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["Retinoids and male repro",null,null,null,null,null,"PubMed query used: (retinoid OR retinoic OR Vitamin A) AND (((Reproduction[mh] OR reproduction) AND male) OR Genitalia, male[mh] OR Genital Diseases, Male[mh] OR spermatogenesis) AND (review[pt] OR review[tiab])"]
[null,"Your search terms"]
["PMID","retino","sertoli","testis","Total","Pub Yr","Title","Fauthor","LinkPMID","tiab"]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I4,I4)","v":7808025},{"$f":"(LEN($J4) - LEN(SUBSTITUTE(LOWER($J4),LOWER(B$3),\"\")))/LEN(B$3)","v":14},{"$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$3)","v":3},{"$f":"SUM(B4:D4)","v":17},1994,"Retinoids in bladder, testis and prostate cancer: epidemiologic, pre-clinical and clinical observations.","Trump",7808025,"Retinoids in bladder, testis and prostate cancer: epidemiologic, pre-clinical and clinical observations.    Abstract:   Genitourinary cancers--bladders, testis and prostate--account for almost 50,000 deaths per year. Epidemiologic data suggest that individuals with low serum retinoid levels or low dietary intake of retinoid-containing foodstuffs have an increased risk of bladder and prostate cancer. Preclinical investigations show that a variety of retinoids suppress the proliferation of prostate and bladder cancer cells and induce differentiation in teratocarcinoma cells. Retinoids prevent the emergence of murine bladder and prostate cancers in carcinogen-treated animals. Clinical data are disappointing or inconclusive. A single well-conducted phase 2 trial of 13-cis retinoic acid in patients with germ cell tumors was negative. Several historically controlled as well as prospectively randomized, placebo-controlled trials of retinoids in superficial bladder cancer have failed to provide evidence of the efficacy of retinoids. Two studies of all-trans-retinoic acid in advanced prostate cancer have been negative. Despite compelling preclinical rationale, retinoids have failed to yield positive results in the clinical management of prostate, bladder or testis cancers. Further work is needed to define subsets of patients in whom retinoids might be active, and whether new retinoids or new approaches to retinoid delivery will improve the clinical usefulness of retinoids in these tumors."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I5,I5)","v":16129372},{"$f":"(LEN($J5) - LEN(SUBSTITUTE(LOWER($J5),LOWER(B$3),\"\")))/LEN(B$3)","v":15},{"$f":"(LEN($J5) - LEN(SUBSTITUTE(LOWER($J5),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J5) - LEN(SUBSTITUTE(LOWER($J5),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B5:D5)","v":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."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I6,I6)","v":2672955},{"$f":"(LEN($J6) - LEN(SUBSTITUTE(LOWER($J6),LOWER(B$3),\"\")))/LEN(B$3)","v":8},{"$f":"(LEN($J6) - LEN(SUBSTITUTE(LOWER($J6),LOWER(C$3),\"\")))/LEN(C$3)","v":2},{"$f":"(LEN($J6) - LEN(SUBSTITUTE(LOWER($J6),LOWER(D$3),\"\")))/LEN(D$3)","v":3},{"$f":"SUM(B6:D6)","v":13},1989,"Function of vitamin A in normal and synchronized seminiferous tubules.","Griswold",2672955,"Function of vitamin A in normal and synchronized seminiferous tubules.    Abstract:   Vitamin A is clearly an important factor in spermatogenesis. Some of the new data on metabolism of retinoids in the testis has contributed to our understanding of the mechanism(s) involved in the action of vitamin A. It is probable that the requirement of the testis of vitamin A deficient rats for retinol but not retinoic acid involves access of the retinoids to various testicular compartments. Retinol may be required by germinal cells because of a requirement for esterification in order to be successfully transported by the Sertoli cells. Existing evidence suggests that both the Sertoli cells and the germinal cells have specific requirements for retinoids. In the vitamin A deficient rat there appears to be a developmental block at preleptotene spermatocyte and type Al spermatogonia stages. This block is removed by retinol and germinal cell development reinitiates in a synchronous manner. The synchronous testis model offers a number of advantages for the study of molecular events associated with the cycle of the seminiferous epithelium and the development of germinal cells as well as for investigations into the mechanism of action of the retinoids."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I7,I7)","v":12141930},{"$f":"(LEN($J7) - LEN(SUBSTITUTE(LOWER($J7),LOWER(B$3),\"\")))/LEN(B$3)","v":8},{"$f":"(LEN($J7) - LEN(SUBSTITUTE(LOWER($J7),LOWER(C$3),\"\")))/LEN(C$3)","v":3},{"$f":"(LEN($J7) - LEN(SUBSTITUTE(LOWER($J7),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B7:D7)","v":12},2002,"Regulation and perturbation of testicular functions by vitamin A.","Livera",12141930,"Regulation and perturbation of testicular functions by vitamin A.    Abstract:   In addition to playing a fundamental role in very diverse processes such as vision and the growth and differentiation of numerous types of cell, vitamin A (retinol) and its principal biologically active derivative, retinoic acid, are clearly involved in the regulation of testicular functions in rodents. An excess of vitamin A leads to testicular lesions and spermatogenetic disorders, and a deficiency induces early cessation of spermatogenesis and adversely affects testosterone secretion. Furthermore, mice mutant for retinoic acid alpha receptors and retinoid X beta receptors are sterile. Retinoids appear to exert an action on the three main testicular types of cell (Sertoli, germinal and Leydig cells), as they act on the signalling pathways and Sertoli cell metabolism, and modify numerous factors secreted in Sertoli cells. Retinoids also appear to be necessary for the proliferation and differentiation of A spermatogonia, and for spermiogenesis. In addition, vitamin A deficiency leads to atrophy of the accessory sex organs after decreased testosterone production. Recent studies have shown that retinoids already affect these three types of cell in fetuses. Curiously, the effects of retinoids on fetal and adult testis seem opposed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I8,I8)","v":21198520},{"$f":"(LEN($J8) - LEN(SUBSTITUTE(LOWER($J8),LOWER(B$3),\"\")))/LEN(B$3)","v":11},{"$f":"(LEN($J8) - LEN(SUBSTITUTE(LOWER($J8),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J8) - LEN(SUBSTITUTE(LOWER($J8),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B8:D8)","v":11},2010,"Adverse effects of isotretinoin: A retrospective review of 1743 patients started on isotretinoin.","Rademaker",21198520,"Adverse effects of isotretinoin: A retrospective review of 1743 patients started on isotretinoin.    Abstract:    BACKGROUND/OBJECTIVES : Isotretinoin has revolutionized the management of acne vulgaris. However, concerns continue regarding the adverse effect profile of isotretinoin. This study aims to review the adverse effects experienced by patients started on isotretinoin by a single dermatologist.  METHODS : Retrospective chart review of 1743 patients started on isotretinoin for various dermatological conditions over a 6-year period. Details of the dose of isotretinoin used, concomitant medications, adverse effects and outcome were recorded.  RESULTS : One-fifth (18.5%) of patients reported no adverse effects during the study period. Cheilitis was the most commonly reported adverse effect, affecting 78% of users, followed by eczema and tiredness, seen in 12% each. However, these were clearly dose-dependent, as the group treated with doses of isotretinoin under 0.25 mg/kg/day only reported cheilitis in 47%, eczema in 7% and tiredness in 5%, compared with 96%, 16% and 18%, respectively, in those treated with more than 0.75 mg/gm/day. Twenty-four patients (1.4%) stopped isotretinoin because of adverse effects; a further three patients complained of severe adverse effects on at least one occasion, but continued taking the medication. The adverse effect(s) that led to patients stopping isotretinoin were cheilitis (22 patients), mood change (13), tiredness (12), eczema (6) and pregnancy (2). There were no reported instances of suicidal ideation or attempted suicide.  CONCLUSIONS : Other than the two oral contraceptive failures, there were no serious adverse events recorded during this review period. Isotretinoin is a very effective medication with a low adverse-effect profile when used at lower doses."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I9,I9)","v":16724957},{"$f":"(LEN($J9) - LEN(SUBSTITUTE(LOWER($J9),LOWER(B$3),\"\")))/LEN(B$3)","v":11},{"$f":"(LEN($J9) - LEN(SUBSTITUTE(LOWER($J9),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J9) - LEN(SUBSTITUTE(LOWER($J9),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B9:D9)","v":11},2006,"Natural and synthetic retinoids in prostate cancer.","Pasquali",16724957,"Natural and synthetic retinoids in prostate cancer.    Abstract:   Prostate cancer (PCa) is the most common cancer for men in Europe, North America, and some parts of Africa. Initially, growth of prostate cancer is usually androgen-dependent, but often it becomes androgen-independent after androgen-deprivation therapy. Managing hormone-refractory prostate carcinoma remains a difficult challenge for clinicians. Retinoids, vitamin A and its synthetic analogs are one of the most studied class of chemopreventive drugs for PCa. Retinoids play a key role in several vital functions as vision and development, and also exert anti-proliferative actions. Anti-proliferative effects of retinoids rely on the regulation of many biological processes, including differentiation, cell proliferation, and apoptosis. Retinoid actions are mediated by two classes of nuclear proteins called retinoic acid (RARalpha,beta and gamma and retinoic alpha,beta and gamma receptors, which are ligand-regulated transcription factors. Effects of both all-trans-retinoic acid (RA), the natural active derivative of vitamin A, and its synthetic derivatives, on prostate gland or prostate cell lines implicate retinoids in the regulation of prostate growth and suppression of PCa development. Deficient retinoid availability and action at the cellular level because of either decreased content or altered metabolism in PCa cells can play a key role in abnormal cellular differentiation pathways, and the loss of anti-proliferative effects. Here we review the in vitro and in vivo effects of retinoids in PCa."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I10,I10)","v":16433796},{"$f":"(LEN($J10) - LEN(SUBSTITUTE(LOWER($J10),LOWER(B$3),\"\")))/LEN(B$3)","v":10},{"$f":"(LEN($J10) - LEN(SUBSTITUTE(LOWER($J10),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J10) - LEN(SUBSTITUTE(LOWER($J10),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B10:D10)","v":10},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."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I11,I11)","v":1664678},{"$f":"(LEN($J11) - LEN(SUBSTITUTE(LOWER($J11),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J11) - LEN(SUBSTITUTE(LOWER($J11),LOWER(C$3),\"\")))/LEN(C$3)","v":5},{"$f":"(LEN($J11) - LEN(SUBSTITUTE(LOWER($J11),LOWER(D$3),\"\")))/LEN(D$3)","v":3},{"$f":"SUM(B11:D11)","v":9},1991,"Expression of receptors during the cycle of the seminiferous epithelium.","Linder",1664678,"Expression of receptors during the cycle of the seminiferous epithelium.    Abstract:   The data presented in this manuscript are all based on some inferences drawn from past experimental observations. The first is that the synchronized testis model is representative of the normal testis. Support for this premise comes from the studies on SGP-2, SGP-1 and transferrin where results using in situ hybridization and Northern blots are similar for normal and for synchronized testes. The second inference is that normalizing all of the data to the relative levels of SGP-1 mRNA adjusts for the possible differential loading of mRNA samples. The logic of this practice is based on the observation obtained using in situ hybridization that SGP-1 mRNA levels did not change across the cycle. The third assumption was that total mRNA levels do not change greatly across the cycle. Wholesale changes in testicular mRNA such as the doubling of all of the mRNA transcripts per testis would not be accounted for by these studies. We feel that this is an unlikely complication because of the strong correlation between much of the data and the known biology. In addition, there is a strong correlation between our data on the FSHR mRNA and the binding data for FSH obtained by another laboratory and different techniques. The available data in the literature reveals that most of the Sertoli cell products which change in relative concentrations during the cycle of the seminiferous epithelium appear to have a maximum in either stages VII or IX or in stages XIII to III. Thus, the Sertoli cells in the cycle could be described has having two different functional modes. In mode A maximal levels of mRNA for a specific Sertoli cell product are roughly found in stages VII-IX and in mode B the maximal levels are found in stages XIII to III (Fig. 5). The distribution of the receptor mRNA and ABP mRNA can also be described in terms of these two modes of Sertoli cell function. Transferrin receptors, retinoic acid receptors, and androgen-binding protein appear to fall into mode A while FSH and androgen receptors fall into mode B (Table 1). Products which have antithetical functions such as FSH and inhibin or cystatin and cathepsin L are found in different modes. We propose that most of the actions of the Sertoli cell during the cycle can be specified by the dual modes described above rather than by an infinite number of operational modes.(ABSTRACT TRUNCATED AT 400 WORDS)"]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I12,I12)","v":6279709},{"$f":"(LEN($J12) - LEN(SUBSTITUTE(LOWER($J12),LOWER(B$3),\"\")))/LEN(B$3)","v":9},{"$f":"(LEN($J12) - LEN(SUBSTITUTE(LOWER($J12),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J12) - LEN(SUBSTITUTE(LOWER($J12),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B12:D12)","v":9},1982,"Retinoid-binding proteins.","Goodman",6279709,"Retinoid-binding proteins.    Abstract:   Much has been learned during the past decade about the specific retinoid-binding proteins that exist in plasma and in the intracellular compartment in a number of tissues. Vitamin A is mobilized from liver stores and transported in plasma in the form of the lipid alcohol retinol, bound to a specific transport protein, retinol-binding protein (RBP). A great deal is now known about the chemical structure, metabolism, and biologic roles of RBP. A number of tissues of rats, humans, and other species contain soluble binding proteins with specificity for either retinol (cellular retinol-binding protein, CRBP) or retinoic acid (cellular retinoic acid-binding protein, CRABP). These intracellular proteins have been purified from several tissues and partly characterized. This paper provides a concise review of our current knowledge about the three retinoid-binding proteins, RBP, CRBP, and CRABP."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I13,I13)","v":25504872},{"$f":"(LEN($J13) - LEN(SUBSTITUTE(LOWER($J13),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J13) - LEN(SUBSTITUTE(LOWER($J13),LOWER(C$3),\"\")))/LEN(C$3)","v":6},{"$f":"(LEN($J13) - LEN(SUBSTITUTE(LOWER($J13),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B13:D13)","v":8},2015,"Regulation of spermatogonial stem cell self-renewal and spermatocyte meiosis by Sertoli cell signaling.","Chen",25504872,"Regulation of spermatogonial stem cell self-renewal and spermatocyte meiosis by Sertoli cell signaling.    Abstract:   Spermatogenesis is a continuous and productive process supported by the self-renewal and differentiation of spermatogonial stem cells (SSCs), which arise from undifferentiated precursors known as gonocytes and are strictly controlled in a special niche microenvironment in the seminiferous tubules. Sertoli cells, the only somatic cell type in the tubules, directly interact with SSCs to control their proliferation and differentiation through the secretion of specific factors. Spermatocyte meiosis is another key step of spermatogenesis, which is regulated by Sertoli cells on the luminal side of the blood-testis barrier through paracrine signaling. In this review, we mainly focus on the role of Sertoli cells in the regulation of SSC self-renewal and spermatocyte meiosis, with particular emphasis on paracrine and endocrine-mediated signaling pathways. Sertoli cell growth factors, such as glial cell line-derived neurotrophic factor (GDNF) and fibroblast growth factor 2 (FGF2), as well as Sertoli cell transcription factors, such as ETS variant 5 (ERM; also known as ETV5), nociceptin, neuregulin 1 (NRG1), and androgen receptor (AR), have been identified as the most important upstream factors that regulate SSC self-renewal and spermatocyte meiosis. Other transcription factors and signaling pathways (GDNF-RET-GFRA1 signaling, FGF2-MAP2K1 signaling, CXCL12-CXCR4 signaling, CCL9-CCR1 signaling, FSH-nociceptin/OPRL1, retinoic acid/FSH-NRG/ERBB4, and AR/RB-ARID4A/ARID4B) are also addressed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I14,I14)","v":23559397},{"$f":"(LEN($J14) - LEN(SUBSTITUTE(LOWER($J14),LOWER(B$3),\"\")))/LEN(B$3)","v":8},{"$f":"(LEN($J14) - LEN(SUBSTITUTE(LOWER($J14),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J14) - LEN(SUBSTITUTE(LOWER($J14),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B14:D14)","v":8},2013,"Important controversies associated with isotretinoin therapy for acne.","Wolverton",23559397,"Important controversies associated with isotretinoin therapy for acne.    Abstract:   Isotretinoin is a remarkably effective drug for severe, recalcitrant acne vulgaris. Soon after the drugs release in the early 1980s, a number of important adverse effects were reported subsequently leading to a variety of medical and medicolegal controversies. Three of these controversies will be highlighted concerning the putative role of isotretinoin in (1) depression and suicide, (2) inflammatory bowel disease, and (3) iPledge and pregnancy prevention programs. It appears that a very small subset of patients receiving isotretinoin for acne are at risk for depression, which is very manageable provided there is adequate patient awareness of the possibility, maximum communication between the patient and physician, and cessation of therapy if clinically important depression occurs (after which the depression rapidly resolves in a week or less). Multiple controlled studies actually suggest a very favorable effect of isotretinoin on depression and anxiety common in the population requiring isotretinoin. With regard to inflammatory bowel disease, in just one study, only ulcerative colitis association with isotretinoin reached statistical significance. The actual incidence of this association is strikingly low. Finally, it is clear that even the most recent pregnancy prevention program (iPledge) is no more successful than prior programs; there will likely always be a small number of female patients becoming pregnant while receiving isotretinoin for acne vulgaris."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I15,I15)","v":12558532},{"$f":"(LEN($J15) - LEN(SUBSTITUTE(LOWER($J15),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J15) - LEN(SUBSTITUTE(LOWER($J15),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J15) - LEN(SUBSTITUTE(LOWER($J15),LOWER(D$3),\"\")))/LEN(D$3)","v":6},{"$f":"SUM(B15:D15)","v":8},2003,"Development of the foetal and neonatal testis.","Rouiller-Fabre",12558532,"Development of the foetal and neonatal testis.    Abstract:   The foetal testis originates from a proliferation of the mesonephric and the coelomic epithelia which are colonized by the primordial germ cells. In the foetal testis, the development and functions of the three main cell type precursors (Leydig, Sertoli and germ cells) do not depend upon gonadotropins. Numerous intra- and extra-testicular factors are candidates for the control of its development and functions. To study the potential involvement of these factors, we developed an organotypic culture system. In absence of any growth factors or hormone, this system allows a development of the three main cell types which mimics that observed in vivo. The effects of different regulators (gonadotropin-releasing hormone, follicle-stimulating hormone, transforming growth factor-beta, insulin-like growth factor-I, anti-Mullerian hormone, retinoic acid, oestrogens) were tested in this system. Whether or not some of the effects observed in vitro have a physiological relevance was evaluated using appropriate transgenic mice. It is concluded that the foetal testis cannot be considered as an adult mini-testis since it has a specific physiology which largely differs from that of the immature or adult testis."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I16,I16)","v":17566257},{"$f":"(LEN($J16) - LEN(SUBSTITUTE(LOWER($J16),LOWER(B$3),\"\")))/LEN(B$3)","v":7},{"$f":"(LEN($J16) - LEN(SUBSTITUTE(LOWER($J16),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J16) - LEN(SUBSTITUTE(LOWER($J16),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B16:D16)","v":7},2007,"Retinoid signaling during spermatogenesis as revealed by genetic and metabolic manipulations of retinoic acid receptor alpha.","Wolgemuth",17566257,"Retinoid signaling during spermatogenesis as revealed by genetic and metabolic manipulations of retinoic acid receptor alpha.    Abstract:   The importance of dietary retinol (vitamin A) and retinoid signaling for normal development and differentiation has been recognised for many years. Vitamin A deficiency results in a variety of abnormalities, most of which can be corrected by supplementing the diet with all-trans-retinoic acid (ATRA), with the exception of blindness and male sterility. ATRA, an active metabolite of vitamin A, functions primarily by binding to nuclear receptors of the steroid hormone superfamily, the retinoic acid receptors (RARs). Gene targeting studies revealed the importance of ATRA signaling through the RARs for spermatogenesis. Mice that are homozygous for a null mutation in the gene encoding RARalpha, Rara-/-, exhibit defects in spermatogenesis and male sterility. The abnormalities in these RARalpha-deficient testes have been examined in detail in a series of recent studies from our laboratory and will be summarised in this paper. We also review how dietary, pharmacologic and genetic strategies, alone or in combination, can be used to gain further insight into retinoid function in mammalian spermatogenesis."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I17,I17)","v":8597162},{"$f":"(LEN($J17) - LEN(SUBSTITUTE(LOWER($J17),LOWER(B$3),\"\")))/LEN(B$3)","v":7},{"$f":"(LEN($J17) - LEN(SUBSTITUTE(LOWER($J17),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J17) - LEN(SUBSTITUTE(LOWER($J17),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B17:D17)","v":7},1995,"Receptors as tools for understanding the toxicity of retinoids.","Levin",8597162,"Receptors as tools for understanding the toxicity of retinoids.    Abstract:   Retinoids are derivatives of vitamin A that have numerous biologic activities including induction of epithelial differentiation, pattern formation in embryos, and maintenance of spermatogenesis. Retinoids are used to treat various dermatologic maladies and specific forms of cancer but their use is limited by toxic liabilities: most notably teratogenesis. Retinoids interact with 2 families of receptors, the retinoic acid receptors (RARs) and retinoid X receptors (RXRs). The RARs and RXRs bind and transactivate distinct response elements of numerous genes. This multiplicity of receptors and gene products provides us with multiple targets for developing novel receptor-selective agonists. We are exploiting our knowledge of ligand receptor interactions to design better, more selective drugs and to understand the toxicity of retinoids and their metabolic products."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I18,I18)","v":3015289},{"$f":"(LEN($J18) - LEN(SUBSTITUTE(LOWER($J18),LOWER(B$3),\"\")))/LEN(B$3)","v":7},{"$f":"(LEN($J18) - LEN(SUBSTITUTE(LOWER($J18),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J18) - LEN(SUBSTITUTE(LOWER($J18),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B18:D18)","v":7},1986,"[Metabolism of vitamin A and retinoids].","Jardillier",3015289,"[Metabolism of vitamin A and retinoids].    Abstract:   Dietary vitamin A is stored in the liver as ester derivatives; after hydrolysis it is transported through the organism bound to a Retinol Binding Protein-Prealbumin complex. Intracellular metabolism is complex and involves the binding to specific receptors for retinol (CRBP) and retinoic acid (CRABP) followed by a nuclear translocation. In addition, retinol can be phosphorylated and implicated in glycosylation processes. Retinoids are characterized by their action on cellular growth and differentiation. Such properties result in anticancer activities which have been clearly put in evidence in vitro and begin to be applied in human oncology. Nevertheless there is always a need for a better comprehension on fundamental mechanisms of natural or synthetic retinoids."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I19,I19)","v":26656623},{"$f":"(LEN($J19) - LEN(SUBSTITUTE(LOWER($J19),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J19) - LEN(SUBSTITUTE(LOWER($J19),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J19) - LEN(SUBSTITUTE(LOWER($J19),LOWER(D$3),\"\")))/LEN(D$3)","v":4},{"$f":"SUM(B19:D19)","v":6},2016,"Timing in the Testis.","Bittman",26656623,"Timing in the Testis.    Abstract:   The testis provides not just one but several models of temporal organization. The complexity of its rhythmic function arises in part from its compartmentalization and diversity of cell types: not only does the testis produce gametes, but it also serves as the major source of circulating androgens. Within the seminiferous tubules, the germ cells divide and differentiate while in intimate contact with Sertoli cells. The tubule is highly periodic: a spermatogenic wave travels along its length to determine the timing of the commitment of spermatogonia to differentiate, the phases of meiotic division, and the rate of differentiation of the postmeiotic germ cells. Recent evidence indicates that oscillations of retinoic acid play a major role in determining periodicity of the seminiferous epithelium. In the interstitial space, Leydig cells produce the steroid hormones required both for the completion of spermatogenesis and the development and maintenance of male sexual characteristics throughout the body. This endocrine output also oscillates; although the pulse generator lies outside the gonad, the steroidogenic function of Leydig cells is tuned to a regular episodic input. While the oscillations of the intratubular and interstitial cells have multihour (ultradian) and multiday (infradian) periodicities, respectively, the functions of both compartments also display dramatic seasonal rhythms. Furthermore, circadian rhythms are evident in some of the cell types, although their amplitude and pervasiveness are not as great as in many other tissues of the same organism, and their detection may require methods that recognize the heterogeneity of the testis. This review examines the periodicity of testicular function along multiple time scales."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I20,I20)","v":24497529},{"$f":"(LEN($J20) - LEN(SUBSTITUTE(LOWER($J20),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J20) - LEN(SUBSTITUTE(LOWER($J20),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J20) - LEN(SUBSTITUTE(LOWER($J20),LOWER(D$3),\"\")))/LEN(D$3)","v":5},{"$f":"SUM(B20:D20)","v":6},2014,"Concerns about the widespread use of rodent models for human risk assessments of endocrine disruptors.","Habert",24497529,"Concerns about the widespread use of rodent models for human risk assessments of endocrine disruptors.    Abstract:   Fetal testis is a major target of endocrine disruptors (EDs). During the last 20 years, we have developed an organotypic culture system that maintains the function of the different fetal testis cell types and have used this approach as a toxicological test to evaluate the effects of various compounds on gametogenesis and steroidogenesis in rat, mouse and human testes. We named this test rat, mouse and human fetal testis assay. With this approach, we compared the effects of six potential EDs ((mono-(2-ethylhexyl) phthalate (MEHP), cadmium, depleted uranium, diethylstilboestrol (DES), bisphenol A (BPA) and metformin) and one signalling molecule (retinoic acid (RA)) on the function of rat, mouse and human fetal testis at a comparable developmental stage. We found that the response is similar in humans and rodents for only one third of our analyses. For instance, RA and MEHP have similar negative effects on gametogenesis in the three species. For another third of our analyses, the threshold efficient concentrations that disturb gametogenesis and/or steroidogenesis differ as a function of the species. For instance, BPA and metformin have similar negative effects on steroidogenesis in human and rodents, but at different threshold doses. For the last third of our analyses, the qualitative response is species specific. For instance, MEHP and DES affect steroidogenesis in rodents, but not in human fetal testis. These species differences raise concerns about the extrapolation of data obtained in rodents to human health risk assessment and highlight the need of rigorous comparisons of the effects in human and rodent models, when assessing ED risk."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I21,I21)","v":23511242},{"$f":"(LEN($J21) - LEN(SUBSTITUTE(LOWER($J21),LOWER(B$3),\"\")))/LEN(B$3)","v":5},{"$f":"(LEN($J21) - LEN(SUBSTITUTE(LOWER($J21),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J21) - LEN(SUBSTITUTE(LOWER($J21),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B21:D21)","v":6},2013,"Retinoic acid regulation of male meiosis.","Hogarth",23511242,"Retinoic acid regulation of male meiosis.    Abstract:    PURPOSE OF REVIEW : Description of new evidence to support the model for how retinoic acid regulates spermatogonial differentiation, male meiosis and the cycle of the seminiferous epithelium.  RECENT FINDINGS : It has been known since the 1920s that vitamin A is essential for spermatogenesis. However, only recently has significant progress been made toward understanding how the active metabolite of vitamin A, retinoic acid, regulates spermatogenesis at multiple different differentiation steps, including the onset of meiosis. Current publications suggest that the initiation and maintenance of the cycle of the seminiferous epithelium is linked to retinoic-acid-driving spermatogonial differentiation and meiotic onset.  SUMMARY : Retinoic acid appears to act in a pulsatile manner, periodically driving spermatogonial differentiation and meiotic onset at discrete points along testis tubules, and as a result, is likely to be responsible for generating and maintaining the cycle of the seminiferous epithelium."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I22,I22)","v":12814997},{"$f":"(LEN($J22) - LEN(SUBSTITUTE(LOWER($J22),LOWER(B$3),\"\")))/LEN(B$3)","v":6},{"$f":"(LEN($J22) - LEN(SUBSTITUTE(LOWER($J22),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J22) - LEN(SUBSTITUTE(LOWER($J22),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B22:D22)","v":6},2003,"The association between lung and prostate cancer risk, and serum micronutrients: results and lessons learned from beta-carotene and retinol efficacy trial.","Goodman",12814997,"The association between lung and prostate cancer risk, and serum micronutrients: results and lessons learned from beta-carotene and retinol efficacy trial.    Abstract:   beta-Carotene and Retinol Efficacy Trial is a nationwide chemoprevention trial that recruited 18,314 high-risk individuals to test the effect of supplemental beta-carotene and retinol on lung cancer incidence. In this report, we conducted a prospective nested case-control study of the association between serum carotenoids, retinoids, and tocopherols on both lung and prostate cancer incidence. Prerandomization serum samples were selected from 278 lung cancer cases and 205 prostate cancer cases, and 483 controls matched by high-risk population, study center location, age, sex (lung cancer only), smoking status, and year of randomization. Carotenoids, retinoids, and tocopherols were analyzed by high-performance liquid chromatography. Endpoints were confirmed by pathology review (lung cancer) or review of the pathology report (prostate cancer). In the control-only population, there was a significant association between tobacco use and serum micronutrient concentration. Current smokers compared with former smokers had lower mean levels of all of the micronutrients tested with zeaxanthin, beta-cryptoxanthin, alpha-carotene, alpha-tocopherol, retinol, and retinyl palmitate reaching statistical significance at P = 0.05. In the overall population, the mean serum concentrations of all of the micronutrients except gamma-tocopherol were lower for lung cancer cases than controls. Statistically significant trends across quartiles were observed in lutein (P = 0.02), zeaxanthin (P = 0.02), and alpha-tocopherol (P = 0.03). The carotenoid findings in the overall population were because of the strong inverse association between serum micronutrients and lung cancer in females. Statistically significant odds ratios (ORs) comparing 4(th) to 1st quartiles in the female population were seen in lutein [OR, 0.31; confidence interval (CI), 0.13-0.75], zeaxanthin (OR, 0.31; CI, 0.12-0.77), and beta-cryptoxanthin (OR, 0.34; CI, 0.14-0.81). For prostate cancer, mean serum concentrations were lower in cases for all of the nutrients except alpha-carotene. Only for alpha-tocopherol (P(trend) = 0.04) were the findings statistically significant. There was no statistically significant association between serum carotenoids and prostate cancer. Our findings provide additional support for the association between physiological levels of dietary micronutrients and cancer incidence."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I23,I23)","v":12394261},{"$f":"(LEN($J23) - LEN(SUBSTITUTE(LOWER($J23),LOWER(B$3),\"\")))/LEN(B$3)","v":6},{"$f":"(LEN($J23) - LEN(SUBSTITUTE(LOWER($J23),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J23) - LEN(SUBSTITUTE(LOWER($J23),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B23:D23)","v":6},2002,"The prospects of retinoids in the treatment of prostate cancer.","Hammond",12394261,"The prospects of retinoids in the treatment of prostate cancer.    Abstract:   Prostate cancer is the most prevalent cancer amongst males and accounts for 13% of cancer deaths in this population in the US. Aggressive, androgen-independent, metastatic prostate cancer is incurable, and the search for new therapies has been directed towards identifying agents that block proliferation and induce differentiation and/or apoptosis of prostate cancer cells. Retinoid receptor agonists, such as all- retinoic acid, can induce apoptosis of prostate cancer cells, but clinical studies have demonstrated only mild to moderate efficacy. Retinoic acid receptor antagonists are a new class of retinoids, and pre-clinical studies have shown that they potently inhibit the growth of prostate cancer cells and induce apoptosis. Here, we review whether retinoids have a role in the fight against prostate cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I24,I24)","v":10645266},{"$f":"(LEN($J24) - LEN(SUBSTITUTE(LOWER($J24),LOWER(B$3),\"\")))/LEN(B$3)","v":6},{"$f":"(LEN($J24) - LEN(SUBSTITUTE(LOWER($J24),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J24) - LEN(SUBSTITUTE(LOWER($J24),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B24:D24)","v":6},1998,"Structure and putative function of a murine epididymal retinoic acid-binding protein (mE-RABP).","Lareyre",10645266,"Structure and putative function of a murine epididymal retinoic acid-binding protein (mE-RABP).    Abstract:   Vitamin A is required to maintain the epididymal epithelium. In this report, the characterization and putative functions of a murine epididymal retinoic acid-binding protein (mE-RABP) that is secreted into the lumen from the mid-/distal caput epididymidis are discussed. The amino acid sequence analysis of the mE-RABP preprotein shows that mE-RABP is the mouse orthologue of the rat epididymal secretory protein I (ESPI). These proteins belong to the lipocalin superfamily and bind to active retinoids but not to retinol. Therefore, we propose that mE-RABP may function as an extracellular retinoid carrier-protein involved in the paracrine regulation of epididymal function by retinoids."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I25,I25)","v":2974796},{"$f":"(LEN($J25) - LEN(SUBSTITUTE(LOWER($J25),LOWER(B$3),\"\")))/LEN(B$3)","v":6},{"$f":"(LEN($J25) - LEN(SUBSTITUTE(LOWER($J25),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J25) - LEN(SUBSTITUTE(LOWER($J25),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B25:D25)","v":6},1988,"Isotretinoin revisited.","Shalita",2974796,"Isotretinoin revisited.    Abstract:   Isotretinoin (13-cis-retinoic acid) remains the drug of choice for treatment of severe, recalcitrant nodulocystic acne that is unresponsive to conventional therapy, including oral antibiotics. The drug has been shown to produce dramatic clearing of lesions and prolonged remissions. The length of remission may be dependent on both the dosage used and the duration of therapy. Since fetal malformations have been observed in infants born of mothers taking isotretinoin during pregnancy, it is mandatory to prevent women who are pregnant or may become pregnant during treatment from taking isotretinoin. Because the half-life of isotretinoin is ten to twenty hours, and because it is eliminated from the body rapidly enough, women may become pregnant one month after discontinuation of therapy without an increased risk of birth defects. Common side effects of the drug include mucocutaneous reactions, serum lipid alterations, eye irritation, and myalgias. Less commonly observed are hyperostoses and exuberant granulation tissue, and rarely, pseudotumor cerebri. Recommendations for substantially reducing or eliminating these effects are made."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I26,I26)","v":3324684},{"$f":"(LEN($J26) - LEN(SUBSTITUTE(LOWER($J26),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J26) - LEN(SUBSTITUTE(LOWER($J26),LOWER(C$3),\"\")))/LEN(C$3)","v":4},{"$f":"(LEN($J26) - LEN(SUBSTITUTE(LOWER($J26),LOWER(D$3),\"\")))/LEN(D$3)","v":2},{"$f":"SUM(B26:D26)","v":6},1987,"Hormonal regulation of Sertoli cell function.","Sanborn",3324684,"Hormonal regulation of Sertoli cell function.    Abstract:   The Sertoli cell is clearly influenced, directly and indirectly, by hormones. Among these are FSH, T, insulin and Vitamin A, but others may also be involved. Mechanisms are still not well understood. The biochemical effects of these hormones can be divided into quantitative and qualitative influences, with the former predominating. Specific cellular and secretory proteins and metabolites are affected, in many cases by more than one hormone. Often these same functions are influenced by other factors in the environment of the testis as well. Hormonal responsiveness of the Sertoli cell is determined in part by the maturational state of the cell. Some secreted products bind to specific cell types in the testis and epididymis and may influence the process of spermatogenesis. However, detailed mechanisms are not known at the present time. Understanding Sertoli cell function at the biochemical level and its control by hormones is clearly of key importance in understanding the control of the spermatogenic process."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I27,I27)","v":6349358},{"$f":"(LEN($J27) - LEN(SUBSTITUTE(LOWER($J27),LOWER(B$3),\"\")))/LEN(B$3)","v":6},{"$f":"(LEN($J27) - LEN(SUBSTITUTE(LOWER($J27),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J27) - LEN(SUBSTITUTE(LOWER($J27),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B27:D27)","v":6},1983,"Vitamin A.","Schoeff",6349358,"Vitamin A.    Abstract:   Vitamin A refers collectively to a number of compounds, the most biologically active of which is retinol. Named after its earliest discovered function, visual excitation, retinol is also needed for growth and reproduction, and differentiation of epithelial tissue. A closely related form, retinoic acid, has selective biologic activity for normal growth and epithelial differentiation. The term retinoids has been used in recent years to include both natural and synthetic analogs of vitamin A. Carotene and carotenoids refer to vitamin A precursors (pro-vitamins) of vegetable origin. Following a brief historical account of vitamin A and description of dietary information this article focuses on the chemistry and physiology of retinoids. The biological roles of vitamin A compounds are elaborated, as well as the clinical significance of vitamin A deficiency and excess. Discussion of retinoids in therapy includes their use as anti-cancer agents and as therapeutics for dermatological disorders. Finally, a review of analytical techniques for laboratory assessment of vitamin A is presented."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I28,I28)","v":27353840},{"$f":"(LEN($J28) - LEN(SUBSTITUTE(LOWER($J28),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J28) - LEN(SUBSTITUTE(LOWER($J28),LOWER(C$3),\"\")))/LEN(C$3)","v":2},{"$f":"(LEN($J28) - LEN(SUBSTITUTE(LOWER($J28),LOWER(D$3),\"\")))/LEN(D$3)","v":2},{"$f":"SUM(B28:D28)","v":5},2016,"Regulation of the blood-testis barrier.","Stanton",27353840,"Regulation of the blood-testis barrier.    Abstract:    NlmCategory=UNASSIGNEDThe purpose of this review is to describe the endocrine and local testicular factors that contribute to the regulation of the blood-testis barrier (BTB), using information gained from in vivo and in vitro models of BTB formation during/after puberty, and from the maintenance of BTB function during adulthood. In vivo the BTB, in part comprised of tight junctions between adjacent somatic Sertoli cells, compartmentalizes meiotic spermatocytes and post-meiotic spermatids away from the vasculature, and therefore prevents autoantibody production by the immune system against these immunogenic germ cells. This adluminal compartment also features a unique biochemical milieu required for the completion of germ cell development. During the normal process of spermatogenesis, earlier germ cells continually cross into the adluminal compartment, but the regulatory mechanisms and changes in junctional proteins that allow this translocation step without causing a leak remain poorly understood. Recent data describing the roles of FSH and androgen on the regulation of Sertoli cell tight junctions and tight junction proteins will be discussed, followed by an examination of the role of paracrine factors, including members of the TGFβ superfamily (TGFβ3, activin A) and retinoid signalling, as potential mediators of junction assembly and disassembly during the translocation process."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I29,I29)","v":25225624},{"$f":"(LEN($J29) - LEN(SUBSTITUTE(LOWER($J29),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J29) - LEN(SUBSTITUTE(LOWER($J29),LOWER(C$3),\"\")))/LEN(C$3)","v":4},{"$f":"(LEN($J29) - LEN(SUBSTITUTE(LOWER($J29),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B29:D29)","v":5},2014,"Receptors and signaling pathways involved in proliferation and differentiation of Sertoli cells.","Lucas",25225624,"Receptors and signaling pathways involved in proliferation and differentiation of Sertoli cells.    Abstract:   The identification of the hormones and other factors regulating Sertoli cell survival, proliferation, and maturation in neonatal, peripubertal, and pubertal life remains one of the most critical questions in testicular biology. The regulation of Sertoli cell proliferation and differentiation is thought to be controlled by cell-cell junctions and a set of circulating and local hormones and growth factors. In this review, we will focus on receptors and intracellular signaling pathways activated by androgen, follicle-stimulating hormone, thyroid hormone, activin, retinoids, insulin, insulin-like growth factor, relaxin, and estrogen, with special emphasis on estrogen receptors. Estrogen receptors activate intracellular signaling pathways that converge on cell cycle and transcription factors and play a role in the regulation of Sertoli cell proliferation and differentiation."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I30,I30)","v":24324457},{"$f":"(LEN($J30) - LEN(SUBSTITUTE(LOWER($J30),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J30) - LEN(SUBSTITUTE(LOWER($J30),LOWER(C$3),\"\")))/LEN(C$3)","v":3},{"$f":"(LEN($J30) - LEN(SUBSTITUTE(LOWER($J30),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B30:D30)","v":5},2013,"Paracrine mechanisms involved in the control of early stages of Mammalian spermatogenesis.","Rossi",24324457,"Paracrine mechanisms involved in the control of early stages of Mammalian spermatogenesis.    Abstract:   Within the testis, Sertoli-cell is the primary target of pituitary FSH. Several growth factors have been described to be produced specifically by Sertoli cells and modulate male germ cell development through paracrine mechanisms. Some have been shown to act directly on spermatogonia such as GDNF, which acts on self-renewal of spermatogonial stem cells (SSCs) while inhibiting their differentiation; BMP4, which has both a proliferative and differentiative effect on these cells, and KIT ligand (KL), which stimulates the KIT tyrosine-kinase receptor expressed by differentiating spermatogonia (but not by SSCs). KL not only controls the proliferative cycles of KIT-positive spermatogonia, but it also stimulates the expression of genes that are specific of the early phases of meiosis, whereas the expression of typical spermatogonial markers is down-regulated. On the contrary, FGF9 acts as a meiotic inhibiting substance both in fetal gonocytes and in post-natal spermatogonia through the induction of the RNA-binding protein NANOS2. Vitamin A, which is metabolized to Retinoic Acid in Sertoli cells, controls both SSCs differentiation through KIT induction and NANOS2 inhibition, and meiotic entry of differentiating spermatogonia through STRA8 upregulation."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I31,I31)","v":22995542},{"$f":"(LEN($J31) - LEN(SUBSTITUTE(LOWER($J31),LOWER(B$3),\"\")))/LEN(B$3)","v":5},{"$f":"(LEN($J31) - LEN(SUBSTITUTE(LOWER($J31),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J31) - LEN(SUBSTITUTE(LOWER($J31),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B31:D31)","v":5},2013,"New approaches to male non-hormonal contraception.","Nya-Ngatchou",22995542,"New approaches to male non-hormonal contraception.    Abstract:   A non-hormonal male contraceptive is a contraceptive that does not involve the administration of hormones or hormone blockers. This review will focus on the use of lonidamine derivatives and inhibitors of retinoic acid biosynthesis and function as approaches to male non-hormonal contraception. Two current lonidamine derivatives, adjudin and H2-gamendazole, are in development as male contraceptives. These potent anti-spermatogenic compounds impair the integrity of the apical ectoplasmic specialization, resulting in premature spermiation and infertility. Another approach to male contraceptive development is the inhibition of retinoic acid in the testes, as retinoic acid signaling is necessary for spermatogenesis. The administration of the retinoic acid receptor antagonist BMS-189453 reversibly inhibits spermatogenesis in mice. Similarly, oral dosing of WIN 18,446, which inhibits testicular retinoic acid biosynthesis, effectively contracepts rabbits. Hopefully, one of these approaches to non-hormonal male contraception will prove to be safe and effective in future clinical trials."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I32,I32)","v":20865785},{"$f":"(LEN($J32) - LEN(SUBSTITUTE(LOWER($J32),LOWER(B$3),\"\")))/LEN(B$3)","v":5},{"$f":"(LEN($J32) - LEN(SUBSTITUTE(LOWER($J32),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J32) - LEN(SUBSTITUTE(LOWER($J32),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B32:D32)","v":5},2010,"The neurobehavioral teratology of retinoids: a 50-year history.","Adams",20865785,"The neurobehavioral teratology of retinoids: a 50-year history.    Abstract:   This review of the central nervous system (CNS) and behavioral teratology of the retinoids over the last 50 years is a commemorative retrospective organized by decade to show the prominent research focus within each period and the most salient findings. In the 1960s, research focused on the gross CNS malformations associated with exposure and the delineation of dose-response and stage-specific responses in rodent models. Relevant scientific events before and during the 1960s are also discussed to provide the zeitgeist in which the field of neurobehavioral teratology emerged in the 1970s. During this period, studies demonstrated that adverse effects on postnatal behavior could be produced in animals exposed to doses of vitamin A lower than those that were teratogenic or impacted growth. Work during the 1980s showed an overrepresentation of behavioral studies focused on the reliability of screening methods, while the marked effects of human exposure were illustrated in children born to women treated with isotretinoin during pregnancy. The human catastrophe invigorated research during the 1990s, a period when technological advances allowed more elegant examinations of the developing CNS, of biochemical, cellular, and molecular developmental events and regulatory actions, and of the effects of direct genetic manipulations. Likewise, research in the 1990s reflected a reinvigoration of research in neurobehavioral teratology evinced in studies that used animal models to try to better understand human vulnerability. These foci continued in the 2000-2010 period while examinations of the role of retinoids in brain development and lifelong functioning became increasingly sophisticated and broader in scope. This review of the work on retinoids also provides a lens on the more general ontogeny of the field of neurobehavioral teratology. Birth Defects Research (Part A), 2010. © 2010 Wiley-Liss, Inc."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I33,I33)","v":16984470},{"$f":"(LEN($J33) - LEN(SUBSTITUTE(LOWER($J33),LOWER(B$3),\"\")))/LEN(B$3)","v":5},{"$f":"(LEN($J33) - LEN(SUBSTITUTE(LOWER($J33),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J33) - LEN(SUBSTITUTE(LOWER($J33),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B33:D33)","v":5},2006,"Bovine early embryonic development and vitamin A.","Gómez",16984470,"Bovine early embryonic development and vitamin A.    Abstract:   Vitamin A and its derivatives, collectively termed as retinoids, have been paid attention in recent years because of their effects in bovine reproduction. However, the role of retinoids in the pre-implantation period continues to be largely unexplored, in contrast to later stages of development. Retinoids control cell growth, differentiation and death through binding to specific nuclear receptors by retinoic acid and other active metabolites. This paper reviews how retinoids can influence early embryonic development in cattle through their influence on the follicle, the extrafollicular oocyte and the pre-implantation embryo itself."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I34,I34)","v":15773539},{"$f":"(LEN($J34) - LEN(SUBSTITUTE(LOWER($J34),LOWER(B$3),\"\")))/LEN(B$3)","v":5},{"$f":"(LEN($J34) - LEN(SUBSTITUTE(LOWER($J34),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J34) - LEN(SUBSTITUTE(LOWER($J34),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B34:D34)","v":5},2005,"An update on the safety and efficacy of topical retinoids.","Phillips",15773539,"An update on the safety and efficacy of topical retinoids.    Abstract:   Adapalene, tazarotene, and tretinoin are topical retinoids that are approved by the US Food and Drug Administration (FDA) and have overall favorable safety profiles. These agents are effective in a variety of skin disorders. Local adverse events, seen especially during the early course of treatment, include peeling, erythema, dryness, burning, and itching. The degree of local skin intolerance varies among patients and may relate to the vehicle formulation used. These local effects can be minimized by decreasing exposure to sunlight, avoiding extreme temperatures, and using moisturizers. Use of these agents has been found to be advantageous over current systemic retinoids from a toxicologic perspective. This article reviews the safety, efficacy, and photostability of the available topical retinoids."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I35,I35)","v":15046740},{"$f":"(LEN($J35) - LEN(SUBSTITUTE(LOWER($J35),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J35) - LEN(SUBSTITUTE(LOWER($J35),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J35) - LEN(SUBSTITUTE(LOWER($J35),LOWER(D$3),\"\")))/LEN(D$3)","v":5},{"$f":"SUM(B35:D35)","v":5},2004,"Sex determination: a window of DAX1 activity.","Ludbrook",15046740,"Sex determination: a window of DAX1 activity.    Abstract:   Traditionally, DAX1 was considered an anti-testis gene because DAX1 duplications in XY individuals cause male-to-female sex reversal: dosage-sensitive sex reversal (DSS). In DSS, two active DAX1 genes on one X chromosome can abrogate testis formation. By contrast, mutations and deletions of DAX1 cause adrenal hypoplasia congenita (AHC). Although AHC patients develop testes, gonadal defects include disorganized testis cords and hypogonadotropic hypogonadism, which is not completely restored with gonadotropin or androgen therapy. Recent evidence of XY sex reversal in Dax1-deficient mice strongly supports a role for Dax1 as a pro-testis gene. Therefore, perhaps DAX1/Dax1 acts within a window of activity, outside of which testis formation does not occur. Here, we discuss the function and possible mechanisms of DAX1 action in male gonadogenesis."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I36,I36)","v":12790775},{"$f":"(LEN($J36) - LEN(SUBSTITUTE(LOWER($J36),LOWER(B$3),\"\")))/LEN(B$3)","v":5},{"$f":"(LEN($J36) - LEN(SUBSTITUTE(LOWER($J36),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J36) - LEN(SUBSTITUTE(LOWER($J36),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B36:D36)","v":5},2003,"The role of vitamin D and retinoids in controlling prostate cancer progression.","Peehl",12790775,"The role of vitamin D and retinoids in controlling prostate cancer progression.    Abstract:   Prostate cancer is a leading cause of cancer-related deaths in many countries. Premalignant lesions and invasive cancer occur more frequently in the prostate than in any organ other than the skin. Yet, the incidence of clinically detected prostate cancer is much lower than the histopathological incidence. The slow growth of prostate cancer and the low incidence of clinically manifest disease in some geographical locations or racial/ethnic groups suggest that prostate cancer can be controlled, perhaps by dietary factors. Vitamin D and retinoids have emerged as leading candidates both to prevent and to treat prostate cancer. Many of the activities of these compounds, established from epidemiological studies, research with cell culture and animal models, and clinical trials, are consistent with tumor suppressor effects. However, retinoids may have additional tumor enhancer properties that balance or negate anti-cancer activity. This perhaps explains the overall lack of protective effects of vitamin A compounds against prostate cancer found in epidemiological studies, and the minimal efficacy of retinoids in clinical trials to treat prostate cancer. While current efforts focus on developing strategies to use vitamin D compounds to control prostate cancer, the possibility exists that prostate cancer cells may become resistant to tumor suppressor effects of vitamin D. Analyses of experimental model systems show that prostate cancer cells become less sensitive to vitamin D through loss of receptors or signaling molecules that mediate vitamin Ds actions, or through changes in metabolic enzymes that synthesize or degrade vitamin D compounds. The potential promise of exploiting vitamin D to control prostate cancer is tempered by the possibility that prostate cancer, perhaps even at early stages, may develop mechanisms to escape tumor suppressor activities of vitamin D and/or retinoids."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I37,I37)","v":9181129},{"$f":"(LEN($J37) - LEN(SUBSTITUTE(LOWER($J37),LOWER(B$3),\"\")))/LEN(B$3)","v":4},{"$f":"(LEN($J37) - LEN(SUBSTITUTE(LOWER($J37),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J37) - LEN(SUBSTITUTE(LOWER($J37),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B37:D37)","v":5},1997,"[Genetic control of the development by retinoic acid].","Mark",9181129,"[Genetic control of the development by retinoic acid].    Abstract:   Two families of nuclear receptors for retinoic acid (RA) have been characterized. Members of the RAR family (types alpha, beta and gamma and their isoforms alpha 1, alpha 2, beta 1 to beta 4, and gamma 1 and gamma 2) are activated by most physiologically occurring retinoids (all-trans RA, 9-cis RA, 4oxo RA and 3,4 dihyroRA). In contrast, members of the RXR family (types alpha, beta and gamma and their isoforms) are activated by 9cis-RA only. In addition to the multiplicity of receptors, the complexity of retinoid signalling is further increased by the fact that, at least in vitro, RARs bind to their cognate response elements as heterodimers with RXRs. Moreover, RXRs can also bind, in vitro, to some DNA elements as homodimers, and are heterodimeric partners for other nuclear receptors, including TRs, VDR, PPARs and a number of orphan nuclear receptors. To evaluate the functions of the different RARs and RXRs types and isoforms, we have generated null mutant mice by targeted gene disruption in ES cells. As to the functions of RARs, we found that RAR alpha 1 and RAR gamma 2 null mutant mice are apparently normal. Mice deficient in RAR alpha or RAR gamma (i.e., all alpha or gamma isoforms disrupted) show aspects of the post-natal vitamin A deficiency (VAD) syndrome which can be cured or prevented by RA, including post-natal lethality, poor weight gain and male sterility. RAR beta 2 (and RAR beta) null mutants display a retrolenticular membrane which represents the most frequent defect of the fetal VAD syndrome. That these abnormalities were restricted to a small subset of the tissues normally expressing these receptors suggested that some degree of functional redundancy should exist in the RAR family. To test this hypothesis we then generated RAR double null mutants. RAR alpha beta, RAR alpha gamma and RAR beta gamma compound mutants exhibit all the malformations of the fetal VAD syndrome, thus demonstrating that RA is the vitamin A derivative which plays a crucial role at many different stages and in different structures during organogenesis. Interestingly, almost all the structures derived from mesenchymal neural crests cells (NCC) are affected in RAR compound mutants. As to the functions of RXRs, RXR gamma null mutants are viable, fertile and morphologically normal. In contrast, RXR alpha null fetuses display a thin ventricular wall and die in utero from cardiac failure. A myocardial hypoplasia has also been observed in some RAR compound mutants as well as in VAD fetuses. Thus, RXR alpha seems to act as an inhibitor of ventricular cardiocyte differentiation and/or as a positive regulator of their proliferation, and these functions might involve heterodimerization with RARs and activation by RA. RXR beta null mutants are viable but the males are sterile, most probably because of an abnormal lipid metabolism in the Sertoli cells. New abnormalities, absent in RXR alpha mutants, are generated in RXR alpha/RAR (alpha, beta or gamma) compound mutants. All these abnormalities are also seen in RAR double mutants as well as in VAD fetuses. In contrast, such manifestations of synergism are not observed between the RXR beta or RXR gamma and the RAR (alpha, beta or gamma) null mutations. These data strongly support the conclusion that RXR alpha/RAR heterodimers represent the main functional units of the RA signalling pathway during embryonic development. Moreover, since RXR gamma-/-/RXR beta-/-/RXR alpha +/-mutants are viable, a single allele of RXR alpha can perform most of the developmental RXR functions."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I38,I38)","v":9025880},{"$f":"(LEN($J38) - LEN(SUBSTITUTE(LOWER($J38),LOWER(B$3),\"\")))/LEN(B$3)","v":5},{"$f":"(LEN($J38) - LEN(SUBSTITUTE(LOWER($J38),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J38) - LEN(SUBSTITUTE(LOWER($J38),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B38:D38)","v":5},1996,"Retinoic acid embryopathy: case report and review of literature.","Coberly",9025880,"Retinoic acid embryopathy: case report and review of literature.    Abstract:   Isotretinoin use as a treatment for acne has increased tremendously and, with it, the problems of associated birth defects. We feel that pathologists should be familiar with isotretinoin embryopathy and its pathogenesis in order to assist in differentiating this syndrome from other genetic syndromes that involve branchial arch defects, such as DiGeorge syndrome or velocardiofacial syndrome. Although selected autopsy findings have been presented in epidemiologic reports, to our knowledge a detailed autopsy report has not been published. We therefore wish to present a complete case study of isotretinoin embryopathy that illustrates the pathologic diagnostic criteria and correlates these with the clinical findings. Although the syndromes major features are explained by the drugs effect on neural crest cells, it has been postulated that isotretinoin also affects other cells in the central nervous system. Our current case supports this theory and shows that these changes in the nervous system may present significant functional impairment, while not presenting visible anatomic changes on either imaging studies or routine histologic examinations."