting of the cardiac neural crest cells are reviewed. The cardiac neural crest cells play a critical role in the pathogenesis of various human cardiocraniofacial syndromes such as DiGeorge, Velocardiofacial, CHARGE, Fetal Alcohol, Alagille, LEOPARD, and Noonan syndromes, as well as Retinoic Acid Embryopathy. The loss of neural crest cells or their dysfunction may not always directly cause abnormal cardiovascular development, but are involved secondarily because crest cells represent a major component in the complex tissue interactions in the head, pharynx and outflow tract. Thus many of the human syndromes linking defects in the heart, face and brain can be better understood when considered within the context of a single cardiocraniofacial developmental module with the neural crest being a key cell type that interconnects the regions."]

{"sheet":"Notes","index":2,"n_rows":4,"n_cols":8,"rows_kept":4,"cut":false,"hidden":false,"merged":[]}
[null,"My Notes"]
["Chemical","PMID ","DOI","Note ","Title","LinkDOI","LinkID","Link"]
[null,{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & G3,G3)","v":12955859},null,"This may be useful - basic.","Revisiting the role of retinoid signaling in skeletal development.",null,12955859]
[null,{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & G4,G4)","v":2258296},null,"This may be useful.","[Retinoid-induced changes of the bones and ligaments].",null,2258296]