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I39,I39)","v":27300178},{"$f":"(LEN($J39) - LEN(SUBSTITUTE(LOWER($J39),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J39) - LEN(SUBSTITUTE(LOWER($J39),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J39) - LEN(SUBSTITUTE(LOWER($J39),LOWER(D$3),\"\")))/LEN(D$3)","v":3},{"$f":"SUM(B39:D39)","v":4},2016,"Germ Cell Commitment to Oogenic Versus Spermatogenic Pathway: The Role of Retinoic Acid.","Agrimson",27300178,"Germ Cell Commitment to Oogenic Versus Spermatogenic Pathway: The Role of Retinoic Acid.    Abstract:   The core of the decision to commit to either oogenesis or spermatogenesis lies in the timing of meiotic entry. Primordial germ cells within the fetal ovary become committed to the female pathway prior to birth and enter meiosis during embryonic development. In the fetal testis, however, the germ cells are protected from this signal before birth and instead receive this trigger postnatally. There is a growing body of evidence to indicate that RA is the meiosis-inducing factor in both sexes, with the gender-specific timing of meiotic entry controlled via degradation of this molecule only within the fetal testis. This chapter will review our current understanding of how RA controls germ cell fate in both the embryonic ovary and postnatal testis, highlighting the key studies that have led to the hypothesis that RA can drive the commitment to meiosis in both sexes and discussing the current debate over whether RA truly is the meiosis-inducing factor in the fetal ovary."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I40,I40)","v":23784827},{"$f":"(LEN($J40) - LEN(SUBSTITUTE(LOWER($J40),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J40) - LEN(SUBSTITUTE(LOWER($J40),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J40) - LEN(SUBSTITUTE(LOWER($J40),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B40:D40)","v":4},2013,"Cycling to and from a stem cell niche: the temporal and spatial odyssey of mitotic male germ cells.","Payne",23784827,"Cycling to and from a stem cell niche: the temporal and spatial odyssey of mitotic male germ cells.    Abstract:   The development of male germ cells within the prenatal and prepubertal periods in mammals combines multiple biological events that integrate cell cycle regulation, epigenetic reprogramming, and cell migration along temporally and spatially dynamic lines. Germ cells arise from their precursor primordial germ cells in the mid-gestation embryo, forming gonocytes that enter G0 phase cell cycle arrest within the fetal testis. Cyclin-dependent kinase inhibitors, activated retinoblastoma 1 protein, and increased levels of transforming growth factor beta 2 collectively influence this cell cycle arrest. Gonocyte quiescence persists until shortly after birth, whereupon the cells concomitantly re-enter the cell cycle and migrate towards a niche that establishes and maintains self-renewing spermatogonial stem cells and balances them with differentiating spermatogonia. Platelet-derived growth factor signaling is one of the mechanisms that regulates both mitotic activation and migration in neonatal gonocytes, along with mitogens, 17β-estradiol and retinoic acid, and chemoattractants C-C-motif ligand 9 and members of the ADAM, integrin, and tetraspanin families. Numerous germ cell-intrinsic proteins have been identified that ensure the retention of germ cells within the spermatogonial stem cell niche. Sertoli cells are a significant component of this niche, contributing essential growth factors and chemokines to spermatogonia. This review focuses on the dynamic events that occur to mitotic male germ cells before and during their arrival at this niche, with an emphasis on the cell cycle and directed migration."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I41,I41)","v":23675444},{"$f":"(LEN($J41) - LEN(SUBSTITUTE(LOWER($J41),LOWER(B$3),\"\")))/LEN(B$3)","v":4},{"$f":"(LEN($J41) - LEN(SUBSTITUTE(LOWER($J41),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J41) - LEN(SUBSTITUTE(LOWER($J41),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B41:D41)","v":4},2013,"The association of retinoic acid receptor beta2(RARβ2) methylation status and prostate cancer risk: a systematic review and meta-analysis.","Gao",23675444,"The association of retinoic acid receptor beta2(RARβ2) methylation status and prostate cancer risk: a systematic review and meta-analysis.    Abstract:   The retinoic acid receptor beta2(RARβ2) is a type of nuclear receptor that is activated by both all-trans retinoic acid and 9-cis retinoic acid, which has been shown to function as a tumor suppressor gene in different types of human tumors. Previous reports demonstrated that the frequency of RARβ2 methylation was significantly higher in prostate cancer patients compared with controls, but the relationship between RARβ2 promoter methylation and pathological stage or Gleason score of prostate cancer remained controversial. Therefore, a meta-analysis of published studies investigating the effects of RARβ2 methylation status in prostate cancer occurrence and association with both pathological stage and Gleason score in prostate cancer was performed in the study. A total of 12 eligible studies involving 777 cases and 404 controls were included in the pooled analyses. Under the random-effects model, the pooled OR of RARβ2 methylation in prostate cancer patients, compared to non-cancer controls, was 17.62 with 95%CI = 6.30-49.28. The pooled OR with the fixed-effects model of pathological stage in RASSF1A methylated patients, compared to unmethylated patients, was 0.67 (95%CI = 0.40-1.09) and the pooled OR of low-GS in RARβ2 methylated patients by the random-effect model, compared to high-GS RARβ2 methylated patients, was 0.54 (95%CI = 0.28-1.04). This study showed that RARβ2 might be a potential biomarker in prostate cancer prevention and diagnosis. The detection of RARβ2 methylation in urine or serum is a potential non-invasive diagnostic tool in prostate cancer. The present findings also require confirmation through adequately designed prospective studies."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I42,I42)","v":23441462},{"$f":"(LEN($J42) - LEN(SUBSTITUTE(LOWER($J42),LOWER(B$3),\"\")))/LEN(B$3)","v":4},{"$f":"(LEN($J42) - LEN(SUBSTITUTE(LOWER($J42),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J42) - LEN(SUBSTITUTE(LOWER($J42),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B42:D42)","v":4},2013,"[Signaling pathway of meiosis induced by retinoic acid during spermatogenesis].","Wang",23441462,"[Signaling pathway of meiosis induced by retinoic acid during spermatogenesis].    Abstract:   Retinoic acid (RA) is an oxidative metabolite of vitamin A (retinol, ROH) and plays an important role in the spermatogenesis (as in meiosis) of mammals. In mammalian testes, RA, in combination with its retinoic acid receptor (RAR), regulates the expressions of related target genes in various types of cells at different times. It activates meiosis by up-regulating the expressions of the genes that promote meiosis and down-regulate those that inhibit it during spermatogenesis in a specific stage. The results of researches on mammalian spermatogenesis have a great application value in reproductive biology, developmental biology, and reproductive engineering. Therefore, it is of considerable significance to study the signaling pathway of RA-induced meiosis during mammalian spermatogenesis. This article presents an introduction of the RA signal transduction system and its action mechanisms, as well as an overview on the signaling pathway of RA-activated meiosis during spermatogenesis."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I43,I43)","v":20842651},{"$f":"(LEN($J43) - LEN(SUBSTITUTE(LOWER($J43),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J43) - LEN(SUBSTITUTE(LOWER($J43),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J43) - LEN(SUBSTITUTE(LOWER($J43),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B43:D43)","v":4},2010,"The role of CYP26 enzymes in defining appropriate retinoic acid exposure during embryogenesis.","Pennimpede",20842651,"The role of CYP26 enzymes in defining appropriate retinoic acid exposure during embryogenesis.    Abstract:   Retinoic acid (RA) is a pleiotropic derivative of vitamin A, or retinol, which is responsible for all of the bioactivity associated with this vitamin. The teratogenic influences of vitamin A deficiency and excess RA in rodents were first observed more than 50 years ago. Efforts over the last 15-20 years have refined these observations by defining the molecular mechanisms that control RA availability and signaling during murine embryonic development. This review will discuss our current understanding of the role of RA in teratogenesis, with specific emphasis on the essential function of the RA catabolic CYP26 enzymes in preventing teratogenic consequences caused by uncontrolled distribution of RA. Particular focus will be paid to the RA-sensitive tissues of the caudal and cranial regions, the limb, and the testis, and how genetic mutation of factors controlling RA distribution have revealed important roles for RA during embryogenesis."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I44,I44)","v":15237207},{"$f":"(LEN($J44) - LEN(SUBSTITUTE(LOWER($J44),LOWER(B$3),\"\")))/LEN(B$3)","v":4},{"$f":"(LEN($J44) - LEN(SUBSTITUTE(LOWER($J44),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J44) - LEN(SUBSTITUTE(LOWER($J44),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B44:D44)","v":4},2004,"Role of retinoid signaling in the regulation of spermatogenesis.","Chung",15237207,"Role of retinoid signaling in the regulation of spermatogenesis.    Abstract:   While the need for vitamin A for the normal progression of male germ cell differentiation has been known for many years, the molecular mechanisms underlying this requirement are poorly understood. This review will explore the aspects of the effects on spermatogenesis of dietary deprivation of vitamin A, in particular as to how they compare to the male sterility that results from the genetic ablation of function of the retinoid receptor RARalpha. The effects of other genes involved with retinoid synthesis, transport, and degradation are also considered. The possible cellular mechanisms that may be affected by the lack of retinoid signaling are discussed, in particular, cell cycle regulation and cell-cell interaction, both of which are critical for normal spermatogenesis."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I45,I45)","v":15037365},{"$f":"(LEN($J45) - LEN(SUBSTITUTE(LOWER($J45),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J45) - LEN(SUBSTITUTE(LOWER($J45),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J45) - LEN(SUBSTITUTE(LOWER($J45),LOWER(D$3),\"\")))/LEN(D$3)","v":2},{"$f":"SUM(B45:D45)","v":4},2004,"Cell biology of Leydig cells in the testis.","Haider",15037365,"Cell biology of Leydig cells in the testis.    Abstract:   This article reviews results on differentiation, structure, and regulation of Leydig cells in the testes of rodents and men. Two different populations-fetal and adult Leydig cells-can be recognized in rodents. The cells in these two populations are different in ultrastructure, life span, capacity for androgen synthesis, and mechanisms of regulation. A brief survey on the origin, ontogenesis, characterization of precursors, ultrastructure, and functional markers of fetal and adult Leydig cells is presented, followed by an analysis of genes in Leydig cells and the role of luteinizing hormone and its receptor, steroidogenic acute regulatory protein, hydroxysteroid dehydrogenases, androgen and its receptor, anti-Müllerian hormone, estrogens, and thyroid hormones. Various growth factors modulate Leydig cell differentiation, regeneration, and steroidogenic capacity, for example, interleukin 1alpha, transforming growth factor beta, inhibin, insulin-like growth factors I and II, vascular endothelial growth factor, and relaxin-like growth factor. Retinol and retinoic acid increase basal testosterone secretion in adult Leydig cells, but decrease it in fetal Leydig cells. Resident macrophages in the interstitial tissue of the testis are important for differentiation and function of Leydig cells. Apoptosis of Leydig cells is involved in the regulation of Leydig cell number and can be induced by cytotoxins. Characteristics of aging Leydig cells in rodents seem to be species specific. 11beta-hydroxysteroid dehydrogenase protects testosterone synthesis in the Leydig cells of stressed rats. Last, the following aspects of human Leydig cells are briefly described: origin, differentiation, triphasic development, aging changes, pathological changes, and gene mutations leading to infertility."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I46,I46)","v":14713755},{"$f":"(LEN($J46) - LEN(SUBSTITUTE(LOWER($J46),LOWER(B$3),\"\")))/LEN(B$3)","v":4},{"$f":"(LEN($J46) - LEN(SUBSTITUTE(LOWER($J46),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J46) - LEN(SUBSTITUTE(LOWER($J46),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B46:D46)","v":4},2004,"Vitamin A, retinoids and carotenoids as chemopreventive agents for prostate cancer.","Kristal",14713755,"Vitamin A, retinoids and carotenoids as chemopreventive agents for prostate cancer.    Abstract:    PURPOSE : Evidence is examined for the use of vitamin A, retinoids and carotenoids as chemopreventive agents for prostate cancer.  MATERIALS AND METHODS : Studies in in vitro and animal experimental models as well as in human observational (epidemiologic) and experimental studies are reviewed.  RESULTS : There is little evidence that dietary vitamin A is associated with prostate cancer risk and, thus, it is unlikely that vitamin A or retinyl palmitate, the form most often used in dietary supplements, would be useful as chemoprevention agents. Several pharmaceutical formulations of retinoids show cancer prevention properties in animal experimental models but their high toxicity makes them unlikely candidates for cancer prevention. There is also currently no evidence that dietary carotenoids (except for lycopene and possibly other bioactive compounds found in tomato products) will be useful for prostate cancer prevention. Epidemiological and experimental studies show no association of beta-carotene with prostate cancer risk. There is inconsistent though intriguing evidence from epidemiological studies that tomato products and/or lycopene is associated with reduced prostate cancer risk. However, animal experimental studies of lycopene and prostate cancer are not strongly supportive, and the results of human experimental studies are not interpretable due to poor design.  CONCLUSIONS : There is currently no evidence that vitamin A, synthetic retinoids or carotenoids can be used as prostate cancer chemopreventive agents. Experimental studies are needed to determine whether lycopene or other compounds in tomatoes have chemopreventive properties."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I47,I47)","v":12213681},{"$f":"(LEN($J47) - LEN(SUBSTITUTE(LOWER($J47),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J47) - LEN(SUBSTITUTE(LOWER($J47),LOWER(C$3),\"\")))/LEN(C$3)","v":3},{"$f":"(LEN($J47) - LEN(SUBSTITUTE(LOWER($J47),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B47:D47)","v":4},2002,"Rapid signal transduction in Sertoli cells.","Silva",12213681,"Rapid signal transduction in Sertoli cells.    Abstract:   The importance of non-genomic signaling as a complementary route for cell regulation has recently become evident. This rapid mechanism is utilized not just by peptide hormones, but also by steroids and other lipid-related substances, resulting in amplification and fine-tuning of the signals. The Sertoli cell is the principal target for hormone action in the seminiferous tubules. The involvement of FSH, testosterone and tri-iodothyronine (T(3)) in the spermatogenetic process is widely known. This paper discusses some rapid responses to FSH, retinol, testosterone and T(3) in the control of Sertoli cell function. Studies employing various methodologies and techniques are described and several hypotheses are considered in an attempt to explain the interactions of hormones with plasma membrane receptors. Recent knowledge about these new signaling mechanisms and cross-talk between them opens new fields of research on the communication and integration of the multiple hormonal signaling systems."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I48,I48)","v":12121833},{"$f":"(LEN($J48) - LEN(SUBSTITUTE(LOWER($J48),LOWER(B$3),\"\")))/LEN(B$3)","v":4},{"$f":"(LEN($J48) - LEN(SUBSTITUTE(LOWER($J48),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J48) - LEN(SUBSTITUTE(LOWER($J48),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B48:D48)","v":4},2002,"Vitamin A and apoptosis in prostate cancer.","Zhang",12121833,"Vitamin A and apoptosis in prostate cancer.    Abstract:   Apoptosis represents an effective way to eliminate cancer cells. Unfortunately, advanced prostate tumors eventually progress to androgen-independent tumors, which are resistant to current therapeutic approaches that act by triggering apoptosis. Vitamin A and its natural and synthetic analogs (retinoids) induce apoptosis in prostate cancer cells in vitro and in animal models, mainly through induction of retinoic acid receptor-beta (RARbeta). Expression levels of RARbeta, however, are significantly reduced in hormone-independent prostate cancer cells. Recently, a new class of synthetic retinoids related to 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid (AHPN) (also called CD437) that effectively induces apoptosis of both hormone-dependent and -independent prostate cancer cells in a retinoid receptor-independent manner was identified and has drawn a lot of attention in the field. The apoptotic effect of AHPN requires expression of orphan receptor TR3 (also called nur77 or NGFI-B). Paradoxically, TR3 expression is also induced by androgen and other mitogenic agents in prostate cancer cells to confer their proliferation. The recent finding that TR3 migrates from the nucleus to mitochondria to trigger apoptosis in response to AHPN suggests that the opposing biological activities of TR3 are regulated by its subcellular localization. Thus, agents that induce translocalization of TR3 from the nucleus to mitochondria will have improved efficacy against prostate cancer. TR3, therefore, represents an unexplored molecule that may be an ideal target for developing new agents for prostate cancer therapy."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I49,I49)","v":11787685},{"$f":"(LEN($J49) - LEN(SUBSTITUTE(LOWER($J49),LOWER(B$3),\"\")))/LEN(B$3)","v":4},{"$f":"(LEN($J49) - LEN(SUBSTITUTE(LOWER($J49),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J49) - LEN(SUBSTITUTE(LOWER($J49),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B49:D49)","v":4},2001,"Development of a topical vaginal microbicide: lessons learned from human milk.","Isaacs",11787685,"Development of a topical vaginal microbicide: lessons learned from human milk.    Abstract:   Vaccines are not presently available to prevent adherence and transmission of many common pathogens at mucosal surfaces. As a result, sexually transmitted diseases were one of the most commonly reported infections in the US in 1999. New methods are needed to reduce the spread of mucosal infections. Providing nonspecific protective factors, such as lipids and retinoids found in human milk to mucosal surfaces could reduce mucosal infection caused by viruses, e.g., herpes simplex virus-1 (HSV-1) and bacteria, e.g., Pseudomonas aeruginosa. Human milk lipids enzymatically modified to produce monoglycerides were antimicrobial and inactivated enveloped viruses, as well as gram-positive and gram-negative bacteria. Enveloped viruses were inactivated in seconds following contact with antimicrobial lipids, and P. aeruginosa infectivity was reduced by 99.9% after 2 hours. Transmission of pathogens at mucosal surfaces can also be prevented using retinoids that inhibit viral replication. In a human embryonic intestinal cell line the retinoic acid (RA) derivatives all-trans-RA and 9-cis-RA (10 microg/mL) decreased the production of HSV-1 and Echo-6 viruses by 1-2 log10 over a 48-hour period. In addition, all-trans-RA inhibited HSV-1 replication in Vero cells as effectively as interferon beta, reducing viral production by 2.5log10. These studies indicate that lipids and retinoids could be part of a topical microbicide to prevent mucosal infections."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I50,I50)","v":11420125},{"$f":"(LEN($J50) - LEN(SUBSTITUTE(LOWER($J50),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J50) - LEN(SUBSTITUTE(LOWER($J50),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J50) - LEN(SUBSTITUTE(LOWER($J50),LOWER(D$3),\"\")))/LEN(D$3)","v":4},{"$f":"SUM(B50:D50)","v":4},2001,"Testis determination in mammals: more questions than answers.","Veitia",11420125,"Testis determination in mammals: more questions than answers.    Abstract:   In humans, testis development depends on a regulated genetic hierarchy initiated by the Y-linked SRY gene. Failure of testicular determination results in the condition termed 46,XY gonadal dysgenesis (GD). Several components of the testis determining pathway have recently been identified though it has been difficult to articulate a cascade with the known elements of the system. It seems, however, that early gonadal development is the result of a network of interactions instead of the outcome of a linear cascade. Accumulating evidence shows that testis formation in man is sensitive to gene dosage. Haploinsufficiency of SF1, WT1 and SOX9 is responsible for 46,XY gonadal dysgenesis. Besides, data on SRY is consistent with possible dosage anomalies in certain cases of male to female sex reversal. 46,XY GD due to monosomy of distal 9p and 10q might also be associated with an insufficient gene dosage effect. Duplications of the locus DSS can lead to a failure of testicular development and a duplication of the region containing SOX9 has been implicated in XX sex reversal. Transgenic studies in mouse have shown, however, that this mammal is less sensitive to gene dosage than man. Here, we will try to put in place the known pieces of the jigsaw puzzle that is sex determination in mammals, as far as current knowledge obtained from man and animal models allows. We are certain that from this attempt more questions than answers will arise."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I51,I51)","v":10874923},{"$f":"(LEN($J51) - LEN(SUBSTITUTE(LOWER($J51),LOWER(B$3),\"\")))/LEN(B$3)","v":4},{"$f":"(LEN($J51) - LEN(SUBSTITUTE(LOWER($J51),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J51) - LEN(SUBSTITUTE(LOWER($J51),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B51:D51)","v":4},2000,"[Acne today. Whats new?].","Auffret",10874923,"[Acne today. Whats new?].    Abstract:   WELL-CONDUCTED TREATMENT: Acne is a common condition in adolescents and requires careful management both in terms of therapeutic care and psychological support. Treatment is long and requires strict compliance. A well-conducted treatment can be expected to provide major improvement in most patients. LOCAL CARE: Local care is often sufficient for retentional or discretely inflammatory acne. A retinoid and/or a benzoyl peroxide can be associated with a local antibiotic. SEVERE FORMS: An oral antibiotic regimen for at least 3 months is proposed in association with the local treatment (retinoid, benzoyl peroxide, local antibiotic) in case of severe acne. ISOTRETINOIN: In case of unsuccessful treatment for nodular or conglobata acne, isotretinoin can be proposed in an oral preparation. This highly teratogenic drug must not be prescribed for women of reproductive age unless a well proven contraception has been instituted for more than 1 month and maintained for the entire duration of the treatment and 1 month after discontinuation. The patient must be informed of the risk in case of pregnancy and consent to regular monitoring of beta hCG less than 3 days before treatment onset, every 2 months during treatment and 5 weeks after treatment withdrawal)."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I52,I52)","v":10325500},{"$f":"(LEN($J52) - LEN(SUBSTITUTE(LOWER($J52),LOWER(B$3),\"\")))/LEN(B$3)","v":4},{"$f":"(LEN($J52) - LEN(SUBSTITUTE(LOWER($J52),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J52) - LEN(SUBSTITUTE(LOWER($J52),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B52:D52)","v":4},1999,"Retinoids in chemoprevention.","Whelan",10325500,"Retinoids in chemoprevention.    Abstract:   Over several decades, in vitro experimental studies have demonstrated that retinoids effect the process of carcinogenesis and tend towards the alteration of cells back to more normal differentiation. This hypothesis has formed the basis of several chemopreventive studies in breast cancer, cervical cancer, head and neck cancer and lung cancer. Experimental evidence exists to suggest that chemoprevention with retinoids may well have a beneficial effect in patients at high risk of acquiring prostate cancer. None of the studies, however, in any of the cancers have yet been definitive, but opportunities exist with newer retinoids that appear to be able to be given on a long-term basis with minimal toxic side effects, to explore this exciting potential treatment pathway."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I53,I53)","v":7967726},{"$f":"(LEN($J53) - LEN(SUBSTITUTE(LOWER($J53),LOWER(B$3),\"\")))/LEN(B$3)","v":4},{"$f":"(LEN($J53) - LEN(SUBSTITUTE(LOWER($J53),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J53) - LEN(SUBSTITUTE(LOWER($J53),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B53:D53)","v":4},1994,"Clinical pharmacology of all-trans retinoic acid.","Muindi",7967726,"Clinical pharmacology of all-trans retinoic acid.    Abstract:   The clinical pharmacology of all-trans retinoic acid (RA) has distinct differences from that of its widely studied stereoisomer 13-cis retinoic acid (cRA). RA is much more rapidly cleared from plasma following oral administration; their respective half-lives are lt; 1 h and 13 h. There is extensive accumulation of the 4-oxo-cRA in plasma following repeated doses of cRA, while 4-oxo-RA is only a minor metabolite in plasma following RA administration. The extent of isomerization in vivo differs for the two retinoids. In contrast to cRA, where up to a 1:3 ratio of RA to cRA is observed in patient plasma following drug administration, cRA concentrations in excess of 10 ng/ml are rarely observed in plasma of patients receiving exogenous RA. RA administration produces autoinduction of its own oxidative catabolism; this effect does not occur with cRA. These pharmacokinetic differences have been observed in leukemia and solid tumor patients. Detailed analysis of the results of the population studied suggest that both constitutive and RA-induced hypercatabolism of RA occurs. Both of these hypercatabolic states can be modulated by concurrent administration of ketoconazole, an inhibitor of cytochrome P-450 and lipoxygenase-mediated oxidations."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I54,I54)","v":1616447},{"$f":"(LEN($J54) - LEN(SUBSTITUTE(LOWER($J54),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J54) - LEN(SUBSTITUTE(LOWER($J54),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J54) - LEN(SUBSTITUTE(LOWER($J54),LOWER(D$3),\"\")))/LEN(D$3)","v":4},{"$f":"SUM(B54:D54)","v":4},1992,"Local control systems within the testis.","Verhoeven",1616447,"Local control systems within the testis.    Abstract:   A number of physiological and pathological observations cannot readily be explained unless one accepts that there exists within the testis some sort of local control system. This local network of regulatory interactions offers not only an additional level of fine regulation for individual testicular functions, but also creates an opportunity for co-ordination and integration of distinct activities such as germ cell development and androgen production. There is an overwhelming amount of data indicating that the testis produces a variety of regulatory molecules and that many of these agonists have marked effects on the function of testicular cells in vitro. Some of these molecules are identical with or are at least related to known hormonal and humoral agonists. Others are novel and require further characterization. The exact cellular origin of many of these regulatory factors remains unknown. This overview has been limited to regulatory interactions between somatic testicular cells. Particular attention has been paid to communications between the interstitial and the tubular compartment. It should be evident that the nature and the significance of these interactions is only beginning to emerge. The major difficulty remains to distinguish effects that are restricted to the specific and often artificial conditions of in vitro systems from phenomena that are relevant to testicular control in vivo. Further progress in this field will rely on the development of appropriate systems to study local interactions in vivo. Valuable attempts have been made in this direction: vitamin A induced synchronization of spermatogenesis may offer a model to study stage dependent alterations in the interstitial compartment (Morales and Griswold, 1987; Bartlett et al, 1989); destruction of Leydig cells followed by substitution with androgens might clarify the role of non-steroidal Leydig cell mediators on tubular function (Shape et al, 1988). Up to now these approaches have failed to demonstrate an important role for local regulatory interactions. It is obvious that both models are relatively crude, however, and that subtle changes may have been missed under the experimental conditions used. It should be stressed that some of the observed complexities may be inherent to local regulatory networks. In fact, such networks tend to display a certain level of redundancy. It is evident, for example, that a number of locally produced mediators can also reach the testis via the circulation. In this setting the relative contribution of circulating and locally produced factors may vary depending on developmental stages, physiological or pathological conditions. A relative redundancy may exist for distinct locally produced mediators.(ABSTRACT TRUNCATED AT 400 WORDS)"]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I55,I55)","v":3280622},{"$f":"(LEN($J55) - LEN(SUBSTITUTE(LOWER($J55),LOWER(B$3),\"\")))/LEN(B$3)","v":4},{"$f":"(LEN($J55) - LEN(SUBSTITUTE(LOWER($J55),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J55) - LEN(SUBSTITUTE(LOWER($J55),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B55:D55)","v":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."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I56,I56)","v":26559678},{"$f":"(LEN($J56) - LEN(SUBSTITUTE(LOWER($J56),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J56) - LEN(SUBSTITUTE(LOWER($J56),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J56) - LEN(SUBSTITUTE(LOWER($J56),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B56:D56)","v":3},2016,"The Role of Retinoic Acid (RA) in Spermatogonial Differentiation.","Busada",26559678,"The Role of Retinoic Acid (RA) in Spermatogonial Differentiation.    Abstract:   Retinoic acid (RA) directs the sequential, but distinct, programs of spermatogonial differentiation and meiotic differentiation that are both essential for the generation of functional spermatozoa. These processes are functionally and temporally decoupled, as they occur in distinct cell types that arise over a week apart, both in the neonatal and adult testis. However, our understanding is limited in terms of what cellular and molecular changes occur downstream of RA exposure that prepare differentiating spermatogonia for meiotic initiation. In this review, we describe the process of spermatogonial differentiation and summarize the current state of knowledge regarding RA signaling in spermatogonia."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I57,I57)","v":26537427},{"$f":"(LEN($J57) - LEN(SUBSTITUTE(LOWER($J57),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J57) - LEN(SUBSTITUTE(LOWER($J57),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J57) - LEN(SUBSTITUTE(LOWER($J57),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B57:D57)","v":3},2016,"Spermatogenesis: The Commitment to Meiosis.","Griswold",26537427,"Spermatogenesis: The Commitment to Meiosis.    Abstract:   Mammalian spermatogenesis requires a stem cell pool, a period of amplification of cell numbers, the completion of reduction division to haploid cells (meiosis), and the morphological transformation of the haploid cells into spermatozoa (spermiogenesis). The net result of these processes is the production of massive numbers of spermatozoa over the reproductive lifetime of the animal. One study that utilized homogenization-resistant spermatids as the standard determined that human daily sperm production (dsp) was at 45 million per day per testis (60). For each human that means ∼1,000 sperm are produced per second. A key to this level of gamete production is the organization and architecture of the mammalian testes that results in continuous sperm production. The seemingly complex repetitious relationship of cells termed the quot;cycle of the seminiferous epitheliumquot; is driven by the continuous commitment of undifferentiated spermatogonia to meiosis and the period of time required to form spermatozoa. This commitment termed the A to A1 transition requires the action of retinoic acid (RA) on the undifferentiated spermatogonia or prospermatogonia. In stages VII to IX of the cycle of the seminiferous epithelium, Sertoli cells and germ cells are influenced by pulses of RA. These pulses of RA move along the seminiferous tubules coincident with the spermatogenic wave, presumably undergoing constant synthesis and degradation. The RA pulse then serves as a trigger to commit undifferentiated progenitor cells to the rigidly timed pathway into meiosis and spermatid differentiation."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I58,I58)","v":21277790},{"$f":"(LEN($J58) - LEN(SUBSTITUTE(LOWER($J58),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J58) - LEN(SUBSTITUTE(LOWER($J58),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J58) - LEN(SUBSTITUTE(LOWER($J58),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B58:D58)","v":3},2011,"Inhibiting vitamin A metabolism as an approach to male contraception.","Hogarth",21277790,"Inhibiting vitamin A metabolism as an approach to male contraception.    Abstract:   Although oral contraceptives have been available to women since the 1960s, contraceptive options for men have remained limited. Spermatogenesis relies on the active metabolite of vitamin A, retinoic acid, to drive spermatogonial differentiation and to allow the production of normal numbers of sperm. Recent evidence describes how the enzymes which control vitamin A metabolism in the testis could be targeted to generate effective male contraceptives; however, the detailed mechanism(s) regarding how vitamin A regulates normal spermatogenesis are still unknown. The essential nature of vitamin A to male germ cell development and the prospects of developing the proteins responsible for the generation, transport, and storage of retinoic acid as targets for male contraceptive development are discussed in this review."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I59,I59)","v":20395427},{"$f":"(LEN($J59) - LEN(SUBSTITUTE(LOWER($J59),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J59) - LEN(SUBSTITUTE(LOWER($J59),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J59) - LEN(SUBSTITUTE(LOWER($J59),LOWER(D$3),\"\")))/LEN(D$3)","v":2},{"$f":"SUM(B59:D59)","v":3},2010,"Sex determination in mammalian germ cells: extrinsic versus intrinsic factors.","Bowles",20395427,"Sex determination in mammalian germ cells: extrinsic versus intrinsic factors.    Abstract:   Mammalian germ cells do not determine their sexual fate based on their XX or XY chromosomal constitution. Instead, sexual fate is dependent on the gonadal environment in which they develop. In a fetal testis, germ cells commit to the spermatogenic programme of development during fetal life, although they do not enter meiosis until puberty. In a fetal ovary, germ cells commit to oogenesis by entering prophase of meiosis I. Although it was believed previously that germ cells are pre-programmed to enter meiosis unless they are actively prevented from doing so, recent results indicate that meiosis is triggered by a signaling molecule, retinoic acid (RA). Meiosis is avoided in the fetal testis because a male-specifically expressed enzyme actively degrades RA during the critical time period. Additional extrinsic factors are likely to influence sexual fate of the germ cells, and in particular, we postulate that an additional male-specific fate-determining factor or factors is involved. The full complement of intrinsic factors that underlie the competence of gonadal germ cells to respond to RA and other extrinsic factors is yet to be defined."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I60,I60)","v":20369703},{"$f":"(LEN($J60) - LEN(SUBSTITUTE(LOWER($J60),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J60) - LEN(SUBSTITUTE(LOWER($J60),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J60) - LEN(SUBSTITUTE(LOWER($J60),LOWER(D$3),\"\")))/LEN(D$3)","v":2},{"$f":"SUM(B60:D60)","v":3},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."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I61,I61)","v":16706242},{"$f":"(LEN($J61) - LEN(SUBSTITUTE(LOWER($J61),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J61) - LEN(SUBSTITUTE(LOWER($J61),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J61) - LEN(SUBSTITUTE(LOWER($J61),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B61:D61)","v":3},2006,"Extramammary Pagets disease resistant to surgery and imiquimod monotherapy but responsive to imiquimod combination topical chemotherapy with 5-fluorouracil and retinoic acid: a case report.","Ye",16706242,"Extramammary Pagets disease resistant to surgery and imiquimod monotherapy but responsive to imiquimod combination topical chemotherapy with 5-fluorouracil and retinoic acid: a case report.    Abstract:   Extramammary Pagets disease (EMPD) is an uncommon skin neoplasm that usually affects the elderly population and occurs in the genital, anorectal, or axillary areas. The recommended treatment of EMPD involves surgical excision, including Mohs micrographic surgery; however, surgery is associated with a high rate of recurrence. There have been reports of successful treatment of recurrence with monochemotherapy involving topical imiquimod 5% cream. We report a case of EMPD recurrence after surgery that was resistant to imiquimod monotherapy but that completely resolved after imiquimod was combined with topical 5-fluorouracil (5-FU) and retinoic acid. To our knowledge, this is the first reported case of imiquimod combination therapy with 5-FU and retinoic acid for the treatment of recurrent EMPD."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I62,I62)","v":12813911},{"$f":"(LEN($J62) - LEN(SUBSTITUTE(LOWER($J62),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J62) - LEN(SUBSTITUTE(LOWER($J62),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J62) - LEN(SUBSTITUTE(LOWER($J62),LOWER(D$3),\"\")))/LEN(D$3)","v":3},{"$f":"SUM(B62:D62)","v":3},2003,"Battle of the sexes: new insights into genetic pathways of gonadal development.","Jameson",12813911,"Battle of the sexes: new insights into genetic pathways of gonadal development.    Abstract:   Sex determination is governed by a series of genetic switches that influence cell fate and differentiation during critical periods of gonadal development. Remarkably, the primordial fetal gonad is bipotential. Therefore, gonadal development provides an excellent opportunity to identify genes involved in differential organogenesis. The identification of the testis-determining gene, SRY (Sex-reversed on the Y), was a pivotal first step towards unraveling this genetic pathway. It is now clear that numerous other genes, in addition to SRY, are necessary for normal testis development. For example, human mutations in a variety of genes (SOX9, WT1, SF1) impair testis development. Murine models provide evidence for additional genes (Lhx9, Emx2, M33, Dmrt, Fgf9). This lecture will highlight insights gleaned from human mutations in the nuclear receptors, SF1 (Steroidogenic Factor1) (NR5A1) and DAX1 (Dosage-sensitive sex reversal, Adrenal hypoplasia congenita, X chromosome) (NR0B1). These studies reveal the exquisite sensitivity of SF1-dependent developmental pathways to gene dosage and function in humans."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I63,I63)","v":10668982},{"$f":"(LEN($J63) - LEN(SUBSTITUTE(LOWER($J63),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J63) - LEN(SUBSTITUTE(LOWER($J63),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J63) - LEN(SUBSTITUTE(LOWER($J63),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B63:D63)","v":3},1999,"Morphogenetic action of retinoids and estrogens.","van der Burg",10668982,"Morphogenetic action of retinoids and estrogens.    Abstract:   Retinoids and estrogens are small lipophilic compounds fulfilling important biological roles in vertebrate development, reproduction and homeostasis. Both types of ligands are regulators of gene transcription by binding to (nuclear) proteins acting as ligand-activatable transcription factors, members of the nuclear receptor gene superfamily. Retinoids and their multiple receptors (RARs/RXRs) are particularly well-known for their role in early development and spermatogenesis, while much less is known about the two estrogen receptors (ERalpha/beta) during development. In this article we describe some of our previous and present work in both areas of research."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I64,I64)","v":10452726},{"$f":"(LEN($J64) - LEN(SUBSTITUTE(LOWER($J64),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J64) - LEN(SUBSTITUTE(LOWER($J64),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J64) - LEN(SUBSTITUTE(LOWER($J64),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B64:D64)","v":3},1999,"Vitamin A deficiency in Bangladesh: a review and recommendations for improvement.","Ahmed",10452726,"Vitamin A deficiency in Bangladesh: a review and recommendations for improvement.    Abstract:    OBJECTIVE : This article provides a comprehensive review of the change in vitamin A status and the extent of vitamin A deficiency among different population groups in Bangladesh up to the present time. The result of experience with different strategies and interventions designed to improve vitamin A status are then reviewed, leading to a discussion of key options for action, as well as important areas for research and evaluation.  DESIGN AND SETTING : All the available data have been examined in detail, including data from nationally representative samples and nationwide surveys, as well as small studies in different population groups. Reports on the effectiveness of different intervention programmes have been used.  RESULTS : Over the past three decades a number of studies, which include national nutrition surveys, have been carried out to investigate the prevalence of vitamin A deficiency among different population groups in Bangladesh, and they have demonstrated a significant public health problem. Studies have shown that the prevalence of severe deficiency, based on the prevalence of night blindness in preschool children, decreased from 3.6% in 1982-83 to 1.78% in 1989 and 0.6% in 1996. However, there is still a high prevalence of subclinical vitamin A deficiency, based on the biochemical assessment of serum retinol levels in preschool children, estimated mainly from hospital-based groups. Night blindness and Bitots spot are also found to exist among school-age children and adolescents. Recent reports indicate that night blindness among rural mothers is as high as 1.4%. Only a limited number of studies, with small sample sizes, are available where serum retinol has been reported for school-age children, adolescents and pregnant women. Nevertheless, these studies confirm the presence of low levels of serum retinol and hence, the existence of subclinical vitamin A deficiency. Furthermore, the dietary intake of vitamin A in each population group has been found to be less than the Recommended Daily Allowance (RDA), indicating a significant risk of deficient intakes of vitamin A. To address the problem of vitamin A deficiency, the government of Bangladesh started the Nutritional Blindness Programme in 1973. The main activities of the programme include vitamin A capsule (VAC) supplementation to children of 6 months to 6 years old, nutrition education to increase the production and consumption of vitamin A rich foods, and training of primary health-care workers on the clinical diagnosis and treatment of vitamin A deficiency, VAC distribution and nutrition education. Since 1988, as a long-term strategy, Helen Keller International has been implementing community home gardening promotion projects. To date, the possibility that foods may be fortified with vitamin A, has not been explored as a possible approach in Bangladesh.  CONCLUSION : Although short- to long-term prevention and control programmes are to some extent in place, to improve the situation of vitamin A deficiency, Bangladesh needs a more appropriate mix of interventions for the entire population. More operational research and evaluation are needed if a fully effective programme to alleviate the problem of vitamin A deficiency is to be developed. Finally, to achieve the goal of virtual elimination of vitamin A deficiency will require an integrated approach which brings together appropriate actions at every level, within and across the many sectors of society."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I65,I65)","v":10338266},{"$f":"(LEN($J65) - LEN(SUBSTITUTE(LOWER($J65),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J65) - LEN(SUBSTITUTE(LOWER($J65),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J65) - LEN(SUBSTITUTE(LOWER($J65),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B65:D65)","v":3},1999,"A lifetime of healthy skin: implications for women.","Bergfeld",10338266,"A lifetime of healthy skin: implications for women.    Abstract:   During her lifetime, a woman faces the possibility of seeking dermatological assistance for a myriad of conditions, including acne, rosacea, striae, photodamage, and skin cancers. It is important for clinicians and patients to be aware of the symptoms of these conditions as well as the most beneficial approaches for prevention, diagnosis, treatment, and management. The life expectancy of women has increased and predictions for the year 2050 estimate the average age at 81 years. This will place women at greater risk for dermatological problems, especially photodamage and skin cancer. In addition, various ethnic groups may manifest these conditions differently. Although acne is most prevalent among teenaged males, most can expect clearing by age 25. Females may continue to experience acne into the adult years, sometimes beyond the age of 40. Although it is not a life-threatening disease, acne may have psychosocial and quality-of-life consequences. Treatments for acne can be topical or systemic, and include retinoids, antibiotics, benzoyl peroxide, azelaic acid, and hormonal therapy. Rosacea is more common in women (especially during menopause) than in men. It is a chronic condition that can cause complications, including telangiectasia, conjunctivitis, and blepharitis. Although there is no cure, rosacea can be managed and controlled with medication. Topical antibiotics, such as metronidazole, and systemic antibiotics, such as tetracycline, clarithromycin, and doxycycline, are used to manage rosacea. Striae, or stretch marks, occur most frequently in pregnant women, adolescents experiencing growth spurts, weight lifters, and the obese. Although not a health threat, they can be psychologically distressing. There are not many treatment options for striae, but topical tretinoin and the pulsed dye laser offer promising results. Intrinsic, or normal, aging of the skin results from the process of chronological aging. Photodamage is skin damage caused by chronic exposure to ultraviolet (UV) light. It is the leading cause of extrinsic aging, or alterations of the skin due to environmental exposure. Estimates indicate that almost half of a persons UV exposure occurs by age 18. Photoaging causes numerous histologic, physiologic, and clinical changes; it also increases the risk for skin cancer. Photodamage can be prevented through the use of sun screens, protective clothing, and avoidance of the sun during peak intensity time. The only product approved by the FDA for the treatment of photodamage (fine wrinkles, mottled hyperpigmentation, and skin roughness), topical tretinoin emollient cream, may help prevent additional photoaging when it is used to treat existing photoaging. Other management options for photodamaged skin include alpha-hydroxy acids, antioxidants, antiandrogens, moisturizers, and exfoliants. In patients with excessive manifestations of photodamage, surgical management may be needed, including dermabrasion, chemical peels, soft tissue augmentation, laser resurfacing, botulism toxin, and Gortex threads. Clinicians must educate their patients about the most appropriate skin care regimen as well as approaches for preventing and treating common afflictions. In this way, women will have the best opportunity for having and maintaining healthy skin."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I66,I66)","v":9842220},{"$f":"(LEN($J66) - LEN(SUBSTITUTE(LOWER($J66),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J66) - LEN(SUBSTITUTE(LOWER($J66),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J66) - LEN(SUBSTITUTE(LOWER($J66),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B66:D66)","v":3},1998,"New aspects on prostate cancer: hereditary form, developmental estrogenization and differentiation therapy.","Sciarra",9842220,"New aspects on prostate cancer: hereditary form, developmental estrogenization and differentiation therapy.    Abstract:   Three new different aspects of prostate cancer have been considered in this review: the existence of an hereditary form, the role of estrogens as predisposing factors and the efficacy of differentiation therapies. Prostate cancer shows a stronger familial aggregation than colon and breast carcinoma. Hereditary prostate cancer is distinguished by early age at onset and autosomal dominant inheritance within families. However, only 2% of all prostate cancer in United States white men occur in those 55 years old or younger. Thus, the impact of hereditary prostate cancer in the population is the greatest at younger ages but this accounts for only a small proportion of the total disease burden. Using the developmentally estrogenized mouse model, an alternative role for estrogens as a predisposing factor for prostate diseases was proposed: estrogen exposure during development may initiate cellular changes in the prostate which would require estrogens and/or androgens later in life for promotion to neoplasia. A combination therapy employing both differentiation therapy and hormone therapy may be effective in the treatment of advanced prostate cancers. Recent advances in the field of differentiation therapy have resulted in the development of novel retinoic acid metabolism blocking agents. Unlike previous differentiating agents such as the retinoids, these agents increase the endogenous levels of retinoic acid by inhibiting its breakdown in cancer cells."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I67,I67)","v":8603034},{"$f":"(LEN($J67) - LEN(SUBSTITUTE(LOWER($J67),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J67) - LEN(SUBSTITUTE(LOWER($J67),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J67) - LEN(SUBSTITUTE(LOWER($J67),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B67:D67)","v":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."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I68,I68)","v":8454548},{"$f":"(LEN($J68) - LEN(SUBSTITUTE(LOWER($J68),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J68) - LEN(SUBSTITUTE(LOWER($J68),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J68) - LEN(SUBSTITUTE(LOWER($J68),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B68:D68)","v":3},1993,"Effects of supplemental beta-carotene and vitamin A on reproduction in swine.","Chew",8454548,"Effects of supplemental beta-carotene and vitamin A on reproduction in swine.    Abstract:   Since its discovery some 80 yr ago, many advances have been made in understanding the many diverse roles of vitamin A (retinoids). Among these are the critical roles that vitamin A plays in regulating reproduction in both the male and female. The identification of retinol-binding proteins produced by the pig uterus and conceptus marks an exciting event. It will be pivotal to future efforts in elucidating the mechanism by which retinoids regulate conceptus development and steroidogenesis. However, relatively little is known of the possible direct role played by its provitamin, beta-carotene, in controlling reproduction in the pig. However, future research likely will address this aspect of carotenoid function."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I69,I69)","v":3547226},{"$f":"(LEN($J69) - LEN(SUBSTITUTE(LOWER($J69),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J69) - LEN(SUBSTITUTE(LOWER($J69),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J69) - LEN(SUBSTITUTE(LOWER($J69),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B69:D69)","v":3},1986,"[Mechanism of action of vitamin A on cell differentiation and function].","Pozniakov",3547226,"[Mechanism of action of vitamin A on cell differentiation and function].    Abstract:   The vitamin A effects on cell proliferation, differentiation and functioning might be due to its influence on genome expression at the level of regulation of the transcription of certain genes, posttranscriptional modification of mRNA levels, or changes in the membrane structural-functional organization. Vitamin A can affect the biosynthesis of various proteins, including those involved in regulation of development and cell functioning or determining cell sensitivity to hormones and hormone-like factors. Vitamin A can also influence the formation of secretory proteins which play the role of hormones. It is proposed to use the differential sensitivity of various cells in cell populations to vitamin A or its forms for studying intercellular relations. In particular, the capacity of retinol and retinoic acid to maintain the development and functioning of various vitamin A-dependent cells of the testis can be used for studying local regulation of spermatogenesis in mammals."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I70,I70)","v":6385136},{"$f":"(LEN($J70) - LEN(SUBSTITUTE(LOWER($J70),LOWER(B$3),\"\")))/LEN(B$3)","v":3},{"$f":"(LEN($J70) - LEN(SUBSTITUTE(LOWER($J70),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J70) - LEN(SUBSTITUTE(LOWER($J70),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B70:D70)","v":3},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."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I71,I71)","v":26469117},{"$f":"(LEN($J71) - LEN(SUBSTITUTE(LOWER($J71),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J71) - LEN(SUBSTITUTE(LOWER($J71),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J71) - LEN(SUBSTITUTE(LOWER($J71),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B71:D71)","v":2},2015,"Brdt Bromodomains Inhibitors and Other Modern Means of Male Contraception.","Zdrojewicz",26469117,"Brdt Bromodomains Inhibitors and Other Modern Means of Male Contraception.    Abstract:   Compared to efficient and secure female contraception, a vasectomy and condoms are the only options for men. The choice of male contraceptive methods is limited, so contraception mainly rests on the shoulders of women. Several concepts are considered: testosterone administration--inhibiting pituitary secretion of lutropin (LH) and follicle stimulating hormone (FSH), progestogen--affecting the secretion of gonadotropin and gonadoliberin (GnRH) antagonists. New potential targets for non-hormonal male contraception were discovered: glyceraldehyde-3-phosphate-dehydrogenase (GAPDHS)--specific to male germ cells and voltage-gated cation channel (CatSper). Both are responsible for sperm motility. Drugs such as thioridazine used in schizophrenia treatment and phenoxybenzamine (antihypertensive activity) exhibit a contraceptive effect. Similar action exhibits an analogue of lonidamine--adjudin and an antagonist of retinoic acid receptors (BMS-189453). Researchers are working on a contraceptive vaccine, whose active ingredient is epididymal protease inhibitor (Eppin). Another promising method acts by blocking Bromodomain testis-specific proteins (Brdt) involved in the process of spermatogenesis. JQ1-the Brdt inhibitor causes reversible infertility without affecting the endocrine signaling pathways. A recent discovery of Juno as the binding partner for Izumo1 identifies these proteins as the cell-surface receptor pair, essential for gamete recognition and this interaction can be inhibited by an anti-Juno monoclonal antibody. Our review shows that the situation of men can change and investigators are close to the optimal solution. In the near future men will be able to choose the best contraceptive suited to their needs."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I72,I72)","v":25683035},{"$f":"(LEN($J72) - LEN(SUBSTITUTE(LOWER($J72),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J72) - LEN(SUBSTITUTE(LOWER($J72),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J72) - LEN(SUBSTITUTE(LOWER($J72),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B72:D72)","v":2},2015,"Triorganotin compounds--ligands for quot;rexinoidquot; inducible transcription factors: biological effects.","Brtko",25683035,"Triorganotin compounds--ligands for quot;rexinoidquot; inducible transcription factors: biological effects.    Abstract:   We review trialkyltin and triaryltin compounds, representing a class of organometallic compounds that function as nuclear retinoid X receptors (RXR) agonists due to their capability to bind to the ligand-binding domain of RXR subtypes and function as transcriptional activators. RXRs act predominantly as heterodimers with other nuclear receptors as permissive heterodimers with peroxisome proliferator-activated receptors, liver X receptors, farnesoid X receptor, pregnane X receptor and constitutive androstan receptor or as non-permissive heterodimer with vitamin D receptor, and as conditional heterodimers with retinoid receptors, and thyroid hormone receptors. RXR - quot;partnerquot; receptor heterodimers are considered to be ligand-activated, DNA-binding, trans-acting, transcription-modulating proteins involved in a general molecular mechanism responsible for transcriptional responses in target genes. Tributyltin at even pico- or nanomolar concentrations may cause the superimposition of male genitalia on female in several aquatic organisms, since they are DNA-targeted, mitotic, and their actions are occurring through target gene(s)-mediated pathways. They may cause molecular interactions with reproductive system in mammals, and as potent environmental obesogens, they promote adipocyte differentiation. Organotin compounds become known also for their immunotoxicity, neurotoxicity, for their effects on reproduction and/or development. We also review effects of organotins with respect to levels and activities of hepatic P450s and aromatase activity."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I73,I73)","v":25670871},{"$f":"(LEN($J73) - LEN(SUBSTITUTE(LOWER($J73),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J73) - LEN(SUBSTITUTE(LOWER($J73),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J73) - LEN(SUBSTITUTE(LOWER($J73),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B73:D73)","v":2},2015,"Mammalian gonocyte and spermatogonia differentiation: recent advances and remaining challenges.","Manku",25670871,"Mammalian gonocyte and spermatogonia differentiation: recent advances and remaining challenges.    Abstract:   The production of spermatozoa relies on a pool of spermatogonial stem cells (SSCs), formed in infancy from the differentiation of their precursor cells, the gonocytes. Throughout adult life, SSCs will either self-renew or differentiate, in order to maintain a stem cell reserve while providing cells to the spermatogenic cycle. By contrast, gonocytes represent a transient and finite phase of development leading to the formation of SSCs or spermatogonia of the first spermatogenic wave. Gonocyte development involves phases of quiescence, cell proliferation, migration, and differentiation. Spermatogonia, on the other hand, remain located at the basement membrane of the seminiferous tubules throughout their successive phases of proliferation and differentiation. Apoptosis is an integral part of both developmental phases, allowing for the removal of defective cells and the maintenance of proper germ-Sertoli cell ratios. While gonocytes and spermatogonia mitosis are regulated by distinct factors, they both undergo differentiation in response to retinoic acid. In contrast to postpubertal spermatogenesis, the early steps of germ cell development have only recently attracted attention, unveiling genes and pathways regulating SSC self-renewal and proliferation. Yet, less is known on the mechanisms regulating differentiation. The processes leading from gonocytes to spermatogonia have been seldom investigated. While the formation of abnormal gonocytes or SSCs could lead to infertility, defective gonocyte differentiation might be at the origin of testicular germ cell tumors. Thus, it is important to better understand the molecular mechanisms regulating these processes. This review summarizes and compares the present knowledge on the mechanisms regulating mammalian gonocyte and spermatogonial differentiation."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I74,I74)","v":24875094},{"$f":"(LEN($J74) - LEN(SUBSTITUTE(LOWER($J74),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J74) - LEN(SUBSTITUTE(LOWER($J74),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J74) - LEN(SUBSTITUTE(LOWER($J74),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B74:D74)","v":2},2015,"Role of retinoic acid receptor (RAR) signaling in post-natal male germ cell differentiation.","Mark",24875094,"Role of retinoic acid receptor (RAR) signaling in post-natal male germ cell differentiation.    Abstract:   All-trans retinoic acid (atRA), the active metabolite of vitamin A, plays critical functions in spermatogenesis, a complex, highly organized and regulated process comprising three phases. During the proliferative phase, undifferentiated spermatogonia divide to maintain a stem cell population and expand a progenitor cell population, of which a fraction enters the differentiation pathway yielding primary spermatocytes. During the meiotic phase, primary spermatocytes undergo recombination, segregation and reduction by half of chromosomes to produce haploid round spermatids. During the morphogenetic, post-meiotic phase, spermatids differentiate and elongate to ultimately form spermatozoa. Studies performed during the past 20 years have significantly improved our knowledge on the location of the proteins transducing the atRA signal, on the target genes of atRA and on its mechanism of action. This article is part of a Special Issue entitled: Nuclear receptors in animal development."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I75,I75)","v":23973941},{"$f":"(LEN($J75) - LEN(SUBSTITUTE(LOWER($J75),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J75) - LEN(SUBSTITUTE(LOWER($J75),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J75) - LEN(SUBSTITUTE(LOWER($J75),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B75:D75)","v":2},2013,"Retinoid signaling in control of progenitor cell differentiation during mouse development.","Duester",23973941,"Retinoid signaling in control of progenitor cell differentiation during mouse development.    Abstract:   The vitamin A metabolite retinoic acid (RA) serves as a ligand for nuclear RA receptors that control differentiation of progenitor cells important for vertebrate development. Genetic studies in mouse embryos deficient for RA-generating enzymes have been invaluable for deciphering RA function. RA first begins to act during early organogenesis when RA generated in trunk mesoderm begins to function as a diffusible signal controlling progenitor cell differentiation. In neuroectoderm, RA functions as an instructive signal to stimulate neuronal differentiation of progenitor cells in the hindbrain and spinal cord. RA is not required for early neuronal differentiation of the forebrain, but at later stages RA stimulates neuronal differentiation in forebrain basal ganglia. RA also acts as a permissive signal for differentiation by repressing fibroblast growth factor (FGF) signaling in differentiated cells as they emerge from progenitor populations in the caudal progenitor zone and second heart field. In addition, RA signaling stimulates differentiation of spermatogonial germ cells and induces meiosis in male but not female gonads. A more complete understanding of the normal functions of RA signaling during development will guide efforts to use RA as a differentiation agent for therapeutic purposes."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I76,I76)","v":22947624},{"$f":"(LEN($J76) - LEN(SUBSTITUTE(LOWER($J76),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J76) - LEN(SUBSTITUTE(LOWER($J76),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J76) - LEN(SUBSTITUTE(LOWER($J76),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B76:D76)","v":2},2013,"Precious cargo: regulation of sex-specific germ cell development in mice.","Bowles",22947624,"Precious cargo: regulation of sex-specific germ cell development in mice.    Abstract:   Although mammalian sex determination is normally specified genetically by an XX or XY chromosome complement, germ cells develop as sperm or oocytes in response to molecular cues provided by the gonadal somatic cells. In an ovary, germ cells enter meiosis during fetal life, thereby committing to oogenesis. In a testis, germ cells do not enter meiosis until after birth, at puberty. Recent findings indicate that, in mice, the sex-specific timing of entry into meiosis is governed by the balance between 2 secreted signalling molecules, retinoic acid (RA), which promotes entry into meiosis, and fibroblast growth factor 9 (FGF9), which counteracts RA. The combined action of these 2 molecular regulators provides a safety mechanism to guard against germ cell dysregulation that can lead to infertility or germ cell cancers."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I77,I77)","v":22254103},{"$f":"(LEN($J77) - LEN(SUBSTITUTE(LOWER($J77),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J77) - LEN(SUBSTITUTE(LOWER($J77),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J77) - LEN(SUBSTITUTE(LOWER($J77),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B77:D77)","v":2},2011,"Vitamin A in reproduction and development.","Clagett-Dame",22254103,"Vitamin A in reproduction and development.    Abstract:   The requirement for vitamin A in reproduction was first recognized in the early 1900s, and its importance in the eyes of developing embryos was realized shortly after. A greater understanding of the large number of developmental processes that require vitamin A emerged first from nutritional deficiency studies in rat embryos, and later from genetic studies in mice. It is now generally believed that all-trans retinoic acid (RA) is the form of vitamin A that supports both male and female reproduction as well as embryonic development. This conclusion is based on the ability to reverse most reproductive and developmental blocks found in vitamin A deficiency induced either by nutritional or genetic means with RA, and the ability to recapitulate the majority of embryonic defects in retinoic acid receptor compound null mutants. The activity of the catabolic CYP26 enzymes in determining what tissues have access to RA has emerged as a key regulatory mechanism, and helps to explain why exogenous RA can rescue many vitamin A deficiency defects. In severely vitamin A-deficient (VAD) female rats, reproduction fails prior to implantation, whereas in VAD pregnant rats given small amounts of carotene or supported on limiting quantities of RA early in organogenesis, embryos form but show a collection of defects called the vitamin A deficiency syndrome or late vitamin A deficiency. Vitamin A is also essential for the maintenance of the male genital tract and spermatogenesis. Recent studies show that vitamin A participates in a signaling mechanism to initiate meiosis in the female gonad during embryogenesis, and in the male gonad postnatally. Both nutritional and genetic approaches are being used to elucidate the vitamin A-dependent pathways upon which these processes depend."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I78,I78)","v":22075477},{"$f":"(LEN($J78) - LEN(SUBSTITUTE(LOWER($J78),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J78) - LEN(SUBSTITUTE(LOWER($J78),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J78) - LEN(SUBSTITUTE(LOWER($J78),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B78:D78)","v":2},2012,"Initiating meiosis: the case for retinoic acid.","Griswold",22075477,"Initiating meiosis: the case for retinoic acid.    Abstract:   The requirement for vitamin A in reproduction and development was first determined from studies of nutritional deficiencies. Subsequent research has shown that embryonic development and both male and female reproduction are modulated by retinoic acid (RA), the active form of vitamin A. Because RA is active in multiple developmental systems, its synthesis, transport, and degradation are tightly regulated in different tissues. A growing body of evidence implicates RA as a requirement for the initiation of meiosis in both male and female mammals, resulting in a mechanistic model involving the interplay of RA, RA synthesis enzymes, RA receptors, and degradative cytochrome P450 enzymes in this system. Recently, that model has been challenged, prompting a review of the established paradigm. While it remains possible that additional molecules may be involved in regulating entry into meiosis, the weight of evidence supporting a key role for RA is incontrovertible."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I79,I79)","v":19856159},{"$f":"(LEN($J79) - LEN(SUBSTITUTE(LOWER($J79),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J79) - LEN(SUBSTITUTE(LOWER($J79),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J79) - LEN(SUBSTITUTE(LOWER($J79),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B79:D79)","v":2},2008,"Spermatogenesis and cycle of the seminiferous epithelium.","Hess",19856159,"Spermatogenesis and cycle of the seminiferous epithelium.    Abstract:   Spermatogenesis is a complex biological process of cellular transformation that produces male haploid germ cells from diploid spermatogonial stem cells. This process has been simplified morphologically by recognizing cellular associations or stages and phases of spermatogenesis, which progress through precisely timed and highly organized cycles. These cycles of spermatogenesis are essential for continuous sperm production, which is dependent upon numerous factors, both intrinsic (Sertoli and germ cells) and extrinsic (androgens, retinoic acids), as well as being species-specific."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I80,I80)","v":19760653},{"$f":"(LEN($J80) - LEN(SUBSTITUTE(LOWER($J80),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J80) - LEN(SUBSTITUTE(LOWER($J80),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J80) - LEN(SUBSTITUTE(LOWER($J80),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B80:D80)","v":2},2009,"Vitamin A deficiency in an infant with PAGOD syndrome.","Gavrilova",19760653,"Vitamin A deficiency in an infant with PAGOD syndrome.    Abstract:   PAGOD syndrome is a rare condition characterized by multiple congenital anomalies including pulmonary artery and lung hypoplasia, agonadism, diaphragmatic abnormalities, cardiac defects, omphalocele, and various genital anomalies. The etiology of this condition is unknown but the spectrum of birth defects is similar to the developmental anomalies observed in vitamin A deficiency animal models. We describe an infant with PAGOD syndrome phenotype. The patient had a normal male karyotype and no copy number changes were seen on chromosome genomic hybridization (CGH) microarray. Endocrine evaluation was consistent with primary hypogonadism. The testes and Müllerian structures were absent by imaging studies, raising the possibility of arrest of early gonadogenesis. The plasma free vitamin A was low, consistent with moderate to severe vitamin A deficiency; the maternal plasma vitamin A level was normal. During pregnancy maternal vitamin A is taken up by retinol binding protein 4 (RBP4) which is expressed in the embryonic visceral endoderm from pregastrulational stages. This transport is mediated via the specific membrane receptor for RBP, stimulated by retinoic acid 6 (STRA6). STRA6 is widely expressed in human organ systems including the placenta during embryonic development. Mutations in the STRA6 gene result in Matthew-Wood syndrome, which demonstrates significant phenotypic overlap with PAGOD syndrome. Sequencing of STRA6 coding regions in our patient, revealed no mutations. We present a case of PAGOD syndrome with a review of the literature, posing the hypothesis that a vitamin A metabolic defect, other than transport mediated by STRA6 receptor, might have an etiological role in the development of this multiple congenital anomalies syndrome."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I81,I81)","v":17715177},{"$f":"(LEN($J81) - LEN(SUBSTITUTE(LOWER($J81),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J81) - LEN(SUBSTITUTE(LOWER($J81),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J81) - LEN(SUBSTITUTE(LOWER($J81),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B81:D81)","v":2},2007,"Retinoic acid, meiosis and germ cell fate in mammals.","Bowles",17715177,"Retinoic acid, meiosis and germ cell fate in mammals.    Abstract:   Although mammalian sex is determined genetically, the sex-specific development of germ cells as sperm or oocytes is initiated by cues provided by the gonadal environment. During embryogenesis, germ cells in an ovary enter meiosis, thereby committing to oogenesis. By contrast, germ cells in a testicular environment do not enter meiosis until puberty. Recent findings indicate that the key to this sex-specific timing of meiosis entry is the presence or absence of the signaling molecule retinoic acid. Although this knowledge clarifies a long-standing mystery in reproductive biology, it also poses many new questions, which we discuss in this review."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I82,I82)","v":17702191},{"$f":"(LEN($J82) - LEN(SUBSTITUTE(LOWER($J82),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J82) - LEN(SUBSTITUTE(LOWER($J82),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J82) - LEN(SUBSTITUTE(LOWER($J82),LOWER(D$3),\"\")))/LEN(D$3)","v":2},{"$f":"SUM(B82:D82)","v":2},2007,"[Future treatment strategies for cryptorchidism to improve spermatogenesis].","Kojima",17702191,"[Future treatment strategies for cryptorchidism to improve spermatogenesis].    Abstract:   Orchiopexy is one of the most frequently used surgical procedures for cryptorchidism and has been shown to have a beneficial effect on fertility. However, orchiopexy, especially for bilateral cryptorchidism, does not always guarantee subsequent fertility and paternity. Compared with a control group, paternity was significantly compromised in men with previous bilateral, but not unilateral cryptorchidism. Recent techniques of assisted reproductive technology, especially testicular sperm extraction with intracytoplasmic sperm injection (TESE-ICSI), have brought revolutionary changes in clinical therapy for infertiliy. If spermatozoa exists in testis of infertile men, logically there is a possibility of paternity. However, our study demonstrated that about 20% of pubertal boys who had had orchiopexy, were predicted to have lost their future paternity potential even if TESE-ICSI were conducted, because they were predicted to have no spermatozoa in the testis. To prevent or reverse the damage of spermatogenesis at prepuberty or puberty, we should not take a wait-and-see attitude but should consider a countermeasure for the pubertal boys who had had bilateral orchiopexy in childhood, especially when the serum follicle stimulating hormone level is elevated and testicular volume is lowered, before paternity is lost. In this review, we discuss the potential approaches including epidermal growth facter therapy, gene therapy and stem-cell therapy for cryptorchid patients in the future."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I83,I83)","v":17589794},{"$f":"(LEN($J83) - LEN(SUBSTITUTE(LOWER($J83),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J83) - LEN(SUBSTITUTE(LOWER($J83),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J83) - LEN(SUBSTITUTE(LOWER($J83),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B83:D83)","v":2},2007,"Androgenic regulation of novel genes in the epididymis.","Robaire",17589794,"Androgenic regulation of novel genes in the epididymis.    Abstract:   The epididymis is critically dependent on the presence of the testis. Although several hormones, such as retinoids and progestins, and factors secreted directly into the epididymal lumen, such as androgen binding protein and fibroblast growth factor, might play regulatory roles in epididymal function, testosterone (T) and its metabolites, dihydrotestosterone (DHT) and estradiol (E2), are accepted as the primary regulators of epididymal structure and functions, with the former playing the greater role. To ascertain the molecular action of androgens on the epididymis, three complementary approaches were pursued to monitor changes in gene expression in response to different hormonal milieux. The first was to establish changes in gene expression along the epididymis as androgenic support is withdrawn. The second was to determine the sequence of responses that occur in an androgen deprived tissue upon re-administration of the two metabolites of T, DHT and E2. The third was to study the effects of androgen withdrawal and re-administration on gene expression in immortalized murine caput epididymidal principal cells. Specific responses were observed under each of these conditions, with an expected major difference in the panoply of genes expressed upon hormone withdrawal and re-administration; however, some key common features were the common roles of genes in insulin like growth factor/epidermal growth factor and the relatively minor and specific effects of E2 as compared to DHT. Together, these results provide novel insights into the mechanisms of androgen regulation in epididymal principal cells."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I84,I84)","v":17459383},{"$f":"(LEN($J84) - LEN(SUBSTITUTE(LOWER($J84),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J84) - LEN(SUBSTITUTE(LOWER($J84),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J84) - LEN(SUBSTITUTE(LOWER($J84),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B84:D84)","v":2},2008,"Interference of endocrine disrupting chemicals with aromatase CYP19 expression or activity, and consequences for reproduction of teleost fish.","Cheshenko",17459383,"Interference of endocrine disrupting chemicals with aromatase CYP19 expression or activity, and consequences for reproduction of teleost fish.    Abstract:   Many natural and synthetic compounds present in the environment exert a number of adverse effects on the exposed organisms, leading to endocrine disruption, for which they were termed endocrine disrupting chemicals (EDCs). A decrease in reproduction success is one of the most well-documented signs of endocrine disruption in fish. Estrogens are steroid hormones involved in the control of important reproduction-related processes, including sexual differentiation, maturation and a variety of others. Careful spatial and temporal balance of estrogens in the body is crucial for proper functioning. At the final step of estrogen biosynthesis, cytochrome P450 aromatase, encoded by the cyp19 gene, converts androgens into estrogens. Modulation of aromatase CYP19 expression and function can dramatically alter the rate of estrogen production, disturbing the local and systemic levels of estrogens. In the present review, the current progress in CYP19 characterization in teleost fish is summarized and the potential of several classes of EDCs to interfere with CYP19 expression and activity is discussed. Two cyp19 genes are present in most teleosts, cyp19a and cyp19b, primarily expressed in the ovary and brain, respectively. Both aromatase CYP19 isoforms are involved in the sexual differentiation and regulation of the reproductive cycle and male reproductive behavior in diverse teleost species. Alteration of aromatase CYP19 expression and/or activity, be it upregulation or downregulation, may lead to diverse disturbances of the above mentioned processes. Prediction of multiple transcriptional regulatory elements in the promoters of teleost cyp19 genes suggests the possibility for several EDC classes to affect cyp19 expression on the transcriptional level. These sites include cAMP responsive elements, a steroidogenic factor 1/adrenal 4 binding protein site, an estrogen-responsive element (ERE), half-EREs, dioxin-responsive elements, and elements related to diverse other nuclear receptors (peroxisome proliferator activated receptor, retinoid X receptor, retinoic acid receptor). Certain compounds including phytoestrogens, xenoestrogens, fungicides and organotins may modulate aromatase CYP19 activity on the post-transcriptional level. As is shown in this review, diverse EDCs may affect the expression and/or activity of aromatase cyp19 genes through a variety of mechanisms, many of which need further characterization in order to improve the prediction of risks posed by a contaminated environment to teleost fish population."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I85,I85)","v":15776785},{"$f":"(LEN($J85) - LEN(SUBSTITUTE(LOWER($J85),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J85) - LEN(SUBSTITUTE(LOWER($J85),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J85) - LEN(SUBSTITUTE(LOWER($J85),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B85:D85)","v":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."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I86,I86)","v":15663994},{"$f":"(LEN($J86) - LEN(SUBSTITUTE(LOWER($J86),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J86) - LEN(SUBSTITUTE(LOWER($J86),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J86) - LEN(SUBSTITUTE(LOWER($J86),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B86:D86)","v":2},2004,"Interaction of nuclear receptor ligands with the Vitamin D signaling pathway in prostate cancer.","Peehl",15663994,"Interaction of nuclear receptor ligands with the Vitamin D signaling pathway in prostate cancer.    Abstract:   A number of hormonal ligands and/or the nuclear receptors that mediate their actions have been targeted for prostate cancer therapy. Androgens, the ligands for the androgen receptor (AR), are critical for the growth of prostate cancer. Inhibition of androgen production has been the mainstay of treatment for advanced prostate cancer for decades. Other more recently tested targets include retinoid receptors (RAR and RXR), glucocorticoid receptors (GR), estrogen receptors (ER) and peroxisome proliferator-activated receptors (PPAR). Calcitriol, acting through the Vitamin D receptor (VDR), has many tumor suppressive activities in the prostate, including inhibition of proliferation, induction of apoptosis and/or differentiation, and reduction of cellular invasion. Because of these properties, calcitriol and its less hypercalcemic analogs are being evaluated as agents to prevent or treat prostate cancer. Androgens, retinoids, glucocorticoids, estrogens and agonists of PPAR directly or indirectly impact Vitamin D signaling pathways, and vice versa. In order to design the most effective strategies to use calcitriol to prevent or treat prostate cancer, the interactions of other nuclear receptors and their ligands with the Vitamin D signaling pathway need to be considered."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I87,I87)","v":14594936},{"$f":"(LEN($J87) - LEN(SUBSTITUTE(LOWER($J87),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J87) - LEN(SUBSTITUTE(LOWER($J87),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J87) - LEN(SUBSTITUTE(LOWER($J87),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B87:D87)","v":2},2003,"Chemoprevention of cancer--focusing on clinical trials.","Kakizoe",14594936,"Chemoprevention of cancer--focusing on clinical trials.    Abstract:   Chemoprevention of cancer is reviewed from the viewpoints of action mechanisms and methodology of clinical trials in order to introduce promising agents discovered by in vitro and/or in vivo studies to applications in humans. The clinical trial procedure essentially follows the phase study which has been employed for chemotherapeutic drugs. Chemoprevention of bladder cancer, prostate cancer, gastric cancer, hepatocellular carcinoma, breast cancer, head and neck cancer, colorectal cancer and lung cancer is reviewed, mainly focusing on clinical trials. Previous clinical trials have shown the effectiveness of the following: polyprenoic acid (acyclic retinoid) for hepatocellular carcinoma; tamoxifen for breast cancer; retinoic acids for head and neck tumor; and aspirin, a COX-2 inhibitor, for colorectal cancer. Despite the advantageous effects of some of these agents, their toxic effects must also be of concern at the same time. For example, in a chemoprevention trial of lung cancer, beta-carotene was unexpectedly found to increase the risk of lung cancer among high-risk groups. It is also noted that large-scale clinical trials demand large research grants, which may not be affordable in Japan. Chemoprevention is still an emerging field of oncology where researchers in both basic and clinical sciences face great challenges."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I88,I88)","v":12682772},{"$f":"(LEN($J88) - LEN(SUBSTITUTE(LOWER($J88),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J88) - LEN(SUBSTITUTE(LOWER($J88),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J88) - LEN(SUBSTITUTE(LOWER($J88),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B88:D88)","v":2},2003,"Evolving strategies for prostate cancer chemoprevention trials.","Lieberman",12682772,"Evolving strategies for prostate cancer chemoprevention trials.    Abstract:   Prostate cancer chemoprevention (CP) can be defined as the use of natural and synthetic agents that inhibit, reverse or regress precancer and delay progression to invasive cancer. During the past two decades several CP strategies have evolved. The first generation of CP trials tested the efficacy of antioxidants and vitamins including B-carotene, vitamin A, retinol, 13 cis retinoic acid, vitamins E, C and selenium. Although these trials were disappointing, provocative hypotheses were generated for selenium and vitamin E that set the stage for future prostate trials. In the 1990s, the NCI launched a second generation of large CP trials aimed at breast and prostate cancer. One of these trials is the PCPT, testing the efficacy of a 5 alpha-reductase inhibitor-finasteride to prevent prostate cancer in 18,000 men. Although PCPT is still in progress, the NCI recently launched a second large primary prostate CP trial called SELECT, testing the efficacy of selenium and vitamin E in 32,400 men. The Prostate Cancer Progress Report to the Director of NCI in 1998 challenged the research community to design more efficient CP trials for prostate cancer. In response, the NCI has evolved a third generation of CP trials. This involves pharmacologically driven translational science research including agents and their targets, biomarker endpoints, suitable clinical models for testing agents and efficient trial designs employing high risk cohorts and surrogate endpoints. In summary, a dual strategy for CP is being developed which includes public health measures and a medical intervention approach."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I89,I89)","v":11555853},{"$f":"(LEN($J89) - LEN(SUBSTITUTE(LOWER($J89),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J89) - LEN(SUBSTITUTE(LOWER($J89),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J89) - LEN(SUBSTITUTE(LOWER($J89),LOWER(D$3),\"\")))/LEN(D$3)","v":2},{"$f":"SUM(B89:D89)","v":2},2001,"Regulation of male sexual development by Sry and Sox9.","Koopman",11555853,"Regulation of male sexual development by Sry and Sox9.    Abstract:   Sry, a gene from the Y chromosome, is known to initiate testis formation and subsequent male differentiation in mammals. A related gene, Sox9, also plays a critical role in testis determination, possibly in all vertebrates. A number of models have been presented regarding the molecular modes of action of these two genes. However, details regarding their regulation, regulatory target genes, and interacting protein factors and co-factors have not been established with any certainty. In this review, we examine new evidence and re-examine existing evidence bearing on these issues, in an effort to build up an integrative model of the network of gene activity centred around Sry and Sox9. J. Exp. Zool. 290:463-474, 2001."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I90,I90)","v":11226060},{"$f":"(LEN($J90) - LEN(SUBSTITUTE(LOWER($J90),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J90) - LEN(SUBSTITUTE(LOWER($J90),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J90) - LEN(SUBSTITUTE(LOWER($J90),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B90:D90)","v":2},2001,"Proliferation and differentiation of spermatogonial stem cells.","de Rooij",11226060,"Proliferation and differentiation of spermatogonial stem cells.    Abstract:   Spermatogonial stem cells (A(s) spermatogonia) are single cells that either renew themselves or produce A(pr) (paired) spermatogonia predestined to differentiate. In turn, the A(pr) divide into chains of A(al) (aligned) spermatogonia that also divide. The ratio between self-renewal and differentiation of the stem cells is regulated by glial cell line-derived neurotrophic factor produced by Sertoli cells, while the receptors are expressed in stem cells. A(s), A(pr) and A(al) spermatogonia proliferate during part of the epithelial cycle forming many A(al) spermatogonia. During epithelial stage VIII, almost all A(al) spermatogonia, few A(pr) and very few A(s) spermatogonia differentiate into A1 spermatogonia. A number of molecules are involved in this differentiation step including the stem cell factor-c-kit system, the Dazl RNA binding protein, cyclin D(2) and retinoic acid. There is no fine regulation of the density of spermatogonial stem cells and consequently, in some areas, many A1 and, in other areas, few A1 spermatogonia are formed. An equal density of spermatocytes is then obtained by the apoptosis of A2, A3 or A4 spermatogonia to remove the surplus cells. The Bcl-2 family members Bax and Bcl-x(L) are involved in this density regulation. Several mechanisms are available to cope with major or minor shortages in germ cell production. After severe cell loss, stem cell renewal is preferred above differentiation and the period of proliferation of A(s), A(pr) and A(al) spermatogonia is extended. Minor shortages are dealt with, at least in part, by less apoptosis among A2-A4 spermatogonia."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I91,I91)","v":10931168},{"$f":"(LEN($J91) - LEN(SUBSTITUTE(LOWER($J91),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J91) - LEN(SUBSTITUTE(LOWER($J91),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J91) - LEN(SUBSTITUTE(LOWER($J91),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B91:D91)","v":2},2000,"Scrotal ulceration during all-trans retinoic (ATRA) therapy for acute promyelocytic leukaemia.","Charles",10931168,"Scrotal ulceration during all-trans retinoic (ATRA) therapy for acute promyelocytic leukaemia.    Abstract:   We report the development of painful scrotal ulceration in two patients during treatment with all-trans-retinoic acid (ATRA) for acute promyelocytic leukaemia (APL). ATRA 45 mg/m2 was administered orally for 8 days prior to the addition of standard induction chemotherapy. Painful scrotal ulceration developed in both cases within 2 weeks of therapy (9 and 13 days) and responded slowly to drug withdrawal and systemic, or topical, corticosteroids. A total of 17 APL patients have been treated with ATRA at our institution during the last 10 years, giving an incidence of approximately 12%. The present report, together with a review of literature, suggests that scrotal ulceration is a specific adverse effect of ATRA therapy and that this complication may be more common than previously documented."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I92,I92)","v":10604265},{"$f":"(LEN($J92) - LEN(SUBSTITUTE(LOWER($J92),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J92) - LEN(SUBSTITUTE(LOWER($J92),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J92) - LEN(SUBSTITUTE(LOWER($J92),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B92:D92)","v":2},1999,"Approaches to the treatment of patients with hormone-sensitive prostate cancer.","DiPaola",10604265,"Approaches to the treatment of patients with hormone-sensitive prostate cancer.    Abstract:   Androgen ablation therapy provides effective palliation for patients with advanced cancer of the prostate for only a short duration because the tumor eventually develops resistance. Among the many potential molecular mechanisms involved in the development of tumor resistance to both androgen ablation therapy and chemotherapy, mutations in the p53 tumor suppressor gene, overexpression of the antiapoptotic protein bcl-2, and overexpression of the multidrug resistance protein probably play a role. Because hormone-resistant tumors demonstrate greater expression of bcl-2 and because transfection of the bcl-2 gene into hormone-sensitive tumor cells confers resistance to both hormone therapy and chemotherapy, efforts to abrogate bcl-2 in prostate tumors represent one approach to improve clinical results. Of several agents recently shown to reduce prostate-specific antigen levels in phase II studies, 13-cis-retinoic acid and interferon-alpha can reduce the expression of bcl-2 and overcome bcl-2-mediated resistance to paclitaxel in resistant cell lines. For these reasons, our current studies test the hypothesis that reducing the expression of bcl-2 with 13-cis-retinoic acid and interferon-alpha in combination with taxanes will improve clinical results. Additionally, other studies test the hypothesis that treatment early, before the development of resistance mechanisms, in hormone-sensitive disease will improve results. Studies with docetaxel (Taxotere; Rhône-Poulenc Rorer, Collegeville, PA) and with estramustine combination therapy are also ongoing."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I93,I93)","v":10412367},{"$f":"(LEN($J93) - LEN(SUBSTITUTE(LOWER($J93),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J93) - LEN(SUBSTITUTE(LOWER($J93),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J93) - LEN(SUBSTITUTE(LOWER($J93),LOWER(D$3),\"\")))/LEN(D$3)","v":2},{"$f":"SUM(B93:D93)","v":2},1999,"Sry and Sox9: mammalian testis-determining genes.","Koopman",10412367,"Sry and Sox9: mammalian testis-determining genes.    Abstract:   Sry is the Y-chromosomal gene that acts as a trigger for male development in mammalian embryos. This gene encodes a high mobility group (HMG) box transcription factor that is known to bind to specific target sequences in DNA and to cause a bend in the chromatin. DNA bending appears to be part of the mechanism by which Sry influences transcription of genes downstream in a cascade of gene regulation leading to maleness, but the direct targets of Sry remain to be positively identified. One gene known to be downstream from Sry in this cascade is Sox9, which encodes a transcription factor related to Sry by the HMG box. Like Sry, mutations in Sox9 disrupt male development, but unlike Sry, the role of Sox9 is not limited to mammals. This review focuses on what is known about the two genes and their likely modes of action, and draws together recent data relating to how they might interconnect with the network of gene activity implicated in testis determination in mammals."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I94,I94)","v":10190792},{"$f":"(LEN($J94) - LEN(SUBSTITUTE(LOWER($J94),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J94) - LEN(SUBSTITUTE(LOWER($J94),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J94) - LEN(SUBSTITUTE(LOWER($J94),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B94:D94)","v":2},1999,"Overcoming bcl-2- and p53-mediated resistance in prostate cancer.","DiPaola",10190792,"Overcoming bcl-2- and p53-mediated resistance in prostate cancer.    Abstract:   Most prostate cancers eventually develop resistance to hormonal therapy and chemotherapies. Many mechanisms for resistance to chemotherapy have been identified. Mutations or inactivation of the p53 suppressor gene and overexpression of bcl-2 are among such mechanisms. Mutations in the p53 gene can lead to resistance to certain chemotherapy agents, and such mutations are seen more often in metastatic than in primary prostate cancers. Thus, agents that are active in the setting of mutated p53 may have some advantage in prostate cancer. Overexpression of bcl-2 occurs frequently in prostate cancer and is associated with both hormonal therapy and chemotherapy resistance. In experimental systems, bcl-2 overexpression occurs after androgen deprivation and transfection of bcl-2 into sensitive cell lines makes them resistant to chemotherapy and hormonal therapies. Bcl-2 can be inactivated by phosphorylation as occurs with taxanes. The retinoids, as a class, can inhibit the growth of resistant cell lines that overexpress bcl-2, and the combination of interferon (IFN) and cis-retinoic acid (CRA) demonstrated increased antitumor activity. In our cell line model the combination of IFN and CRA greatly enhanced the cytotoxicity of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ). Based on these observations, we conducted a phase I/II trial of CRA and IFN-alpha in patients with biochemical recurrence of prostate cancer. Twenty-six percent achieved a decrease of prostate-specific antigen (PSA), which was correlated to elevated serum transforming growth factor-beta. We then conducted a phase I trial of 13-CRA, IFN-alpha, and escalating doses of paclitaxel. Eighteen patients were treated with 1 mg/kg CRA and 1x10(6) unit IFN on days 1 to 4 and paclitaxel at doses from 100 to 175 mg/m2. Eleven patients received the 175 mg/m2 paclitaxel dose. Two patients in the phase I study achieved partial responses (one cervix and one prostate cancer). We subsequently initiated a phase II study of 13-CRA, IFN-alpha, and paclitaxel in hormone refractory prostate cancer. For entry patients must show progressive disease after androgen ablation. To test the mechanism of action, we are assaying peripheral blood monocytes and, when possible, tumor tissue for bcl-2 expression. As our understanding of the mechanisms of tumor resistance to chemotherapy improves, we will be able to design better approaches in treatment targeted to overcome the mechanisms of resistance."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I95,I95)","v":9787988},{"$f":"(LEN($J95) - LEN(SUBSTITUTE(LOWER($J95),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J95) - LEN(SUBSTITUTE(LOWER($J95),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J95) - LEN(SUBSTITUTE(LOWER($J95),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B95:D95)","v":2},1998,"Pharmacologic profile of tazarotene.","Duvic",9787988,"Pharmacologic profile of tazarotene.    Abstract:   The majority of patients with psoriasis exhibit a mild to moderate form of the disease. While topically applied agents represent the ideal therapeutic approach for these patients, our treatment options have been hampered by their inconsistent or limited efficacy, expense, and cosmetic properties. Furthermore, some of the topically applied preparations have the potential for systemic absorption and associated adverse events. Tazarotene is the first synthetically developed retinoid indicated for the topical treatment of patients with psoriasis. Pharmacologically, tazarotene affects the three primary abnormalities associated with psoriasis: it normalizes epidermal differentiation, it exhibits a potent antiproliferative effect, and it decreases epidermal inflammation. Following topical application, tazarotene is rapidly metabolized in the skin to tazarotenic acid, its primary and active metabolite. While tazarotenic acid achieves measurable levels in the systemic circulation, no drug-related hematologic, ophthalmologic, or metabolic adverse events have been observed. Only a minimal amount of tazarotene is absorbed into the circulation. While animal studies have found tazarotene to be nonmutagenic and nonteratogenic, women of child-bearing potential should be counseled regarding the potential risks of retinoid use during pregnancy. In summary, animal and clinical patient trials have found tazarotene to be effective, safe, and well-tolerated. The availability of such an agent in a topical formulation is a welcome treatment alternative for the management of patients with psoriasis."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I96,I96)","v":9524574},{"$f":"(LEN($J96) - LEN(SUBSTITUTE(LOWER($J96),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J96) - LEN(SUBSTITUTE(LOWER($J96),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J96) - LEN(SUBSTITUTE(LOWER($J96),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B96:D96)","v":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."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I97,I97)","v":9480037},{"$f":"(LEN($J97) - LEN(SUBSTITUTE(LOWER($J97),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J97) - LEN(SUBSTITUTE(LOWER($J97),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J97) - LEN(SUBSTITUTE(LOWER($J97),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B97:D97)","v":2},1997,"[Vitamin A deficiency: epidemiological aspects and control methods].","Ag Bendech",9480037,"[Vitamin A deficiency: epidemiological aspects and control methods].    Abstract:   Vitamin A deficiency is one of the most common nutrient deficiency syndromes in children from developing countries. It is also correlated with the increased severity and incidence of certain infections. Until recently, vitamin A research was focused on preventing xerophthalmia and blindness in Third World Countries and on the development of synthetic retinoid molecules, with lower toxicity than vitamin A, for the treatment of skin diseases. However, there has been a major shift of emphasis in the last five to ten years. There is a risk of death from xerophthalmia, primarily from complications with infectious diseases. Intermittent treatment with the very large doses of vitamin A prescribed to combat blindness was shown to be effective. This suggests that vitamin A may affect specific elements of the immune system. High-dose vitamin A supplements have been given, at widely-spaced time intervals, to preschool children in communities where vitamin A deficiency causes xerophthalmia and blindness, over the last 20 to 30 years. A strong correlation between mortality and xerophthalmia was identified. Death then became the principal outcome measured because it was easier to detect than xerophthalmia, particularly in large clinical trials in high risk regions where clinical expertise was minimal and vitamin A deficiency was a commoner cause of death than blindness. Other, food-based approaches to the treatment and prevention of vitamin A deficiency, involving foods naturally rich in retinol or carotenoid, or foods artificially fortified with these nutrients, should be developed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I98,I98)","v":9434866},{"$f":"(LEN($J98) - LEN(SUBSTITUTE(LOWER($J98),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J98) - LEN(SUBSTITUTE(LOWER($J98),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J98) - LEN(SUBSTITUTE(LOWER($J98),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B98:D98)","v":2},1997,"Cell death/apoptosis: normal, chemically induced, and teratogenic effect.","Zakeri",9434866,"Cell death/apoptosis: normal, chemically induced, and teratogenic effect.    Abstract:   Cell death is an integral part of a variety of biological processes including cell proliferation, differentiation, and morphogenesis. We review here the morphological and biochemical nature as well as the genetic basis for cell death during normal and abnormal development. Most often referred to in normal development as programmed cell death, this controlled process determines the size, patterning, and function of many tissues. The importance of its proper genetic regulation is demonstrated by the discovery of cell death-specific genes and the several disorders including cancer and teratogenesis that result from repression or enhancement of cell death. In our studies we employed the developing mouse limb, which provides a defined window of active cell death, to elucidate mechanisms of cell death. We have developed markers that reveal in the developing normal limb an apoptotic morphology with phagocytosis and DNA fragmentation. In the limb deformity mutant Hammertoe there is a defective (restricted) cell death pattern, but the morphology remains apoptotic. By the use of these markers, we were able to observe that the teratogen retinoic acid produced enhanced apoptotic cell death. Most interestingly, retinoic acid-induced cell death in the Hammertoe mutant resulted in correction of the mutant phenotype. Future studies will determine the relationship between exogenous agents and endogenous signaling pathways as well as indicate how these interactions can alter the fate of a given cell and potentially ameliorate a genetic abnormality."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I99,I99)","v":8589015},{"$f":"(LEN($J99) - LEN(SUBSTITUTE(LOWER($J99),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J99) - LEN(SUBSTITUTE(LOWER($J99),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J99) - LEN(SUBSTITUTE(LOWER($J99),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B99:D99)","v":2},1995,"Therapy-related acute promyelocytic leukemia with t(15;17) (q22;q12) following chemotherapy with drugs targeting DNA topoisomerase II. A report of two cases and a review of the literature.","Hoffmann",8589015,"Therapy-related acute promyelocytic leukemia with t(15;17) (q22;q12) following chemotherapy with drugs targeting DNA topoisomerase II. A report of two cases and a review of the literature.    Abstract:    BACKGROUND : The development of therapy-related acute myeloid leukemia (t-AML) with balanced translocations to chromosome bands 11q23 and 21q22 has recently been significantly related to previous treatment with several cytostatic drugs poisoning DNA topoisomerase II. A similar association was suspected for other balanced chromosomal aberrations such as the t(15;17) characteristic of acute promyelocytic leukemia (APL).  PATIENTS AND METHODS : Two cases of acute promyelocytic leukemia were observed following treatment for seminoma with etoposide, cisplatin, and bleomycin and treatment for breast cancer with 4-epi-doxorubicin and subsequent cyclophosphamide, methotrexate, and 5-fluorouracil followed by radiotherapy. Both cases presented a t(15;17) (q22;q12) and were examined for the characteristic chimeric rearrangement of the RAR alpha and PML genes observed in acute promyelocytic leukemia de-novo.  RESULTS : In both cases the characteristic chimeric rearrangement was demonstrated. Case no. 2 in addition to the t(15;17) showed an inversion of the long arm of a chromosome no. 5 and a del(7)(q22) in all abnormal mitoses studied. Despite these findings the patient obtained a complete morphological and cytogenetic remission of the leukemia following treatment with all-trans-retinoic acid.  CONCLUSIONS : Based on these two cases and a review of the literature it is concluded that the development of t-APL with the balanced translocation t(15;17) is related to previous treatment with cytostatic drugs targeting DNA topoisomerase II and that additional abnormalities of the long arms of chromosomes no. 5 and no. 7 do not interfere with the induction of remission with all-trans-retinoic acid."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I100,I100)","v":8600562},{"$f":"(LEN($J100) - LEN(SUBSTITUTE(LOWER($J100),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J100) - LEN(SUBSTITUTE(LOWER($J100),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J100) - LEN(SUBSTITUTE(LOWER($J100),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B100:D100)","v":2},1995,"[Vitamin and mineral deficiency in Mexico. A critical review of the state of the art. II. Vitamin deficiency].","Rosado",8600562,"[Vitamin and mineral deficiency in Mexico. A critical review of the state of the art. II. Vitamin deficiency].    Abstract:   We carried out a review of the studies related to vitamin deficiencies in the Mexican population published since 1950. Forty four studies were published from which we can conclude that: a) dietary intake data suggest that ascorbic acid, riboflavin and retinol intake are deficient: reported intakes were 40-70%, 35-64% and 20-72% of the recommended daily amounts respectively; niacin intake was also deficient in some studies; b) about 10% of Mexican children in rural areas had deficient values of plasma retinol (lt; 100 ng/ml) and about 25 to 30% had low values (100-200 ng/ml); this prevalence is reduced in children with a higher socioeconomic level; c) some studies were found that show the existence of marginal deficiencies of vitamin E, riboflavin and vitamin B12 in apparently healthy populations. Further studies are required to identify the magnitude of these and perhaps other vitamin deficiencies and their potential effects on the health and function of the Mexican population."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I101,I101)","v":8202283},{"$f":"(LEN($J101) - LEN(SUBSTITUTE(LOWER($J101),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J101) - LEN(SUBSTITUTE(LOWER($J101),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J101) - LEN(SUBSTITUTE(LOWER($J101),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B101:D101)","v":2},1994,"Vitamin A and cancers of the breast, large bowel, and prostate: epidemiologic evidence.","Willett",8202283,"Vitamin A and cancers of the breast, large bowel, and prostate: epidemiologic evidence.    Abstract:   In this review we have examined epidemiological data from a variety of sources to assess the relation between vitamin A intake and cancer risk. The potential for recall bias in case-control studies makes their interpretation difficult, particularly if we are searching for modest associations. Prospective data are preferable, but sparse. Studies of blood levels of carotenoids may be informative if the blood is stored at ultra-low temperatures; however, studies of blood retinol levels are largely uninformative as an index of dietary intake because blood retinol is not well correlated with intake except in vitamin A-deficient populations. We have also reviewed the evidence for an influence of vitamin A intake on the incidence of cancer at the three major cancer sites accounting for a substantial portion of cancers in developed countries. The available data are compatible with a modest inverse association between intake of vitamin A and breast cancer, although it is not clear whether this effect may be due to preformed vitamin A, carotenoids, or both. The evidence that vitamin A protects against colon cancer is unconvincing. In the case of prostate cancer, early suggestions that vitamin A may increase incidence have not been confirmed by subsequent studies. Fortunately, prospective data from a number of large ongoing cohort studies in the United States and Europe should be available within the next 5 years or so. These data will permit further assessment of potential correlations between vitamin A and cancer at various sites by analysis of much larger numbers of cases than are presently available.(ABSTRACT TRUNCATED AT 250 WORDS)"]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I102,I102)","v":2672954},{"$f":"(LEN($J102) - LEN(SUBSTITUTE(LOWER($J102),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J102) - LEN(SUBSTITUTE(LOWER($J102),LOWER(C$3),\"\")))/LEN(C$3)","v":2},{"$f":"(LEN($J102) - LEN(SUBSTITUTE(LOWER($J102),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B102:D102)","v":2},1989,"Regulation of spermatogonial proliferation.","De Rooij",2672954,"Regulation of spermatogonial proliferation.    Abstract:   In nonprimates the spermatogonial compartment can be subdivided into (morphologically) undifferentiated spermatogonia and differentiating spermatogonia. Each cycle of the seminiferous epithelium the proliferative activity of the undifferentiated spermatogonia is stimulated, probably by factors secreted by Sertoli cells. Subsequently, during a period of active proliferation many Aal spermatogonia are formed. In the normal situation around epithelial stage III, proliferation is inhibited by the differentiating spermatogonia by way of a negative feedback system, probably involving a spermatogonial chalone. Then most of the Aal spermatogonia formed differentiate into Al spermatogonia. For this differentiation vitamin A, or factors secreted by Sertoli cells under the influence of vitamin A, is/are necessary. In the normal situation there is no regulation of the density of the undifferentiated spermatogonia. Different tubular areas can contain widely varying numbers of stem cells and other undifferentiated spermatogonia and consequently can produce widely varying numbers of Al spermatogonia. Only in extreme circumstances, such as after irradiation, the stem cells change the ratio between self-renewing and differentiating divisions in favor of self-renewal. Furthermore, in this situation the proliferation of the undifferentiated spermatogonia is not inhibited at epithelial stage III because of the lack of differentiating spermatogonia. Density regulation does take place during the development of the differentiating spermatogonia. In the chinese hamster it appeared that despite the variation in the numbers of Al spermatogonia produced in different areas, the density of the preleptotene spermatocytes was very much the same. It was found that the even distribution of spermatocytes in the epithelium was achieved by a density-dependent degeneration of differentiating spermatogonia in such a way that many of the latter cells degenerated in high density areas and only few or none in low density areas. In primates the undifferentiated spermatogonia can be subdivided into Ap and Ad spermatogonia. Both Ap and Ad spermatogonia can be seen to be topographically arranged in clones of 1 or 2n cells in situations in which their density is low. The Ad spermatogonia do not proliferate, but after cell loss these cells were found to transform into Ap spermatogonia that start to proliferate. The Ap spermatogonia only divide once every epithelial cycle, renewing themselves and giving rise to B spermatogonia. In the monkey the number of Ap spermatogonia could be increased by FSH treatment. Hence, there may be a correlation between FSH levels and the numbers of Ap spermatogonia. Fu"]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I103,I103)","v":6303065},{"$f":"(LEN($J103) - LEN(SUBSTITUTE(LOWER($J103),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J103) - LEN(SUBSTITUTE(LOWER($J103),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J103) - LEN(SUBSTITUTE(LOWER($J103),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B103:D103)","v":2},1983,"Cellular retinol- and retinoic acid-binding proteins.","Chytil",6303065,"Cellular retinol- and retinoic acid-binding proteins.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I104,I104)","v":6750459},{"$f":"(LEN($J104) - LEN(SUBSTITUTE(LOWER($J104),LOWER(B$3),\"\")))/LEN(B$3)","v":2},{"$f":"(LEN($J104) - LEN(SUBSTITUTE(LOWER($J104),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J104) - LEN(SUBSTITUTE(LOWER($J104),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B104:D104)","v":2},1982,"The function of retinol and retinoic acid in the testes.","Hemken",6750459,"The function of retinol and retinoic acid in the testes.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I105,I105)","v":26947703},{"$f":"(LEN($J105) - LEN(SUBSTITUTE(LOWER($J105),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J105) - LEN(SUBSTITUTE(LOWER($J105),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J105) - LEN(SUBSTITUTE(LOWER($J105),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B105:D105)","v":1},2016,"Beyond the Condom: Frontiers in Male Contraception.","Roth",26947703,"Beyond the Condom: Frontiers in Male Contraception.    Abstract:   Nearly half of all pregnancies worldwide are unplanned, despite numerous contraceptive options available. No new contraceptive method has been developed for men since the invention of condom. Nevertheless, more than 25% of contraception worldwide relies on male methods. Therefore, novel effective methods of male contraception are of interest. Herein we review the physiologic basis for both male hormonal and nonhormonal methods of contraception. We review the history of male hormonal contraception development, current hormonal agents in development, as well as the potential risks and benefits of male hormonal contraception options for men. Nonhormonal methods reviewed will include both pharmacological and mechanical approaches in development, with specific focus on methods which inhibit the testicular retinoic acid synthesis and action. Multiple hormonal and nonhormonal methods of male contraception are in the drug development pathway, with the hope that a reversible, reliable, safe method of male contraception will be available to couples in the not too distant future."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I106,I106)","v":26373900},{"$f":"(LEN($J106) - LEN(SUBSTITUTE(LOWER($J106),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J106) - LEN(SUBSTITUTE(LOWER($J106),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J106) - LEN(SUBSTITUTE(LOWER($J106),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B106:D106)","v":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."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I107,I107)","v":25791730},{"$f":"(LEN($J107) - LEN(SUBSTITUTE(LOWER($J107),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J107) - LEN(SUBSTITUTE(LOWER($J107),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J107) - LEN(SUBSTITUTE(LOWER($J107),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B107:D107)","v":1},2015,"Sex determination in mammalian germ cells.","Spiller",25791730,"Sex determination in mammalian germ cells.    Abstract:   Germ cells are the precursors of the sperm and oocytes and hence are critical for survival of the species. In mammals, they are specified during fetal life, migrate to the developing gonads and then undergo a critical period during which they are instructed, by the soma, to adopt the appropriate sexual fate. In a fetal ovary, germ cells enter meiosis and commit to oogenesis, whereas in a fetal testis, they avoid entry into meiosis and instead undergo mitotic arrest and mature toward spermatogenesis. Here, we discuss what we know so far about the regulation of sex-specific differentiation of germ cells, considering extrinsic molecular cues produced by somatic cells, as well as critical intrinsic changes within the germ cells. This review focuses almost exclusively on our understanding of these events in the mouse model."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I108,I108)","v":25657097},{"$f":"(LEN($J108) - LEN(SUBSTITUTE(LOWER($J108),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J108) - LEN(SUBSTITUTE(LOWER($J108),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J108) - LEN(SUBSTITUTE(LOWER($J108),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B108:D108)","v":1},2015,"Endogenous molecular-cellular hierarchical modeling of prostate carcinogenesis uncovers robust structure.","Zhu",25657097,"Endogenous molecular-cellular hierarchical modeling of prostate carcinogenesis uncovers robust structure.    Abstract:   We explored endogenous molecular-cellular network hypothesis for prostate cancer by constructing relevant endogenous interaction network model and analyzing its dynamical properties. Molecular regulations involved in cell proliferation, apoptosis, differentiation and metabolism are included in a hierarchical mathematical modeling scheme. This dynamical network organizes into multiple robust functional states, including physiological and pathological ones. Some states have characteristics of cancer: elevated metabolic and immune activities, high concentration of growth factors and different proliferative, apoptotic and adhesive behaviors. The molecular profile of calculated cancer state agrees with existing experiments. The modeling results have additional predictions which may be validated by further experiment: 1) Prostate supports both stem cell like and liver style proliferation; 2) While prostate supports multiple cell types, including basal, luminal and endocrine cell type differentiated from its stem cell, luminal cell is most likely to be transformed malignantly into androgen independent type cancer; 3) Retinoic acid pathway and C/EBPα are possible therapeutic targets."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I109,I109)","v":25546083},{"$f":"(LEN($J109) - LEN(SUBSTITUTE(LOWER($J109),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J109) - LEN(SUBSTITUTE(LOWER($J109),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J109) - LEN(SUBSTITUTE(LOWER($J109),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B109:D109)","v":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."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I110,I110)","v":25455729},{"$f":"(LEN($J110) - LEN(SUBSTITUTE(LOWER($J110),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J110) - LEN(SUBSTITUTE(LOWER($J110),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J110) - LEN(SUBSTITUTE(LOWER($J110),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B110:D110)","v":1},2014,"Orphan nuclear receptors as drug targets for the treatment of prostate and breast cancers.","Roshan-Moniri",25455729,"Orphan nuclear receptors as drug targets for the treatment of prostate and breast cancers.    Abstract:   Nuclear receptors (NRs), a family of 48 transcriptional factors, have been studied intensively for their roles in cancer development and progression. The presence of distinctive ligand binding sites capable of interacting with small molecules has made NRs attractive targets for developing cancer therapeutics. In particular, a number of drugs have been developed over the years to target human androgen- and estrogen receptors for the treatment of prostate cancer and breast cancer. In contrast, orphan nuclear receptors (ONRs), which in many cases lack known biological functions or ligands, are still largely under investigated. This review is a summary on ONRs that have been implicated in prostate and breast cancers, specifically retinoic acid-receptor-related orphan receptors (RORs), liver X receptors (LXRs), chicken ovalbumin upstream promoter transcription factors (COUP-TFs), estrogen related receptors (ERRs), nerve growth factor 1B-like receptors, and ‘‘dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1’’ (DAX1). Discovery and development of small molecules that can bind at various functional sites on these ONRs will help determine their biological functions. In addition, these molecules have the potential to act as prototypes for future drug development. Ultimately, the therapeutic value of targeting the ONRs may go well beyond prostate and breast cancers."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I111,I111)","v":25372763},{"$f":"(LEN($J111) - LEN(SUBSTITUTE(LOWER($J111),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J111) - LEN(SUBSTITUTE(LOWER($J111),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J111) - LEN(SUBSTITUTE(LOWER($J111),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B111:D111)","v":1},2014,"Regulation of meiotic entry and gonadal sex differentiation in the human: normal and disrupted signaling.","Jørgensen",25372763,"Regulation of meiotic entry and gonadal sex differentiation in the human: normal and disrupted signaling.    Abstract:   Meiosis is a unique type of cell division that is performed only by germ cells to form haploid gametes. The switch from mitosis to meiosis exhibits a distinct sex-specific difference in timing, with female germ cells entering meiosis during fetal development and male germ cells at puberty when spermatogenesis is initiated. During early fetal development, bipotential primordial germ cells migrate to the forming gonad where they remain sexually indifferent until the sex-specific differentiation of germ cells is initiated by cues from the somatic cells. This irreversible step in gonadal sex differentiation involves the initiation of meiosis in fetal ovaries and prevention of meiosis in the germ cells of fetal testes. During the last decade, major advances in the understanding of meiosis regulation have been accomplished, with the discovery of retinoic acid as an inducer of meiosis being the most prominent finding. Knowledge about the molecular mechanisms regulating meiosis signaling has mainly been established by studies in rodents, while this has not yet been extensively investigated in humans. In this review, the current knowledge about the regulation of meiosis signaling is summarized and placed in the context of fetal gonad development and germ cell differentiation, with emphasis on results obtained in humans. Furthermore, the consequences of dysregulated meiosis signaling in humans are briefly discussed in the context of selected pathologies, including testicular germ cell cancer and some forms of male infertility."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I112,I112)","v":25277428},{"$f":"(LEN($J112) - LEN(SUBSTITUTE(LOWER($J112),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J112) - LEN(SUBSTITUTE(LOWER($J112),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J112) - LEN(SUBSTITUTE(LOWER($J112),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B112:D112)","v":1},2014,"Melatonin in sperm biology: breaking paradigms.","Cebrián-Pérez",25277428,"Melatonin in sperm biology: breaking paradigms.    Abstract:   Melatonin is a ubiquitous molecule, present in a wide range of organisms, and involved in multiple functions. Melatonin relays the information about the photoperiod to the tissues that express melatonin-binding sites in both central and peripheral nervous systems. This hormone has a complex mechanism of action. It can cross the cell plasma membrane and exert its actions in all cells of the body. Certain melatonin actions are mediated by receptors that belong to the superfamily of G-protein-coupled receptors (GPCRs), the MT1 and MT2 membrane. Melatonin can also bind to calmodulin as well as to nuclear receptors of the retinoic acid receptor family, RORα1, RORα2 and RZRβ. The purpose of this review is to report on recent developments in the physiological role of melatonin and its receptors. Specific issues concerning the biological function of melatonin in mammalian seasonal reproduction and spermatozoa are considered. The significance of the continuous presence of melatonin in seminal plasma with a fairly constant concentration is also discussed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I113,I113)","v":24953623},{"$f":"(LEN($J113) - LEN(SUBSTITUTE(LOWER($J113),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J113) - LEN(SUBSTITUTE(LOWER($J113),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J113) - LEN(SUBSTITUTE(LOWER($J113),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B113:D113)","v":1},2014,"[Management of chronic hand eczema].","Lahfa",24953623,"[Management of chronic hand eczema].    Abstract:   The management of hand eczema, more readily called chronic hand dermatitis, is complex. This heaviness is related not only to the disease itself by its different clinical forms but also the multiplicity and diversity of etiological factors, triggering / maintaining or aggravating factors. The repeated therapeutic failures are ransom of incorrect information about the disease and its environment, a lack of clarity in the prescription and duration of treatment in general too short. The reference treatment is high potency topical steroids with or without occlusion for 4-8 weeks followed by alitretinoin 30 mg / day for at least 3-6 months with a monthly lipid and liver monitoring and mandatory monthly pregnancy test in women of childbearing. Associated measures and patient education are the cornerstones of successful treatment. Other alternative treatments such as phototherapy, methotrexate, cyclosporin, mycophenolate mofetil etc. can be considered in case of resistance or for clearing followed by topical treatments."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I114,I114)","v":24378460},{"$f":"(LEN($J114) - LEN(SUBSTITUTE(LOWER($J114),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J114) - LEN(SUBSTITUTE(LOWER($J114),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J114) - LEN(SUBSTITUTE(LOWER($J114),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B114:D114)","v":1},2013,"The Di Bella Method (DBM) in the treatment of prostate cancer: a preliminary retrospective study of 16 patients and a review of the literature.","Di Bella",24378460,"The Di Bella Method (DBM) in the treatment of prostate cancer: a preliminary retrospective study of 16 patients and a review of the literature.    Abstract:    OBJECTIVE : To evaluate the objective clinical response and the safety of the combined administration of somatostatin, melatonin, retinoids, vitamin D3, dopamine subtype 2 receptor (D2R) agonists and low doses of cyclophosphamide, associated with androgen ablation, in patients with a histological diagnosis of prostate adenocarcinoma (Pac).  MATERIALS AND METHODS : The clinical data of 30 patients with non-invasive and metastatic prostate cancer, who attended our institution over a period of more than 5 years, were retrospectively reviewed.  RESULTS : 16 patients satisfied the evaluation criteria. Median age: 64 years. Disease stages: 8 patients (50%) were in Stage II. For advanced stages (Stage IV), secondary lesions were located in the bones and lymph nodes. Taken together, an overall objective response (OR) [Complete response (CR) + Partial Response (PR)] was achieved in 69% of the patients, with 88% of objective clinical benefit [CR+PR+SD]. For local Prostate Cancer group, an OR was achieved in 87.5% of patients (7 cases; 53-98; 95% CI), with CR in 62.5% (5 cases, 31-86; 95% CI). In metastatic disease, the OR was 50% (4 cases; 21-78; 95% CI), with a 20% of CR (2 cases; 7-59; 95% CI) and 75% of clinical benefit.  CONCLUSIONS : This preliminary study shows that patients with early and advanced forms of prostate cancer, not previously treated by surgery and/or chemo-radiotherapy, can achieve a more than positive clinical benefit with the protocol foreseen by the Di Bella Method. Further clinical investigations are strongly recommended."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I115,I115)","v":23914891},{"$f":"(LEN($J115) - LEN(SUBSTITUTE(LOWER($J115),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J115) - LEN(SUBSTITUTE(LOWER($J115),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J115) - LEN(SUBSTITUTE(LOWER($J115),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B115:D115)","v":1},2013,"Dermatological medication effects on male fertility.","Millsop",23914891,"Dermatological medication effects on male fertility.    Abstract:   Many drugs have been reported to impair semen parameters, leading to temporary or persistent infertility. Therefore, potential fathers may be concerned about the effect of medications on fertility. We searched the MEDLINE database of articles in English combining key terms including quot;male infertility,quot; quot;spermatogenesis,quot; quot;fertility,quot; quot;drug effects,quot; and quot;dermatology.quot; Administration of methotrexate and finasteride has resulted in severe oligospermia and reversible infertility. Ketoconazole has had negative effects on sperm motility and testosterone production. Few individual case reports and a limited number of studies have demonstrated negative effects of tetracyclines, erythromycin, chloroquine, glucocorticoids, spironolactone, and antihistamines on fertility. It is important to counsel male patients when appropriate about the reversible negative effect on fertility when taking methotrexate and finasteride, and the adverse effect of ketoconazole. Patients may be reassured that taking oral retinoids, cyclosporine, azathioprine, and tumor necrosis factor alpha inhibitors should not affect their fertility."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I116,I116)","v":23500006},{"$f":"(LEN($J116) - LEN(SUBSTITUTE(LOWER($J116),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J116) - LEN(SUBSTITUTE(LOWER($J116),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J116) - LEN(SUBSTITUTE(LOWER($J116),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B116:D116)","v":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."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I117,I117)","v":23483003},{"$f":"(LEN($J117) - LEN(SUBSTITUTE(LOWER($J117),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J117) - LEN(SUBSTITUTE(LOWER($J117),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J117) - LEN(SUBSTITUTE(LOWER($J117),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B117:D117)","v":1},2013,"Is lycopene an effective agent for preventing prostate cancer?","Sporn",23483003,"Is lycopene an effective agent for preventing prostate cancer?    Abstract:   The role of lycopene, an open-chain carotenoid found in tomatoes and devoid of retinoid activity, as an anticarcinogenic, chemopreventive agent, especially for use in prostate cancer, is still under active investigation. In this issue, Qui and colleagues show that lycopene induces responses in human prostate epithelial cells that are antiproliferative, antioxidative, and anti-inflammatory, as well as downregulating targets in the androgen receptor signaling pathway. In this perspective, we review aspects of the molecular and cellular biology of lycopene that support its use for prevention of prostate cancer. Whether lycopene itself or its metabolites induce most of its benefits is still uncertain. At present, meta-analysis of clinical studies of lycopene for prevention of prostate cancer in men does not yet support the definitive clinical use of this carotenoid in a preventive setting."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I118,I118)","v":23390117},{"$f":"(LEN($J118) - LEN(SUBSTITUTE(LOWER($J118),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J118) - LEN(SUBSTITUTE(LOWER($J118),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J118) - LEN(SUBSTITUTE(LOWER($J118),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B118:D118)","v":1},2014,"Mid-hindbrain malformations due to drugs taken during pregnancy.","Merlini",23390117,"Mid-hindbrain malformations due to drugs taken during pregnancy.    Abstract:   Although genetic defects are the leading cause of central nervous system malformations including in the posterior fossa, specific malformative patterns should alert the clinician to consider rather a teratogenic etiology. We discuss the imaging features of 2 mid-hindbrain malformations consecutive to the intake of isotretinoin (Roaccuatane®; case 1) and misoprostol (Cytotec®; case 2) during pregnancy and review the pertinent literature. We correlate the morphological appearance of the mid-hindbrain malformation, as seen on high-resolution magnetic resonance imaging to possible drug-induced pathogenetical mechanisms. The recognition of characteristic imaging patterns enables diagnosis of and/or confirmation of suspected drug-induced hindbrain malformations. This has important medicolegal implications and also clinical significance to avoid unsuccessful and misleading genetic testing."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I119,I119)","v":23329078},{"$f":"(LEN($J119) - LEN(SUBSTITUTE(LOWER($J119),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J119) - LEN(SUBSTITUTE(LOWER($J119),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J119) - LEN(SUBSTITUTE(LOWER($J119),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B119:D119)","v":1},2013,"Diagnosis and treatment of lichen sclerosus: an update.","Fistarol",23329078,"Diagnosis and treatment of lichen sclerosus: an update.    Abstract:   Lichen sclerosus (LS) is a chronic, inflammatory, mucocutaneous disorder of genital and extragenital skin. LS is a debilitating disease, causing itch, pain, dysuria and restriction of micturition, dyspareunia, and significant sexual dysfunction in women and men. Many findings obtained in recent years point more and more towards an autoimmune-induced disease in genetically predisposed patients and further away from an important impact of hormonal factors. Preceding infections may play a provocative part. The role for Borrelia is still controversial. Trauma and an occlusive moist environment may act as precipitating factors. Potent and ultrapotent topical corticosteroids still head the therapeutic armamentarium. Topical calcineurin inhibitors are discussed as alternatives in the treatment of LS in patients who have failed therapy with ultrapotent corticosteroids, or who have a contraindication for the use of corticosteroids. Topical and systemic retinoids may be useful in selected cases. Phototherapy for extragenital LS and photodynamic therapy for genital LS may be therapeutic options in rare cases refractory to the already mentioned treatment. Surgery is restricted to scarring processes leading to functional impairment. In men, circumcision is effective in the majority of cases, but recurrences are well described. Anogenital LS is associated with an increased risk for squamous cell carcinoma of the vulva or penis. This review updates the epidemiology, clinical presentation, histopathology, pathogenesis, and management of LS of the female and male genitals and extragenital LS in adults and children."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I120,I120)","v":22822476},{"$f":"(LEN($J120) - LEN(SUBSTITUTE(LOWER($J120),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J120) - LEN(SUBSTITUTE(LOWER($J120),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J120) - LEN(SUBSTITUTE(LOWER($J120),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B120:D120)","v":1},2012,"The promyelocytic leukemia zinc finger protein: two decades of molecular oncology.","Suliman",22822476,"The promyelocytic leukemia zinc finger protein: two decades of molecular oncology.    Abstract:   The promyelocytic leukemia zinc finger (PLZF) protein, also known as Zbtb16 or Zfp145, was first identified in a patient with acute promyelocytic leukemia, where a reciprocal chromosomal translocation t(11;17)(q23;q21) resulted in a fusion with the RARA gene encoding retinoic acid receptor alpha. The wild-type Zbtb16 gene encodes a transcription factor that belongs to the POK (POZ and Krüppel) family of transcriptional repressors. In addition to nine Krüppel-type sequence-specific zinc fingers, which make it a member of the Krüppel-like zinc finger protein family, the PLZF protein contains an N-terminal BTB/POZ domain and RD2 domain. PLZF has been shown to be involved in major developmental and biological processes, such as spermatogenesis, hind limb formation, hematopoiesis, and immune regulation. PLZF is localized mainly in the nucleus where it exerts its transcriptional repression function, and many post-translational modifications affect this ability and also have an impact on its cytoplasmic/nuclear dissociation. PLZF achieves its transcriptional regulation by binding to many secondary molecules to form large multi-protein complexes that bind to the regulatory elements in the promoter region of the target genes. These complexes are also capable of physically interacting with its target proteins. Recently, PLZF has become implicated in carcinogenesis as a tumor suppressor gene, since it regulates the cell cycle and apoptosis in many cell types. This review will examine the major advances in our knowledge of PLZF biological activities that augment its value as a therapeutic target, particularly in cancer and immunological diseases."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I121,I121)","v":22428115},{"$f":"(LEN($J121) - LEN(SUBSTITUTE(LOWER($J121),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J121) - LEN(SUBSTITUTE(LOWER($J121),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J121) - LEN(SUBSTITUTE(LOWER($J121),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B121:D121)","v":1},2012,"Are lycopene metabolites metabolically active?","Ford",22428115,"Are lycopene metabolites metabolically active?    Abstract:   Lycopene is the most abundant carotenoid found in tomatoes and thus has been touted as the bioactive component for the reduced risk of chronic diseases such as prostate cancer. We and others hypothesize that lycopene metabolites are responsible for positively modulating biomarkers and risk factors for the prevention of chronic diseases. Lycopene metabolites circulate in serum and accumulate in tissues at concentrations equivalent to bioactive retinoids. Recent studies report that lycopene metabolites reduce the proliferation of cancer cells, induce apoptosis, enhance gap junction communication between cells, alter normal cell cycle progression, and modulate androgen signaling pathways. Here we review recent literature and provide new evidence to suggest that lycopene metabolites may be bioactive at physiological concentrations."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I122,I122)","v":22232934},{"$f":"(LEN($J122) - LEN(SUBSTITUTE(LOWER($J122),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J122) - LEN(SUBSTITUTE(LOWER($J122),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J122) - LEN(SUBSTITUTE(LOWER($J122),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B122:D122)","v":1},2011,"[The mammalian gonocytes fate: oogenesis or spermatogenesis].","Kozhuhar",22232934,"[The mammalian gonocytes fate: oogenesis or spermatogenesis].    Abstract:   Germ line cells become gonocytes after the completion of migration and colonization of gonadal anlages. After the contact with the somatic cells of genital ridges the reprogramming of gonocytes takes place. Upon entry the embryonic gonads germ cells undergo the most complete demethylation during germ line development, their chromatin tends to have an open conformation for a short period. This event promotes the susceptibility to meiosis-inducing factors signaling. The choice of the further path of gonocytes development just after the gonadal sex differentiation, mitotic arrest and meiotic entry are discussed. Analisis of the action mechanisms of meiosis-inducing and meiosis-preventing factors, especially retinoic acid and enzymes of its degradation and synthesis, was performed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I123,I123)","v":22031630},{"$f":"(LEN($J123) - LEN(SUBSTITUTE(LOWER($J123),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J123) - LEN(SUBSTITUTE(LOWER($J123),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J123) - LEN(SUBSTITUTE(LOWER($J123),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B123:D123)","v":1},2011,"Extramammary Paget disease.","Hartman",22031630,"Extramammary Paget disease.    Abstract:   We report the case of a 60-year-old man with penile-scrotal extramammary Paget disease (EMPD). The patient initially underwent Mohs micrographic surgery, but the margins remained positive after several sections; multiple scouting punch biopsies used to define the extent of the tumor were also positive. Because of concerns about functional impairment and cosmesis associated with wide local excision, the patient instead chose treatment with topical 5 percent imiquimod cream as a cytoreductive and margin-defining treatment. Owing to the association between EMPD and underlying malignant conditions, a thorough metastatic evaluation is necessary, particularly to rule out genitourinary cancer in the setting of penile-scrotal EMPD. Management of EMPD is complicated by the multifocal, non-contiguous nature of the disease and the presence of clinically occult extensions. As a result, recurrence rates after surgery are high. Several non-surgical modalities have been used to treat EMPD, which include radiotherapy, topical imiquimod, topical 5-fluorouracil, topical bleomycin, photodynamic therapy, CO2 laser ablation, and topical retinoids. Systemic chemotherapy also has been used to treat advanced EMPD. However, because EMPD is so uncommon, clinical trials comparing the various methods of treatment are lacking. Regardless of the mode of treatment, long-term follow up is essential, given the high rate of recurrence."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I124,I124)","v":22001108},{"$f":"(LEN($J124) - LEN(SUBSTITUTE(LOWER($J124),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J124) - LEN(SUBSTITUTE(LOWER($J124),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J124) - LEN(SUBSTITUTE(LOWER($J124),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B124:D124)","v":1},2011,"Nutrition, dietary supplements and adenocarcinoma of the prostate.","Schultz",22001108,"Nutrition, dietary supplements and adenocarcinoma of the prostate.    Abstract:   Three well-known and indisputable risk factors contribute to the development of prostate cancer, namely heredity, ethnic origin and increasing age. Geographic variations in incidence rates are considerable and it has, therefore, been suggested that environmental factors may also play a role. Migration studies clearly show that men with the same genetic background raised in different environments show a similar risk of developing the disease to those in their country of residency. Prostate cancer is a good candidate for studies on primary prevention thanks to specific features such as high prevalence, long latency, hormonal dependency, serum markers for monitoring (prostate-specific antigen) and histological precursor lesions (prostatic intraepithelial neoplasia). Nutritional factors that may influence the disease include total energy intake (as reflected by body mass index), dietary fat, cooked meat, micronutrients and vitamins (carotenoids, retinoids, vitamins C, D and E), fruit and vegetable intake, minerals (calcium, selenium), and phytoestrogens (isoflavonoids, flavonoids, lignans). Most published studies have been case-control analyses. The selenium and vitamin E cancer prevention trial (SELECT), however, was a population-based, prospective, randomized clinical trial that examined the effect of selenium and vitamin E alone or in combination on prostate cancer risk reduction. The trial was recently discontinued due to no evidence of benefit from either agent. Nevertheless, lifestyle changes can still be recommended for men at risk of developing clinical prostate cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I125,I125)","v":21253792},{"$f":"(LEN($J125) - LEN(SUBSTITUTE(LOWER($J125),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J125) - LEN(SUBSTITUTE(LOWER($J125),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J125) - LEN(SUBSTITUTE(LOWER($J125),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B125:D125)","v":1},2011,"Nutritional aspects of primary prostate cancer prevention.","Schmid",21253792,"Nutritional aspects of primary prostate cancer prevention.    Abstract:   There are three well-known and indisputable risk factors for development of prostate cancer, namely heredity, ethnic origin, and increasing age. Geographic variations in incidence rates are considerable and, therefore, it has been suggested that environmental factors may also play a role. Data from migration studies clearly show that men with the same genetic background raised in different environments present the risk of the disease associated with their country of residency. Prostate cancer is a good candidate for studies on primary prevention due to several specific features such as high prevalence, long latency, hormonal dependency, serum markers for monitoring (prostate specific antigen), and histological precursor lesions (prostatic intraepithelial neoplasia). Nutritional factors that may influence the disease include total energy intake (as reflected by body mass index), dietary fat, cooked meat, micronutrients and vitamins (carotenoids, retinoids, vitamins C, D and E), fruit and vegetable intake, minerals (calcium, selenium), and phytoestrogens (isoflavonoids, flavonoids, lignans). Most studies reported to date are case-control analysis. The selenium and vitamin E cancer prevention trial (SELECT), however, is a population-based, prospective, randomized clinical trial to examine the effect of selenium and vitamin E alone or in combination on prostate cancer risk reduction. The trial was discontinued recently as there was no evidence of a benefit from either agent. Nevertheless, lifestyle changes could be recommended to men at risk for developing clinical prostate cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I126,I126)","v":20417372},{"$f":"(LEN($J126) - LEN(SUBSTITUTE(LOWER($J126),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J126) - LEN(SUBSTITUTE(LOWER($J126),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J126) - LEN(SUBSTITUTE(LOWER($J126),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B126:D126)","v":1},2010,"[Alitretinoin: Toctino].","Berbis",20417372,"[Alitretinoin: Toctino].    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I127,I127)","v":20403868},{"$f":"(LEN($J127) - LEN(SUBSTITUTE(LOWER($J127),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J127) - LEN(SUBSTITUTE(LOWER($J127),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J127) - LEN(SUBSTITUTE(LOWER($J127),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B127:D127)","v":1},2010,"Androgens and spermatogenesis: lessons from transgenic mouse models.","Verhoeven",20403868,"Androgens and spermatogenesis: lessons from transgenic mouse models.    Abstract:   Transgenic mouse models have contributed considerably to our understanding of the cellular and molecular mechanisms by which androgens control spermatogenesis. Cell-selective ablation of the androgen receptor (AR) in Sertoli cells (SC) results in a complete block in meiosis and unambiguously identifies the SC as the main cellular mediator of the effects of androgens on spermatogenesis. This conclusion is corroborated by similar knockouts in other potential testicular target cells. Mutations resulting in diminished expression of the AR or in alleles with increased length of the CAG repeat mimick specific human forms of disturbed fertility that are not accompanied by defects in male sexual development. Transcriptional profiling studies in mice with cell-selective and general knockouts of the AR, searching for androgen-regulated genes relevant to the control of spermatogenesis, have identified many candidate target genes. However, with the exception of Rhox5, the identified subsets of genes show little overlap. Genes related to tubular restructuring, cell junction dynamics, the cytoskeleton, solute transportation and vitamin A metabolism are prominently present. Further research will be needed to decide which of these genes are physiologically relevant and to identify genes that can be used as diagnostic tools or targets to modulate the effects of androgens in spermatogenesis."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I128,I128)","v":20336012},{"$f":"(LEN($J128) - LEN(SUBSTITUTE(LOWER($J128),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J128) - LEN(SUBSTITUTE(LOWER($J128),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J128) - LEN(SUBSTITUTE(LOWER($J128),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B128:D128)","v":1},2010,"Vitamins and prostate cancer risk.","Donkena",20336012,"Vitamins and prostate cancer risk.    Abstract:   Prostate cancer (PC) is the second most common cancer in men worldwide. Its prevention and treatment remain a challenge to clinicians. Here we review the relationship of vitamins to PC risk. Many vitamins and related chemicals, including vitamin A, retinoids, several B vitamins, vitamin C, vitamin D and vitamin E have shown their anti-cancer activities as anti-oxidants, activators of transcription factors or factors influencing epigenetic events. Although laboratory tests including the use of animal models showed these vitamins may have anti-PC properties, whether they can effectively prevent the development and/or progression of PC in humans remains to be intensively studied subjects. This review will provide up-to-date information regarding the recent outcomes of laboratory, epidemiology and/or clinical trials on the effects of vitamins on PC prevention and/or treatment."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I129,I129)","v":20080321},{"$f":"(LEN($J129) - LEN(SUBSTITUTE(LOWER($J129),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J129) - LEN(SUBSTITUTE(LOWER($J129),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J129) - LEN(SUBSTITUTE(LOWER($J129),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B129:D129)","v":1},2010,"X-linked ichthyosis: an oculocutaneous genodermatosis.","Fernandes",20080321,"X-linked ichthyosis: an oculocutaneous genodermatosis.    Abstract:   X-linked ichthyosis (XLI) is an X-linked recessive disorder of cutaneous keratinization with possible extracutaneous manifestations. It was first described as a distinct type of ichthyosis in 1965. XLI is caused by a deficiency in steroid sulfatase activity, which results in abnormal desquamation and a retention hyperkeratosis. XLI is usually evident during the first few weeks of life as polygonal, loosely adherent translucent scales in a generalized distribution that desquamate widely. These are quickly replaced by large, dark brown, tightly adherent scales occurring primarily symmetrically on the extensor surfaces and the side of the trunk. In addition, extracutaneous manifestations such as corneal opacities, cryptorchidism, and abnormalities related to contiguous gene syndromes may be observed. Diagnosis of XLI is usually made clinically, as the histopathology is nonspecific, but confirmation may be obtained through either biochemical or genetic analysis. Treatment should focus on cutaneous hydration, lubrication, and keratolysis and includes topical moisturizers and topical retinoids."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I130,I130)","v":19502515},{"$f":"(LEN($J130) - LEN(SUBSTITUTE(LOWER($J130),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J130) - LEN(SUBSTITUTE(LOWER($J130),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J130) - LEN(SUBSTITUTE(LOWER($J130),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B130:D130)","v":1},2009,"Endocrine-disrupting chemicals: an Endocrine Society scientific statement.","Diamanti-Kandarakis",19502515,"Endocrine-disrupting chemicals: an Endocrine Society scientific statement.    Abstract:   There is growing interest in the possible health threat posed by endocrine-disrupting chemicals (EDCs), which are substances in our environment, food, and consumer products that interfere with hormone biosynthesis, metabolism, or action resulting in a deviation from normal homeostatic control or reproduction. In this first Scientific Statement of The Endocrine Society, we present the evidence that endocrine disruptors have effects on male and female reproduction, breast development and cancer, prostate cancer, neuroendocrinology, thyroid, metabolism and obesity, and cardiovascular endocrinology. Results from animal models, human clinical observations, and epidemiological studies converge to implicate EDCs as a significant concern to public health. The mechanisms of EDCs involve divergent pathways including (but not limited to) estrogenic, antiandrogenic, thyroid, peroxisome proliferator-activated receptor gamma, retinoid, and actions through other nuclear receptors; steroidogenic enzymes; neurotransmitter receptors and systems; and many other pathways that are highly conserved in wildlife and humans, and which can be modeled in laboratory in vitro and in vivo models. Furthermore, EDCs represent a broad class of molecules such as organochlorinated pesticides and industrial chemicals, plastics and plasticizers, fuels, and many other chemicals that are present in the environment or are in widespread use. We make a number of recommendations to increase understanding of effects of EDCs, including enhancing increased basic and clinical research, invoking the precautionary principle, and advocating involvement of individual and scientific society stakeholders in communicating and implementing changes in public policy and awareness."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I131,I131)","v":18977204},{"$f":"(LEN($J131) - LEN(SUBSTITUTE(LOWER($J131),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J131) - LEN(SUBSTITUTE(LOWER($J131),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J131) - LEN(SUBSTITUTE(LOWER($J131),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B131:D131)","v":1},2009,"AHR signaling in prostate growth, morphogenesis, and disease.","Vezina",18977204,"AHR signaling in prostate growth, morphogenesis, and disease.    Abstract:   Most evidence of aryl hydrocarbon receptor (AHR) signaling in prostate growth, morphogenesis, and disease stems from research using 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to pharmacologically activate the AHR at various stages of development. This review discusses effects of TCDD on prostate morphogenesis and highlights interactions between AHR and other signaling pathways during normal and aberrant prostate growth. Although AHR signaling modulates estrogen and androgen signaling in other tissues, crosstalk between these steroid hormone receptors and AHR signaling cannot account for actions of TCDD on prostate morphogenesis. Instead, the AHR appears to act within a cooperative framework of developmental signals to regulate timing and patterning of prostate growth. Inappropriate activation of AHR signaling as a result of early life TCDD exposure disrupts the balance of these signals, impairs prostate morphogenesis, and has an imprinting effect on the developing prostate that predisposes to prostate disease in adulthood. Mechanisms of AHR signaling in prostate growth and disease are only beginning to be unraveled and recent studies have revealed its interactions with WNT5A, retinoic acid, fibroblast growth factor 10, and vascular endothelial growth factor signaling pathways."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I132,I132)","v":18752475},{"$f":"(LEN($J132) - LEN(SUBSTITUTE(LOWER($J132),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J132) - LEN(SUBSTITUTE(LOWER($J132),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J132) - LEN(SUBSTITUTE(LOWER($J132),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B132:D132)","v":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."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I133,I133)","v":18430166},{"$f":"(LEN($J133) - LEN(SUBSTITUTE(LOWER($J133),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J133) - LEN(SUBSTITUTE(LOWER($J133),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J133) - LEN(SUBSTITUTE(LOWER($J133),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B133:D133)","v":1},2008,"Sexual development of mouse germ cells: Nanos2 promotes the male germ cell fate by suppressing the female pathway.","Saga",18430166,"Sexual development of mouse germ cells: Nanos2 promotes the male germ cell fate by suppressing the female pathway.    Abstract:   Much research has been conducted in recent years to elucidate the mechanisms underlying the crucial developmental process of sex determination. It has now been shown that somatic sex is principally determined by the chromosomal sex and the molecular mechanisms involved in this process have become relatively well understood in both human and mouse. However, the pathways involved in the sex determination of the germ cells remain largely unknown except for the fact that the somatic cues surrounding these cells play a significant role. Moreover, which sexual pathway of the germ cells is induced or suppressed has long been a subject of some dispute. Recent findings indicate that the key molecule that influences this choice is retinoic acid. In addition, the Nanos protein has been shown to play a critical role in promoting male germ cell differentiation. In this review, the possible mechanisms underlying these events, which have been brought to light by recent findings, are summarized to provide a better and more precise understanding of our current knowledge of the sex determination and subsequent differentiation of germ cells."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I134,I134)","v":17665093},{"$f":"(LEN($J134) - LEN(SUBSTITUTE(LOWER($J134),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J134) - LEN(SUBSTITUTE(LOWER($J134),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J134) - LEN(SUBSTITUTE(LOWER($J134),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B134:D134)","v":1},2007,"The importance of beta-carotene as a source of vitamin A with special regard to pregnant and breastfeeding women.","Strobel",17665093,"The importance of beta-carotene as a source of vitamin A with special regard to pregnant and breastfeeding women.    Abstract:   Vitamin A is essential for growth and differentiation of a number of cells and tissues. Notably during pregnancy and throughout the breastfeeding period, vitamin A has an important role in the healthy development of the fetus and the newborn, with lung development and maturation being particularly important. The German Nutrition Society (DGE) recommends a 40% increase in vitamin A intake for pregnant women and a 90% increase for breastfeeding women. However, pregnant women or those considering becoming pregnant are generally advised to avoid the intake of vitamin A rich liver and liver foods, based upon unsupported scientific findings. As a result, the provitamin A carotenoid beta-carotene remains their essential source of vitamin A. Basic sources of provitamin A are orange and dark green vegetables, followed by fortified beverages which represent between 20% and 40% of the daily supply. The average intake of beta-carotene in Germany is about 1.5-2 mg a day. Assuming a vitamin A conversion rate for beta-carotene for juices of 4:1, and fruit and vegetables between 12:1 and 26:1; the total vitamin A contribution from beta-carotene intake represents 10-15% of the RDA. The American Pediatrics Association cites vitamin A as one of the most critical vitamins during pregnancy and the breastfeeding period, especially in terms of lung function and maturation. If the vitamin A supply of the mother is inadequate, her supply to the fetus will also be inadequate, as will later be her milk. These inadequacies cannot be compensated by postnatal supplementation. A clinical study in pregnant women with short birth intervals or multiple births showed that almost 1/3 of the women had plasma retinol levels below 1.4 micromol/l corresponding to a borderline deficiency. Despite the fact that vitamin A and beta-carotene rich food is generally available, risk groups for low vitamin A supply exist in the western world. It is therefore highly critical to restrict the beta-carotene supply from diet, particularly from sources of beta-carotene with high consumer acceptance such as fortified juices (e.g. quot;ACE juicesquot;) or dietary supplements (e.g. multivitamins for pregnant women). For the part of the population unable to meet vitamin A requirements according to the DACH recommendations, sufficient intake of beta-carotene may be crucial to help improve and maintain adequate vitamin A status and prevention of developmental disorders. At this time it has to be urgently advised against restricting the beta-carotene supply or putting warning labels on beta-carotene fortified products. It is, however, highly recommended to improve the available data on nutrient intakes in Germany, especially for pregnant and breastfeeding women. For them, recommendations to be aware of potential nutrient intake inadequacies might prove useful."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I135,I135)","v":17368322},{"$f":"(LEN($J135) - LEN(SUBSTITUTE(LOWER($J135),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J135) - LEN(SUBSTITUTE(LOWER($J135),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J135) - LEN(SUBSTITUTE(LOWER($J135),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B135:D135)","v":1},2007,"Effects of vitamins, including vitamin A, on HIV/AIDS patients.","Mehta",17368322,"Effects of vitamins, including vitamin A, on HIV/AIDS patients.    Abstract:   An estimated 25 million lives have been lost to acquired immune-deficiency syndrome (AIDS) since the immunodeficiency syndrome was first described in 1981. The progress made in the field of treatment in the form of antiretroviral therapy (ART) for HIV disease/AIDS has prolonged as well as improved the quality of life of HIV-infected individuals. However, access to such treatment remains a major concern in most parts of the world, especially in the developing countries. Hence, there is a constant need to find low-cost interventions to complement the role of ART in prevention of HIV infection and slowing clinical disease progression. Nutritional interventions, particularly vitamin supplementation, have the potential to be a low-cost method for being such an intervention by virtue of their modulation of the immune system. Among all the vitamins, the role of vitamin A has been studied most extensively; most observational studies have found that low vitamin A levels are associated with increased risk of transmission of HIV from mother to child. This finding has not been supported by large randomized trials of vitamin A supplementation; on the contrary, these trials have found that vitamin A supplementation increases the risk of mother-to-child transmission (MTCT). There are a number of potential mechanisms that might explain these contradictory findings. One is the issue of reverse causality in observational studies-for instance, advanced HIV disease may suppress release of vitamin A from the liver. This would lead to low levels of vitamin A in the plasma despite the body having enough vitamin A liver stores. Further, advanced HIV disease is likely to increase the risk of MTCT, and hence it would appear that low serum vitamin A levels are associated with increased MTCT. The HIV genome also has a retinoic acid receptor element-hence, vitamin A may increase HIV replication via interacting with this element, thus increasing risk of MTCT. Finally, vitamin A is known to increase lymphoid cell differentiation, which leads to an increase in CCR5 receptors. These receptors are essential for attachment of HIV to the lymphocytes and therefore, an increase in their number is likely to increase HIV replication. Vitamin A supplementation in HIV-infected children, on the other hand, has been associated with protective effects against mortality and morbidity, similar to that seen in HIV-negative children. The risk for lower respiratory tract infection and severe watery diarrhea has been shown to be lower in HIV-infected children supplemented with vitamin A. All-cause mortality and AIDS-related deaths have also been found to be lower in vitamin A-supplemented HIV-infected children. The benefits of multivitamin supplementation, particularly vitamins B, C, and E, have been more consistent across studies. Multivitamin supplementation in HIV-infected pregnant mothers has been shown to reduce the incidence of adverse pregnancy outcomes such as fetal loss and low birth weight. It also has been shown to decrease rates of MTCT among women who have poor nutritional or immunologic status. Further, multivitamin supplementation reduces the rate of HIV disease progression among patients in early stage of disease, thus delaying the need for ART by prolonging the pre-ART stage. In brief, there is no evidence to recommend vitamin A supplementation of HIV-infected pregnant women; however, periodic vitamin A supplementation of HIV-infected infants and children is beneficial in reducing all-cause mortality and morbidity and is recommended. Similarly, multivitamin supplementation of people infected with HIV, particularly pregnant women, is strongly suggested."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I136,I136)","v":17302190},{"$f":"(LEN($J136) - LEN(SUBSTITUTE(LOWER($J136),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J136) - LEN(SUBSTITUTE(LOWER($J136),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J136) - LEN(SUBSTITUTE(LOWER($J136),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B136:D136)","v":1},2007,"Prevention of prostate cancer: more questions than data.","Schmid",17302190,"Prevention of prostate cancer: more questions than data.    Abstract:   Established risk factors for prostatic adenocarcinoma include increasing age, ethnical origin (race), and familial/hereditary factors. Moreover, the epidemiology of the disease gives some indications that its etiology is probably not only genetic but also environmental. Pathological studies support the fact that geographic differences in incidence and prevalence do not stem from genetic variations as men with the same genetic background raised in different environments present the risk of prostate cancer associated with their country of residency. Prostate cancer is basically an ideal candidate for exogenous preventive measures, such as dietary and pharmacological prevention, due to some specific features: high prevalence, long latency, endocrine dependency, availability of serum markers (prostate-specific antigen) and histological precursor lesions (prostatic intraepithelial neoplasia). Dietary/nutritional factors that may influence disease development include total energy intake (as reflected by body mass index), dietary fat, cooked meat, micronutrients and vitamins (carotenoids, retinoids, vitamins C, D, and E), fruit and vegetable intake, minerals (calcium, selenium), and phytoestrogens (isoflavonoids, flavonoids, lignans). Pharmacological prevention may use drugs that act on intraprostatic testosterone metabolism (finasteride, dutasteride) or induce apoptosis and inhibit tumor growth and metastasis (statins). Since most studies reported to date are case-control analyses, there remain more questions than evidence-based data. However, several large randomized trials are ongoing to clarify the potential for successful prostate cancer prevention. Until we have the results, lifestyle changes could be recommended to men at risk for developing clinical prostate cancer and 5-alpha-reductase inhibitors need to be discussed with men who are concerned about prostate cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I137,I137)","v":17261752},{"$f":"(LEN($J137) - LEN(SUBSTITUTE(LOWER($J137),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J137) - LEN(SUBSTITUTE(LOWER($J137),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J137) - LEN(SUBSTITUTE(LOWER($J137),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B137:D137)","v":1},2006,"The role of estrogens in normal and abnormal development of the prostate gland.","Prins",17261752,"The role of estrogens in normal and abnormal development of the prostate gland.    Abstract:   Estrogens play a physiologic role during prostate development with regard to programming stromal cells and directing early morphogenic events. However, if estrogenic exposures are abnormally high during the critical developmental period, permanent alterations in prostate branching morphogenesis and cellular differentiation will result, a process referred to as neonatal imprinting or developmental estrogenization. These perturbations are associated with an increased incidence of prostatic lesions with aging, which include hyperplasia, inflammation, and dysplasia. To understand how early estrogenic exposures can permanently alter the prostate and predispose it to neoplasia, we examined the effects of estrogens on prostatic steroid receptors and key developmental genes. Transient and permanent alterations in prostatic AR, ERalpha, ERbeta, and RARs are observed. We propose that estrogen-induced alterations in these critical transcription factors play a fundamental role in initiating prostatic growth and differentiation defects by shifting the prostate from an androgen-dominated gland to one whose development is regulated by estrogens and retinoids. This in turn leads to specific disruptions in the expression patterns of key prostatic developmental genes that normally dictate morphogenesis and differentiation. Specifically, we find transient reductions in Nkx3.1 and permanent reductions in Hoxb-13, which lead to differentiation defects particularly within the ventral lobe. Prolonged developmental expression of Bmp-4 contributes to hypomorphic growth throughout the prostatic complex. Reduced expression of Fgf10 and Shh and their cognate receptors in the dorsolateral lobes leads to branching defects in those specific regions in response to neonatal estrogens. We hypothesize that these molecular changes initiated early in life predispose the prostate to the neoplastic state upon aging."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I138,I138)","v":17229200},{"$f":"(LEN($J138) - LEN(SUBSTITUTE(LOWER($J138),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J138) - LEN(SUBSTITUTE(LOWER($J138),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J138) - LEN(SUBSTITUTE(LOWER($J138),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B138:D138)","v":1},2007,"Systemic dermatological treatment with relevance for male fertility.","Grunewald",17229200,"Systemic dermatological treatment with relevance for male fertility.    Abstract:   The dermatologist employs systemic agents with likely gametotoxic side effects, including cytotoxic, immunosuppressive, immunomodulatory and biological agents. The impact of chemotherapy on male fertility depends on the treatment protocol as well as the pre-treatment spermatogenesis status. Sperm concentration starts to drop about 2 weeks after beginning chemotherapy and reaches a maximum after 2-3 months. About half show recovery after 12-36 months. One year after therapy is completed, a treated patient has no increased risk of fathering a malformed child. There are no reports of methotrexate patients fathering children with malformations, most likely because impaired fertility or embryogenesis arrest. Cryopreservation of male gametes should be recommended prior to cytotoxic treatment, since the likelihood of post-treatment fertility is unpredictable. The cryopreservation causes a loss of vital spermatozoa by 30-70% but does not influence the genetic information of gametes. Males treated with retinoids have no reproductive safety risk. Biologicals inhibiting TNF alpha show a positive effect on sperm function in vitro."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I139,I139)","v":17067545},{"$f":"(LEN($J139) - LEN(SUBSTITUTE(LOWER($J139),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J139) - LEN(SUBSTITUTE(LOWER($J139),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J139) - LEN(SUBSTITUTE(LOWER($J139),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B139:D139)","v":1},2007,"Lycopenoids: are lycopene metabolites bioactive?","Lindshield",17067545,"Lycopenoids: are lycopene metabolites bioactive?    Abstract:   In vitro lycopene is the most potent antioxidant among carotenoids. While antioxidant function may be relevant to health, we hypothesize that metabolites of lycopene may be bioactive and responsible for the beneficial effects of tomato product consumption. We term these metabolites quot;lycopenoids,quot; which we believe may be produced from carotenoid monooxygenase (CMO) II, paralleling the production of retinoids from beta-carotene by CMO I. We present evidence suggesting that tomato carotenoid metabolites may be responsible for the reduced risk of prostate cancer seen in men consuming high levels of tomato products. Finally, we identify gaps in knowledge in this evolving area of carotenoid research."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I140,I140)","v":17016954},{"$f":"(LEN($J140) - LEN(SUBSTITUTE(LOWER($J140),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J140) - LEN(SUBSTITUTE(LOWER($J140),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J140) - LEN(SUBSTITUTE(LOWER($J140),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B140:D140)","v":1},2003,"Efficacy trials of a micronutrient dietary supplement in schoolchildren and pregnant women in Tanzania.","Latham",17016954,"Efficacy trials of a micronutrient dietary supplement in schoolchildren and pregnant women in Tanzania.    Abstract:   Traditionally, the main strategies used to control micronutrient deficiencies have been food diversification, consumption of medicinal supplements, and food fortification. In Tanzania, we conducted efficacy trials using a dietary supplement as a fourth approach. These were randomized, double-blind, placebo-controlled efficacy trials conducted separately first in children and later in pregnant women. The dietary supplement was a powder used to prepare an orange-flavored beverage. In the school trial, children consumed 25 g per school day attended. In the pregnancy trial, women consumed the contents of two 25-g sachets per day with meals. This dietary supplement, unlike most medicinal supplements, provided 11 micronutrients, including iron and vitamin A, in physiologic amounts. In both trials we compared changes in subjects consuming either the fortified or the nonfortified supplement. Measures of iron and vitamin A status were similar in the groups at the baseline examination, but significantly different at follow-up, always in favor of the fortified groups. Children receiving the fortified supplement had significantly improved anthropometric measures when compared with controls. At four weeks postpartum, the breast milk of a supplemented group of women had significantly higher mean retinol content than did the milk of mothers consuming the nonfortified supplement. The advantages of using a fortified dietary supplement, compared with other approaches, include its ability to control several micronutrient deficiencies simultaneously; the use of physiologic amounts of nutrients, rather than megadoses that require medical supervision; and the likelihood of better compliance than with the use of pills because subjects liked the beverage used in these trials."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I141,I141)","v":16728568},{"$f":"(LEN($J141) - LEN(SUBSTITUTE(LOWER($J141),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J141) - LEN(SUBSTITUTE(LOWER($J141),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J141) - LEN(SUBSTITUTE(LOWER($J141),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B141:D141)","v":1},2006,"The emerging roles of DNA methylation in the clinical management of prostate cancer.","Perry",16728568,"The emerging roles of DNA methylation in the clinical management of prostate cancer.    Abstract:   Aberrant DNA methylation is one of the hallmarks of carcinogenesis and has been recognized in cancer cells for more than 20 years. The role of DNA methylation in malignant transformation of the prostate has been intensely studied, from its contribution to the early stages of tumour development to the advanced stages of androgen independence. The most significant advances have involved the discovery of numerous targets such as GSTP1, Ras-association domain family 1A (RASSF1A) and retinoic acid receptor beta2 (RARbeta2) that become inactivated through promoter hypermethylation during the course of disease initiation and progression. This has provided the basis for translational research into methylation biomarkers for early detection and prognosis of prostate cancer. Investigations into the causes of these methylation events have yielded little definitive data. Aberrant hypomethylation and how it impacts upon prostate cancer has been less well studied. Herein we discuss the major developments in the fields of prostate cancer and DNA methylation, and how this epigenetic modification can be harnessed to address some of the key issues impeding the successful clinical management of prostate cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I142,I142)","v":16368536},{"$f":"(LEN($J142) - LEN(SUBSTITUTE(LOWER($J142),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J142) - LEN(SUBSTITUTE(LOWER($J142),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J142) - LEN(SUBSTITUTE(LOWER($J142),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B142:D142)","v":1},2006,"APO2 ligand/tumor necrosis factor-related apoptosis-inducing ligand in prostate cancer therapy.","Bucur",16368536,"APO2 ligand/tumor necrosis factor-related apoptosis-inducing ligand in prostate cancer therapy.    Abstract:   Prostate cancer is one of the most common cancers in men and is the second leading cause of cancer-related death in the USA. Many anti-tumor agents against prostate cancer cells have been developed, but their unacceptable systemic toxicity to normal tissues usually limits their use in the clinic. Apo2 ligand (Apo2L), also called Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), is one of several members of the TNF gene superfamily that induces apoptosis through engagement of death receptors. This protein has generated tremendous enthusiasm as a potential tumor-specific cancer therapeutic because, as a stable trimer, it selectively induces apoptosis in many transformed cells, but not in most normal cells. In this review we discuss its potential use in prostate cancer therapy, the mechanisms by which induces apoptosis or that underlie resistance to it, and strategies for sensitization to overcome them. Conventional chemotherapeutic and chemopreventive drugs, irradiation, and other therapeutic agents, such as histone deacetylase inhibitors or retinoids can sensitize Apo2L/TRAIL-resistant cells and tumors. Investigating the apoptotic effects of Apo2L/TRAIL, a unique tumor-specific cell death ligand, now in clinical trials, alone or in combination may not only help in understanding its antineoplastic role in prostate carcinoma but may also provide insights into basic mechanisms of apoptosis."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I143,I143)","v":16285276},{"$f":"(LEN($J143) - LEN(SUBSTITUTE(LOWER($J143),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J143) - LEN(SUBSTITUTE(LOWER($J143),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J143) - LEN(SUBSTITUTE(LOWER($J143),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B143:D143)","v":1},2003,"[Systemic treatment of cutaneous lupus erythematosus].","Wenzel",16285276,"[Systemic treatment of cutaneous lupus erythematosus].    Abstract:   The treatment of cutaneous lupus erythematosus (CLE) remains a therapeutic challenge. In many cases, systemic treatment of the disease is necessary, especially in cases resistant to topical treatment or with internal organ involvement. Even though many different agents can be employed in this situation, most are not approved in Germany for the treatment of CLE. We give an overview of the agents used in the systemic treatment of CLE and review their mechanisms of action, indications and their practical use in cutaneous LE based on literature results and our own experience. We discuss corticosteroids, antimalarials, dapsone, azathioprine, cyclophosphamide, methotrexate, retinoids, cyclosporine A, mycophenolate mofetil, sulfasalazine, thalidomide, clofazimine, tacrolimus, immunoglobulins, monoclonal antibodies, plasmapheresis, etanercept, infliximab, feflunomid, gold and interferon-alpha."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I144,I144)","v":15897691},{"$f":"(LEN($J144) - LEN(SUBSTITUTE(LOWER($J144),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J144) - LEN(SUBSTITUTE(LOWER($J144),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J144) - LEN(SUBSTITUTE(LOWER($J144),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B144:D144)","v":1},2005,"Can we prevent prostate cancer? Rationale and current status of prostate cancer chemoprevention.","Fujimoto",15897691,"Can we prevent prostate cancer? Rationale and current status of prostate cancer chemoprevention.    Abstract:   Prostate cancer has been one of the most frequent cancers among men in Western countries for the past decade. Investigation of prostate cancer prevention is very attractive, because prostate cancer has a high incidence, long-term natural history, regional difference in incidence, and is effected by sex steroids. Chemoprevention is defined as the use of specific agents to suppress or reverse carcinogenesis and to prevent the development of cancer. The development of chemoprevention strategies against prostate cancer would be of medical and economic importance. Basic and clinical research of chemoprevention of prostate cancer are under active investigation. This article aims to summarize and review the basic evidence and clinical trials on prostate cancer chemoprevention. Recent research has demonstrated that many agents, such as agents altering sex steroid signaling, drugs inducing antiproliferation/differentiation, retinoids, anti-inflammatory drugs, and antioxidants, could be potential preventatives for prostate cancer. Large-scale clinical trials have suggested that 5alpha-reductase inhibitor finasteride, selenium, and vitamin E can function as a chemopreventive agent. Although no definitely effective strategies of prostate cancer prevention have been identified yet, increasing evidence will provide effective and safe strategies that bring clinical benefits."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I145,I145)","v":15328191},{"$f":"(LEN($J145) - LEN(SUBSTITUTE(LOWER($J145),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J145) - LEN(SUBSTITUTE(LOWER($J145),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J145) - LEN(SUBSTITUTE(LOWER($J145),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B145:D145)","v":1},2004,"Optimal use of a panel of methylation markers with GSTP1 hypermethylation in the diagnosis of prostate adenocarcinoma.","Tokumaru",15328191,"Optimal use of a panel of methylation markers with GSTP1 hypermethylation in the diagnosis of prostate adenocarcinoma.    Abstract:    PURPOSE : In this study, we tested the ability of a panel of hypermethylation markers to improve the sensitivity of histologic prostate cancer detection in sextant needle biopsies.  EXPERIMENTAL DESIGN : We obtained fresh-frozen sextant biopsies from 72 excised prostates and directly compared blinded histologic review and quantitative real-time methylation-specific PCR for hypermethylation of four genes, Tazarotene-induced gene 1 (TIG1), adenomatous polyposis coli (APC), retinoic acid receptor beta2 (RARbeta2), and glutathione S-transferase pi (GSTP1) to detect the presence of prostate cancer. Results were compared with the final surgical pathological review of the resected prostates as the gold standard.  RESULTS : Histologic review alone detected carcinoma with a sensitivity of 64% (39 of 61 cases) and 100% specificity. Quantitative real-time methylation-specific PCR for TIG1, APC, RARbeta2, and GSTP1 detected carcinoma with a sensitivity of 70%, 79%, 89%, and 75%, respectively, with 100% specificity for all of the genes. Using this panel of methylation markers in combination with histology resulted in the detection of 59 of 61 (97%) cases of prostate with 100% specificity, a 33% improvement over histology alone.  CONCLUSION : The use of a panel of methylation markers as an adjunct to histologic review may substantially augment prostate cancer diagnosis from needle biopsies."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I146,I146)","v":15289752},{"$f":"(LEN($J146) - LEN(SUBSTITUTE(LOWER($J146),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J146) - LEN(SUBSTITUTE(LOWER($J146),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J146) - LEN(SUBSTITUTE(LOWER($J146),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B146:D146)","v":1},2004,"[Celiac disease and its endocrine and nutritional implications on male reproduction].","Stazi",15289752,"[Celiac disease and its endocrine and nutritional implications on male reproduction].    Abstract:   The problem of the interference of celiac disease (CD) with the male reproductive system is made evident both by the recognized adverse effects on female reproduction and by the multifactorial nature of the disease. It is important to consider CD as a multifactorial condition since its diverse effects can be modulated, besides gluten, by different concurrent genetic and environmental factors. The male CD patient has a greater risk of infertility and other reproductive disturbances, as well as a greater incidence of hypoandrogenism. In this paper the problems of CD associated to endocrine disorders and to deficiencies of micronutrients are discussed. Affected males show a picture of tissue resistance to androgens. Moreover, attention should be paid to increases of FSH and prolactin; these are not associated to infertility and/or impotence, but they may indicate an imbalance at hypothalamus-pituitary level, with general effects on health: an example is the increased risk of male osteoporosis in CD patients. Hormone alterations are reversible upon start of the gluten-free diet, emphasizing the importance of early diagnosis; this should be performed in the case of clinical suspicion, e.g., unexplained hypoandrogenism. As regards nutritional aspects, the folic acid deficiency of CD can affect rapidly proliferating tissues, such as the embryo and the seminiferous epithelium. More attention should be paid to deficiencies of fat-soluble vitamins, such as A and E, observed in CD. Vitamin A is important for Sertoli cell function as well as for early spermatogenetic phases. Vitamin E supports the correct differentiation and function of epidydimal epithelium, spermatid maturation and secretion of proteins by the prostate. Therefore, CD male patients should be considered as vulnerable subjects; thus, the detection of early biomarkers of andrological or endocrinological dysfunctions should trigger timely strategies for prevention and treatment."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I147,I147)","v":15153892},{"$f":"(LEN($J147) - LEN(SUBSTITUTE(LOWER($J147),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J147) - LEN(SUBSTITUTE(LOWER($J147),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J147) - LEN(SUBSTITUTE(LOWER($J147),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B147:D147)","v":1},2004,"American Academy of Dermatology Consensus Conference on the safe and optimal use of isotretinoin: summary and recommendations.","Goldsmith",15153892,"American Academy of Dermatology Consensus Conference on the safe and optimal use of isotretinoin: summary and recommendations.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I148,I148)","v":14979475},{"$f":"(LEN($J148) - LEN(SUBSTITUTE(LOWER($J148),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J148) - LEN(SUBSTITUTE(LOWER($J148),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J148) - LEN(SUBSTITUTE(LOWER($J148),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B148:D148)","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."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I149,I149)","v":14571416},{"$f":"(LEN($J149) - LEN(SUBSTITUTE(LOWER($J149),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J149) - LEN(SUBSTITUTE(LOWER($J149),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J149) - LEN(SUBSTITUTE(LOWER($J149),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B149:D149)","v":1},2003,"The development of differentiation agents for the treatment of prostate cancer.","Galsky",14571416,"The development of differentiation agents for the treatment of prostate cancer.    Abstract:   Given their novel mechanisms of action and relatively favorable toxicity profiles, differentiation agents have been the focus of much investigation in the field of oncology. Among the most well studied of these agents in prostate cancer have been the retinoids, vitamin D, peroxisome-proliferator-activated receptor gamma (PPARgamma) ligands, and, most recently, the histone deacetylase (HDAC) inhibitors. While the clinical activity of these agents has been limited, several obstacles to the development of these novel drugs have become apparent. A lack of validated measures of outcome and uncertainty regarding the appropriate disease states in which to test these agents have led to difficulty in trial design. Furthermore, a better understanding of the biologic targets and genes manipulated by these therapies is required such that more potent and selective drugs may be developed. By overcoming these obstacles, the full potential of this therapeutic class may be realized."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I150,I150)","v":12899524},{"$f":"(LEN($J150) - LEN(SUBSTITUTE(LOWER($J150),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J150) - LEN(SUBSTITUTE(LOWER($J150),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J150) - LEN(SUBSTITUTE(LOWER($J150),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B150:D150)","v":1},2003,"The role of vitamin D in prostate cancer.","Krishnan",12899524,"The role of vitamin D in prostate cancer.    Abstract:   Prostate cancer (PCa) cells harbor receptors for vitamin D (VDR) as well as androgens (AR). 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] increases AR expression and enhances androgen actions linking the two receptor systems. 1,25(OH)2D3 exhibits antiproliferative activity in both AR-positive and AR-negative PCa cells. Less calcemic analogs of 1,25(OH)2D3, with more antiproliferative activity, are being developed and will be more useful clinically. The mechanisms underlying differential analog activity are being investigated. In target cells, 1,25(OH)2D3 induces 24-hydroxylase, the enzyme that catalyzes its self-inactivation. Co-treatment with 24-hydroxylase inhibitors enhances the antiproliferative activity of calcitriol. Primary cultures of normal or cancer-derived prostatic epithelial cells express 1alpha-hydroxylase, the enzyme that catalyzes the synthesis of 1,25(OH)2D3, the levels being much lower in the cancer-derived cells and in PCa cell lines. This finding raises the possibility of using 25-hydroxyvitamin D3 [25(OH)D3] as a chemopreventive agent in PCa. In LNCaP human PCa cells, 1,25(OH)2D3 and its analogs exert antiproliferative activity predominantly by cell cycle arrest, but also induce apoptosis, although to a much lesser degree. Growth arrest is mediated by induction of IGF binding protein-3 (IGFBP-3), which in turn increases the expression of the cell cycle inhibitor p21, leading to growth arrest. Other actions of 1,25(OH)2D3 in PCa cells include promotion of pro-differentiation effects and inhibition of tumor cell invasion, metastasis and angiogenesis. Combination therapy with retinoids, other anticancer agents or 24-hydroxylase inhibitors augments the inhibitory activity of 1,25(OH)2D3 in PCa and provides another effective approach in PCa treatment. Small clinical trials have shown that 1,25(OH)2D3 can slow the rate of prostate specific antigen (PSA) rise in PCa patients, demonstrating proof of concept that 1,25(OH)2D3 or its analogs will be clinically effective in PCa therapy. Current research involves further investigation of the role of 1,25(OH)2D3 and its analogs for the therapy or chemoprevention of PCa."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I151,I151)","v":12840225},{"$f":"(LEN($J151) - LEN(SUBSTITUTE(LOWER($J151),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J151) - LEN(SUBSTITUTE(LOWER($J151),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J151) - LEN(SUBSTITUTE(LOWER($J151),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B151:D151)","v":1},2003,"Pathways mediating the growth-inhibitory actions of vitamin D in prostate cancer.","Peehl",12840225,"Pathways mediating the growth-inhibitory actions of vitamin D in prostate cancer.    Abstract:   Vitamin D is emerging as an important dietary factor that affects the incidence and progression of many malignancies including prostate cancer. The active form of vitamin D, 1,25-dihydroxycholecalciferol [1,25(OH)(2)D(3)], inhibits the growth and stimulates the differentiation of prostate cancer cells. We have studied primary cultures of normal and cancer-derived prostatic epithelial cells as well as established human prostate cancer cell lines to elucidate the molecular pathways of 1,25(OH)(2)D(3) actions. These pathways are varied and appear to be cell specific. In LNCaP cells, 1,25(OH)(2)D(3) mainly causes growth arrest through the induction of insulin-like growth factor binding protein-3 and also stimulates apoptosis to a much smaller extent. We have used cDNA-microarray analyses to identify additional genes that are regulated by 1,25(OH)(2)D(3) and to raise novel therapeutic targets for use in the chemoprevention or treatment of prostate cancer. Less calcemic analogs of 1,25(OH)(2)D(3) that have more antiproliferative activity are being developed that will be more useful clinically. In target cells, 1,25(OH)(2)D(3) induces 24-hydroxylase, the enzyme that catalyzes its self inactivation. Cotreatment with 24-hydroxylase inhibitors enhances the antiproliferative activity of 1,25(OH)(2)D(3). The combination of other anticancer agents such as retinoids with vitamin D offers another promising therapeutic approach. A small clinical trial has shown that 1,25(OH)(2)D(3) can slow the rate of prostate-specific antigen increase in prostate cancer patients, which demonstrates proof of the concept that vitamin D or its analogs are clinically effective. Our research is directed at understanding the mechanisms of vitamin D action in prostate cells with the goal of developing chemoprevention and treatment strategies to improve prostate cancer therapy."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I152,I152)","v":12636926},{"$f":"(LEN($J152) - LEN(SUBSTITUTE(LOWER($J152),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J152) - LEN(SUBSTITUTE(LOWER($J152),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J152) - LEN(SUBSTITUTE(LOWER($J152),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B152:D152)","v":1},2003,"The role of nutrition in preventing prostate cancer: a review of the proposed mechanism of action of various dietary substances.","Willis",12636926,"The role of nutrition in preventing prostate cancer: a review of the proposed mechanism of action of various dietary substances.    Abstract:    BACKGROUND : Dietary modifications to prevent prostate cancer (PCa) continue to gain attention as research demonstrates that various dietary nutrients/supplements are related to decreased risk of developing prostate cancer (PCa). Several studies have focused on the antioxidant and nonantioxidant effects of various dietary substances in the prevention of PCa. Research into the mechanisms by which PCa is prevented, or its disease severity is reduced by dietary micronutrients and vitamins continues to enrich our understanding of the mechanisms by which PCa is initiated and progresses.  METHODS : We reviewed the literature on dietary nutrients with antioxidant properties that have been shown to have a positive effect in reducing the incidence or preventing the occurrence of PCa including carotenoids (e.g., lycopene), retinoids (e.g., vitamin A), vitamin E, vitamin C, selenium, and polyphenols. Other nutrients examined included vitamin D and calcium.  RESULTS : Many dietary micronutrients have demonstrated significant and complex effects on PCa cell proliferation, differentiation, and signaling related to the initiation, progression, and regression of PCa.  CONCLUSION : Understanding the mechanisms by which various dietary nutrients exert their effects on PCa may make it possible to design effective drugs for treating PCa and to promote better nutrition and lifestyle changes in those at risk for PCa."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I153,I153)","v":12570331},{"$f":"(LEN($J153) - LEN(SUBSTITUTE(LOWER($J153),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J153) - LEN(SUBSTITUTE(LOWER($J153),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J153) - LEN(SUBSTITUTE(LOWER($J153),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B153:D153)","v":1},2002,"Chemoprevention strategies for prostate cancer.","Bosland",12570331,"Chemoprevention strategies for prostate cancer.    Abstract:   Prostate cancer is the most common male malignancy in western countries. Although primary prevention of prostate cancer is not possible, screening using prostate-specific antigen (PSA) may eliminate prostate cancers by definitive treatments. Prevention of clinically detectable prostate cancer requires earlier chemoprevention interventions. Because prostate cancer is histologically present in 30-50% of 30- to 50-year-old men, effective chemoprevention needs to inhibit not only prostate carcinogenesis but also growth and progression of these cancers. A prostate carcinogenesis animal model has been used to screen chemopreventive agents; inhibitory effects were found with 9-cis-retinoic acid, dehydroepiandrosterone, fluasterone, and the Bowman-Birk inhibitor and an isoflavone mixture which both occur in soy. Such results can be used to select agents for clinical trials. Besides large-scale long-duration prevention trials, trials of short/intermediate duration using smaller cohorts prior to or following radical prostatectomy may provide excellent and cost-effective approaches for chemopreventive agent efficacy testing. Intervention prior to surgery allows measurements of intervention agents and intermediate end-points in the prostate. These peri-surgical trials only assess inhibition of growth and progression of preexisting cancer, not real preventive effects, but they focus on clinically significant cancers. Such trials are an essential step in the development of antiprostate cancer chemoprevention agents."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I154,I154)","v":12462073},{"$f":"(LEN($J154) - LEN(SUBSTITUTE(LOWER($J154),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J154) - LEN(SUBSTITUTE(LOWER($J154),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J154) - LEN(SUBSTITUTE(LOWER($J154),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B154:D154)","v":1},2002,"[The genetics of sex determination].","Vialard",12462073,"[The genetics of sex determination].    Abstract:   The male sex determination controls the testis determination and differentiation. So far more than a dozen of gene have been characterised, including the primary Y male sex determinant: SRY gene. All the genes encode transcription factor except FDF9 which encodes a growth factor allowing mesonephritic cell to divide and migrate to the mesenchyme. All these gene products are sensitive in man (but not in the mouse model) to gene dosage: haplo-insufficiency and or duplication of these genes all lead to sex reversal. Today, we still do not know how their products are epistatic in the sex determining cascade. So far no ovary sex determining gene has been characterised."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I155,I155)","v":12431818},{"$f":"(LEN($J155) - LEN(SUBSTITUTE(LOWER($J155),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J155) - LEN(SUBSTITUTE(LOWER($J155),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J155) - LEN(SUBSTITUTE(LOWER($J155),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B155:D155)","v":1},2002,"Angiogenesis in prostate cancer: its role in disease progression and possible therapeutic approaches.","van Moorselaar",12431818,"Angiogenesis in prostate cancer: its role in disease progression and possible therapeutic approaches.    Abstract:   The interaction between cancer cells and their microenvironment is a promising area for the development of novel therapeutic anti-cancer modalities. The formation of new blood vessels, angiogenesis, is an important step in cancer progression. Angiogenesis is a complex multistep process involving close orchestration of endothelial cells, extracellular matrix, and soluble factors. Essentially every step has been found to be regulated by inducers and inhibitors. Prostate cancer has the ability to produce angiogenic factors such as metalloproteinases, vascular endothelial growth factor, fibroblast growth factor 2, transforming growth factor-beta and cyclooxygenase-2. In several studies in prostate cancer an increased microvessel density is associated with poorer prognosis. On the other hand several endogenous inhibitors of angiogenesis have been described in prostate cancer e.g., angiostatin, endostatin, prostate specific antigen (PSA), thrombospondin-1, interleukin 10, interferons and retinoids. The expanding insight in the process of angiogenesis has resulted in a large number of pharmaceutical agents that have been tested in preclinical studies and are currently tested in clinical trials. These agents inhibit endothelial cell proliferation or migration and induce apoptosis. This ultimately will affect the formation of new vessels thereby inducing tumor dormancy. Because antiangiogenic treatment is cytostatic rather than cytotoxic, patients will need long-term therapy to prevent regrowth of the tumor. Prostate cancer is an ideal tumor for antiangiogenic studies because of the availability of a reliable tumor marker, PSA, the indolent clinical course of this cancer and the low rate of proliferation even in metastatic sites. Furthermore, clinical studies showed limited side effects, which is advantageous in this elderly patient group. Whether the ultimate antiangiogenic treatment is effective as a single agent or in combination with radiation therapy, chemotherapy or immunotherapy remains to be determined."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I156,I156)","v":12218221},{"$f":"(LEN($J156) - LEN(SUBSTITUTE(LOWER($J156),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J156) - LEN(SUBSTITUTE(LOWER($J156),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J156) - LEN(SUBSTITUTE(LOWER($J156),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B156:D156)","v":1},2002,"Is there a reproductive safety risk in male patients treated with acitretin (neotigason/soriatane?","Geiger",12218221,"Is there a reproductive safety risk in male patients treated with acitretin (neotigason/soriatane?    Abstract:   Review of preclinical data including genotoxicity assays and a male rat reproduction toxicology study demonstrates that acitretin (Neotigason)/Soriatane) does not affect the reproductive outcome in naive females mated with treated males. Prospective studies of teratogenic risk or impairment of fertility cannot be ethically conducted in humans. However, it is highly unlikely that any fetal malformation could be induced by an ejaculate containing traces of acitretin. Indeed, worldwide postmarketing surveillance has not revealed any cases of retinoid embryopathy associated with paternal treatment with acitretin. Birth defects seen in pregnancies fathered by male acitretin patients were all events expected to occur in the general population at known frequencies. In conclusion, therefore, available data do not appear to indicate any reproductive safety risk due to paternal treatment with acitretin."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I157,I157)","v":11891692},{"$f":"(LEN($J157) - LEN(SUBSTITUTE(LOWER($J157),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J157) - LEN(SUBSTITUTE(LOWER($J157),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J157) - LEN(SUBSTITUTE(LOWER($J157),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B157:D157)","v":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."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I158,I158)","v":11790281},{"$f":"(LEN($J158) - LEN(SUBSTITUTE(LOWER($J158),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J158) - LEN(SUBSTITUTE(LOWER($J158),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J158) - LEN(SUBSTITUTE(LOWER($J158),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B158:D158)","v":1},2001,"Advancing perspectives on prostate cancer: multihormonal influences in pathogenesis.","Porter",11790281,"Advancing perspectives on prostate cancer: multihormonal influences in pathogenesis.    Abstract:   Nonandrogenic hormones are implicated in the growth and function of the prostate, which is itself an endocrine gland that synthesizes and secretes hormones and growth factors, including follicle-stimulating hormone (FSH) and prostatic inhibin peptide (PIP). Findings of increased FSH concentrations and receptor expression in diseased prostate tissue suggest a role for FSH in prostate cancer growth. Not only does PIP suppress circulating levels of FSH, but it responds to and modulates prostatic FSH, suggesting a close interlinkage of these compounds in controlling both healthy and diseased prostate cells. Other focuses of endocrinologic research include androgen receptors, vitamin D, growth factors (including insulin-like growth factors I and II), and retinoids. Issues such as optimal therapy timing, intermittent administration, and the adoption of a multihormonal approach to the management of prostate cancer remain to be resolved."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I159,I159)","v":11738790},{"$f":"(LEN($J159) - LEN(SUBSTITUTE(LOWER($J159),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J159) - LEN(SUBSTITUTE(LOWER($J159),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J159) - LEN(SUBSTITUTE(LOWER($J159),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B159:D159)","v":1},2001,"Phenotypic spectrum of mutations in DAX-1 and SF-1.","Achermann",11738790,"Phenotypic spectrum of mutations in DAX-1 and SF-1.    Abstract:   SF-1 (steroidogenic factor-1) (NR5A1) and DAX-1 (dosage-sensitive sex-reversal, adrenal hypoplasia congenital, X chromosome) (NR0B1) are orphan nuclear receptors that are expressed in the adrenal gland, gonads, ventromedial hypothalamus (VMH), and pituitary gonadotrope cells. The function of these genes has been clarified by examining the consequences of naturally occurring mutations in humans, as well as targeted disruption of the genes in mice. Mutations in DAX1 cause adrenal hypoplasia congenita (AHC), an X-linked disorder characterized by adrenal insufficiency and failure to undergo puberty because of hypogonadotropic hypogonadism. Most DAX1 mutations introduce frameshifts and/or cause premature termination of the protein. Relatively few missense mutations have been described and all are located within the carboxy-terminal half of the protein. Transfection assays demonstrate that AHC-associated DAX1 mutations abrogate its ability to act as a transcriptional repressor of SF-1. Most boys affected with AHC present with adrenal insufficiency in early infancy, although a significant fraction present in later childhood or even as young adults. The degree of gonadotropin deficiency is also variable. With the exception of one mild missense DAX1 mutation, genotype-phenotype correlations have been elusive, suggesting an important role for modifier genes. Targeted mutagenesis of Dax1 (Ahch) in mice reveals an additional role in testis development and spermatogenesis. Similar abnormalities appear to be present in humans. Targeted mutagenesis of Sf1 (FtzF1) prevents gonadal and adrenal development, and causes male-to-female sex-reversal. A human XY individual with a heterozygous SF1 mutation presented with adrenal insufficiency and complete sex-reversal; this DNA-binding domain mutation prevents SF-1 stimulation of its target genes. In addition to their clinical relevance, studies of SF1 and DAX1 are proving useful for unraveling the genetic pathways that govern adrenal and gonadal development."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I160,I160)","v":11374314},{"$f":"(LEN($J160) - LEN(SUBSTITUTE(LOWER($J160),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J160) - LEN(SUBSTITUTE(LOWER($J160),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J160) - LEN(SUBSTITUTE(LOWER($J160),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B160:D160)","v":1},2001,"Treatment of patients with metastatic germ cell tumors relapsing after high-dose chemotherapy.","Kollmannsberger",11374314,"Treatment of patients with metastatic germ cell tumors relapsing after high-dose chemotherapy.    Abstract:   With the use of cisplatin-based combination chemotherapy, metastatic testicular germ cell tumors can be cured in 70-80% of patients. Patients refractory to cisplatin-based chemotherapy have a very poor prognosis. Several mechanisms have been discussed for the development of platinum resistance such as a decreased intracellular concentration of the drug, increased repair of the drug induced damage, or an altered apoptotic response to this damage. Various chemotherapeutic agents have been evaluated in intensively pretreated or cisplatin-refractory patients. Neither the antracyclines nor vinorelbine, bendamustine, topotecan, nor biological agents such as suramin and retinoic acid have demonstrated clinical activity. Paclitaxel has been evaluated at different doses and schedules and yielded a response rate of 21% (range 11-30%) with individual patients achieving complete remissions. This has led to the inclusion of paclitaxel in salvage regimens in combination with cisplatin and/or ifosfamide. Two recent studies have evaluated gemcitabine in refractory germ cell tumors, demonstrating a response rate of 17% (95% CI: 7-28%) in 52 intensively pretreated patients, two-thirds of whom had relapsed after previous high-dose chemotherapy plus autologous stem cell transplantation. The nonhematologic toxicity of weekly gemcitabine at doses of 1000-1250 mg/m2 was tolerable and hematologic side effects included thrombocytopenia in approximately 20% of patients. Ongoing studies in refractory germ cell tumors performed by the German Testicular Cancer Study Group (GTCSG) are evaluating oxaliplatin, a platinum derivative with incomplete cross-resistance to cisplatin. Future trials combining new active agents may make it possible to test the use of alternating treatment strategies in patients with quot;poor prognosticquot; disease or as salvage treatment. It is hoped that the increase in knowledge of the molecular mechanism of testicular cancer may lead to the development of new therapeutic options."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I161,I161)","v":11301600},{"$f":"(LEN($J161) - LEN(SUBSTITUTE(LOWER($J161),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J161) - LEN(SUBSTITUTE(LOWER($J161),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J161) - LEN(SUBSTITUTE(LOWER($J161),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B161:D161)","v":1},2001,"DAX-1, an quot;antitestisquot; gene.","Goodfellow",11301600,"DAX-1, an quot;antitestisquot; gene.    Abstract:   The DAX-1 gene has been involved in the dosage sensitive sex reversal (DSS) phenotype, a male-to-female sex-reversal syndrome due to the duplication of a small region of human chromosome Xp21. Dax-1 and Sry have been shown to act antagonistically in the mouse system, where increasing expression of the former leads to female development and increasing activity of the latter to male development. Although these data strongly implicate DAX-1 in sex determination, the mouse and human proteins appear to behave differently. Absence of DAX-1 is responsible for adrenal hypoplasia congenita, a human inherited disorder characterized by adrenal insufficiency and hypogonadotropic hypogonadism. Unlike human patients, Dax-1-deficient XY mice have normal levels of corticotropins and adrenal hormones but are sterile. Dax-1-deficient females are fertile. The DAX-1 protein, an unusual member of the nuclear hormone receptor, may act as a transcriptional repressor. It has been shown to both repress transcriptional activators by direct protein-protein interactions and to bind DNA hairpin structures and repress target genes."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I162,I162)","v":11058762},{"$f":"(LEN($J162) - LEN(SUBSTITUTE(LOWER($J162),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J162) - LEN(SUBSTITUTE(LOWER($J162),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J162) - LEN(SUBSTITUTE(LOWER($J162),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B162:D162)","v":1},2000,"Epididymal retinoic acid-binding protein.","Ong",11058762,"Epididymal retinoic acid-binding protein.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I163,I163)","v":10898344},{"$f":"(LEN($J163) - LEN(SUBSTITUTE(LOWER($J163),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J163) - LEN(SUBSTITUTE(LOWER($J163),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J163) - LEN(SUBSTITUTE(LOWER($J163),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B163:D163)","v":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."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I164,I164)","v":10626293},{"$f":"(LEN($J164) - LEN(SUBSTITUTE(LOWER($J164),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J164) - LEN(SUBSTITUTE(LOWER($J164),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J164) - LEN(SUBSTITUTE(LOWER($J164),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B164:D164)","v":1},2000,"The cell biology and molecular genetics of testis determination.","Smith",10626293,"The cell biology and molecular genetics of testis determination.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I165,I165)","v":10361557},{"$f":"(LEN($J165) - LEN(SUBSTITUTE(LOWER($J165),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J165) - LEN(SUBSTITUTE(LOWER($J165),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J165) - LEN(SUBSTITUTE(LOWER($J165),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B165:D165)","v":1},1999,"Differentiating agents and nontoxic therapies.","Myers",10361557,"Differentiating agents and nontoxic therapies.    Abstract:   The discovery of the oncogene and the mechanism by which these genetic changes create malignant transformation has provided new opportunities for drug development. Suramin is the first drug shown to exert its anticancer activity by blocking autocrine loops involved in malignant transformation. Phenylacetate and related aromatic fatty acids are potent inducers of differentiation in normal and malignant cells. Arachidonate, a fatty acid, plays a role in prostate cancer survival, growth, invasiveness, and immunosuppression. The actions of arachidonic acid can be moderated by diet or blocked by pharmacologic agents. Other agents that promise low toxicity include vitamin D and its analogs, genistein and related isoflavones, green tea polyphonols, and retinoic acid analogs."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I166,I166)","v":10325499},{"$f":"(LEN($J166) - LEN(SUBSTITUTE(LOWER($J166),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J166) - LEN(SUBSTITUTE(LOWER($J166),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J166) - LEN(SUBSTITUTE(LOWER($J166),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B166:D166)","v":1},1999,"New agents for chemoprevention of prostate cancer.","Sporn",10325499,"New agents for chemoprevention of prostate cancer.    Abstract:   The magnitude of the problem of prostate cancer, and the failure of conventional chemotherapy and surgery to effect a marked diminution in the total number of deaths from this disease, now indicate that chemoprevention of prostatic carcinogenesis must be seriously considered. We describe the development of a new system for quantitating the process of prostatic carcinogenesis in an experimental animal, and the use of this system to demonstrate that the retinoid, 4-hydroxyphenylretinamide, the deltanoid, Ro24-5531, and the estrogen analog, tamoxifen, all are effective agents for prevention of experimental prostate cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I167,I167)","v":10325487},{"$f":"(LEN($J167) - LEN(SUBSTITUTE(LOWER($J167),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J167) - LEN(SUBSTITUTE(LOWER($J167),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J167) - LEN(SUBSTITUTE(LOWER($J167),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B167:D167)","v":1},1999,"Chemoprevention of prostate cancer: concepts and strategies.","Kelloff",10325487,"Chemoprevention of prostate cancer: concepts and strategies.    Abstract:   Chemoprevention is the administration of agents to prevent induction and inhibit or delay progression of cancers. For prostate, as for other cancer targets, successful chemopreventive strategies require well-characterized agents, suitable cohorts, and reliable intermediate biomarkers of cancer for evaluating chemopreventive efficacy. Agent requirements are experimental or epidemiological data showing chemopreventive efficacy, safety on chronic administration, and a mechanistic rationale for the observed chemopreventive activity. On this basis, promising chemopreventive drugs in prostate include retinoids, antiandrogens, antiestrogens, steroid aromatase inhibitors, 5alpha-reductase inhibitors, vitamins D and E, selenium, lycopene, and 2-difluoromethylornithine. Phase II trials are critical for evaluating chemopreventive efficacy. Cohorts in these trials should be suitable for measuring the chemopreventive activity of the agent and the intermediate biomarkers chosen as endpoints. Many cohorts proposed for phase II trials are patients with previous cancers or premalignant lesions. For such patients, trials should be conducted within the context of standard treatment. Two cohorts currently used in phase II prostate cancer chemoprevention trials are patients with PIN and patients scheduled for prostate cancer surgery. Biomarkers should fit expected biological mechanisms, be assayed reliably and quantitatively, measured easily, and correlate to decreased cancer incidence. Protocols for adequately sampling tissue are essential. Changes in PIN provide prostate biomarkers with the ability to be quantified and a high correlation to cancer. PIN measurements include nuclear polymorphism, nucleolar size and number of nucleoli/nuclei, and DNA ploidy. Other potentially useful biomarkers are associated with cellular proliferation kinetics (e.g. PCNA and apoptosis), differentiation (e.g. blood group antigens, vimentin), genetic damage (e.g. LOH on chromosome 8), signal transduction (e.g. TGFalpha, TGFbeta, IGF-I, c-erbB-2 expression), angiogenesis, and biochemical changes (e.g. PSA levels)."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I168,I168)","v":10234899},{"$f":"(LEN($J168) - LEN(SUBSTITUTE(LOWER($J168),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J168) - LEN(SUBSTITUTE(LOWER($J168),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J168) - LEN(SUBSTITUTE(LOWER($J168),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B168:D168)","v":1},1999,"Insulin-like growth factors and cancer.","Yu",10234899,"Insulin-like growth factors and cancer.    Abstract:   Insulin-like growth factors (IGFs) regulate important cellular activities involving cell proliferation, differentiation, and apoptosis. Emerging evidence suggests that members of the IGF family, including IGF-1, IGF-2, the IGF-1 receptor (IGF-1R), and the IGF binding proteins (IGFBPs), play important roles in the development and progression of cancer. Both in vitro and in vivo studies show that IGFs are strong mitogens for a variety of cancer cells. IGF-1 also has an antiapoptotic action on cancer. IGF-1R, overexpressed in cancer cells, mediates the effects of IGFs and plays a role in cell transformation induced by tumor virus and oncogene products. IGFBPs inhibit the actions of IGFs and mediate the anti-proliferative effect of wild-type p53 protein, retinoic acid, vitamin D, and transforming growth factor-beta (TGF-beta). Findings from epidemiologic studies support the involvement of IGF in cancer etiology. Diet, nutrition, and other lifestyle features affect the expression and production of IGF-1 and other members of the IGF family. This may provide new approaches for cancer prevention. Growth hormone (GH) stimulates the production of IGF-1. Use of GH replacement therapy to improve physiological and psychological well-being and to prevent aging-related diseases has been recommended. Given the close relationship between GH and IGF-1, the long-term safety of GH treatment warrants a serious concern."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I169,I169)","v":9890059},{"$f":"(LEN($J169) - LEN(SUBSTITUTE(LOWER($J169),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J169) - LEN(SUBSTITUTE(LOWER($J169),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J169) - LEN(SUBSTITUTE(LOWER($J169),LOWER(D$3),\"\")))/LEN(D$3)","v":1},{"$f":"SUM(B169:D169)","v":1},1998,"Genetic control of gonadal differentiation.","Lim",9890059,"Genetic control of gonadal differentiation.    Abstract:   The study of naturally occurring mutations in humans and induced mutations in mice that cause sex reversal has been instrumental in the cloning and functional analysis of genes involved in gonadal differentiation. Several genes required for this complex developmental process have now been identified. The genes LIM1, WT1 and FTZ-F1 have been demonstrated to be involved in the formation of the gonads prior to their differentiation as testes or ovaries. Subsequent sex-specific gonadal differentiation appears to be mediated by the SRY and SOX9 genes in the testis, and the DAX-1 gene in the ovary."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I170,I170)","v":9706339},{"$f":"(LEN($J170) - LEN(SUBSTITUTE(LOWER($J170),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J170) - LEN(SUBSTITUTE(LOWER($J170),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J170) - LEN(SUBSTITUTE(LOWER($J170),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B170:D170)","v":1},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."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I171,I171)","v":9691832},{"$f":"(LEN($J171) - LEN(SUBSTITUTE(LOWER($J171),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J171) - LEN(SUBSTITUTE(LOWER($J171),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J171) - LEN(SUBSTITUTE(LOWER($J171),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B171:D171)","v":1},1998,"[Molecular effects of vitamin D on cell cycle and oncogenesis].","Schmidt",9691832,"[Molecular effects of vitamin D on cell cycle and oncogenesis].    Abstract:   The active metabolite of vitamin D, 1,25 (OH)2D3, exerts its cell cycle regulating effects via binding to VDR (Vitamin D Receptor). This complex forms a heterodimer with RXR (Retinoic X Receptor). The VDR-RXR heterodimer binds to promoter regions of cell cycle regulating genes through a vitamin D response element (VDRE). The tumour suppressor gene cyclin kinase inhibitor (Cki) p21, one of the well known cell cycle regulating genes, is one of the genes regulated in this manner. Its tumour suppressive action is through inhibition of cell division. These molecular biological mechanisms and large epidemiological investigations give strong support for the benefits of vitamin D in preventing colon cancer and prostate cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I172,I172)","v":9563695},{"$f":"(LEN($J172) - LEN(SUBSTITUTE(LOWER($J172),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J172) - LEN(SUBSTITUTE(LOWER($J172),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J172) - LEN(SUBSTITUTE(LOWER($J172),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B172:D172)","v":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."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I173,I173)","v":9554481},{"$f":"(LEN($J173) - LEN(SUBSTITUTE(LOWER($J173),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J173) - LEN(SUBSTITUTE(LOWER($J173),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J173) - LEN(SUBSTITUTE(LOWER($J173),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B173:D173)","v":1},1998,"Growth factor involvement in progression of prostate cancer.","Russell",9554481,"Growth factor involvement in progression of prostate cancer.    Abstract:   Understanding how the regulation of growth factor pathways alters during prostate cancer (PC) progression may enable researchers to develop targeted therapeutic strategies for advanced disease. PC progression involves the shifting of cells from androgen-dependent growth to an androgen-independent state, sometimes with the loss or mutation of the androgen receptors in PC cells. Both autocrine and paracrine pathways are up-regulated in androgen-independent tumors and may replace androgens as primary growth stimulatory factors in cancer progression. Our discussion focuses on growth factor families that maintain homeostasis between epithelial and stromal cells in the normal prostate and that undergo changes as PC progresses, often making stromal cells redundant. These growth factors include fibroblast growth factor, insulin-like growth factors, epidermal growth factor, transforming growth factor alpha, retinoic acid, vitamin D3, and the transforming growth factor beta families. We review their role in normal prostate development and in cancer progression, using evidence from clinical specimens and models of PC cell growth."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I174,I174)","v":9488752},{"$f":"(LEN($J174) - LEN(SUBSTITUTE(LOWER($J174),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J174) - LEN(SUBSTITUTE(LOWER($J174),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J174) - LEN(SUBSTITUTE(LOWER($J174),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B174:D174)","v":1},1997,"[Treatment of acne].","Delanoë",9488752,"[Treatment of acne].    Abstract:   The treatment of acne is based upon simple pathogenic arguments, but needs to be adapted to the type of acne. Patients must always be informed that it is long and difficult and that no significant response will be expected before 2 to 3 months of regular treatment. The authors present the different therapeutic agents and strategies. Isotretinoin should be used only in severe acne after failure of at least 3 months of a well conducted classical treatment and in nodulo-cystic acne; because of its major side effect of teratogenicity its use in adolescent girls requires pregnancy testings before and during treatment and an effective contraception."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I175,I175)","v":12321668},{"$f":"(LEN($J175) - LEN(SUBSTITUTE(LOWER($J175),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J175) - LEN(SUBSTITUTE(LOWER($J175),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J175) - LEN(SUBSTITUTE(LOWER($J175),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B175:D175)","v":1},1997,"Chemoprevention and prostate cancer.","Crawford",12321668,"Chemoprevention and prostate cancer.    Abstract:   Over the past 15 years, the number of US males diagnosed with prostate cancer has increased 350% because of the aging of the population and improved detection with the prostate specific antigen (PSA) blood test. A new strategy to case management is chemoprevention, or early intervention with a well-tolerated drug. It is believed that prostate cancer is initiated when a cell undergoes genetic changes with malignant potential. Next, the cancer grows, or is promoted, until it is prominent, detectable, and has acquired a propensity to spread. Primary chemoprevention intervenes in the initiation and promotion process. Secondary chemoprevention involves early detection, treatment, and cure. Chemoprevention research, therefore, is focusing on identification of active agents that will be well tolerated in the general population, such as micronutrients as vitamins and minerals. For example, research indicates that intake of lycopene or other components in tomatoes may reduce prostate cancer risk. Other researchers are testing a drug to block the activity of the enzyme 5-alpha reductase, because men deficient in this enzyme fail to develop prostate cancer. Other agents under investigation are selenium, vitamin E, nonsteroidal anti-inflammatory drugs, retinoids, and a compound known as DFMO, which stabilizes cellular DNA. Efforts are also being made to reverse cases of prostatic intraepithelial neoplasia, which is thought to be a precursor of cancer. Eventually, predictions of degree of risk will be used to include men in chemoprevention trials."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I176,I176)","v":9361778},{"$f":"(LEN($J176) - LEN(SUBSTITUTE(LOWER($J176),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J176) - LEN(SUBSTITUTE(LOWER($J176),LOWER(C$3),\"\")))/LEN(C$3)","v":1},{"$f":"(LEN($J176) - LEN(SUBSTITUTE(LOWER($J176),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B176:D176)","v":1},1997,"Sertoli cell-specific gene expression in conditionally immortalized cell lines.","Walther",9361778,"Sertoli cell-specific gene expression in conditionally immortalized cell lines.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I177,I177)","v":9238852},{"$f":"(LEN($J177) - LEN(SUBSTITUTE(LOWER($J177),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J177) - LEN(SUBSTITUTE(LOWER($J177),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J177) - LEN(SUBSTITUTE(LOWER($J177),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B177:D177)","v":1},1997,"Steroidogenic factor 1 plays multiple roles in endocrine development and function.","Wong",9238852,"Steroidogenic factor 1 plays multiple roles in endocrine development and function.    Abstract:   The nuclear hormone receptor family comprises a group of structurally related transcriptional regulators that mediate the actions of diverse ligands, including steroid hormones, thyroid hormone, vitamin D, and retinoids. The nuclear receptor family also contains members for which activating ligands have not been identified-the orphan nuclear receptors. One of these orphan nuclear receptors, steroidogenic factor 1 (SF-1), has emerged as an essential regulator of steroidogenic cell function within the adrenal cortex and gonads; SF-1 also plays important roles in reproduction at all three levels of the hypothalamic-pituitary-gonadal axis. First identified as a tissue-specific regulator of the transcription of the cytochrome P450 steroid hydroxylases, considerably broader roles for SF-1 were revealed by genetic studies in mice lacking SF-1 due to targeted gene disruption. These SF-1-knockout mice had agenesis of their adrenal glands and gonads, male-to-female sex reversal of their internal and external genitalia, impaired gonadotrope function, and agenesis of the ventromedial hypothalamic nucleus. These studies delineated essential roles of SF-1 in regulating endocrine differentiation and function at multiple levels. Despite these insights into roles of SF-1, the precise mechanisms by which SF-1 exerts its multiple effects remain to be determined. This review highlights experiments that have established SF-1 as a pivotal determinant of endocrine differentiation and function and identifies areas in which additional studies are needed to expand our understanding of SF-1 action."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I178,I178)","v":8725886},{"$f":"(LEN($J178) - LEN(SUBSTITUTE(LOWER($J178),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J178) - LEN(SUBSTITUTE(LOWER($J178),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J178) - LEN(SUBSTITUTE(LOWER($J178),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B178:D178)","v":1},1996,"Screening for prostate cancer: opportunities for prevention.","Thompson",8725886,"Screening for prostate cancer: opportunities for prevention.    Abstract:   Although early detection and treatment of prostate cancer is widely advocated, this so-called secondary prevention approach has a number of drawbacks. First, it is not yet certain that active treatment of localized prostate cancer offers any advantage over surveillance. Second, screening may detect indolent tumors while missing some virulent ones. Third, treatment is not uniformly successful, even in patients with early disease. Fourth, radical prostatectomy and radiotherapy are associated with considerable side effects. And finally, the economic and psychological costs of large-scale screening cannot be overlooked. Although attention has been focused on the possibility of primary prevention, neither large-scale dietary manipulation nor long-term prophylactic use of retinoids is considered feasible. With the recent approval of the 5-alpha-reductase inhibitor finasteride for the treatment of benign prostatic hyperplasia, the opportunity for primary chemoprevention has moved closer to reality. The Prostate Cancer Prevention Trial (PCPT), a randomized, placebo-controlled study expected to enroll 18,000 healthy men over the age of 55, is currently addressing the question of whether finasteride prophylaxis can reduce the incidence of prostate cancer over a 7-year period. This is a US government work. There are no restrictions on its use."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I179,I179)","v":8875211},{"$f":"(LEN($J179) - LEN(SUBSTITUTE(LOWER($J179),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J179) - LEN(SUBSTITUTE(LOWER($J179),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J179) - LEN(SUBSTITUTE(LOWER($J179),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B179:D179)","v":1},1996,"Chemoprevention for prostatic intraepithelial neoplasia.","Nelson",8875211,"Chemoprevention for prostatic intraepithelial neoplasia.    Abstract:    OBJECTIVES : To evaluate the potential application of chemoprevention strategies in prostatic intraepithelial neoplasia.  METHODS : Review of relevant literature on chemoprevention with emphasis on prostate cancer and premalignant lesions.  RESULTS : Chemoprevention represents a strategy designed to inhibit or reverse the process of carcinogenesis by administering one or several noncytotoxic chemical compounds. The epidemiology of prostate carcinoma indicates that this cancer is a prime candidate for a strategy aimed at prevention due to the extremely high prevalence rate, rising annual incidence, and long latent interval between the cancer-initiating events and the development of invasive disease. Chemopreventive agents may exert their inhibitory effects at different stages of the multistep carcinogenic process broadly categorized as initiation, promotion, and progression. The synthetic retinoids, polyamine synthesis inhibitors, and antiandrogens are among the compounds shown to have in vitro or in vivo chemopreventive effects in prostate carcinogenesis. A major limitation in the evaluation of such agents in a human prostate cancer is the long duration of clinical trials required to assess the efficacy with an endpoint of cancer development. Premalignant epithelial changes such as prostate intraepithelial neoplasia, or PIN, are highly associated with prostate cancer, and share many molecular features of invasive cancer. If the reversal or inhibition of intraepithelial neoplasia translates to a concomitant reduction in clinically relevant prostate cancer, then the pharmacological modulation of PIN may provide a rapid means to evaluate the effects and benefits of potential chemopreventive agents.  CONCLUSION : Men with PIN may represent ideal candidates for chemoprevention protocols. The ideal agent and duration of therapy remains to be defined."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I180,I180)","v":7492140},{"$f":"(LEN($J180) - LEN(SUBSTITUTE(LOWER($J180),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J180) - LEN(SUBSTITUTE(LOWER($J180),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J180) - LEN(SUBSTITUTE(LOWER($J180),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B180:D180)","v":1},1995,"Melasma. Etiologic and therapeutic considerations.","Grimes",7492140,"Melasma. Etiologic and therapeutic considerations.    Abstract:    BACKGROUND : Melasma is a common acquired symmetric hypermelanosis characterized by irregular light- to gray-brown macules and patches involving sun-exposed areas of skin. Etiologic factors in the pathogenesis of melasma include genetic influences, exposure to UV radiation, pregnancy, hormonal therapies, cosmetics, phototoxic drugs, and antiseizure medications.  OBSERVATIONS : Melasma is often a therapeutically challenging disease, and current treatments include hypopigmenting agents, chemical peels, and lasers. Hypopigmenting agents include phenolic and nonphenolic derivatives. Phenolic agents include hydroquinone and hydroquinone combination preparations. Despite controversies regarding the issue of hydroquinone-induced ochronosis, hydroquinone remains the most effective topically applied bleaching agent approved by the Food and Drug Administration for the treatment of melasma. Nonphenolic bleaching agents include tretinoin and azelaic acid. Superficial, medium, and deep chemical peels are more often used in lighter-complexioned patients. Such peels should be used with caution in blacks. Although lasers have demonstrated significant efficacy in the treatment of a variety of hyperpigmentary disorders, their precise efficacy and place in the therapy of melasma have yet to be established.  CONCLUSIONS : In the hierarchy of therapies for melasma, the treating physician must consider the devastating psychosocial impact of pigmentary imperfections within the realm of the benefits and risks associated with each treatment."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I181,I181)","v":7621473},{"$f":"(LEN($J181) - LEN(SUBSTITUTE(LOWER($J181),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J181) - LEN(SUBSTITUTE(LOWER($J181),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J181) - LEN(SUBSTITUTE(LOWER($J181),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B181:D181)","v":1},1995,"Endocrine control of prostate cancer.","Wilding",7621473,"Endocrine control of prostate cancer.    Abstract:   Steroid hormones play an important part in prostate biology. Androgens are crucial for the normal development of the prostate gland and in maintaining its functional state in the adult. It seems that the prolonged presence of androgens might also be an important factor in the development of prostate cancer. In addition, androgens and oestrogens appear to play a part in the development of benign prostatic hypertrophy, although the exact nature of their role has not been clearly defined. Stimulation of prostate cancer growth by androgens is well established with androgen withdrawal therapy being the most effective therapy in men with prostate cancer. Additive steroid therapy of metastatic prostate cancer with oestrogens or progestogens has also proved effective. The effects of androgens on prostate cancer cell growth might be mediated through modulation of growth factor expression and alteration of growth factor receptor levels. Androgen response can be modulated by the expression of mutated oncogenes such as ras. Androgen independence can occur through a loss of AR expression or mutation of the AR; however, the patterns of AR expression in normal prostatic tissue from development to adulthood and in cancer are now just beginning to be described. Other steroids, such as the retinoids, show promise as preventive agents, possibly through the modulation of growth factors. Vitamin D compounds modulate prostate cancer cell growth, but their role in prevention and therapy is unclear."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I182,I182)","v":8005001},{"$f":"(LEN($J182) - LEN(SUBSTITUTE(LOWER($J182),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J182) - LEN(SUBSTITUTE(LOWER($J182),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J182) - LEN(SUBSTITUTE(LOWER($J182),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B182:D182)","v":1},1994,"Chemoprevention of cancer.","Szarka",8005001,"Chemoprevention of cancer.    Abstract:   Chemoprevention is a strategy used to block the development of cancers in human beings. This emerging field has broad potential for influencing cancer incidence rates in defined high-risk groups and the general population. In this review, we define some of the mechanisms of carcinogenesis, describe some of the genetic markers of carcinogenesis, and list possible biomarkers that may serve as surrogate end points in chemoprevention studies. A major component of this review is a description of the agents that are currently under investigation in animal systems or in human trials. They are grouped according to the agents that block or suppress mutation, such as oltipraz, selenium, vitamin C and the flavones, or according to agents that block promotion and proliferation, such as difluoromethylornithine, tamoxifen, nonsteroidal antiinflammatory drugs, and the vitamin A derivatives. We describe the issues that are considered in the design of chemoprevention trials and in the phase I, II, and III components of these trials. The following national trials are discussed: the Breast Cancer Prevention Trial, which uses tamoxifen; the Prostate Cancer Prevention Trial, which uses finasteride; and a Lung Cancer Prevention Trial, which uses 13-cis-retinoic acid. The review ends with some insights about future studies in chemoprevention."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I183,I183)","v":7569034},{"$f":"(LEN($J183) - LEN(SUBSTITUTE(LOWER($J183),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J183) - LEN(SUBSTITUTE(LOWER($J183),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J183) - LEN(SUBSTITUTE(LOWER($J183),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B183:D183)","v":1},1994,"Development and validation of swine embryonic stem cells: a review.","Wheeler",7569034,"Development and validation of swine embryonic stem cells: a review.    Abstract:   The establishment of embryonic cell lines from swine should be useful for studies of cell differentiation, developmental gene regulation and the production of transgenics. This paper summarizes the establishment of porcine (Sus scrofa) embryonic stem (ES) cell lines from preimplantation blastocysts and their ability to develop into normal chimaeras. ES cells can spontaneously differentiate into cystic embryoid bodies with ectodermal, endodermal, and mesodermal cell types. Further, culture of ES cells to confluence or induction of differentiation with retinoic acid or dimethylsulfoxide results in morphological differentiation into fibroblasts, adipocytes, and epithelial, neuronal, and muscle cells. These ES cells have a normal diploid complement of 38 chromosomes. Scanning electron microscopy of the ES cells reveals a rounded or polygonal, epithelial-like cell with numerous microvilli. The differentiation of these embryonic cell lines into several cell types indicates a pluripotent cell. Furthermore, chimaeric swine have been successfully produced using such ES cells."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I184,I184)","v":8428329},{"$f":"(LEN($J184) - LEN(SUBSTITUTE(LOWER($J184),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J184) - LEN(SUBSTITUTE(LOWER($J184),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J184) - LEN(SUBSTITUTE(LOWER($J184),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B184:D184)","v":1},1993,"Ketoconazole and liarozole in the treatment of advanced prostatic cancer.","Mahler",8428329,"Ketoconazole and liarozole in the treatment of advanced prostatic cancer.    Abstract:    BACKGROUND : Ketoconazole, an imidazole derivative, is an orally active antifungal agent. In high doses (400 mg three times a day), it inhibits the biosynthesis of testicular and adrenal androgens and may therefore be useful for the treatment of hormone dependent diseases such as advanced prostatic cancer. Similarly, a new imidazole derivative, liarozole, was recently found to interfere with testicular and adrenal steroid biosynthesis in animals and healthy volunteers.  METHODS : The therapeutic and endocrine effects of ketoconazole and liarozole in patients with disseminated prostatic cancer are discussed, including data from the literature and personal experience.  RESULTS : Using high-dose ketoconazole, medical castration with the expected clinical response was achieved easily in previously untreated patients in all clinical series (personal data include seven patients). In patients with prostatic cancer who had relapses after castration, few objective remissions were achieved. By contrast, long-lasting subjective remissions, especially pain relief, were seen in more than half of the patients (personal data include 20 patients). Gastrointestinal intolerance, which was the main side effect, severely limits the routine use of the drug. Recently, the authors studied the effect of liarozole on adrenal steroid production in castrated patients whose disease was progressive after first-line treatment. Unlike ketoconazole therapy, adrenal androgen and cortisol levels were not modified. A Phase I-II trial was then done in 44 patients with metastatic prostatic cancer in clinical relapse. In patients with measurable disease, objective responses, including tumoral volume reduction, occurred in approximatively 30%. A prostate specific antigen reduction of 50% or more was noted in approximatively 50% of patients. Pain relief occurred in most patients. Mucocutaneous side effects were observed in most patients--dryness of the skin and onychomalacia. Raised tissue retinoic acid levels suggested a possible pathway by which this drug might exert its cytotoxic effects.  CONCLUSIONS : Ketoconazole in high doses is effective in first-line and second-line therapy for advanced prostatic cancer, but gastrointestinal side effects limit its routine use. Liarozole is a new imidazole that is also effective in second-line therapy for prostatic cancer and has fewer side effects. Unlike ketoconazole, its effect is not mediated by inhibition of steroid biosynthesis."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I185,I185)","v":1423327},{"$f":"(LEN($J185) - LEN(SUBSTITUTE(LOWER($J185),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J185) - LEN(SUBSTITUTE(LOWER($J185),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J185) - LEN(SUBSTITUTE(LOWER($J185),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B185:D185)","v":1},1992,"The importance of steroid hormones in prostate cancer.","Wilding",1423327,"The importance of steroid hormones in prostate cancer.    Abstract:   Steroid hormones have an important role in prostate biology. Androgens are crucial for the normal development of the prostate gland and in maintaining its functional state in the adult. It seems that the prolonged presence of androgens might also be an important factor in the development of prostate cancer. In addition, androgens and oestrogens appear to play some part in the development of benign prostatic hyperplasia, although the exact nature of their role has not been clearly defined. Stimulation of prostate cancer growth by androgens is well established, with androgen withdrawal therapy constituting the most effective therapy in men with prostate cancer. Additive steroid therapy of metastatic prostate cancer with oestrogens or progestins has also proven effective. The effects of androgens on prostate cancer cell growth might be mediated through modulation of growth factor expression and alteration of growth factor receptor levels. Androgen response can be modulated by the expression of mutated oncogenes such as ras. Androgen independence can occur through a loss of AR expression or mutation of the AR; however, the patterns of AR expression in normal prostatic tissue from development to adulthood and in cancer are now just beginning to be described. Other steroids, such as the retinoids, show promise as preventive agents, possibly through the modulation of growth factors."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I186,I186)","v":1289678},{"$f":"(LEN($J186) - LEN(SUBSTITUTE(LOWER($J186),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J186) - LEN(SUBSTITUTE(LOWER($J186),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J186) - LEN(SUBSTITUTE(LOWER($J186),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B186:D186)","v":1},1992,"The Lobund-Wistar rat model of prostate cancer.","Pollard",1289678,"The Lobund-Wistar rat model of prostate cancer.    Abstract:   Two models of preventable metastasizing autochthonous prostate adenocarcinoma (PA) have been described in Lobund-Wistar (L-W) rats: spontaneous PAs that develop at a mean age of 26 months; and induced PAs that develop at a mean time of 10.5 months. Both are similar in many respects to the counterpart disease in man. PAs develop spontaneously, and by induction through a combination of N-methyl-N-nitrosourea (MNU)/testosterone treatments. Our investigations with L-W rats show that PA is manifested spontaneously in 26% of aged L-W rats, and by induction in approximately 90% of younger rats. It is characterized by metastatic adenocarcinoma initiated in, and expanding from, the dorso-lateral and anterior lobes, and occasionally in the seminal vesicles. It is regulated by genetic, hormonal, and age-related mechanisms. Spontaneous PAs are prevented by life-long moderate (25%) diet restriction and, in rats at risk of developing induced PA, by early treatments with estradiol, with dihydrotestosterone, with a retinoid, and by castration. While the quot;premalignantquot; stages of induced tumorigenesis are susceptible to intervention, the overtly malignant stage resists therapeutic trials with the same agents and procedures. The transition from dependency to autonomy has not yet been defined."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I187,I187)","v":1695775},{"$f":"(LEN($J187) - LEN(SUBSTITUTE(LOWER($J187),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J187) - LEN(SUBSTITUTE(LOWER($J187),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J187) - LEN(SUBSTITUTE(LOWER($J187),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B187:D187)","v":1},1990,"Clinical and experimental studies of benign prostatic hyperplasia.","Coffey",1695775,"Clinical and experimental studies of benign prostatic hyperplasia.    Abstract:   The canine prostate appears to be a suitable model for investigating many aspects of abnormal prostate growth related to BPH. This model has indicated that BPH is a complex pathologic process that varies with age and produces a gland that is composed of a mixture of glandular, cystic, and stromal hyperplasia juxtapositioned with foci of atrophy. Canine BPH first occurs very early in life as a glandular hyperplasia before the onset of more complex BPH. As the prostate increases in size with age, the tissue dihydrotestosterone content falls, as does the secretory capacity of the gland. The fall in glandular dihydrotestosterone content is counterbalanced by a concomitant increase in the metabolism of androgens toward dihydrotestosterone and an increase in nuclear androgen receptors. As the prostate ages, it thus becomes more sensitive to androgens, which are required for maintaining the abnormal size of the gland. Established BPH can be maintained in the absence of the testes in the presence of normal testosterone levels, and it appears that the abnormal growth is primarily attributable to an inherent change that has occurred in the aged prostate. In the dog and man, both the normal prostate and BPH are rich in growth factors and dihydrotestosterone receptor in the nucleus, yet mitotic cells are rare. Established BPH is not growing rapidly; the abnormal size of the aged prostate is maintained, not by an increase in the rate of cell replication, but rather by an apparent decrease in the rate of cell death. It appears that a combination of estrogens and 5 alpha-reduced androgens can cause this decrease in the rate of cell death and replication and that this imbalance can produce abnormal cell accumulation and an experimental prostatic hyperplasia. Besides affecting cell death and replication, estradiol has a marked effect in stimulating the stroma and collagen synthesis. Current investigations are focusing on determining the distribution of stem cells for both the epithelial and the stromal elements of the prostate, how these stem cells are recruited to form transiently proliferating cells, and how they mature and subsequently are programmed for cell death. It is believed that steroid imprinting in the neonatal and prepubertal period may be of great importance in determining the ultimate growth of the prostate. Preliminary attempts to control abnormal canine prostate growth by forcing maturation with retinoic acid, or by interfering with growth factors through the use of suramin, have not proved effective; only androgen ablation is. Important leads in the search for the etiology and control of BPH can be studied in the canine model. These concepts must ultimately be tested and confirmed for human BPH in well-controlled clinical investigations."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I188,I188)","v":2217456},{"$f":"(LEN($J188) - LEN(SUBSTITUTE(LOWER($J188),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J188) - LEN(SUBSTITUTE(LOWER($J188),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J188) - LEN(SUBSTITUTE(LOWER($J188),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B188:D188)","v":1},1990,"Retinoic acid and prostatic cancer cell growth.","Whelan",2217456,"Retinoic acid and prostatic cancer cell growth.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I189,I189)","v":1964622},{"$f":"(LEN($J189) - LEN(SUBSTITUTE(LOWER($J189),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J189) - LEN(SUBSTITUTE(LOWER($J189),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J189) - LEN(SUBSTITUTE(LOWER($J189),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B189:D189)","v":1},1990,"Comparative biology of mouse and human embryonal carcinoma.","Pera",1964622,"Comparative biology of mouse and human embryonal carcinoma.    Abstract:   The biology of human germ cell neoplasia has been the subject of increasing investigation during the past decade. The objectives of such investigations include better understanding of the pathogenesis of the diseases, improvement in patient management, and insights into cancer cell differentiation and human development. Many of the approaches to human germ cell tumour biology have been strongly influenced by work in the mouse. Here we review some comparative aspects of germ cell tumours in mouse and man. There are striking differences between the two species in the mechanisms of tumour development, the role of genetic background in tumour susceptibility, the cytogenetics of the tumours, and the phenotype of the embryonal carcinoma stem cells. Despite these differences, certain common themes emerge from a survey of work on growth factors and their receptors, extracellular matrix molecules and transcriptional regulators. Both mouse and human embryonal carcinoma cells produce growth factors, but strong evidence for autocrine regulation of stem cell growth is lacking in both species. Differentiated derivatives (primarily extraembryonic endoderm) of mouse embryonal carcinoma cells may respond to factors produced by the stem cells. These differentiated cells also secrete high levels of growth factors and extracellular matrix molecules in both species, supporting a role for paracrine growth interactions in peri-implantation development. The requirements of embryonal carcinoma stem cells for cell substrate adhesion molecules are specific and differ in mouse and man. There are some similarities in the induction of putative transcriptional regulators by retinoids in human and mouse embryonal carcinoma cells.(ABSTRACT TRUNCATED AT 250 WORDS)"]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I190,I190)","v":3146293},{"$f":"(LEN($J190) - LEN(SUBSTITUTE(LOWER($J190),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J190) - LEN(SUBSTITUTE(LOWER($J190),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J190) - LEN(SUBSTITUTE(LOWER($J190),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B190:D190)","v":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."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I191,I191)","v":6390391},{"$f":"(LEN($J191) - LEN(SUBSTITUTE(LOWER($J191),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J191) - LEN(SUBSTITUTE(LOWER($J191),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J191) - LEN(SUBSTITUTE(LOWER($J191),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B191:D191)","v":1},1984,"Late determinants of cancer.","Tulinius",6390391,"Late determinants of cancer.    Abstract:   The paper reviews some findings on the frequency of latent carcinoma. Latent carcinomas are found much more frequently in the prostate, than would be expected from mortality or incidence data. The same applies to neuroblastomas in the adrenal cortex in infants. The problem has not been studied in detail in other organs. A satisfactory explanation of spontaneous regression of human cancers or the variable disease-free survival time of cancer patients has not been found. It is concluded that defence mechanisms of paramount importance exist, and need to be studied. Recent reports on serum retinol and serum cholesterol are reviewed since these are both lower in people who later develop cancer. Much more knowledge is needed but these phenomena could be linked."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I192,I192)","v":6356585},{"$f":"(LEN($J192) - LEN(SUBSTITUTE(LOWER($J192),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J192) - LEN(SUBSTITUTE(LOWER($J192),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J192) - LEN(SUBSTITUTE(LOWER($J192),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B192:D192)","v":1},1983,"[Vitamin A, retinoids and tumor development].","Nozdrin",6356585,"[Vitamin A, retinoids and tumor development].    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I193,I193)","v":6989103},{"$f":"(LEN($J193) - LEN(SUBSTITUTE(LOWER($J193),LOWER(B$3),\"\")))/LEN(B$3)","v":1},{"$f":"(LEN($J193) - LEN(SUBSTITUTE(LOWER($J193),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J193) - LEN(SUBSTITUTE(LOWER($J193),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B193:D193)","v":1},1980,"[Vitamin A transport mechanism: retinol cell reception and the intracellular proteins that bind vitamin A (a review)].","Kon",6989103,"[Vitamin A transport mechanism: retinol cell reception and the intracellular proteins that bind vitamin A (a review)].    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I194,I194)","v":26454096},{"$f":"(LEN($J194) - LEN(SUBSTITUTE(LOWER($J194),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J194) - LEN(SUBSTITUTE(LOWER($J194),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J194) - LEN(SUBSTITUTE(LOWER($J194),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B194:D194)","v":0},2015,"Molecular events and signalling pathways of male germ cell differentiation in mouse.","Rossitto",26454096,"Molecular events and signalling pathways of male germ cell differentiation in mouse.    Abstract:   Germ cells, the precursors of gametes, represent a unique cell lineage that is able to differentiate into spermatozoa or oocytes depending on the chromosomal sex of the organism. In the mammalian embryonic gonad, commitment to oogenesis involves pre-meiotic DNA replication and entry into the first meiotic division; whereas, commitment to spermatogenesis involves inhibition of meiotic initiation, suppression of pluripotency, mitotic arrest and expression of specific markers that will control the development of the male germ cells. The crucial decision made by the germ line to commit to either a male or a female fate has been partially explained by genetic and ex vivo studies in mice which have implicated a complex network of regulatory genes, numerous factors and pathways. Besides the reproductive failure that may follow a deregulation of this complex network, the germ cells may, in view of their proliferative and pluripotent nature, act as precursors of potential malignant transformation and as putative targets for exogenous environmental compounds. Our review summarizes and discusses recent developments that have improved our understanding on how germ cell precursors are committed to a male or a female cell fate in the mouse gonad."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I195,I195)","v":26425706},{"$f":"(LEN($J195) - LEN(SUBSTITUTE(LOWER($J195),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J195) - LEN(SUBSTITUTE(LOWER($J195),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J195) - LEN(SUBSTITUTE(LOWER($J195),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B195:D195)","v":0},2015,"Interventions to Improve Neonatal Health and Later Survival: An Overview of Systematic Reviews.","Lassi",26425706,"Interventions to Improve Neonatal Health and Later Survival: An Overview of Systematic Reviews.    Abstract:    BACKGROUND : Evidence-based interventions and strategies are needed to improve child survival in countries with a high burden of neonatal and child mortality. An overview of systematic reviews can focus implementation on the most effective ways to increase child survival.  METHODS : In this overview we included published Cochrane and other systematic reviews of experimental and observational studies on antenatal, childbirth, postnatal and child health interventions aiming to prevent perinatal/neonatal and child mortality using the WHO list of essential interventions. We assessed the methodological quality of the reviews using the AMSTAR criteria and assessed the quality of the outcomes using the GRADE approach. Based on the findings from GRADE criteria, interventions were summarized as effective, promising or ineffective.  FINDINGS : The overview identified 148 Cochrane and other systematic reviews on 61 reproductive, maternal, newborn and child health interventions. Of these, only 57 reviews reported mortality outcomes. Using the GRADE approach, antenatal corticosteroids for preventing neonatal respiratory distress syndrome in preterm infants; early initiation of breastfeeding; hygienic cord care; kangaroo care for preterm infants; provision and promotion of use of insecticide treated bed nets (ITNs) for children; and vitamin A supplementation for infants from six months of age, were identified as clearly effective interventions for reducing neonatal, infant or child mortality. Antenatal care, tetanus immunization in pregnancy, prophylactic antimalarials during pregnancy, induction of labour for prolonged pregnancy, case management of neonatal sepsis, meningitis and pneumonia, prophylactic and therapeutic use of surfactant, continuous positive airway pressure for neonatal resuscitation, case management of childhood malaria and pneumonia, vitamin A as part of treatment for measles associated pneumonia for children above 6 months, and home visits across the continuum of care, were identified as promising interventions for reducing neonatal, infant, child or perinatal mortality.  INTERPRETATION : Comprehensive adoption of the above six effective and 11 promising interventions can improve neonatal and child survival around the world. Choice of intervention and degree of implementation currently depends on resources available and policies in individual countries and geographical settings.  FUNDING : This review was part of doctoral thesis which was funded by University of Adelaide, Australia."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I196,I196)","v":26370648},{"$f":"(LEN($J196) - LEN(SUBSTITUTE(LOWER($J196),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J196) - LEN(SUBSTITUTE(LOWER($J196),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J196) - LEN(SUBSTITUTE(LOWER($J196),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B196:D196)","v":0},2015,"Alopecias due to drugs and other skin and systemic disorders.","Guzmán-Sánchez",26370648,"Alopecias due to drugs and other skin and systemic disorders.    Abstract:   In this chapter, we will discuss the most common alopecias due to drugs and other skin and systemic disorders. The following hair disorders will be analyzed: telogen effluvium (acute and chronic); anagen effluvium; folliculotropic mycosis fungoides; and folliculitis due to bacteria, fungi, parasites, human immunodeficiency virus disease, lupus erythematosus, and sarcoidosis. We will cover topics including the epidemiology, etiology, clinical picture, and diagnosis of and current treatments for each disease."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I197,I197)","v":26166560},{"$f":"(LEN($J197) - LEN(SUBSTITUTE(LOWER($J197),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J197) - LEN(SUBSTITUTE(LOWER($J197),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J197) - LEN(SUBSTITUTE(LOWER($J197),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B197:D197)","v":0},2015,"Nutrition and maternal, neonatal, and child health.","Christian",26166560,"Nutrition and maternal, neonatal, and child health.    Abstract:   This article reviews the central role of nutrition in advancing the maternal, newborn, and child health agenda with a focus on evidence for effective interventions generated using randomized controlled trials in low- and middle-income countries (LMIC). The 1000 days spanning from conception to 2 years of life are a critical period of time when nutritional needs must be ensured; failure to do so can lead to adverse impacts on short-term survival as well as long-term health and development [corrected]. The burden of maternal mortality continues to be high in many under-resourced settings; prenatal calcium supplementation in populations with low intakes can reduce the risk of pre-eclampsia and eclampsia morbidity and mortality and is recommended, and antenatal iron-folic acid use in many countries may reduce anemia, a condition that may be an underlying factor in postpartum hemorrhage. Sufficient evidence exists to promote multiple micronutrient supplementation during pregnancy to reduce fetal growth restriction and low birth weight. Early initiation of breastfeeding (within an hour), exclusive breastfeeding in the first 6 months of life, and vitamin A supplementation in the first few days of life in Asia (but not in Africa) reduce infant mortality. Biannual large-dose vitamin A supplements to children 6-59 months of age and zinc for treatment of diarrhea continue to be important strategies for improving child health and survival. Early nutrition and micronutrient status can influence child development but should be integrated with early responsive learning interventions. Future research is needed that goes beyond the 1000 days to ensure adequate preconceptional nutrition and health, with special emphasis on adolescents who contribute to a large proportion of first births in many LMIC. Thus, we make the case for integrating proven nutrition interventions with those for health in pregnant women, and with those for health and child development in neonates, infants, and young children to help advance the global MNCH agenda."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I198,I198)","v":26143434},{"$f":"(LEN($J198) - LEN(SUBSTITUTE(LOWER($J198),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J198) - LEN(SUBSTITUTE(LOWER($J198),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J198) - LEN(SUBSTITUTE(LOWER($J198),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B198:D198)","v":0},2015,"Deep Fungal Infections, Blastomycosis-Like Pyoderma, and Granulomatous Sexually Transmitted Infections.","Guidry",26143434,"Deep Fungal Infections, Blastomycosis-Like Pyoderma, and Granulomatous Sexually Transmitted Infections.    Abstract:   Granulomatous diseases are caused by multiple infectious and noninfectious causes. Deep fungal infections can present in the skin or extracutaneously, most commonly with lung manifestations. An Azole or amphotericin B is the universal treatment. Blastomycosis-like pyoderma is a clinically similar condition, which is caused by a combination of hypersensitivity and immunosuppression. Successful treatment has been reported with antibiotics and, more recently, the vitamin A analog, acitretin. Granuloma inguinale and lymphogranuloma venereum cause ulcerative genital lesions with a granulomatous appearance on histology. The Centers for Disease Control and Prevention recommens treatment of these genital infections with doxycycline."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I199,I199)","v":24759120},{"$f":"(LEN($J199) - LEN(SUBSTITUTE(LOWER($J199),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J199) - LEN(SUBSTITUTE(LOWER($J199),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J199) - LEN(SUBSTITUTE(LOWER($J199),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B199:D199)","v":0},2014,"The effect of micronutrient supplements on male fertility.","Buhling",24759120,"The effect of micronutrient supplements on male fertility.    Abstract:    PURPOSE OF REVIEW : To describe the beneficial effects of micronutrient supplementation on male fertility.  RECENT FINDINGS : Several micronutrients have beneficial effects on sperm quality, as well on male fertility (e.g. pregnancy rate). A deliberate use of micronutrients might be helpful for infertile patients. Healthcare providers should be aware that supplements contain the studied dose.  SUMMARY : Male sterility is becoming increasingly important because of various factors. In addition to the avoidable risk factors (alcohol and smoking), unchangeable factors are also likely involved in the genesis. Modern reproductive medicine methods help resulting in decent pregnancy rates in subfertile men. However, in addition to reproductive medicine methods, factors other than cessation of smoking and alcohol consumption can influence the fertility of men. Several studies have reported a significant increase in sperm quality and pregnancy rates when the men were supplemented by specific vitamins and micronutrients.The present review gives an overview of the study results and discusses specific legal requirements (e.g. upper limits)."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I200,I200)","v":25924463},{"$f":"(LEN($J200) - LEN(SUBSTITUTE(LOWER($J200),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J200) - LEN(SUBSTITUTE(LOWER($J200),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J200) - LEN(SUBSTITUTE(LOWER($J200),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B200:D200)","v":0},2013,"[Reference values of vitamin A for the Venezuelan population].","García-Casal",25924463,"[Reference values of vitamin A for the Venezuelan population].    Abstract:   Vitamin A deficiency is one of the most prevalent nutritional deficiencies worldwide, mainly affecting children and women. The cause of vitamin A deficiency is insufficient intake, especially in presence of infection and the consequences of the deficiency are xerophthalmia, night blindness, anemia, increased susceptibility to infections and the still controversial increase in infant mortality. National evidence at this point is insufficient to establish the recommendation, and as in the 2000 review of the Venezuelan RDAs, the actual recommendations are based on the reported for the United States population. The Recommended Dietary Allowances (RDA) for Venezuela are 400-500 RE/day for infants, 300-400 RE/day for children 600 RE/day for adolescents, 900 RE/day for men and 700 RE/day for women, increasing to 750 RE/day for pregnancy and to 1200-1300 RE/day during lactation, depending on the age. The estimated average requirement (EAR) is between 210 and 275 RE/day for children, 445 RE/day for male adolescents, 420 RE/day for female adolescents, 630 RE/day for men and 485 RE/day for women, increasing to 530-550 and 885-900 RE/ day during pregnancy and lactation, respectively. The tolerable upper intake levels (UL) for vitamin A are 600 RE/day for children, 1700 a 2800 RE/day for adolescents and 3000 RE/day for adults, males and females."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I201,I201)","v":24018211},{"$f":"(LEN($J201) - LEN(SUBSTITUTE(LOWER($J201),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J201) - LEN(SUBSTITUTE(LOWER($J201),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J201) - LEN(SUBSTITUTE(LOWER($J201),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B201:D201)","v":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."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I202,I202)","v":23746772},{"$f":"(LEN($J202) - LEN(SUBSTITUTE(LOWER($J202),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J202) - LEN(SUBSTITUTE(LOWER($J202),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J202) - LEN(SUBSTITUTE(LOWER($J202),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B202:D202)","v":0},2013,"Maternal and child undernutrition and overweight in low-income and middle-income countries.","Black",23746772,"Maternal and child undernutrition and overweight in low-income and middle-income countries.    Abstract:   Maternal and child malnutrition in low-income and middle-income countries encompasses both undernutrition and a growing problem with overweight and obesity. Low body-mass index, indicative of maternal undernutrition, has declined somewhat in the past two decades but continues to be prevalent in Asia and Africa. Prevalence of maternal overweight has had a steady increase since 1980 and exceeds that of underweight in all regions. Prevalence of stunting of linear growth of children younger than 5 years has decreased during the past two decades, but is higher in south Asia and sub-Saharan Africa than elsewhere and globally affected at least 165 million children in 2011; wasting affected at least 52 million children. Deficiencies of vitamin A and zinc result in deaths; deficiencies of iodine and iron, together with stunting, can contribute to children not reaching their developmental potential. Maternal undernutrition contributes to fetal growth restriction, which increases the risk of neonatal deaths and, for survivors, of stunting by 2 years of age. Suboptimum breastfeeding results in an increased risk for mortality in the first 2 years of life. We estimate that undernutrition in the aggregate--including fetal growth restriction, stunting, wasting, and deficiencies of vitamin A and zinc along with suboptimum breastfeeding--is a cause of 3·1 million child deaths annually or 45% of all child deaths in 2011. Maternal overweight and obesity result in increased maternal morbidity and infant mortality. Childhood overweight is becoming an increasingly important contributor to adult obesity, diabetes, and non-communicable diseases. The high present and future disease burden caused by malnutrition in women of reproductive age, pregnancy, and children in the first 2 years of life should lead to interventions focused on these groups."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I203,I203)","v":23524531},{"$f":"(LEN($J203) - LEN(SUBSTITUTE(LOWER($J203),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J203) - LEN(SUBSTITUTE(LOWER($J203),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J203) - LEN(SUBSTITUTE(LOWER($J203),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B203:D203)","v":0},2013,"Urinary biomarkers for prostate cancer: a review.","Hessels",23524531,"Urinary biomarkers for prostate cancer: a review.    Abstract:   Although the routine use of serum prostate-specific antigen (PSA) testing has undoubtedly increased prostate cancer (PCa) detection, one of its main drawbacks is its lack of specificity. As a consequence, many men undergo unnecessary biopsies or treatments for indolent tumours. PCa-specific markers are needed for the early detection of the disease and the prediction of aggressiveness of a prostate tumour. Since PCa is a heterogeneous disease, a panel of tumour markers is fundamental for a more precise diagnosis. Several biomarkers are promising due to their specificity for the disease in tissue. However, tissue is unsuitable as a possible screening tool. Since urine can be easily obtained in a non-invasive manner, it is a promising substrate for biomarker testing. This article reviews the biomarkers for the non-invasive testing of PCa in urine."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I204,I204)","v":23252770},{"$f":"(LEN($J204) - LEN(SUBSTITUTE(LOWER($J204),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J204) - LEN(SUBSTITUTE(LOWER($J204),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J204) - LEN(SUBSTITUTE(LOWER($J204),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B204:D204)","v":0},2013,"The environment and the origins of islet autoimmunity and Type 1 diabetes.","Eringsmark Regnéll",23252770,"The environment and the origins of islet autoimmunity and Type 1 diabetes.    Abstract:   Type 1 diabetes involves the specific destruction of the pancreatic islet β-cells, eventually resulting in a complete dependency of exogenous insulin. The clinical onset of diabetes is preceded by the appearance of autoantibodies against β-cell antigens. The human leukocyte antigen (HLA) region is the single most important genetic determinant of Type 1 diabetes susceptibility, yet variability in the HLA region has been estimated to explain only approximately 60% of the genetic influence of the disease. Over 50 identified non-HLA genetic polymorphisms support the notion that genetics alone cannot explain Type 1 diabetes. Several lines of evidence indicate that environmental triggers may be integral in inducing the onset of islet autoimmunity in genetically susceptible individuals. The association between environmental factors and the clinical onset is complicated by observation that the rate of progression to clinical onset may be affected by environmental determinants. Hence, the environment may be aetiological as well as pathogenic. Putative inductive mechanisms include viral, microbial, diet-related, anthropometric and psychosocial factors. Ongoing observational cohort studies such as The Environmental Determinants of Diabetes in the Young (TEDDY) study aim to ascertain environmental determinants that may trigger islet autoimmunity and either speed up or slow down the progression to clinical onset in subjects with persistent islet autoimmunity."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I205,I205)","v":23085014},{"$f":"(LEN($J205) - LEN(SUBSTITUTE(LOWER($J205),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J205) - LEN(SUBSTITUTE(LOWER($J205),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J205) - LEN(SUBSTITUTE(LOWER($J205),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B205:D205)","v":0},2013,"Vitamin D: health panacea or false prophet?","Glade",23085014,"Vitamin D: health panacea or false prophet?    Abstract:   Vitamin D deficiency, diagnosed when the serum 25-hydroxyvitamin D (25-OHD(3)) concentration is less than 20 ng/mL, has joined vitamin A deficiency as two of the most common nutrition-responsive medical conditions worldwide. There have been more scientific articles published about vitamin D in the 21st century than about any other vitamin, reflecting the massive expansion of the field of vitamin D research. Adequate vitamin D status has been linked to decreased risks of developing specific cancers, including cancers of the esophagus, stomach, colon, rectum, gallbladder, pancreas, lung, breast, uterus, ovary, prostate, urinary bladder, kidney, skin, thyroid, and hematopoietic system (e.g., Hodgkins lymphoma, non-Hodgkins lymphoma, multiple myeloma); bacterial infections; rheumatoid arthritis; Crohns disease; periodontal disease; multiple sclerosis; asthma; type 2 diabetes; cardiovascular disease; stroke; peripheral artery disease; hypertension; chronic kidney disease; muscle weakness; cognitive impairment; Alzheimers disease; clinical depression; and premature death. On the other hand, inadequate vitamin D status during human pregnancy may be associated with increased risk for the development of type 1 diabetes in the offspring. However, this point of view may be excessively optimistic. There also is evidence that despite the current heavy reliance on serum 25-OHD(3) concentration for the diagnosis of an individuals vitamin D status, local tissue vitamin D intoxication may be present in individuals with much lower serum 25-OHD(3) concentrations than are currently appreciated. Only rarely are the symptoms of local tissue vitamin D intoxication associated with vitamin D status or intake. An individuals serum 25-OHD(3) concentration may appear to be quot;lowquot; for reasons totally independent of sunlight exposure or vitamin D intake. Serum 25-OHD(3) concentration is only poorly responsive to increases in vitamin D intake, and the prolonged routine consumption of thousands of international units of vitamin D may interfere with the regulation of phosphate homeostasis by fibroblast growth factor-23 (FGF23) and the Klotho gene product, with consequences that are detrimental to human health. In light of these counterbalancing observations, curbing excessive enthusiasm for universally increasing vitamin D intake recommendations may be in order."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I206,I206)","v":23008041},{"$f":"(LEN($J206) - LEN(SUBSTITUTE(LOWER($J206),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J206) - LEN(SUBSTITUTE(LOWER($J206),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J206) - LEN(SUBSTITUTE(LOWER($J206),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B206:D206)","v":0},2012,"Interaction of vitamin A and other micronutrients.","McLaren",23008041,"Interaction of vitamin A and other micronutrients.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I207,I207)","v":22524113},{"$f":"(LEN($J207) - LEN(SUBSTITUTE(LOWER($J207),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J207) - LEN(SUBSTITUTE(LOWER($J207),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J207) - LEN(SUBSTITUTE(LOWER($J207),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B207:D207)","v":0},2012,"Nutrition of children and women in Bangladesh: trends and directions for the future.","Ahmed",22524113,"Nutrition of children and women in Bangladesh: trends and directions for the future.    Abstract:   Although child and maternal malnutrition has been reduced in Bangladesh, the prevalence of underweight (weight-for-age z-score lt;-2) among children aged less than five years is still high (41%). Nearly one-third of women are undernourished with body mass index of lt;18.5 kg/m2. The prevalence of anaemia among young infants, adolescent girls, and pregnant women is still at unacceptable levels. Despite the successes in specific programmes, such as the Expanded Programme on Immunization and vitamin A supplementation, programmes for nutrition interventions are yet to be implemented at scale for reaching the entire population. Given the low annual rate of reduction in child undernutrition of 1.27 percentage points per year, it is unlikely that Bangladesh would be able to achieve the United Nations Millennium Development Goal to address undernutrition. This warrants that the policy-makers and programme managers think urgently about the ways to accelerate the progress. The Government, development partners, non-government organizations, and the academia have to work in concert to improve the coverage of basic and effective nutrition interventions, including exclusive breastfeeding, appropriate complementary feeding, supplementation of micronutrients to children, adolescent girls, pregnant and lactating women, management of severe acute malnutrition and deworming, and hygiene interventions, coupled with those that address more structural causes and indirectly improve nutrition. The entire health system needs to be revitalized to overcome the constraints that exist at the levels of policy, governance, and service-delivery, and also for the creation of demand for the services at the household level. In addition, management of nutrition in the aftermath of natural disasters and stabilization of prices of foods should also be prioritized."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I208,I208)","v":22326691},{"$f":"(LEN($J208) - LEN(SUBSTITUTE(LOWER($J208),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J208) - LEN(SUBSTITUTE(LOWER($J208),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J208) - LEN(SUBSTITUTE(LOWER($J208),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B208:D208)","v":0},2012,"Epidemiology of vitamin A deficiency and xerophthalmia in at-risk populations.","Sherwin",22326691,"Epidemiology of vitamin A deficiency and xerophthalmia in at-risk populations.    Abstract:   Vitamin A deficiency (VAD) is an important public health problem worldwide that contributes significantly to the global burden of disease. Vitamin A deficiency disorders include xerophthalmia and increased risk of infectious diseases, both of which increase risk of mortality. Xerophthalmia is also a leading cause of preventable blindness. Areas with highly prevalent VAD often share common dietary and other environmental exposures, including poverty, infectious diseases, limited development and poor availability of vitamin A containing food. Globally, the prevalence of VAD has been declining, which may be due to widespread vitamin A supplementation in conjunction with measles immunisation in at-risk populations. Recent meta-analyses confirm that provision of vitamin A to children aged between 6 months and 5 years confers a significant mortality benefit. Further preventative measures for VAD comprise improving availability of vitamin A containing food, including foods biofortified with vitamin A. Ensuring vitamin A is available in any form in adequate quantities remains problematic, especially in areas affected by environmental catastrophes and conflict, and other areas where access to vitamin A containing foods and healthcare interventions is limited. Hence, it remains essential that maternal and child health workers remain vigilant for VAD in nutritionally vulnerable populations."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I209,I209)","v":21967161},{"$f":"(LEN($J209) - LEN(SUBSTITUTE(LOWER($J209),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J209) - LEN(SUBSTITUTE(LOWER($J209),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J209) - LEN(SUBSTITUTE(LOWER($J209),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B209:D209)","v":0},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."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I210,I210)","v":21410888},{"$f":"(LEN($J210) - LEN(SUBSTITUTE(LOWER($J210),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J210) - LEN(SUBSTITUTE(LOWER($J210),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J210) - LEN(SUBSTITUTE(LOWER($J210),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B210:D210)","v":0},2011,"Accelerating improvements in nutritional and health status of young children in the Sahel region of Sub-Saharan Africa: review of international guidelines on infant and young child feeding and nutrition.","Wuehler",21410888,"Accelerating improvements in nutritional and health status of young children in the Sahel region of Sub-Saharan Africa: review of international guidelines on infant and young child feeding and nutrition.    Abstract:   The United Nations Convention on the Rights of the Child holds governments responsible to ensure childrens right to the highest attainable standard of health by providing breastfeeding support, and access to nutritious foods, appropriate health care, and clean drinking water. International experts have identified key child care practices and programmatic activities that are proven to be effective at reducing infant and young child undernutrition, morbidity, and mortality. Nevertheless, progress towards reducing the prevalence of undernutrition has been sporadic across countries of the Sahel sub-region of Sub-Saharan Africa. In view of this uneven progress, a working group of international agencies was convened to Reposition childrens right to adequate nutrition in the Sahel. The first step towards this goal was to organize a situational analysis of the legislative, research, and programmatic activities related to infant and young child nutrition (IYCN) in six countries of the sub-region: Burkina Faso, Chad, Mali, Mauritania, Niger, and Senegal. The purposes of this introductory paper are to review current information concerning the nutritional and health status of infants and young children in the Sahel and to summarize international guidelines on optimal IYCN practices. These guidelines were used in completing the above-mentioned situational analyses and encompass specific recommendations on: (i) breastfeeding (introduction within the first hour after birth, exclusivity to 6 months, continuation to at least 24 months); (ii) complementary feeding (introduction at 6 months, use of nutrient dense foods, adequate frequency and consistency, and responsive feeding); (iii) prevention and/or treatment of micronutrient deficiencies (vitamin A, zinc, iron and anaemia, and iodine); (iv) prevention and/or treatment of acute malnutrition; (v) feeding practices adapted to the maternal situation to reduce mother-to-child transmission of HIV; (vi) activities to ensure food security; and (vii) the promotion of hygienic practices concerning food preparation and storage and environmental sanitation. The following papers in this issue will present results of the situational analyses for the individual countries."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I211,I211)","v":21398228},{"$f":"(LEN($J211) - LEN(SUBSTITUTE(LOWER($J211),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J211) - LEN(SUBSTITUTE(LOWER($J211),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J211) - LEN(SUBSTITUTE(LOWER($J211),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B211:D211)","v":0},2011,"Management of acne.","Kraft",21398228,"Management of acne.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I212,I212)","v":21228730},{"$f":"(LEN($J212) - LEN(SUBSTITUTE(LOWER($J212),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J212) - LEN(SUBSTITUTE(LOWER($J212),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J212) - LEN(SUBSTITUTE(LOWER($J212),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B212:D212)","v":0},2011,"Annual drug update: 2010 in review.","Belavic",21228730,"Annual drug update: 2010 in review.    Abstract:   In 2010, the FDA approved several new drugs and new indications for use in primary care. From new therapies for adults with rheumatoid arthritis to a combination drug for benign prostatic hyperplasia, NPs need to be aware of the latest medications now available."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I213,I213)","v":20364093},{"$f":"(LEN($J213) - LEN(SUBSTITUTE(LOWER($J213),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J213) - LEN(SUBSTITUTE(LOWER($J213),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J213) - LEN(SUBSTITUTE(LOWER($J213),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B213:D213)","v":0},2010,"The key role of vitamin A in spermatogenesis.","Hogarth",20364093,"The key role of vitamin A in spermatogenesis.    Abstract:   Spermatogenesis in adult mammals is highly organized, with the goal being continual sperm production. Vertebrate testes are arranged into recurring cellular associations that vary with time and distance along the tubule. These changes over time and distance are designated the cycle of the seminiferous epithelium and the spermatogenic wave, respectively. In this Review, we briefly outline the roles that follicle-stimulating hormone (FSH) and testosterone play in regulating spermatogenesis and describe our current understanding of how vitamin A regulates germ cell differentiation and how it may lead to the generation of both the cycle of the seminiferous epithelium and the spermatogenic wave."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I214,I214)","v":20095133},{"$f":"(LEN($J214) - LEN(SUBSTITUTE(LOWER($J214),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J214) - LEN(SUBSTITUTE(LOWER($J214),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J214) - LEN(SUBSTITUTE(LOWER($J214),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B214:D214)","v":0},2009,"Red palm oil: nutritional, physiological and therapeutic roles in improving human wellbeing and quality of life.","Oguntibeju",20095133,"Red palm oil: nutritional, physiological and therapeutic roles in improving human wellbeing and quality of life.    Abstract:   The link between dietary fats and cardiovascular disease has created a growing interest in dietary red palm oil research. Also, the link between nutrition and health, oxidative stress and the severity or progression of disease has stimulated further interest in the potential role of red palm oil (a natural antioxidant product) to improve oxidative status by reducing oxidative stress in patients with cardiovascular disease, cancer and other chronic diseases. In spite of its level of saturated fatty acid content (50%), red palm oil has not been found to promote atherosclerosis and/or arterial thrombosis. This is probably due to the ratio of its saturated fatty acid to unsaturated fatty acid content and its high concentration of antioxidants such as beta-carotene, tocotrienols, tocopherols and vitamin E. It has also been reported that the consumption of red palm oil reduces the level of endogenous cholesterol, and this seems to be due to the presence of the tocotrienols and the peculiar isomeric position of its fatty acids. The benefits of red palm oil to health include a reduction in the risk of arterial thrombosis and/or atherosclerosis, inhibition of endogenous cholesterol biosynthesis, platelet aggregation, a reduction in oxidative stress and a reduction in blood pressure. It has also been shown that dietary red palm oil, taken in moderation in animals and humans, promotes the efficient utilisation of nutrients, activates hepatic drug metabolising enzymes, facilitates the haemoglobinisation of red blood cells and improves immune function. This review provides a comprehensive overview of the nutritional, physiological and biochemical roles of red palm oil in improving wellbeing and quality of life."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I215,I215)","v":19907408},{"$f":"(LEN($J215) - LEN(SUBSTITUTE(LOWER($J215),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J215) - LEN(SUBSTITUTE(LOWER($J215),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J215) - LEN(SUBSTITUTE(LOWER($J215),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B215:D215)","v":0},2009,"Treatment of moderate-to-severe plaque psoriasis.","Salgo",19907408,"Treatment of moderate-to-severe plaque psoriasis.    Abstract:   Psoriasis, a chronic common immune-mediated disease with frequent remitting/relapsing courses, has a high negative impact on the quality of life, especially in patients moderately or severely affected by the disease. It is also associated with various co-morbidities resulting in a decreased life expectancy and remarkable socioeconomic costs. At least one third of the patients who suffer from it has moderate or severe psoriasis and require continuous treatment to control disease activity. The therapeutic approach in daily practice is usually determined by the severity of the disease. Whether the definition of disease severity is not always clear, there is a considerable number of patients requiring systemic treatment to control the symptoms of psoriasis. The treatment options available for the management of moderate-severe psoriasis have dramatically increased over the past decade, and now range from phototherapy to traditional systemic treatments to biologics. Available data from clinical trials and growing number of patients treated with biologics shows that this new agent are effective and relatively safe to control psoriasis, and are coupled with improved tolerability, convenience and improvement in quality of life. This review shortly presents the characteristics, safety and efficacy profile of the conventional and newer systemic drugs used in moderate-to-severe psoriasis."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I216,I216)","v":19690489},{"$f":"(LEN($J216) - LEN(SUBSTITUTE(LOWER($J216),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J216) - LEN(SUBSTITUTE(LOWER($J216),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J216) - LEN(SUBSTITUTE(LOWER($J216),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B216:D216)","v":0},2009,"Oral vitamin A enhances the effectiveness of formalin 8% in treating chronic hemorrhagic radiation proctopathy.","Patel",19690489,"Oral vitamin A enhances the effectiveness of formalin 8% in treating chronic hemorrhagic radiation proctopathy.    Abstract:    PURPOSE : Chronic radiation proctopathy occurs in 5 to 20% of patients receiving radiation therapy, with rectal bleeding as its most common presentation. Although formalin treatment for rectal bleeding is promising, improvement is possible. Given the success of vitamin A in other radiation-induced treatments, we studied the efficacy of combining formalin with vitamin A in controlling bleeding symptoms of chronic radiation proctopathy.  METHODS : A retrospective review (1993-2007) was performed of patients presenting with features of chronic radiation proctopathy. Formalin 8% in a buffered solution was applied to the affected mucosa with use a tip applicator, and 10,000 units of vitamin A were given orally on a daily basis. Formalin treatments were repeated at three-week to four-week intervals until symptoms resolved.  RESULTS : A comparison was made between patients who received formalin alone (n = 30) and those who received formalin in combination with vitamin A (n = 34). The 64 patients had a mean age of 79 years (range, 54-90 years). The combination group required fewer treatments (mean, 1.9) and a shorter time (11 weeks) for resolution of symptoms compared with the formalin-alone group (mean, 5.2 and 31 weeks, respectively) (P lt; 0.001). The overall success rate in controlling bleeding was only 64% in the formalin-alone group when compared with 94% in the combination group.  CONCLUSIONS : When vitamin A was added to the regimen, a significant reduction was observed in the number of treatments and the time needed for resolution of symptoms, and there was an increased overall success rate. This combination represents a simple, effective, and well tolerated method of controlling hemorrhagic chronic radiation proctopathy."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I217,I217)","v":19339773},{"$f":"(LEN($J217) - LEN(SUBSTITUTE(LOWER($J217),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J217) - LEN(SUBSTITUTE(LOWER($J217),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J217) - LEN(SUBSTITUTE(LOWER($J217),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B217:D217)","v":0},2009,"The kidney from prenatal to adult life: perinatal programming and reduction of number of nephrons during development.","Puddu",19339773,"The kidney from prenatal to adult life: perinatal programming and reduction of number of nephrons during development.    Abstract:   Modified embryonic-fetal development resulting in low birth weight may lead to a reduced nephron endowment, hypertension and renal diseases in adulthood. Regarding the involvement of genetic factors, several environmental conditions may also contribute towards reducing the number of nephrons in the fetus and infant, subsequently constituting a health burden in later life. To date no methods of investigation for the early detection of a reduced nephron reserve are available. However, more structured studies should be implemented to investigate the role of angiotensin-converting enzyme inhibitors in managing proteinurias and glomerulosclerosis in children with renal conditions characterized by reduce nephron number and glomerular hypertrophic changes. In view of the current lack of specific methods of investigation and management, close monitoring of children and young adults at risk of reduced renal reserve should be carried out to enhance the early detection of potential changes in renal function."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I218,I218)","v":19229271},{"$f":"(LEN($J218) - LEN(SUBSTITUTE(LOWER($J218),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J218) - LEN(SUBSTITUTE(LOWER($J218),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J218) - LEN(SUBSTITUTE(LOWER($J218),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B218:D218)","v":0},2009,"Ocular teratogens: old acquaintances and new dangers.","Tandon",19229271,"Ocular teratogens: old acquaintances and new dangers.    Abstract:   Recent research into animal studies has contributed significantly to understanding the pathophysiology of some well-known teratogens, such as alcohol. Techniques, such as positron emission tomography (PET) and retinal synaptogenesis studies, have helped determine the specific areas in the developing brain and ocular structures, which are targeted by various teratogens. In this article, we also highlight a few newer agents, such as benzodiazepines, with potential for ocular malformation and morbidity in the developing foetus."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I219,I219)","v":18948370},{"$f":"(LEN($J219) - LEN(SUBSTITUTE(LOWER($J219),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J219) - LEN(SUBSTITUTE(LOWER($J219),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J219) - LEN(SUBSTITUTE(LOWER($J219),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B219:D219)","v":0},2008,"Performance of a single assay for both type III and type VI TMPRSS2:ERG fusions in noninvasive prediction of prostate biopsy outcome.","Clark",18948370,"Performance of a single assay for both type III and type VI TMPRSS2:ERG fusions in noninvasive prediction of prostate biopsy outcome.    Abstract:    BACKGROUND : TMPRSS2:ERG fusions are promising prostate cancer biomarkers. Because they can occur in multiple forms in a single cancer specimen, we developed a quantitative PCR test that detects both type III and type VI TMPRSS2:ERG fusions. The assay is quantified from a standard curve determined with a plasmid-cloned type III TMPRSS2:ERG fusion target.  METHODS : We collected expressed prostatic secretion (EPS) under an institutional review board-approved, blinded, prospective study from 74 patients undergoing transrectal ultrasound-guided biopsy for prostate cancer. We compared the characteristic performance of the test for type III and type VI TMPRSS2:ERG fusions in predicting biopsy outcome and distinguishing between high and low Gleason scores with similar tests for the expression of PCA3 and DNA methylation levels of the APC, RARB, RASSF1, and GSTP1 genes. We used logistic regression to analyze the effects of multiple biomarkers in linear combinations.  RESULTS : Each test provided a significant improvement in characteristic performance over baseline digital rectal examination (DRE) plus serum prostate-specific antigen (PSA); however, the test for type III and type VI TMPRSS2:ERG fusions yielded the best performance in predicting biopsy outcome [area under the curve (AUC) 0.823, 95% CI 0.728-0.919, P lt; 0.001] and Gleason grade gt;7 (AUC 0.844, 95% CI 0.740-0.948, P lt; 0.001).  CONCLUSIONS : Although each test appears to have diagnostic value, PSA plus DRE plus type III and type VI TMPRSS2:ERG provided the best diagnostic performance in EPS specimens."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I220,I220)","v":18683028},{"$f":"(LEN($J220) - LEN(SUBSTITUTE(LOWER($J220),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J220) - LEN(SUBSTITUTE(LOWER($J220),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J220) - LEN(SUBSTITUTE(LOWER($J220),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B220:D220)","v":0},2008,"Micronutrient status, cognition and behavioral problems in childhood.","Benton",18683028,"Micronutrient status, cognition and behavioral problems in childhood.    Abstract:   It is widely accepted that the rapid rate of growth of the brain during the last third of gestation and the early postnatal stage makes it vulnerable to an inadequate diet, although brain development continues into adulthood and micronutrient status can influence functioning beyond infancy. A deficiency of various micro-nutrients in developing countries has been found to have long-term implication for cognitive development. Vitamin A plays a critical role in visual perception and a deficiency is the leading cause of childhood blindness. A lack of iodine during a critical period in brain development is associated with reduced intellectual ability. Iron shortage is a widespread problem in the developing world but also in industrialized countries. There is evidence that iron deficiency in early life adversely effects brain development. In addition in industrialized countries a role for folate in the prevention of neural tube defects is well established and in a few individuals impaired cognitive functioning is associated with the inadequate provision of vitamin B(12. )The controversial suggestions that sub-clinical deficiencies of micronutrients may in industrialized societies influence anti-social behavior and intelligence are also discussed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I221,I221)","v":18793935},{"$f":"(LEN($J221) - LEN(SUBSTITUTE(LOWER($J221),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J221) - LEN(SUBSTITUTE(LOWER($J221),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J221) - LEN(SUBSTITUTE(LOWER($J221),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B221:D221)","v":0},2008,"Medical treatments for male and female pattern hair loss.","Rogers",18793935,"Medical treatments for male and female pattern hair loss.    Abstract:    UNLABELLEDMale and female pattern hair loss affects a large percentage of the population, and patients frequently present for treatment of this to their dermatologist. Here we review the many treatments available for hair loss. We review the evidence for each, and outline the most effective treatment strategies for both men and women.  LEARNING OBJECTIVE : At the conclusion of this article, the reader should be able to describe the most effective treatments for hair loss, understand their mechanism(s) of action, and explain which treatments are the best in different settings."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I222,I222)","v":18784430},{"$f":"(LEN($J222) - LEN(SUBSTITUTE(LOWER($J222),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J222) - LEN(SUBSTITUTE(LOWER($J222),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J222) - LEN(SUBSTITUTE(LOWER($J222),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B222:D222)","v":0},2008,"Maternal abetalipoproteinemia resulting in multiple fetal anomalies.","Seckeler",18784430,"Maternal abetalipoproteinemia resulting in multiple fetal anomalies.    Abstract:   Abetalipoproteinemia is a rare genetic condition that results in an inability of the body to absorb dietary fats, including fat-soluble vitamins. Deficiencies of these vitamins are known to cause a wide range of clinical effects ranging from blindness to coagulopathy and neuropathy. We present the case of a child with multisystem anomalies born to a mother with abetalipoproteinemia and provide a brief review of the literature about vitamin A and fetal development. Mothers at high risk for vitamin deficiencies should be screened and counseled on the potential benefits, and risks, of vitamin supplementation."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I223,I223)","v":18481432},{"$f":"(LEN($J223) - LEN(SUBSTITUTE(LOWER($J223),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J223) - LEN(SUBSTITUTE(LOWER($J223),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J223) - LEN(SUBSTITUTE(LOWER($J223),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B223:D223)","v":0},2008,"[Genes related with male gonadal morphogenesis in mammals].","Wu",18481432,"[Genes related with male gonadal morphogenesis in mammals].    Abstract:   Gene expressions are sex-specific in the sex development of mammals. Different genes express in different phases and tend to change with the time. The functions of some genes, such as SRY, SOX9, SOX8, DAX1, and FGF9, have already been defined in male gonadal morphogenesis. This paper presents a review of the genes involved in the formation of the male gonad in mammals."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I224,I224)","v":18234138},{"$f":"(LEN($J224) - LEN(SUBSTITUTE(LOWER($J224),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J224) - LEN(SUBSTITUTE(LOWER($J224),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J224) - LEN(SUBSTITUTE(LOWER($J224),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B224:D224)","v":0},2008,"Maternal and child nutrition in Sub-Saharan Africa: challenges and interventions.","Lartey",18234138,"Maternal and child nutrition in Sub-Saharan Africa: challenges and interventions.    Abstract:   Women of child-bearing age (especially pregnant and lactating women), infants and young children are in the most nutritionally-vulnerable stages of the life cycle. Maternal malnutrition is a major predisposing factor for morbidity and mortality among African women. The causes include inadequate food intake, poor nutritional quality of diets, frequent infections and short inter-pregnancy intervals. Evidence for maternal malnutrition is provided by the fact that between 5 and 20% of African women have a low BMI as a result of chronic hunger. Across the continent the prevalence of anaemia ranges from 21 to 80%, with similarly high values for both vitamin A and Zn deficiency levels. Another challenge is the high rates of HIV infection, which compromise maternal nutritional status. The consequences of poor maternal nutritional status are reflected in low pregnancy weight gain and high infant and maternal morbidity and mortality. Suboptimal infant feeding practices, poor quality of complementary foods, frequent infections and micronutrient deficiencies have largely contributed to the high mortality among infants and young children in the region. Feeding children whose mothers are infected with HIV continues to remain an issue requiring urgent attention. There are successful interventions to improve the nutrition of mothers, infants and young children, which will be addressed. Interventions to improve the nutrition of infants and young children, particularly in relation to the improvement of micronutrient intakes of young children, will be discussed. The recent release by WHO of new international growth standards for assessing the growth and nutritional status of children provides the tool for early detection of growth faltering and for appropriate intervention."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I225,I225)","v":17691927},{"$f":"(LEN($J225) - LEN(SUBSTITUTE(LOWER($J225),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J225) - LEN(SUBSTITUTE(LOWER($J225),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J225) - LEN(SUBSTITUTE(LOWER($J225),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B225:D225)","v":0},2007,"Maternal nutrition and predisposition to later kidney disease.","Woods",17691927,"Maternal nutrition and predisposition to later kidney disease.    Abstract:   Although it is well-accepted that size at birth is inversely related to adult blood pressure and cardiovascular risk in humans, the majority of information available with regard to maternal nutrition, prenatal growth, and subsequent renal disease comes from animal models. Restriction of food or protein during specific windows of pregnancy leads to hypertension in adult offspring. Depending on the degree of maternal restriction, nephron number and renal function in the offspring may be reduced, and proteinuria and histological signs of renal disease are present. All of these abnormalities appear to worsen with age. Female gender is relatively protective against these prenatal insults, but with more severe maternal dietary restriction female offspring are also affected. In addition to macronutrients, roles for several micronutrients have been identified in fetal programming for hypertension and renal disease. Ongoing investigations into the roles of sex hormones, the renin-angiotensin system, and vitamin A in these developmental processes may lead to strategies for prevention of dietary programming for hypertension and renal disease in humans."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I226,I226)","v":17589789},{"$f":"(LEN($J226) - LEN(SUBSTITUTE(LOWER($J226),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J226) - LEN(SUBSTITUTE(LOWER($J226),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J226) - LEN(SUBSTITUTE(LOWER($J226),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B226:D226)","v":0},2007,"Epididymis-specific lipocalin promoters.","Suzuki",17589789,"Epididymis-specific lipocalin promoters.    Abstract:   Our goal is to decipher which DNA sequences are required for tissue-specific expression of epididymal genes. At least 6 epididymis-specific lipocalin genes are known. These are differently regulated and regionalized in the epididymis. Lipocalin 5 (Lcn5 or mE-RABP) and Lipocalin 8 (Lcn8 or mEP17) are homologous genes belonging to the epididymis-specific lipocalin gene cluster. Both the 5 kb promoter fragment of the Lcn5 gene and the 5.3 kb promoter fragment of the Lcn8 gene can direct transgene expression in the epididymis (Lcn5 to the distal caput and Lcn8 to the initial segment), indicating that these promoter fragments contain important cis-regulatory element(s) for epididymis-specific gene expression. To define further the fragments regulating gene expression, the Lcn5 promoter was examined in transgenic mice and immortalized epididymal cell lines. After serial deletion, the 1.8 kb promoter fragment of the Lcn5 gene was sufficient for tissue-specific and region-specific gene expression in transgenic mice. Transient transfection analysis revealed that a transcription factor forkhead box A2 (Foxa2) interacts with androgen receptor and binds to the 100 bp fragment of the Lcn5 promoter between 1.2 kb and 1.3 kb and that Foxa2 expression inhibits androgen-dependent induction of the Lcn5 promoter activity. Immunohistochemistry indicated a restricted expression of Foxa2 in the epididymis where endogenous Lcn5 gene expression is suppressed and that the Foxa2 inhibition of the Lcn5 promoter is consistent with the lack of expression of Lcn5 in the corpus and cauda. Our approach provides a basic strategy for further analysis of the epididymal lipocalin gene regulation and flexible control of epididymal function."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I227,I227)","v":17539885},{"$f":"(LEN($J227) - LEN(SUBSTITUTE(LOWER($J227),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J227) - LEN(SUBSTITUTE(LOWER($J227),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J227) - LEN(SUBSTITUTE(LOWER($J227),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B227:D227)","v":0},2007,"Does birth spacing affect maternal or child nutritional status? A systematic literature review.","Dewey",17539885,"Does birth spacing affect maternal or child nutritional status? A systematic literature review.    Abstract:   This review addresses the question of whether a short birth interval is associated with adverse nutritional outcomes for the mother or the child. Indices of anthropometric status (maternal weight or body mass index; child growth) and micronutrient status (e.g. iron or vitamin A) were included as outcomes. A computerized search of all relevant papers published since 1966 was completed, and the snowball method was used to identify additional relevant published or unpublished papers. In total, 57 papers were found to contain data regarding the relationship between birth spacing and nutritional outcomes (35 for child nutrition, 11 for maternal anthropometric status, and 11 for maternal anaemia or micronutrient status). Of these, 23 papers were excluded from further consideration because they did not include any multivariate analysis, leaving 34 papers that met the criteria for the review (22 for child nutrition, eight for maternal anthropometric status, and four for maternal anaemia or micronutrient status). The studies on child nutrition outcomes indicate that a longer birth interval is associated with a lower risk of malnutrition in some populations, but not all. In those countries in which the relationship was significant, the reduction in stunting associated with a previous birth interval gt;or=36 months ranged from approximately 10% to 50%. Some of this reduction may be due to residual confounding, i.e. to factors not included in the analysis (such as breastfeeding and maternal height). The studies on maternal anthropometric outcomes yielded mixed results. Because the nutritional burden on the mother between pregnancies depends on the extent of breastfeeding, the interpregnancy interval is not the best measure of whether the mother has had a chance to recover from the pregnancy, in terms of repleting her nutritional status. Therefore, some studies examined the recuperative interval (duration of the non-pregnant, non-lactating interval) instead. Taken as a whole, the studies do not provide clear evidence of a link between interpregnancy or recuperative interval and maternal anthropometric status. This may be due, in part, to changes in the hormonal regulation of nutrient partitioning between the mother and the fetus when a mother is malnourished. Only four papers were identified that related to micronutrient status, three of which examined maternal anaemia. One study showed an increased risk for maternal anaemia when the interpregnancy interval was lt;6 months, but the analysis did not control for iron supplementation during pregnancy. The other two studies did not show a significant association between interpregnancy interval and maternal anaemia. One study of micronutrient status indicated no significant relationship between interpregnancy interval and maternal serum zinc, copper, magnesium, ferritin, folate or thyroid-stimulating hormone. Important methodological limitations were apparent in most of the studies. Thus, further research with more comprehensive control of potentially confounding variables is needed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I228,I228)","v":17483773},{"$f":"(LEN($J228) - LEN(SUBSTITUTE(LOWER($J228),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J228) - LEN(SUBSTITUTE(LOWER($J228),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J228) - LEN(SUBSTITUTE(LOWER($J228),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B228:D228)","v":0},2007,"[Nutritional deficiencies associated with bariatric surgery].","Folope",17483773,"[Nutritional deficiencies associated with bariatric surgery].    Abstract:   Morbidly obese patients often have nutritional deficiencies, particularly in fat-soluble vitamins, folic acid and zinc. After bariatric surgery, these deficiencies may increase and others can appear, especially because of the limitation of food intake in gastric reduction surgery and of malabsorption in by-pass procedures. The latter result in more important weight loss but also increase the risk of more severe deficiencies. The protein deficiency associated with a decrease in the fat-free mass has been described in both procedures. It can sometimes require an enteral or parenteral support. Anemia can be secondary to iron deficiency, folic acid deficiency and even to vitamin B12 deficiency. Neurological disorders such as Gayet-Wernicke encephalopathy due to thiamine deficiency, or peripheral neuropathies may also be observed. Malabsorption of fat-soluble vitamins and other nutrients, especially if diagnosed after by-pass surgery, rarely cause clinical symptoms. However, some complications have been reported such as bone demineralization due to vitamin D deficiency, hair loss secondary to zinc deficiency or hemeralopia from vitamin A deficiency. A careful nutritional follow-up should be performed during pregnancy after obesity surgery, because possible deficiencies can affect the health of both the mother and child. In conclusion, increased awareness of the risk of deficiency and the systematic dosage of micronutrients are needed in the pre- and postoperative period in obese patients undergoing bariatric surgery. The case by case correction of these deficiencies is mandatory, and their systematic prevention should be evaluated."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I229,I229)","v":17287870},{"$f":"(LEN($J229) - LEN(SUBSTITUTE(LOWER($J229),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J229) - LEN(SUBSTITUTE(LOWER($J229),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J229) - LEN(SUBSTITUTE(LOWER($J229),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B229:D229)","v":0},2007,"The medical management of Peyronies disease.","Akin-Olugbade",17287870,"The medical management of Peyronies disease.    Abstract:   There are a wide variety of medical treatments that are available to the practicing urologist, including oral agents, topical creams and gels with or without iontophoresis, intralesional injection therapy, radiation therapy, extracorporeal shockwave therapy, and laser therapy. Medical management of Peyronies disease might be a valuable treatment option for this debilitating disorder, especially in the early symptomatic stages of the disease. Although no single modality has been demonstrated to have superior efficacy, intralesional therapy appears to confer some benefit. Multicenter, large-scale, randomized, controlled studies are necessary to fully establish the efficacy of the available treatments. Until such trials are conducted, a rational approach involving combination therapy is the most appropriate method to treat these patients. In this Review, the current medical treatment options available for the management of Peyronies disease are discussed and a management algorithm is proposed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I230,I230)","v":17022912},{"$f":"(LEN($J230) - LEN(SUBSTITUTE(LOWER($J230),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J230) - LEN(SUBSTITUTE(LOWER($J230),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J230) - LEN(SUBSTITUTE(LOWER($J230),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B230:D230)","v":0},2006,"Fat-soluble vitamin deficiency in pregnancy: a case report and review of abetalipoproteinemia.","Gaudet",17022912,"Fat-soluble vitamin deficiency in pregnancy: a case report and review of abetalipoproteinemia.    Abstract:    BACKGROUND : Abetalipoproteinemia (ABL) is a metabolic disorder resulting in poor absorption of fat-soluble vitamins.  CASE : Two pregnancies in a woman with ABL are reported, contrasting outcomes with subtherapeutic and normal vitamin levels.  CONCLUSION : Fat-soluble vitamin levels in pregnancy are critical for many aspects of fetal development. This report details a congenital ophthalmologic finding that may be associated with vitamin A deficiency."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I231,I231)","v":17016949},{"$f":"(LEN($J231) - LEN(SUBSTITUTE(LOWER($J231),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J231) - LEN(SUBSTITUTE(LOWER($J231),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J231) - LEN(SUBSTITUTE(LOWER($J231),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B231:D231)","v":0},2003,"Vitamin A deficiency disorders in children and women.","West",17016949,"Vitamin A deficiency disorders in children and women.    Abstract:   Vitamin A deficiency is an endemic nutrition problem throughout much of the developing world, especially affecting the health and survival of infants, young children, and pregnant and lactating women. These age and life-stage groups represent periods when both nutrition stress is high and diet likely to be chronically deficient in vitamin A. Approximately 127 million preschool-aged children and 7 million pregnant women are vitamin A deficient. Health consequences of vitamin A deficiency include mild to severe systemic effects on innate and acquired mechanisms of host resistance to infection and growth, increased burden of infectious morbidity, mild to severe (blinding) stages of xerophthalmia, and increased risk of mortality. These consequences are defined as vitamin A deficiency disorders (VADD). Globally, 4.4 million preschool children have xerophthalmia and 6 million mothers suffer night blindness during pregnancy. Both conditions are associated with increased risk of morbidity and mortality. While reductions of child mortality of 19-54% following vitamin A treatment have been widely reported, more recent work suggests that dosing newborns with vitamin A may, in some settings, lower infant mortality. Among women, one large trial has so far reported a gt; or = 40% reduction in mortality related to pregnancy with weekly, low-dose vitamin A supplementation. Epidemiologic data on vitamin A deficiency disorders can be useful in planning, designing, and targeting interventions."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I232,I232)","v":16541732},{"$f":"(LEN($J232) - LEN(SUBSTITUTE(LOWER($J232),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J232) - LEN(SUBSTITUTE(LOWER($J232),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J232) - LEN(SUBSTITUTE(LOWER($J232),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B232:D232)","v":0},2005,"[Prostate cancer chemoprevention].","Krysiak",16541732,"[Prostate cancer chemoprevention].    Abstract:   Prostatic cancer is the most common malignancy diagnosed in men. Chemoprevention of prostatic cancer is a relatively new concept and seems to be a very promising strategy for preventing and arresting the development of this neoplasm. There is much evidence that the increased consumption of selenium, vitamins E and D, lycopen, soy and isoflavonoids and low-fat diet reduce the risk of the incidence of prostatic cancer. Similar effect is also exhibited by some drugs including finasteride, non-steroid anti-inflammatory drugs and lipoxygenase inhibitors. In this paper we summarize the results of published epidemiologic and scientific studies, trying to critically evaluate the potential clinical role and mechanism of action of these agents in modern chemoprevention of this cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I233,I233)","v":16519822},{"$f":"(LEN($J233) - LEN(SUBSTITUTE(LOWER($J233),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J233) - LEN(SUBSTITUTE(LOWER($J233),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J233) - LEN(SUBSTITUTE(LOWER($J233),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B233:D233)","v":0},2006,"Role of vitamins, minerals and supplements in the prevention and management of prostate cancer.","Santillo",16519822,"Role of vitamins, minerals and supplements in the prevention and management of prostate cancer.    Abstract:   The authors review the current literature on the complementary and alternative medicines most frequently utilized by prostate cancer patients and those at risk for the disease. Products covered are vitamin E, vitamin A, selenium, zinc, soy, lycopene, pomegranate juice, green tea and omega-3 fatty acids. There is no definitive proof that any of the nutritional supplements discussed can impact the course of prostate cancer or its development. The authors believe that simply taking a standard daily multivitamin should be sufficient to ensure that patients have the appropriate levels of vitamins and minerals without risking the over utilization of vitamins, minerals, and supplements which can lead to numerous negative side effects."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I234,I234)","v":16335761},{"$f":"(LEN($J234) - LEN(SUBSTITUTE(LOWER($J234),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J234) - LEN(SUBSTITUTE(LOWER($J234),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J234) - LEN(SUBSTITUTE(LOWER($J234),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B234:D234)","v":0},2004,"Iron deficiency anaemia--an old enemy.","Bagchi",16335761,"Iron deficiency anaemia--an old enemy.    Abstract:   Anaemia has remained a widespread public health problem in countries of the Eastern Mediterranean Region. Prevalence figures vary from a low of 17% to a high of over 70% among preschool children; from 14% to 42% among adolescents and from 11% to over 40% among women of childbearing age. Although the prevalence of anaemia has often been used as a proxy indicator for iron deficiency anaemia, this approach is not valid in settings where the etiology of anaemia is complex or unknown or where other micronutrient deficiencies of folate, vitamin B12 and vitamin A can co-exist. An integrated, multifactorial and multisectoral approach has to be adopted comprising targeted interventions to provide iron supplements to especially vulnerable segments of the population, in particular pregnant women; food-based approaches to increase iron intake through food fortification and dietary diversification; and other measures combined with iron interventions where other causes of anaemia are prevalent."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I235,I235)","v":15988384},{"$f":"(LEN($J235) - LEN(SUBSTITUTE(LOWER($J235),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J235) - LEN(SUBSTITUTE(LOWER($J235),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J235) - LEN(SUBSTITUTE(LOWER($J235),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B235:D235)","v":0},2005,"The role of SF1/DAX1 in adrenal and reproductive function.","Achermann",15988384,"The role of SF1/DAX1 in adrenal and reproductive function.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I236,I236)","v":15940919},{"$f":"(LEN($J236) - LEN(SUBSTITUTE(LOWER($J236),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J236) - LEN(SUBSTITUTE(LOWER($J236),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J236) - LEN(SUBSTITUTE(LOWER($J236),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B236:D236)","v":0},2005,"[From gene to disease; congenital adrenal hypoplasia and the DAX-1 gene].","Verrijn Stuart",15940919,"[From gene to disease; congenital adrenal hypoplasia and the DAX-1 gene].    Abstract:   Congenital adrenal hypoplasia is an X-linked disorder resulting in adrenocortical deficiency, failure to complete puberty due to hypogonadotrophic hypogonadism, and infertility. The disease is caused by mutations in the DAX-1 gene. The DAX-1 protein is a transcription inhibitor; it represses the transcription of other, as yet mostly unknown, genes. Mutation analysis can confirm a clinical diagnosis of congenital adrenal hypoplasia. An early diagnosis might prevent critical damage due to an adrenal crisis in an undiagnosed patient. Molecular testing can be used for carrier detection and genetic counselling."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I237,I237)","v":15940119},{"$f":"(LEN($J237) - LEN(SUBSTITUTE(LOWER($J237),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J237) - LEN(SUBSTITUTE(LOWER($J237),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J237) - LEN(SUBSTITUTE(LOWER($J237),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B237:D237)","v":0},2005,"Diet as a risk factor for atopy and asthma.","Devereux",15940119,"Diet as a risk factor for atopy and asthma.    Abstract:   It has been hypothesized that decreasing antioxidant (fruit and vegetables), increased n-6 polyunsaturated fatty acid (PUFA; (margarine, vegetable oil), and decreased n-3 PUFA (oily fish) intakes have contributed to the recent increases in asthma and atopic disease. Epidemiologic studies in adults and children have reported beneficial associations between dietary antioxidants and lipids and parameters of asthma and atopic disease. The associations with n-6 and n-3 PUFA appear to be very complex and might differ between asthma and atopic dermatitis. Dietary antioxidants are probably exerting antioxidant and nonantioxidant immunomodulatory effects. Dietary lipids exert numerous complex effects on proinflammatory and immunologic pathways. It has also been suggested that atopic dermatitis is associated with an enzyme defect in lipid metabolism. In spite of this, the results of interventional supplementation studies in established disease have been disappointing, and there is now increasing interest in the possibility that dietary antioxidant and lipid intakes might be important in determining expression of disease during pregnancy and early childhood and that dietary interventions should be targeted at these groups. It also seems likely that there is individual variation in the responses of individuals to lipid, and probably antioxidant, supplementation. Further research to determine whether dietary intervention can reduce the risk of asthma and atopic disease is justified."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I238,I238)","v":15854063},{"$f":"(LEN($J238) - LEN(SUBSTITUTE(LOWER($J238),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J238) - LEN(SUBSTITUTE(LOWER($J238),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J238) - LEN(SUBSTITUTE(LOWER($J238),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B238:D238)","v":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."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I239,I239)","v":15570058},{"$f":"(LEN($J239) - LEN(SUBSTITUTE(LOWER($J239),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J239) - LEN(SUBSTITUTE(LOWER($J239),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J239) - LEN(SUBSTITUTE(LOWER($J239),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B239:D239)","v":0},2004,"Tomato phytochemicals and prostate cancer risk.","Campbell",15570058,"Tomato phytochemicals and prostate cancer risk.    Abstract:   Mounting evidence over the past decade suggests that the consumption of fresh and processed tomato products is associated with reduced risk of prostate cancer. The emerging hypothesis is that lycopene, the primary red carotenoid in tomatoes, may be the principle phytochemical responsible for this reduction in risk. A number of potential mechanisms by which lycopene may act have emerged, including serving as an important in vivo antioxidant, enhancing cell-to-cell communication via increasing gap junctions between cells, and modulating cell-cycle progression. Although the effect of lycopene is biologically relevant, the tomato is also an excellent source of nutrients, including folate, vitamin C, and various other carotenoids and phytochemicals, such as polyphenols, which also may be associated with lower cancer risk. Tomatoes also contain significant quantities of potassium, as well as some vitamin A and vitamin E. Our laboratory has been interested in identifying specific components or combination of components in tomatoes that are responsible for reducing prostate cancer risk. We carried out cell culture trials to evaluate the effects of tomato carotenoids and tomato polyphenols on growth of prostate cancer cells. We also evaluated the ability of freeze-dried whole-tomato powder or lycopene alone to reduce growth of prostate tumors in rats. This paper reviews the epidemiological evidence, evaluating the relationship between prostate cancer risk and tomato consumption, and presents experimental data from this and other laboratories that support the hypothesis that whole tomato and its phytochemical components reduce the risk of prostate cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I240,I240)","v":15464421},{"$f":"(LEN($J240) - LEN(SUBSTITUTE(LOWER($J240),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J240) - LEN(SUBSTITUTE(LOWER($J240),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J240) - LEN(SUBSTITUTE(LOWER($J240),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B240:D240)","v":0},2004,"Molecular mechanisms of DAX1 action.","Iyer",15464421,"Molecular mechanisms of DAX1 action.    Abstract:   DAX1 (dosage sensitive sex reversal (DSS), adrenal hypoplasia congenita (AHC) critical region on the X chromosome, gene 1) encoded by the gene NR0B1, is an unusual orphan nuclear receptor that when mutated causes AHC with associated hypogonadotropic hypogonadism (HH), and when duplicated causes DSS. DAX1 expression has been shown in all regions of the hypothalamic-pituitary-adrenal-gonadal (HPAG) axis during development and in adult tissues, suggesting a critical role for DAX1 in the normal development and function of this axis. Steroidogenic factor 1 (SF1, NR5A1) knockout mice show similar developmental defects as AHC and HH patients, but paradoxically, DAX1 is a negative coregulator of SF1 transactivation. The function of DAX1 as an antagonist of SF1 in gonadal development is consistent with the fact that in humans, duplication of the region of the X chromosome containing DAX1 causes a similar phenotype as mutations in SF1. However, how disruption of DAX1 leads to adrenal, hypothalamic, and pituitary developmental defects similar to SF1 disruption remains to be clarified. The exact mechanism of DAX1 action in each of these tissues during adulthood and critical stages of development are not fully understood. Recent evidence suggests a broader functional role for DAX1 as a negative coregulator of estrogen receptor (ER, NR3A1-2), liver receptor homologue-1 (LRH-1, NR5A2), androgen receptor (AR, NR3C4), and progesterone receptor (PR, NR3C3), each by distinct repression mechanisms. DAX1 may have pleiotropic roles in addition to its function as a negative regulator of steroidogenesis during the development and adult function of the HPAG axis."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I241,I241)","v":15362532},{"$f":"(LEN($J241) - LEN(SUBSTITUTE(LOWER($J241),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J241) - LEN(SUBSTITUTE(LOWER($J241),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J241) - LEN(SUBSTITUTE(LOWER($J241),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B241:D241)","v":0},2004,"[Antioxidant vitamin and male reproduction].","Gu",15362532,"[Antioxidant vitamin and male reproduction].    Abstract:   Increased generation of ROS causes the lipid oxidation of the membrane of spermatozoa, but antioxidant vitamins play an important role in reproduction and help clear away ROS and protect the sperm membrane from lipid oxidation. This review focused on the effect of antioxidant vitamins on male reproduction and in the treatment of male infertility."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I242,I242)","v":15125076},{"$f":"(LEN($J242) - LEN(SUBSTITUTE(LOWER($J242),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J242) - LEN(SUBSTITUTE(LOWER($J242),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J242) - LEN(SUBSTITUTE(LOWER($J242),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B242:D242)","v":0},2003,"[Vitamin A deficiency and clinical associations: a review].","El Beitune",15125076,"[Vitamin A deficiency and clinical associations: a review].    Abstract:   An important focus of attention in Public Health has been micronutrient deficiency in human being because of the enhanced vulnerability of individuals to the effects of micronutrient deficiency or imbalance. Among all micronutrients deficiencies, vitamin A has been one of the most important public health problems, affecting a large percentage of people in developing countries. Vitamin A is particularly important for its role in the process of organism defense against infections. This article reviews comprehensively vitamin A metabolism, it highlights hypovitaminosis A relationship with pregnancy and human imunodeficiency, showing its repercussions in several clinical conditions."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I243,I243)","v":15024783},{"$f":"(LEN($J243) - LEN(SUBSTITUTE(LOWER($J243),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J243) - LEN(SUBSTITUTE(LOWER($J243),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J243) - LEN(SUBSTITUTE(LOWER($J243),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B243:D243)","v":0},2003,"Update on the prevalence of malnutrition among children in Asia.","Khor",15024783,"Update on the prevalence of malnutrition among children in Asia.    Abstract:   Approximately 70.0% of the worlds malnourished children live in Asia, resulting in the region having the highest concentration of childhood malnutrition. About half of the preschool children are malnourished ranging from 16.0% in the Peoples Republic of China to 64.0% in Bangladesh. Prevalence of stunting and underweight are high especially in South Asia where one in every two preschool children is stunted. Besides protein-energy malnutrition, Asian children also suffer from micronutrient deficiency. Iron deficiency anaemia affects 40.0-50.0% of preschool and primary school children. Nearly half of all vitamin A deficiency and xeropthalmia in the world occurs in South and Southeast Asia, with large numbers of cases in India (35.3 million), Indonesia (12.6 million) and China (11.4 million). Another major micronutrient problem in the region is iodine deficiency disorders, which result in high goiter rates as manifested in India, Pakistan and parts of Indonesia. While under-nutrition problem persists, overweight problem in children has emerged in Asia, including Taiwan, Singapore and urban China and Malaysia. The etiology of childhood malnutrition is complex involving interactions of multiple determinants that include biological, cultural and socio-economic influences. Protein-energy malnutrition and micronutrient deficiency leading to early growth failure often can be traced to poor maternal nutritional and health care before and during pregnancy, resulting in intrauterine growth retardation and children born with low birth weight. While significant progress has been achieved over the past 30 years in reducing the proportion of malnourished children in developing countries, nonetheless, malnutrition persists affecting large numbers of children. The socio-economic cost of the malnutrition burden to the individual, family and country is high resulting in lower cognitive outcomes in children and lower adult productivity. Interventions that are cost-effective and culturally appropriate for the elimination of childhood malnutrition deserve the support of all."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I244,I244)","v":15000734},{"$f":"(LEN($J244) - LEN(SUBSTITUTE(LOWER($J244),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J244) - LEN(SUBSTITUTE(LOWER($J244),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J244) - LEN(SUBSTITUTE(LOWER($J244),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B244:D244)","v":0},2004,"Haematological profiles of the people of rural southern Malawi: an overview.","Brabin",15000734,"Haematological profiles of the people of rural southern Malawi: an overview.    Abstract:   An integrative review of the results of two published and two unpublished studies of anaemia in children, adolescent females, pregnant women and adults living in southern Malawi is presented. Anaemia was universally present in all age-groups, with the higher prevalences in infants (100%) and adolescent primigravidae (93.8%). Nutritional deficits of iron and vitamin A were major contributory factors but chronic malarial haemolysis also significantly contributed to the anaemia. Among boys, anaemia was more common among those with glucose-6-phosphate-dehydrogenase (G6PD) deficiency than in those without this deficiency (Plt;0.002). This enzymopathy, which occurred in 23.5% [95% confidence interval (CI)=16.7%-30.1%] of the male and 30% (CI=17.3%-42.7%) of the female infants examined, was also associated with neonatal jaundice. The overall prevalences of the-alpha(3.7)/alphaalpha and -alpha(3.7)/-alpha(3.7) thalassaemia genotypes were estimated at 41.0% (CI=28.3%-53.7%) and 8.7% (CI=1.5%-15.9%), respectively. Haemoglobin AS was present in 18.1% (CI=12.8%-23.4%) of the infants and haemoglobin SS in 2.5% (CI=1.4%-3.6%). As the prevalence of infection with Plasmodium falciparum was significantly higher in infants with haemoglobin AS than in those with AA (21.4% v. 6.7%; Plt;0.001), an increased risk of early-onset moderate parasitaemias in young infants probably stimulates the development of immunity, protecting older heterozygotes from severe malarial infection. Innovative community approaches are required to break the cycle of ill health that anaemia supports in those living in rural areas of southern Malawi. Interventions in adolescent girls could be of particular importance, as they could break the cycle in both pregnant women and their infants."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I245,I245)","v":14585302},{"$f":"(LEN($J245) - LEN(SUBSTITUTE(LOWER($J245),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J245) - LEN(SUBSTITUTE(LOWER($J245),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J245) - LEN(SUBSTITUTE(LOWER($J245),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B245:D245)","v":0},2003,"Human requirements for fat-soluble vitamins, and other things concerning these nutrients.","Krinsky",14585302,"Human requirements for fat-soluble vitamins, and other things concerning these nutrients.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I246,I246)","v":12942384},{"$f":"(LEN($J246) - LEN(SUBSTITUTE(LOWER($J246),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J246) - LEN(SUBSTITUTE(LOWER($J246),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J246) - LEN(SUBSTITUTE(LOWER($J246),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B246:D246)","v":0},2003,"Micronutrients and human immunodeficiency virus type 1 disease progression among adults and children.","Fawzi",12942384,"Micronutrients and human immunodeficiency virus type 1 disease progression among adults and children.    Abstract:   The results of randomized trials among men and nonpregnant women have confirmed the potential benefits of vitamins B, C, and E supplements on the immune status of human immunodeficiency virus (HIV)-infected individuals. Larger trials are needed to ascertain whether these benefits are sustained and to examine the effect of supplementation on clinical outcomes. Among pregnant women, vitamin A supplements increase the risk of mother-to-child transmission. Supplementation with vitamins B, C, and E during prenatal and breastfeeding periods should be encouraged, in light of the protective effects on adverse pregnancy and child outcomes. In children aged gt;6 months, vitamin A supplements are beneficial for reducing morbidity and mortality in developing countries, including among HIV-infected children. There are no data on the relationships of other micronutrients and child health. For adults and children, more research is warranted on the role of selenium, zinc, and other trace elements on various measures of health among HIV-infected individuals."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I247,I247)","v":12915216},{"$f":"(LEN($J247) - LEN(SUBSTITUTE(LOWER($J247),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J247) - LEN(SUBSTITUTE(LOWER($J247),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J247) - LEN(SUBSTITUTE(LOWER($J247),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B247:D247)","v":0},2003,"Metabolic effects of plant sterols and stanols (Review).","de Jong",12915216,"Metabolic effects of plant sterols and stanols (Review).    Abstract:   High serum LDL cholesterol concentration is a major risk factor for cardiovascular complications. This risk can be lowered by diet. In this respect foods containing plant sterol or stanol esters can be useful for mildly- and hypercholesteraemic subjects. Plant sterols and stanols, which are structurally related to cholesterol, decrease the incorporation of dietary and biliary cholesterol into micelles. This lowers cholesterol absorption. Furthermore, these components increase ABC-transporter expression, which may also contribute to the decreased cholesterol absorption. Consequently, cholesterol synthesis and LDL receptor activity increase, which ultimately leads to decreased serum LDL cholesterol concentrations. Animal studies have further shown that these dietary components may also lower atherosclerotic lesion development. Plant sterols and stanols also lower plasma lipid-standardized concentrations of the hydrocarbon carotenoids, but not those of the oxygenated cartenoids and tocopherols. Also, vitamin A and D concentrations are not affected. Although absorption of plant sterols and stanols (0.02-3.5%) is low compared to cholesterol (35-70%), small amounts are found in the circulation and may influence other physiological functions. However, there is no consistent evidence that plant sterols or stanols can change the risk of colon or prostate cancer, or immune status. In conclusion, plant sterols and stanols effectively reduce serum LDL cholesterol and atherosclerotic risk. In addition potential effects of plant sterols and stanols on other metabolic processes remain to be elucidated."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I248,I248)","v":12842416},{"$f":"(LEN($J248) - LEN(SUBSTITUTE(LOWER($J248),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J248) - LEN(SUBSTITUTE(LOWER($J248),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J248) - LEN(SUBSTITUTE(LOWER($J248),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B248:D248)","v":0},2003,"Programming the cardiovascular system, kidney and the brain--a review.","Wintour",12842416,"Programming the cardiovascular system, kidney and the brain--a review.    Abstract:   The concept that life before birth or the first environment is important in determining subsequent risk for the development of cardiovascular/metabolic disease is now gaining acceptance. There are substantial data from animal experiments that complement and enhance the epidemiological data from human studies. We argue that any factor which disrupts nephrogenesis, and lowers nephron number, during the period of active nephrogenesis, will induce malapadaptive changes in the future functioning of that kidney and predispose to the onset of adult hypertension. Such factors include exposure of the mother, to a particular low-protein diet, excess synthetic or natural glucocorticoid at certain critical periods, mild vitamin A deficiency, elevated blood glucose, unilateral nephrectomy during the period of nephrogenesis, as well as the deletion of one allele of a gene (GDNF) involved in normal metanephric development. All of these stresses are associated with a reduction (20-40 per cent) in total nephron number in the adult, and the development of hypertension. In some hypertensive models, (rats) there is evidence of alterations in the components of the hippocampal/hypothalamic/pituitary/adrenal axis, whereas in others (sheep) there are alterations in the expression of angiotensinogen (hypothalamus) and angiotensin II receptor type I (AT(1)) in the medulla oblongata. The surprising finding is that the period when the kidney and brain are most vulnerable is very early in development, when both organs are in an extremely primitive state of development."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I249,I249)","v":12833004},{"$f":"(LEN($J249) - LEN(SUBSTITUTE(LOWER($J249),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J249) - LEN(SUBSTITUTE(LOWER($J249),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J249) - LEN(SUBSTITUTE(LOWER($J249),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B249:D249)","v":0},2003,"Management of acne: a report from a Global Alliance to Improve Outcomes in Acne.","Gollnick",12833004,"Management of acne: a report from a Global Alliance to Improve Outcomes in Acne.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I250,I250)","v":12775097},{"$f":"(LEN($J250) - LEN(SUBSTITUTE(LOWER($J250),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J250) - LEN(SUBSTITUTE(LOWER($J250),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J250) - LEN(SUBSTITUTE(LOWER($J250),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B250:D250)","v":0},2002,"Chemoprevention of carcinoma prostate: a review.","Ansari",12775097,"Chemoprevention of carcinoma prostate: a review.    Abstract:    PURPOSE : Chemoprevention of prostate cancer is the administration of agents to prevent, inhibit, or delay progression of prostate cancer. Opportunities exist for testing various types of chemopreventive interventsion.  MATERIAL AND METHODS : The authors reviewed the relevant articles published in the last twenty years and studied the biology of the prostate cancer. An attempt is made to identify intermediate markers and surrogate endpoint markers. The various interventions and initial clinical trial results are described. End points for evaluation are mainly based on changes in PSA, changes of histological precursors, or time of onset of clinical disease.  RESULTS : Nutritional factors such as reduced fat intake, vitamin A, vitamin E, vitamin C, vitamin D, Lycopene and selenium may have a protective effect against prostate cancer.  CONCLUSION : Numerous studies implicate dietary and nutritional factors in the onset and progression of prostate cancer. Hence, it is possible that bioactive compounds (anti-oxidants) like vits. A, C, D, E, minerals like selenium and carotenoids like lycopene can be a part of chemopreventive strategies for prostate cancer. Ongoing studies on nutrition and prostate cancer may bring the required evidence to support what is still only a hypothesis at present. However, absolute recommendation will have to await the results of long term prospective clinical trials."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I251,I251)","v":12599584},{"$f":"(LEN($J251) - LEN(SUBSTITUTE(LOWER($J251),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J251) - LEN(SUBSTITUTE(LOWER($J251),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J251) - LEN(SUBSTITUTE(LOWER($J251),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B251:D251)","v":0},2002,"[A novel molecular target therapeutics for refractory prostate cancer].","Uemura",12599584,"[A novel molecular target therapeutics for refractory prostate cancer].    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I252,I252)","v":12566727},{"$f":"(LEN($J252) - LEN(SUBSTITUTE(LOWER($J252),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J252) - LEN(SUBSTITUTE(LOWER($J252),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J252) - LEN(SUBSTITUTE(LOWER($J252),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B252:D252)","v":0},2003,"SF1 in the development of the adrenal gland and gonads.","Ozisik",12566727,"SF1 in the development of the adrenal gland and gonads.    Abstract:   SF1 (steroidogenic factor-1; NR5A1) is an orphan nuclear receptor that is expressed in the adrenal gland, gonads, spleen, ventromedial hypothalamus and pituitary gonadotroph cells. Combined approaches of targeted mutagenesis in mice and examination of the effects of naturally occurring mutations in humans have clarified the role of SF1 in steroidogenesis and development. Targeted disruption of SF1 (FTZF1) in mice prevents gonadal and adrenal development and causes male-to-female sex reversal. A heterozygous loss-of-function human SF1 mutation (G35E) was described in a patient with adrenal failure and complete 46,XY sex reversal, indicating that haploinsufficiency of this transcription factor is sufficient to cause a severe clinical phenotype. In an infant with a similar clinical phenotype, a homozygous SF1 mutation (R92Q) was identified. In functional assays, this mutant SF1 protein exhibited partial loss of DNA binding and transcriptional activity when compared with the more severe G35E P-box mutant. These patients reveal the exquisite sensitivity of SF1-dependent developmental pathways to gene dosage and function in humans."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I253,I253)","v":12530669},{"$f":"(LEN($J253) - LEN(SUBSTITUTE(LOWER($J253),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J253) - LEN(SUBSTITUTE(LOWER($J253),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J253) - LEN(SUBSTITUTE(LOWER($J253),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B253:D253)","v":0},2002,"SF-1, DAX-1, and acd: molecular determinants of adrenocortical growth and steroidogenesis.","Beuschlein",12530669,"SF-1, DAX-1, and acd: molecular determinants of adrenocortical growth and steroidogenesis.    Abstract:   The formation of the adrenal cortex in humans is notable for the presence of two discrete zones, the fetal zone (FZ) which regresses soon after birth and the definitive zone (DZ) which gives rise to the classic steroidogenic zones of the adult cortex. Mice possess an analogous structure to the FZ referred to as the X-zone (XZ) which regresses at puberty in the male and during the first pregnancy in the female. Similar to the human FZ in X-linked Congenital Adrenal Hypoplasia caused by loss of function mutations in DAX-1 (Dosage-sensitive sex reversal-Adrenal hypoplasia congenita critical region on the X chromosome), the mouse XZ does not regress when DAX-1 is mutated. Only in humans with DAX-1 mutations, however, is the DZ small and hypofunctional. Patients and mice with SF-1 mutations have complete adrenal aplasia with absence of both the DZ and FZ/XZ. Lastly, the phenotype of the Autosomal Recessive Adrenocortical Dysplasia (acd) mouse is strikingly similar to human Miniature Adult Congenital Adrenal Hypoplasia, lacking an XZ/FZ and possessing a dysfunctional DZ. Current work has addressed the regulation of SF-1 and DAX-1 dependent adrenocortical growth and steroidogenesis in vivo utilizing mouse models of simple and combined SF-1 and DAX-1 deficiency. In addition, the model of compensatory adrenal growth in SF-1 haplo-insufficient mice has been applied to evaluate the potential role of SF-1 in adrenocortical proliferation. Additional efforts aim to positionally clone the acd gene, predicated on the hypothesis that it is a critical component of the adrenal developmental cascade."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I254,I254)","v":12390328},{"$f":"(LEN($J254) - LEN(SUBSTITUTE(LOWER($J254),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J254) - LEN(SUBSTITUTE(LOWER($J254),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J254) - LEN(SUBSTITUTE(LOWER($J254),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B254:D254)","v":0},2002,"The sodium iodide symporter: its pathophysiological and therapeutic implications.","Spitzweg",12390328,"The sodium iodide symporter: its pathophysiological and therapeutic implications.    Abstract:   The sodium iodide symporter (NIS) is an intrinsic plasma membrane protein that mediates the active transport of iodide in the thyroid gland and a number of extrathyroidal tissues, in particular lactating mammary gland. Because of its crucial role in the ability of thyroid follicular cells to trap iodide, cloning of NIS opened an exciting and extensive new field of thyroid-related research. Cloning and molecular characterization of NIS allowed investigation of its expression and regulation in thyroidal and nonthyroidal tissues, and its potential pathophysiological and therapeutic implications in benign and malignant thyroid disease. In addition to its key function in thyroid physiology, NIS-mediated iodide accumulation allows diagnostic thyroid scintigraphy as well as effective therapeutic application of radioiodine in benign and malignant thyroid disease. Characterization and application of NIS as a novel therapeutic gene and the presence of high native NIS expression in the majority of breast cancers further suggest a promising role of NIS in diagnosis and therapy of cancer outside the thyroid gland."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I255,I255)","v":12202330},{"$f":"(LEN($J255) - LEN(SUBSTITUTE(LOWER($J255),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J255) - LEN(SUBSTITUTE(LOWER($J255),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J255) - LEN(SUBSTITUTE(LOWER($J255),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B255:D255)","v":0},2002,"Acne vulgaris.","Webster",12202330,"Acne vulgaris.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I256,I256)","v":12185990},{"$f":"(LEN($J256) - LEN(SUBSTITUTE(LOWER($J256),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J256) - LEN(SUBSTITUTE(LOWER($J256),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J256) - LEN(SUBSTITUTE(LOWER($J256),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B256:D256)","v":0},2002,"Targeting peroxisome proliferator-activated receptors (PPARs) in kidney and urologic disease.","Guan",12185990,"Targeting peroxisome proliferator-activated receptors (PPARs) in kidney and urologic disease.    Abstract:   Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of ligand-activated transcription factors. Three PPAR isoforms, designated PPAR-alpha, beta/delta and -gamma, have been identified and were initially investigated in the tissues along urinary tract because of their known role in regulating lipid-activated gene transcription, lipid metabolism, inflammation and cell proliferation and differentiation. Gene distribution studies suggested that 3 PPAR isoforms are differentially expressed in the kidney. PPAR-alpha is predominantly expressed in renal proximal tubules and medullary thick ascending limbs. PPAR-gamma is mainly localized in renal medullary collecting duct with lower expression in renal glomeruli and renal microvasculature. Unlike PPAR-alpha and -gamma, PPAR-beta/delta is ubiquitously expressed in every segment along the nephron. In ureter and urinary bladder, all PPAR isoforms are mainly localized in urothelium of ureter and bladder. The emerging data have suggested physiological and pathophysiological roles of PPARs in tissues along urinary tract. PPAR-alpha plays a major role in triggering fatty acid utilization and the adaptive response to dietary lipids in the kidney. PPAR-beta/delta contributes to cell survival of renal interstitial cell in medullary hyperosmality. PPAR-gamma is involved in regulating renal hemodynamic and water and sodium transport. Furthermore, it also participates in the pathogenesis of glomerulopathy, antidiabetic thiazolidinedione-related water and sodium retention and renal, bladder and prostate carcinomas. PPARs may serve as potential therapeutic targets for certain diseases along urinary tract including glomerulosclerosis, diabetic nephropathy and kidney, prostate and bladder tumors."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I257,I257)","v":12185666},{"$f":"(LEN($J257) - LEN(SUBSTITUTE(LOWER($J257),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J257) - LEN(SUBSTITUTE(LOWER($J257),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J257) - LEN(SUBSTITUTE(LOWER($J257),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B257:D257)","v":0},2002,"Recent insights into organogenesis of the adrenal cortex.","Keegan",12185666,"Recent insights into organogenesis of the adrenal cortex.    Abstract:   The primary endocrine organs responsible for steroid hormone biosynthesis--the adrenal cortex and gonads--are derived from the urogenital ridge. Several recent discoveries in human and mouse genetics have begun to unravel the complex genetic cascade that dictates adrenocortical cell lineage, proliferation and differentiation. The factors that regulate adrenocortical organogenesis and the maintenance of growth promote or block a cascade of transcription factors that differentially coordinate the proliferation and differentiation of the gland. Here, we outline the developmental milestones of the adrenal cortex with recent contributions to the field, focusing on factors that have been shown to play a role in vivo in humans and mice."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I258,I258)","v":12133205},{"$f":"(LEN($J258) - LEN(SUBSTITUTE(LOWER($J258),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J258) - LEN(SUBSTITUTE(LOWER($J258),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J258) - LEN(SUBSTITUTE(LOWER($J258),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B258:D258)","v":0},2002,"Fortification strategies to meet micronutrient needs: successes and failures.","Darnton-Hill",12133205,"Fortification strategies to meet micronutrient needs: successes and failures.    Abstract:   Food fortification is likely to have played an important role in the current nutritional health and well-being of populations in industrialized countries. Starting in the early part of the 20th century, fortification was used to target specific health conditions: goitre with iodized salt; rickets with vitamin D-fortified milk; beriberi, pellagra and anaemia with B-vitamins and Fe-enriched cereals; more recently, in the USA, risk of pregnancy affected by neural-tube defects with folic acid-fortified cereals. A relative lack of appropriate centrally-processed food vehicles, less-developed commercial markets and relatively low consumer awareness and demand, means it has taken about another 50 years for fortification to be seen as a viable option for the less-developed countries. The present paper reviews selected fortification initiatives in developing countries to identify different factors that contributed to their successful implementation, as well as the challenges that continually threaten the future of these programmes. Ultimately, the long-term sustainability of fortification programmes is ensured when consumers are willing and able to bear the additional cost of fortified foods. There has been an enormous increase in fortification programmes over the last couple of decades in developing countries. Considerable progress has been made in reducing vitamin A and I deficiencies, although less so with Fe, even as Zn and folic acid deficiencies are emerging as important public health problems. Food fortification based on sound principles and supported by clear policies and regulations can play an increasingly large role in this progress towards prevention and control of micronutrient malnutrition."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I259,I259)","v":12133204},{"$f":"(LEN($J259) - LEN(SUBSTITUTE(LOWER($J259),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J259) - LEN(SUBSTITUTE(LOWER($J259),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J259) - LEN(SUBSTITUTE(LOWER($J259),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B259:D259)","v":0},2002,"Can supplements help meet the micronutrient needs of the developing world?","Shrimpton",12133204,"Can supplements help meet the micronutrient needs of the developing world?    Abstract:   Supplementation has many potential advantages over fortification and dietary approaches for improving micronutrient intake. Pregnant and lactating women and infants are most likely to benefit from supplementation. Recent experience with vitamin A supplementation in young children has proved to be remarkably successful. Demonstrated efficacy of vitamin A supplements for improved child survival in many settings and a technical consensus on how to implement interventions were major factors in achieving this success. Bilateral and UN agencies worked together so that in 1999 80 % of children under 5 years of age in the least-developed countries received a vitamin A capsule in the last 6 months. At least one million child lives saved were associated with the increase in coverage in the last 2 years of the 1990s. Experience with Fe-folate supplements has not been as successful. Whilst a technical consensus has been reached on how to implement programmes to control Fe deficiency, the lack of convincing evidence of efficacy of Fe-folate supplements in terms of maternal and child survival outcomes has undoubtedly contributed to the limited pursuit of effective action. A new multiple micronutrient supplement for use amongst women of reproductive age in developing countries has been formulated. UNICEF is employing the supplement in programmes aimed at helping to prevent low birth weight. The new supplement is likely to be more efficacious than Fe-folate supplements for both maternal and child survival and development outcomes. Successful completion of rigorous efficacy trials will be critical for creating the political support needed to achieve universal coverage."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I260,I260)","v":12069675},{"$f":"(LEN($J260) - LEN(SUBSTITUTE(LOWER($J260),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J260) - LEN(SUBSTITUTE(LOWER($J260),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J260) - LEN(SUBSTITUTE(LOWER($J260),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B260:D260)","v":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"]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I261,I261)","v":12050127},{"$f":"(LEN($J261) - LEN(SUBSTITUTE(LOWER($J261),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J261) - LEN(SUBSTITUTE(LOWER($J261),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J261) - LEN(SUBSTITUTE(LOWER($J261),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B261:D261)","v":0},2002,"Genetic approaches to unraveling reproductive disorders: examples of bedside to bench research in the genomic era.","Seminara",12050127,"Genetic approaches to unraveling reproductive disorders: examples of bedside to bench research in the genomic era.    Abstract:   Despite the rapid advances in medical genetics, many clinicians and investigators remain unaware of the general approaches that can be used to map genes. Although there are specific challenges to using genetic approaches in reproductive medicine, the following report summarizes mapping efforts for three diseases: adrenal hypoplasia congenita, hypergonadotropic ovarian failure, and polycystic ovary syndrome. The themes of rare and novel phenotypes, genetically homogenous populations, and genotype/phenotype correlations are emphasized."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I262,I262)","v":12039672},{"$f":"(LEN($J262) - LEN(SUBSTITUTE(LOWER($J262),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J262) - LEN(SUBSTITUTE(LOWER($J262),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J262) - LEN(SUBSTITUTE(LOWER($J262),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B262:D262)","v":0},2002,"Micronutrient malnutrition and the pathogenesis of malarial anemia.","Nussenblatt",12039672,"Micronutrient malnutrition and the pathogenesis of malarial anemia.    Abstract:   Malaria is a leading cause of morbidity and mortality worldwide, and anemia is a common and sometimes serious complication of Plasmodium falciparum infection. Although micronutrient malnutrition is usually highly prevalent in malaria endemic areas, the contribution of micronutrient deficiencies to malarial anemia is often overlooked. Recent investigation suggests that micronutrients such as vitamin A, vitamin E, and zinc, may improve the morbidity of malaria through immune modulation and alteration of oxidative stress. Micronutrients are also involved in the pathogenesis of anemia and likely play a role in malarial anemia, but many clinical trials have not specifically addressed the impact of micronutrient supplementation on malarial anemia. Further work is needed to assess the effect of both clinic and community-based micronutrient interventions on malarial anemia in infants, children, and pregnant women."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I263,I263)","v":11990799},{"$f":"(LEN($J263) - LEN(SUBSTITUTE(LOWER($J263),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J263) - LEN(SUBSTITUTE(LOWER($J263),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J263) - LEN(SUBSTITUTE(LOWER($J263),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B263:D263)","v":0},2002,"Concerted regulation of gonad differentiation by transcription factors and growth factors.","Suzuki",11990799,"Concerted regulation of gonad differentiation by transcription factors and growth factors.    Abstract:   It is well known that signals from growth factors regulate gene transcription thus initiating certain steps of cellular and tissue differentiation during development. In gonad differentiation several transcription factors have been identified as the genes underlying human diseases displaying gonadal defects and as the genes necessary for gonad differentiation as demonstrated by gene disruption studies. In addition, one of the growth factors, WNT4, is known to be involved in gonadal differentiation. However, it remains unclear which gene is directly downstream of the WNT4 signal. We have recently demonstrated that Dax1 (NR0B1) gene transcription is significantly up-regulated by the presence of SF1 (NR5A1). Functional analysis showed that DAX1 acts as a repressor against SF1 through direct interaction between the repeated sequences at the N-terminus of DAX1 and a ligand-binding domain of SF1. Considering that the expressions of these factors during gonad differentiation show a sexually dimorphic pattern, it is likely that the Dax1 gene transcription is up-regulated by WNT4 signal and thereafter DAX1 suppresses the genes downstream of SF1 such as Amh and steroidogenic genes in female gonads."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I264,I264)","v":11965516},{"$f":"(LEN($J264) - LEN(SUBSTITUTE(LOWER($J264),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J264) - LEN(SUBSTITUTE(LOWER($J264),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J264) - LEN(SUBSTITUTE(LOWER($J264),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B264:D264)","v":0},2002,"Meat and cancer: meat as a component of a healthy diet.","Biesalski",11965516,"Meat and cancer: meat as a component of a healthy diet.    Abstract:   Based on epidemiological studies it is assumed that meat, especially red meat, enhances risk for cancer, particularly of the colon, breast and prostate. Meat and meat products are important sources of protein, some micronutrients and fat. High fat intake has been blamed for correlation with different diseases, including cancer. Meat protein is reported to contribute to cancer formation. However, meat, including liver, is not only composed of fat and protein, it contains essential nutrients which appear exclusively in meat (vitamin A, vitamin B12) and micronutrients for which meat is the major source because of either high concentrations or better bioavailability (folate, selenium, zinc). In particular, vitamin A, folate and selenium are reported to be cancer-preventive, with respect to colon, breast and prostate cancer. Taken together, meat consists of a few, not clearly defined cancer-promoting and a lot of cancer-protecting factors. The latter can be optimized by a diet containing fruit and vegetables, which contain hundreds of more or less proven bioactive constituents, many of them showing antioxidative and anticarcinogenic effects in vitro."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I265,I265)","v":11965502},{"$f":"(LEN($J265) - LEN(SUBSTITUTE(LOWER($J265),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J265) - LEN(SUBSTITUTE(LOWER($J265),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J265) - LEN(SUBSTITUTE(LOWER($J265),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B265:D265)","v":0},2002,"The anemia of vitamin A deficiency: epidemiology and pathogenesis.","Semba",11965502,"The anemia of vitamin A deficiency: epidemiology and pathogenesis.    Abstract:    OBJECTIVE : To gain insight into vitamin A deficiency as a cause of anemia.  METHODS : Comprehensive review of the scientific literature.  RESULTS : Although vitamin A deficiency is recognized to cause anemia, vitamin A deficiency anemia lacks complete characterization as a distinct clinical entity. Vitamin A appears to be involved in the pathogenesis of anemia through diverse biological mechanisms, such as the enhancement of growth and differentiation of erythrocyte progenitor cells, potentiation of immunity to infection and reduction of the anemia of infection, and mobilization of iron stores from tissues. Epidemiological surveys show that the prevalence of anemia is high in populations affected by vitamin A deficiency in developing countries. Improvement of vitamin A status has generally been shown to reduce anemia, but the actual public health impact on anemia is unclear.  CONCLUSIONS : Further work is needed to elucidate the biological mechanisms by which vitamin A causes anemia. The inclusion of anemia as an outcome measure in future micronutrient intervention studies should help provide further insight into the anemia of vitamin A deficiency."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I266,I266)","v":11856105},{"$f":"(LEN($J266) - LEN(SUBSTITUTE(LOWER($J266),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J266) - LEN(SUBSTITUTE(LOWER($J266),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J266) - LEN(SUBSTITUTE(LOWER($J266),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B266:D266)","v":0},2002,"Can diet affect prostate cancer?","Meyer",11856105,"Can diet affect prostate cancer?    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I267,I267)","v":11834894},{"$f":"(LEN($J267) - LEN(SUBSTITUTE(LOWER($J267),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J267) - LEN(SUBSTITUTE(LOWER($J267),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J267) - LEN(SUBSTITUTE(LOWER($J267),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B267:D267)","v":0},2002,"Nutrition and risk of prostate cancer.","Jankevicius",11834894,"Nutrition and risk of prostate cancer.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I268,I268)","v":11795434},{"$f":"(LEN($J268) - LEN(SUBSTITUTE(LOWER($J268),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J268) - LEN(SUBSTITUTE(LOWER($J268),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J268) - LEN(SUBSTITUTE(LOWER($J268),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B268:D268)","v":0},2001,"The future of prostate cancer prevention.","Brawley",11795434,"The future of prostate cancer prevention.    Abstract:   The dramatic international variation in prostate cancer mortality rates suggest an environmental influence. This combined with a building understanding of the genetic mechanisms of carcinogenesis encourages a search for ways to prevent it. Androgenic stimulation over a period of time has been suggested a cause of prostate cancer. The corollary to this hypothesis is that lowering androgenic stimulation over time will prevent prostate cancer. Decreasing androgenic stimulation of the prostate with 5-alpha-reductase inhibitors such as finasteride has been shown to decrease prostate size and may prevent prostate cancer. A large, long-term clinical trial is underway using finasteride to determine if it can prevent prostate cancer. Results are expected in 2004. Epidemiologic and laboratory studies also suggest that high selenium and vitamin E intake lowers risk of prostate cancer. Recent serendipitous findings of two randomized clinical trials support the hypothesis that selenium and vitamin administration will decrease prostate cancer risk. A study to assess these compounds is beginning. Other promising, but less developed, interventions in chemoprevention of prostate cancer include vitamin D supplementation and diet modification. All will need to be rigorously evaluated before they can be advocated for prostate cancer prevention."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I269,I269)","v":11720341},{"$f":"(LEN($J269) - LEN(SUBSTITUTE(LOWER($J269),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J269) - LEN(SUBSTITUTE(LOWER($J269),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J269) - LEN(SUBSTITUTE(LOWER($J269),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B269:D269)","v":0},2001,"Micronutrients and child health: studies in international nutrition and HIV infection.","Duggan",11720341,"Micronutrients and child health: studies in international nutrition and HIV infection.    Abstract:   Increasing data link micronutrient deficiencies to excess childhood morbidity and mortality, and similar relationships have been noted in the study of nutrition and HIV infection. We review epidemiologic studies that have examined the relationship between micronutrient deficiencies and health outcomes in childhood and HIV infection, as well as clinical trials of micronutrient supplementation. Vitamin A supplementation among communities at risk of deficiency effectively reduces mortality and morbidity in children younger than age 5, and vitamin A may be especially effective in HIV-infected children. Vertical transmission of HIV has not to date been affected by maternal micronutrient supplementation. In children with poor dietary zinc intake and/or bioavailability, zinc supplementation reduces the incidence and severity of diarrheal diseases, as well as the occurrence of pneumonia. Vitamin A therapy has not been associated with improved growth, whereas some trials have shown that zinc supplementation is associated with greater increments in height. Further trials of micronutrient supplementation are warranted."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I270,I270)","v":11525294},{"$f":"(LEN($J270) - LEN(SUBSTITUTE(LOWER($J270),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J270) - LEN(SUBSTITUTE(LOWER($J270),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J270) - LEN(SUBSTITUTE(LOWER($J270),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B270:D270)","v":0},2001,"Targeting apoptosis in prostate cancer.","DiPaola",11525294,"Targeting apoptosis in prostate cancer.    Abstract:   The understanding of apoptotic pathways provides new insights into cancer therapy. Therapies that modulate these pathways may induce apoptosis or sensitize tumor cells to other agents. Because many of the components of these pathways are altered in tumor cells compared with normal cells, therapies that target these abnormal apoptotic proteins may be more selective than traditional cytotoxic agents. Difficulties include the translation of the knowledge of these pathways into clinical trials and monitoring the predicted biologic effects in patients. The continued study of new targets, agents capable of modulating these targets, and markers of biologic effect in patients should improve clinical results."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I271,I271)","v":11411262},{"$f":"(LEN($J271) - LEN(SUBSTITUTE(LOWER($J271),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J271) - LEN(SUBSTITUTE(LOWER($J271),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J271) - LEN(SUBSTITUTE(LOWER($J271),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B271:D271)","v":0},2000,"Micronutrient deficiency conditions in the Middle East region: an overview.","Galal",11411262,"Micronutrient deficiency conditions in the Middle East region: an overview.    Abstract:   The Middle East is perhaps the worlds best laboratory for learning more about iron and zinc deficiencies, and their widespread prevalence contributes much to constraining the quality of life for a large share of the population. Always, in the context of endemic IDD, countries in the region need to make sure that the programs are in place to consign this still-serious problem to the history books. Research is not required so much in relation to IDD, but clearly applications need to be monitored. Vitamin A deficiency is probably widespread at mild to moderate levels, and should be addressed by a combination of appropriate case management for infectious disease, breastfeeding promotion, and dietary diversification/nutrition education. Iron deficiency is the most prevalent, and so far the most intractable, micronutrient problem. It probably will not yield to less than a multipronged strategy including fortification of the food supply with iron. Several other micronutrient deficiencies require our eventual attention as well, and looking forward to their solution should be part of the research agenda."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I272,I272)","v":11386691},{"$f":"(LEN($J272) - LEN(SUBSTITUTE(LOWER($J272),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J272) - LEN(SUBSTITUTE(LOWER($J272),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J272) - LEN(SUBSTITUTE(LOWER($J272),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B272:D272)","v":0},2000,"Global malnutrition.","Stephenson",11386691,"Global malnutrition.    Abstract:   The four most important forms of malnutrition worldwide (protein-energy malnutrition, iron deficiency and anaemias (IDA), vitamin A deficiency (VAD), and iodine deficiency disorders (IDD)) are examined below in terms of their global and regional prevalences, the age and gender groups most affected, their clinical and public health consequences, and, especially, the recent progress in country and regional quantitation and control. Zinc deficiency, with its accompanying diminished host resistance and increased susceptibility to infections, is also reviewed. WHO estimates that malnutrition (underweight) was associated with over half of all child deaths in developing countries in 1995. The prevalence of stunting in developing countries is expected to decline from 36% in 1995 to 32.5% in 2000; the numbers of children affected (excluding China) are expected to decrease from 196.59 millions to 181.92 millions. Stunting affects 48% of children in South Central Asia, 48% in Eastern Africa, 38% in South Eastern Asia, and 13-24% in Latin America. IDA affects about 43% of women and 34% of men in developing countries and usually is most serious in pregnant women and children, though non-pregnant women, the elderly, and men in hookworm-endemic areas also comprise groups at risk. Clinical VAD affects at least 2.80 million preschool children in over 60 countries, and subclinical VAD is considered a problem for at least 251 millions; school-age children and pregnant women are also affected. Globally about 740 million people are affected by goitre, and over two billions are considered at risk of IDD. However, mandatory salt iodisation in the last decade in many regions has decreased dramatically the percentage of the population at risk. Two recent major advances in understanding the global importance of malnutrition are (1) the data of 53 countries that links protein-energy malnutrition (assessed by underweight) directly to increased child mortality rates, and (2) the outcome in 6 of 8 large vitamin A supplementation trials showing decreases of 20-50% in child mortality."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I273,I273)","v":11352180},{"$f":"(LEN($J273) - LEN(SUBSTITUTE(LOWER($J273),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J273) - LEN(SUBSTITUTE(LOWER($J273),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J273) - LEN(SUBSTITUTE(LOWER($J273),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B273:D273)","v":0},2001,"Pathogenesis of anemia during human immunodeficiency virus infection.","Semba",11352180,"Pathogenesis of anemia during human immunodeficiency virus infection.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I274,I274)","v":11317936},{"$f":"(LEN($J274) - LEN(SUBSTITUTE(LOWER($J274),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J274) - LEN(SUBSTITUTE(LOWER($J274),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J274) - LEN(SUBSTITUTE(LOWER($J274),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B274:D274)","v":0},2001,"[Cancer of the prostate: influence of nutritional factors. Vitamins, antioxidants and trace elements].","de la Taille",11317936,"[Cancer of the prostate: influence of nutritional factors. Vitamins, antioxidants and trace elements].    Abstract:    UNLABELLEDCANCER OF THE PROSTATE AND VITAMINS: Four vitamins have been studied, vitamins A, E, D and C. the results of these studies have been contradictory. Vitamin A and vitamin E would have a protective effect. ANTIOXIDANTS: Carotenes have an activity similar to that of vitamin A. Beta-carotene was positively associated with risk of cancer of the prostate in one study while two others were unable to demonstrate any relationship. Lycopene, the red color in fruits and vegetables, particularly tomatoes, would contribute to a lower risk of prostate cancer.  TRACE ELEMENTS NlmCategory=UNASSIGNEDCadmium would increase the risk of cancer while selenium would have a protective effect. However studies concerning selenium carry certain methodological biases."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I275,I275)","v":11295601},{"$f":"(LEN($J275) - LEN(SUBSTITUTE(LOWER($J275),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J275) - LEN(SUBSTITUTE(LOWER($J275),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J275) - LEN(SUBSTITUTE(LOWER($J275),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B275:D275)","v":0},2001,"Prostate cancer prevention strategies using antiproliferative or differentiating agents.","Walczak",11295601,"Prostate cancer prevention strategies using antiproliferative or differentiating agents.    Abstract:   Differentiation or antiproliferative therapies have been most effective in the treatment of promyelocytic leukemia and are being investigated for the treatment of solid tumors including prostate cancer (PCa). Research suggests that these agents may induce terminal differentiation (arrest in G(0)), induce differentiation to a mature cell with cellular functions and a growth pattern similar to nonmalignant cells, or trigger apoptosis. This review focuses on classes of agents under laboratory and clinical evaluation as antiproliferative or differentiating agents: polyamine inhibitors, vitamin D and its analogs, metabolites of vitamin A, the short-chain fatty acid, phenylbutyrate, and nonsteroidal anti-inflammatory agents. Because differentiation therapies offer a reduced toxicity profile and have potential for preventing or slowing cancer progression, they may offer an alternative to chemotherapy for men with advanced PCa, or may be useful as low-toxicity agents given chronically for chemoprevention in men at high risk for PCa. Clinical trials are needed to define the role of these agents in primary and secondary prevention."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I276,I276)","v":11291787},{"$f":"(LEN($J276) - LEN(SUBSTITUTE(LOWER($J276),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J276) - LEN(SUBSTITUTE(LOWER($J276),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J276) - LEN(SUBSTITUTE(LOWER($J276),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B276:D276)","v":0},2000,"Micronutrient malnutrition--present status and future remedies.","Chakravarty",11291787,"Micronutrient malnutrition--present status and future remedies.    Abstract:   Micronutrient deficiency is a serious public health concern in most of the developing countries which leads to malnutrition syndromes. The micronutient deficiencies which are of greatest public health significance include iron deficiency, vitamin A deficiency and iodine deficiency disorder. National Pilot Programme on Control of Micronutrient Malnutrition was launched in 1995 and the department of biochemistry and nutrition of the All India Institute of Hygiene and Public Health, Calcutta was entrusted to co-ordinate the activities. It presently covers five eastern and north-eastern states. Baseline situation analysis was conducted mainly on iron deficiency anaemia, iodine deficiency disorder and vitamin A deficiency. Comparing with WHO cut off figures, point prevalence of anaemia in various age groups was found to be high. Bitots spot was mainly noted in the age group of 6-71 months. Nightblindness was found in the children of the age group of 24-71 months. High prevalence of nightblindness in pregnant women is a point of concern. Action needed to control micronutrient deficiency includes: Intervention strategies, extensive nutrition and health education, to support the problem specific programmes, to stregthen various state government programmes and strengthen role of NGOs."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I277,I277)","v":11243083},{"$f":"(LEN($J277) - LEN(SUBSTITUTE(LOWER($J277),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J277) - LEN(SUBSTITUTE(LOWER($J277),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J277) - LEN(SUBSTITUTE(LOWER($J277),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B277:D277)","v":0},1999,"Integrated Child Development Services scheme (ICDS) and its impact on nutritional status of children in India and recent initiatives.","Kapil",11243083,"Integrated Child Development Services scheme (ICDS) and its impact on nutritional status of children in India and recent initiatives.    Abstract:   Integrated Child Development Services (ICDS) scheme is the largest national programme for the promotion of the mother and child health and their development in the world. The beneficiaries include children below 6 years, pregnant and lactating mothers, and other women in the age group of 15 to 44 years. The package of services provided by the ICDS scheme includes supplementary nutrition, immunization, health check-up, referral services, nutrition and health education, and pre-school education. The distribution of iron and folic acid tablets and megadose of vitamin A is also undertaken, to prevent iron deficiency anaemia and xerophthalmia respectively. The scheme services are rendered essentially through the Anganwadi worker (AWW) at a village centre called quot;Anganwadiquot;. The ICDS had led to (i) reduction in prevalence of severe grades of malnutrition and (ii) better utilization of services of national nutritional anaemia prophylaxis programme and the national programme for prevention of nutritional blindness due to vitamin A deficiency by ICDS beneficiaries. The ICDS scheme is being modified continuously to strengthen the programme. This article presents the impact of Integrated Child Development Services (ICDS) on the nutritional status of mothers and of children under 6 years old in India. ICDS is the first and probably the only program in the country that aims at the holistic development of an individual. The reduction in prevalence of severe malnutrition is comparatively more significant in ICDS scheme population than in other population groups. There has been an extensive improvement in the nutritional status of children living in rural, urban and tribal areas and in those belonging to depressed sections of the community. The new initiative schemes for supplementary nutrition include: (a) improved monitoring mechanisms, (b) increased and improved norms of nutrition, (c) improved acceptability of supplementary recipes, (d) care of the severely malnourished, (e) the formation of a state level committee of experts, (f) inspection of quality, and (g) the introduction of community growth charts for malnourished children. The distribution of iron and folic tablets together with megadoses of vitamin A has also been undertaken for iron deficiency anemia and xerophthalmia prevention. Professionals, administrators, and politicians should feel obliged to continue making their contributions to the effective implementation of ICDS."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I278,I278)","v":11221439},{"$f":"(LEN($J278) - LEN(SUBSTITUTE(LOWER($J278),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J278) - LEN(SUBSTITUTE(LOWER($J278),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J278) - LEN(SUBSTITUTE(LOWER($J278),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B278:D278)","v":0},2001,"State-of-the-art prostate cancer treatment and research. A report from the Cancer Institute of New Jersey.","DiPaola",11221439,"State-of-the-art prostate cancer treatment and research. A report from the Cancer Institute of New Jersey.    Abstract:   Prostate cancer is a devastating disease that will be diagnosed in approximately 200,000 men in 2001. New methods for screening, prevention, and treatment are being developed. In addition, novel agents for the treatment of resistant prostate cancer are being developed in clinical trials. This review summarizes the recent efforts in diet, screening, novel systemic therapies, and alternative medicine for prostate cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I279,I279)","v":11127968},{"$f":"(LEN($J279) - LEN(SUBSTITUTE(LOWER($J279),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J279) - LEN(SUBSTITUTE(LOWER($J279),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J279) - LEN(SUBSTITUTE(LOWER($J279),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B279:D279)","v":0},2000,"Vitamin A and HIV infection: disease progression, mortality, and transmission.","Kennedy",11127968,"Vitamin A and HIV infection: disease progression, mortality, and transmission.    Abstract:   Among HIV-infected individuals, many nutritional factors that influence disease progress, mortality, and transmission are not well understood. Of particular interest is the role of vitamin A. The benefits of vitamin A have been recognized since ancient times by Egyptian physicians who successfully treated night blindness with vitamin A. Contemporary scientists have since recognized the importance of vitamin A and have provided evidence that it may help in repairing damaged mucosal surfaces; what remains unclear, however, is its role during HIV infection. In this review, we examine the evidence provided in both observational studies and randomized controlled trials that assessed the effect of vitamin A during HIV infection."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I280,I280)","v":11037590},{"$f":"(LEN($J280) - LEN(SUBSTITUTE(LOWER($J280),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J280) - LEN(SUBSTITUTE(LOWER($J280),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J280) - LEN(SUBSTITUTE(LOWER($J280),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B280:D280)","v":0},2000,"[Diet probably plays an important role in the development of prostatic cancer].","Damber",11037590,"[Diet probably plays an important role in the development of prostatic cancer].    Abstract:   Prostate cancer is the most common malignant disease in Sweden and the most common cause of cancer-related death among Swedish men. There is, however, a wide geographical variation in the age-standardized incidence and mortality rates. The highest incidence is found in north-western Europe and the US and the lowest in the Asian countries. The reasons for these discrepancies are thought to be related to environmental factors such as variations in dietary pattern. High intake of calories, high Body Mass Index, and consumption of animal fat are all associated with an increased risk of prostate cancer, while high intake of soy and other phytoestrogens, selenium, vitamin A and high serum levels of vitamin D are associated with low risk. As well, gonadal hormones and growth factors are believed to be involved in the complex etiology of prostate cancer. Genetic factors play an important role in the development of prostate cancer, and a hereditary form of the disease, accounting for approximately 5-10% of cases, has been identified. In order to develop effective preventive strategies to reduce prostate cancer mortality and morbidity, it is necessary to expand our knowledge about the etiology of this common disease."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I281,I281)","v":10727993},{"$f":"(LEN($J281) - LEN(SUBSTITUTE(LOWER($J281),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J281) - LEN(SUBSTITUTE(LOWER($J281),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J281) - LEN(SUBSTITUTE(LOWER($J281),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B281:D281)","v":0},1999,"Sex determination and the Y chromosome.","McElreavey",10727993,"Sex determination and the Y chromosome.    Abstract:   Although SRY was first identified 10 years ago, we still know remarkably little about its mode of action or downstream target genes. Recently, potential protein partners have been identified and there has been considerable activity to understand the roles of WT1, SF-1, DAX-1 and SOX9 in gonadogenesis. The emerging picture is one of complex interactions, involving both positive and negative regulatory signals that, depending on the cellular and promoter context, drive the expression of male-specific genes. Despite recent advances, however, we are still unable to explain the genetic cause of most cases of 46,XY gonadal dysgenesis or even a single case of Y-chromosome-negative 46,XX maleness."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I282,I282)","v":10702867},{"$f":"(LEN($J282) - LEN(SUBSTITUTE(LOWER($J282),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J282) - LEN(SUBSTITUTE(LOWER($J282),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J282) - LEN(SUBSTITUTE(LOWER($J282),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B282:D282)","v":0},2000,"Inhibin and activin subunits and spermatogenesis.","Tuohimaa",10702867,"Inhibin and activin subunits and spermatogenesis.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I283,I283)","v":10690166},{"$f":"(LEN($J283) - LEN(SUBSTITUTE(LOWER($J283),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J283) - LEN(SUBSTITUTE(LOWER($J283),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J283) - LEN(SUBSTITUTE(LOWER($J283),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B283:D283)","v":0},1999,"Prostate cancer prevention: review of target populations, pathological biomarkers, and chemopreventive agents.","Montironi",10690166,"Prostate cancer prevention: review of target populations, pathological biomarkers, and chemopreventive agents.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I284,I284)","v":10379880},{"$f":"(LEN($J284) - LEN(SUBSTITUTE(LOWER($J284),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J284) - LEN(SUBSTITUTE(LOWER($J284),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J284) - LEN(SUBSTITUTE(LOWER($J284),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B284:D284)","v":0},1999,"Fertility and infertility: genetic contributions from the hypothalamic-pituitary-gonadal axis.","Achermann",10379880,"Fertility and infertility: genetic contributions from the hypothalamic-pituitary-gonadal axis.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I285,I285)","v":10347664},{"$f":"(LEN($J285) - LEN(SUBSTITUTE(LOWER($J285),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J285) - LEN(SUBSTITUTE(LOWER($J285),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J285) - LEN(SUBSTITUTE(LOWER($J285),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B285:D285)","v":0},1999,"[Clinical significance of extra vitamin supplements and enriched food products].","Hermus",10347664,"[Clinical significance of extra vitamin supplements and enriched food products].    Abstract:   Consumers increasingly use vitamin supplements. Also, since June 1996, foodstuffs enriched with vitamins are available on the Dutch market. These sources of extra vitamins may be useful for groups at risk for marginal vitamin deficiencies. These risk groups include the chronically ill (e.g. diabetics), people using medicaments, older people and pregnant women. Extra vitamins from low-dose supplements or enriched foodstuffs may also constitute a valuable and safe supplement to the diet of children, smokers, people eating unbalanced, people on slimming diets, vegetarians and people engaged in intensive sports. According to the advisory group Nutrition of the Health Council, addition of vitamins to foodstuffs causes no risks of any importance for public health, apart from vitamins A and D and of the trace elements selenium, copper and zinc. Consequently, these should only be added to reconstituted foodstuffs or in a substitution product, not in enriched foodstuffs."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I286,I286)","v":10332429},{"$f":"(LEN($J286) - LEN(SUBSTITUTE(LOWER($J286),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J286) - LEN(SUBSTITUTE(LOWER($J286),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J286) - LEN(SUBSTITUTE(LOWER($J286),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B286:D286)","v":0},1999,"Chemoprevention of urological cancer.","Kamat",10332429,"Chemoprevention of urological cancer.    Abstract:    PURPOSE : Cancer is a major cause of mortality and morbidity throughout the world, and ranks as the second leading cause of death in the United States. Most cancers have a latent period of 10 to 20 years, which provides ample time for preventive measures. Transitional cell carcinoma of the bladder and adenocarcinoma of the prostate have protracted courses and may be ideal for chemopreventive strategies. We review the biochemistry and epidemiology of chemopreventive agents, and the laboratory and clinical studies of their role in urological cancer.  MATERIALS AND METHODS : We performed a computerized MEDLINE search and manual bibliographical review of relevant peer reviewed studies and reports from 1966 to 1998. These reports were analyzed and scrutinized, and the important findings are summarized.  RESULTS : Neoplastic lesions of the bladder and prostate are uniquely suited to the development and evaluation of chemopreventive agents. Epidemiological reports provide the strongest evidence of a protective role for dietary agents in cancer of the bladder, prostate and kidney. Observational and recent experimental trials support these findings in cases of adenocarcinoma of the prostate and transitional cell carcinoma of the bladder. There is strong evidence for a protective effect of vitamin A in bladder cancer. Superior protection has been reported with a combination of high doses of vitamins A, B6, C and E plus zinc. For prostate cancer strong evidence exists for a preventive effect of reduced fat intake, vitamin E, selenium and soy proteins. A lesser benefit is also suggested with intake of vitamins D and C. Evidence of chemoprevention against renal cell cancer is supported mainly by epidemiological studies, and animal studies indicate possible benefit of vitamin D supplementation.  CONCLUSIONS : Although there is no incontrovertible proof, numerous studies implicate dietary and nutritional factors in the onset and progression of cancer of the bladder, prostate and kidney. It is possible that the preventive effect of dietary constituents may be in part from consumption with other nutrients and bioactive compounds in whole foods. Further research is needed before vitamins and other nutritional supplements can be advocated as standard therapy but the preponderance of evidence supports increased intake of vitamins A, B6, C, D and E, reduction of animal fat, and increased consumption of fruits and vegetables."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I287,I287)","v":10216946},{"$f":"(LEN($J287) - LEN(SUBSTITUTE(LOWER($J287),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J287) - LEN(SUBSTITUTE(LOWER($J287),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J287) - LEN(SUBSTITUTE(LOWER($J287),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B287:D287)","v":0},1999,"The role of the 5 untranslated region of an mRNA in translation regulation during development.","van der Velden",10216946,"The role of the 5 untranslated region of an mRNA in translation regulation during development.    Abstract:   Cap-dependent ribosomal scanning occurs on the majority of cellular 5 UTRs. This process is severely hampered on long 5 UTRs, containing AUGs and secondary structure. These characteristics are often found in mRNAs encoding regulatory proteins like proto-oncogenes, growth factors, their receptors, and homeodomain proteins. A number of these mRNAs use an alternative mechanism of translation initiation, involving an internal ribosomal entry site (IRES). Cellular mRNAs containing a complex 5 UTR or an IRES share an intriguing characteristic: their translational efficiency can be very specifically regulated by their 5 UTR, providing post-transcriptional regulation. During embryonic development, the 5 UTRs of Antp. Ubx RAR beta 2 c-mos and c-myc regulate protein expression in a spatio-temporal manner. Translation initiation on a number of growth factor RNAs (IGFII, PDGF2, TGF beta, FGF-2, and VEGF) is specifically regulated during differentiation, growth, and stress. Furthermore, 5 UTR activity, mutations in the 5 UTR, or the occurrence of alternative 5 UTRs have been implicated in the progression of various forms of cancer. The mechanisms involved in 5 UTR mediated control are not well understood. Binding of trans-acting factors could mediate translation stimulation or repression. Furthermore, the precise localization of upstream AUGs and the activity of the cap-binding initiation factor 4E are suggested to be important for translation regulation of these mRNAs. This review focuses on 5 UTRs whose activity is regulated, the processes during which this regulation occurs, and as far as known the mechanisms involved."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I288,I288)","v":10197976},{"$f":"(LEN($J288) - LEN(SUBSTITUTE(LOWER($J288),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J288) - LEN(SUBSTITUTE(LOWER($J288),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J288) - LEN(SUBSTITUTE(LOWER($J288),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B288:D288)","v":0},1999,"Mammalian sex determination: a molecular drama.","Swain",10197976,"Mammalian sex determination: a molecular drama.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I289,I289)","v":9819558},{"$f":"(LEN($J289) - LEN(SUBSTITUTE(LOWER($J289),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J289) - LEN(SUBSTITUTE(LOWER($J289),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J289) - LEN(SUBSTITUTE(LOWER($J289),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B289:D289)","v":0},1998,"Mammalian sex determination: joining pieces of the genetic puzzle.","Jiménez",9819558,"Mammalian sex determination: joining pieces of the genetic puzzle.    Abstract:   Mammalian sex determination is controlled by the Y-linked gene SRY. Studies of sex-reversed patients and experimental data obtained with mice have identified other genes, such as DAX1, SOX9, SF1, and WT1, which take part in the process, and have suggested how these genes interact to determine the sex of a mammalian embryo. A recent paper in Nature by Swain et al. provides experimental data that basically confirm the previously proposed hypothesis that SRY acts by inhibiting the action of DSS/DAX1, which is a repressor of genes of the male pathway."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I290,I290)","v":9793755},{"$f":"(LEN($J290) - LEN(SUBSTITUTE(LOWER($J290),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J290) - LEN(SUBSTITUTE(LOWER($J290),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J290) - LEN(SUBSTITUTE(LOWER($J290),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B290:D290)","v":0},1998,"Gonadotropin-releasing hormone deficiency in the human (idiopathic hypogonadotropic hypogonadism and Kallmanns syndrome): pathophysiological and genetic considerations.","Seminara",9793755,"Gonadotropin-releasing hormone deficiency in the human (idiopathic hypogonadotropic hypogonadism and Kallmanns syndrome): pathophysiological and genetic considerations.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I291,I291)","v":9584502},{"$f":"(LEN($J291) - LEN(SUBSTITUTE(LOWER($J291),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J291) - LEN(SUBSTITUTE(LOWER($J291),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J291) - LEN(SUBSTITUTE(LOWER($J291),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B291:D291)","v":0},1998,"Indonesian recommended dietary allowance.","Muhilal",9584502,"Indonesian recommended dietary allowance.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I292,I292)","v":9008156},{"$f":"(LEN($J292) - LEN(SUBSTITUTE(LOWER($J292),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J292) - LEN(SUBSTITUTE(LOWER($J292),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J292) - LEN(SUBSTITUTE(LOWER($J292),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B292:D292)","v":0},1997,"Transcriptional checkpoints determining the fate of male germ cells.","Sassone-Corsi",9008156,"Transcriptional checkpoints determining the fate of male germ cells.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I293,I293)","v":9087069},{"$f":"(LEN($J293) - LEN(SUBSTITUTE(LOWER($J293),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J293) - LEN(SUBSTITUTE(LOWER($J293),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J293) - LEN(SUBSTITUTE(LOWER($J293),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B293:D293)","v":0},1996,"Subclinical vitamin A deficiency: a potentially unrecognized problem in the United States.","Stephens",9087069,"Subclinical vitamin A deficiency: a potentially unrecognized problem in the United States.    Abstract:   Vitamin A deficiency in its subclinical form is a world health problem in young children. The problem is probably under recognized in the United States and other developed countries who do not normally consider their citizens to be malnourished. Lack of a simple screening test to measure subclinical deficiency adds to this problem. Consequently, focused dietary assessment of vitamin A intake by a Food Frequency Questionnaire (FFQ) is a necessary component of health care maintenance, especially for toddlers and preschool age children. Dietary counseling and vitamin supplementation for high risk children is a necessary health promotion intervention."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I294,I294)","v":8840552},{"$f":"(LEN($J294) - LEN(SUBSTITUTE(LOWER($J294),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J294) - LEN(SUBSTITUTE(LOWER($J294),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J294) - LEN(SUBSTITUTE(LOWER($J294),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B294:D294)","v":0},1996,"Sex determining gene on the X chromosome short arm: dosage sensitive sex reversal.","Ogata",8840552,"Sex determining gene on the X chromosome short arm: dosage sensitive sex reversal.    Abstract:   The present review article summarizes current knowledge concerning the sex determining gene on Xp21, termed DSS (dosage sensitive sex reversal). The presence of DSS has been based on the finding that, in the presence of SRY, partial active Xp duplications encompassing the middle part of Xp result in sex reversal, whereas those of the distal or proximal part of Xp permit male sex development. Because Klinefelter patients develop as males, it is believed that DSS is normally subject to X-inactivation, and that two active copies of DSS override the function of SRY, resulting in gonadal dysgenesis because of meiotic pairing failure. It may be possible that DSS encodes a target sequence for repressing function of SRY or that DSS is involved in an X chromosome-counting mechanism. Molecular approaches have localized DSS to a 160 kb region and isolated candidate genes such as DAX-1 and MAGE-Xp, but there has been no formal evidence equating the candidate gene with DSS. In addition to its clinical importance, the exploration of DSS must provide a useful clue to phylogenetic studies of sex chromosomes and dosage compensation."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I295,I295)","v":9027612},{"$f":"(LEN($J295) - LEN(SUBSTITUTE(LOWER($J295),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J295) - LEN(SUBSTITUTE(LOWER($J295),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J295) - LEN(SUBSTITUTE(LOWER($J295),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B295:D295)","v":0},1996,"The role of prostate-specific antigen in the chemoprevention of prostate cancer.","Crawford",9027612,"The role of prostate-specific antigen in the chemoprevention of prostate cancer.    Abstract:   An understanding of the natural history of changes in prostate-specific antigen (PSA) may be valuable as a surrogate view of prostate dynamics, as a method to differentiate between benign and malignant growth, and as a means to assess the use of PSA as a tool for monitoring activity of chemoprevention agents. Although PSA appears to be useful as a noninvasive marker of prostatic growth, PSA changes should not be confused with a direct measure of tumor growth. Serum PSA levels are a function of tumor volume but are also influenced by the volume of benign epithelium, grade of carcinoma (if any), inflammation, androgen levels, growth factors, and the extracellular matrix. The biological functions of PSA in the prostate and in its secretions need to be more completely elucidated in order that PSA measurements may more accurately describe prostate dynamics. The expression of PSA is androgen-regulated. It is one of the most abundant prostate-derived proteins in the seminal fluid. Seminogelin, a major protein in seminal fluid, is cleaved by PSA, and this cleavage is important in the liquefaction of semen. Less is known about other PSA substrates. Current PSA studies indicate that cancer cases exhibit an early slow linear PSA phase followed by a rapid exponential phase, and that PSA levels begin to increase exponentially approximately 7-9 years before diagnosis. The establishment of age-specific PSA reference ranges (ASRR) and of PSA velocity (PSAV) rates provide elements of a baseline from which prediction models could measure malignant potential of a prostatic carcinoma. Moreover, recent discoveries of different molecular forms of PSA in serum may allow a much more accurate differentiation of benign and malignant growth as well as a more potent measure of the impact of chemoprevention agents. If PSA doubling time is approximately 2.4-3.0 years and accurately reflects tumor doubling time, and if the average man has less than 0.5 ml of latent prostatic tumor tissue and the average stage T2 cancer is approximately 4 ml when detected, then the available PSA data suggest that the 3 doublings necessary to change from 0.5-4.0 ml, would take 7-12 years for a typical small volume tumor to reach the size of most stage T2 tumors. The findings that histologic cancers appear at much younger ages than previously known is disturbing. It indicates that disease initiation may begin sooner than ever thought likely. quot;Normalquot; PSA levels for younger men (lt; 40 years of age) may need to be studied, and an emphasis upon premalignant lesions in this age group may be necessary. Younger men may represent the most appropriate population and premalignant lesions the most relevant clinical factor for prostate cancer chemoprevention studies and trials. The molecular composition and molecular changes of PSA derived from premalignant lesions have yet to be elucidated, but such investigations may lead to a more complete understanding of the possible progression or transformation of normal prostate cells to premalignancy and subsequently to carcinoma. High grade prostatic intraepithelial neoplasia (PIN) in and of itself does not account for elevated serum PSA levels, but subtle changes in the molecular dynamics of PSA may reveal the influence of androgens and the impact of chemopreventive agents."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I296,I296)","v":8959068},{"$f":"(LEN($J296) - LEN(SUBSTITUTE(LOWER($J296),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J296) - LEN(SUBSTITUTE(LOWER($J296),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J296) - LEN(SUBSTITUTE(LOWER($J296),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B296:D296)","v":0},1996,"[Genital erosive lichen planus].","Vilmer",8959068,"[Genital erosive lichen planus].    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I297,I297)","v":8850437},{"$f":"(LEN($J297) - LEN(SUBSTITUTE(LOWER($J297),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J297) - LEN(SUBSTITUTE(LOWER($J297),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J297) - LEN(SUBSTITUTE(LOWER($J297),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B297:D297)","v":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."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I298,I298)","v":8630234},{"$f":"(LEN($J298) - LEN(SUBSTITUTE(LOWER($J298),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J298) - LEN(SUBSTITUTE(LOWER($J298),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J298) - LEN(SUBSTITUTE(LOWER($J298),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B298:D298)","v":0},1996,"Cellular biology of prostatic growth factors.","Peehl",8630234,"Cellular biology of prostatic growth factors.    Abstract:   The etiology of prostate cancer or of benign prostatic hyperplasia (BPH) is essentially not understood. It is becoming clear, however, that major determinants of the malignant or hyperplastic phenotype are various growth-stimulatory or -inhibitory factors and their receptors, whose inappropriate expression or loss disrupts normal regulation of cell proliferation and differentiation. Cell culture has been a versatile tool for studying the expression and interaction of growth factors in prostatic cells. Immunohistochemistry and in situ hybridization have provided a view of growth factor expression coupled with histopathology. The eventual definition of autocrine, paracrine, and endocrine pathways of growth regulation in the human prostate will facilitate the design of new preventative, diagnostic, and therapeutic strategies."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I299,I299)","v":7638469},{"$f":"(LEN($J299) - LEN(SUBSTITUTE(LOWER($J299),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J299) - LEN(SUBSTITUTE(LOWER($J299),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J299) - LEN(SUBSTITUTE(LOWER($J299),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B299:D299)","v":0},1995,"Chemoprevention of prostate cancer.","Thompson",7638469,"Chemoprevention of prostate cancer.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I300,I300)","v":7486827},{"$f":"(LEN($J300) - LEN(SUBSTITUTE(LOWER($J300),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J300) - LEN(SUBSTITUTE(LOWER($J300),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J300) - LEN(SUBSTITUTE(LOWER($J300),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B300:D300)","v":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."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I301,I301)","v":8066863},{"$f":"(LEN($J301) - LEN(SUBSTITUTE(LOWER($J301),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J301) - LEN(SUBSTITUTE(LOWER($J301),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J301) - LEN(SUBSTITUTE(LOWER($J301),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B301:D301)","v":0},1994,"[Relationship between diet, nutritional status and prostatic cancer].","Friis",8066863,"[Relationship between diet, nutritional status and prostatic cancer].    Abstract:   Several epidemiological investigations suggest an association between diet and prostatic cancer. The most consistent finding has been a risk-enhancing effect of a diet rich in fat, especially animal fat. There is some evidence that dietary fat acts in late prostatic carcinogenesis by promoting the progression from focal to clinical disease, and that this effect may be due to an influence on the hormonal system. Data on other dietary factors, especially vitamin A and beta-carotene, are equivocal. This is probably partly due to the fact that most of the epidemiological studies have been based on limited dietary information. It is unclear whether the nutritional status influences the development of prostatic cancer, and if so, which anthropometric measurements are associated with an increased risk. Future studies should aim at estimating dietary exposures more precisely than hitherto by using calibrated dietary assessment methods that permit adjustment for total energy intake and combining these with biochemical methods. It will also be important to further investigate relations between diet, nutritional status and the hormonal system."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I302,I302)","v":8165761},{"$f":"(LEN($J302) - LEN(SUBSTITUTE(LOWER($J302),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J302) - LEN(SUBSTITUTE(LOWER($J302),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J302) - LEN(SUBSTITUTE(LOWER($J302),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B302:D302)","v":0},1994,"Chemoprevention of prostate cancer.","Brawley",8165761,"Chemoprevention of prostate cancer.    Abstract:   Primary prevention of prostate cancer is a relatively new concept. Through large-scale studies it is possible that we may be able to define better the risk for prostate cancer and identify those who would benefit from an intervention to lower their risk of disease. As risk for prostate cancer is better defined, a number of interventions may eventually be tested. Several interventions are sufficiently mature that they can be implemented in large-scale trials. Diet modification is an intervention that is ready for evaluation. It may also have additional benefits by decreasing mortality from other malignancies and cardiac disease. 5 alpha-reductase inhibitors are also ready for testing. The National Cancer Institute and its clinical cooperative groups have begun a large trial to assess finasteride in the prevention of prostate cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I303,I303)","v":8003403},{"$f":"(LEN($J303) - LEN(SUBSTITUTE(LOWER($J303),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J303) - LEN(SUBSTITUTE(LOWER($J303),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J303) - LEN(SUBSTITUTE(LOWER($J303),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B303:D303)","v":0},1994,"Expanded programme on immunization. Programme review.","Brawley",8003403,"Expanded programme on immunization. Programme review.    Abstract:   In Bangladesh an evaluation of the Expanded Programme on Immunization (EPI) was conducted in February 1993. Data, including immunization coverage based on random surveys, were collected from all 4 divisions, 8 rural districts, 25 sub-districts (thanas) and from the cities of Dhaka and Chittagong. The Review Team assessed and made several recommendations concerning immunization coverage, surveillance for the EPI target diseases, immunization in urban areas, the cold chain and logistics, training, communication and social mobilization, other primary health care (PHC) interventions, vaccine supply, and the sustainability of EPI achievements. The population of Bangladesh is 110 million, with an estimated 3.6 million newborns during 1993. More than 90% of the 108,000 routine monthly immunization services are being conducted as scheduled. Nationally, among children 0-11 months of age, BCG coverage is 89%, as measured by evaluation surveys, coverage with 3 doses of diphtheria/pertussis/tetanus (DPT3) and oral polio vaccine (OPV3) is 63%, and measles coverage is 59%. Coverage with a second dose of tetanus toxoid (TT2) for pregnant women is 80%. In urban areas, BCG coverage for infants is 92%, DPT3/OPV3 76%, measles 68%, and TT2 for pregnant women 82%. In 2/3 of the sites visited, immunization was combined with vitamin A supplementation, oral rehydration treatment, or family planning. The coverage for both BCG and DPT3/OPV3 increased from only 2% in 1985 to almost 90% of infants having BCG immunization services in 1992. Yet only 50% of children are reached before their first birthday, and at least 20% of newborns are not protected against neonatal tetanus at birth. DPT1 and DPT3 drop-out is 29% nationally and 17% in urban areas. In 1992, an estimated 117,000 cases of neonatal tetanus and 6700 cases of poliomyelitis were prevented by immunization. Surveys of neonatal tetanus in selected districts have confirmed a reduction in incidence from 40/1000 live births in 1986 to 10/1000 in 1991."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I304,I304)","v":8016056},{"$f":"(LEN($J304) - LEN(SUBSTITUTE(LOWER($J304),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J304) - LEN(SUBSTITUTE(LOWER($J304),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J304) - LEN(SUBSTITUTE(LOWER($J304),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B304:D304)","v":0},1993,"[Vitamins and their role in the functioning of the reproductive system].","Babichev",8016056,"[Vitamins and their role in the functioning of the reproductive system].    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I305,I305)","v":8414269},{"$f":"(LEN($J305) - LEN(SUBSTITUTE(LOWER($J305),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J305) - LEN(SUBSTITUTE(LOWER($J305),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J305) - LEN(SUBSTITUTE(LOWER($J305),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B305:D305)","v":0},1993,"Undernutrition in Nigeria: dimension, causes and remedies for alleviation in a changing socio-economic environment.","Igbedioh",8414269,"Undernutrition in Nigeria: dimension, causes and remedies for alleviation in a changing socio-economic environment.    Abstract:   Undernutrition in Nigeria is a long standing problem which has persisted since the 1960s and whose magnitude is on the increase. This is because food consumption, both in quality and quantity, has decreased appreciably, especially with the commencement of the structural adjustment programme (SAP) in 1986. Available studies from limited data have indicated that the introduction of economic reforms more than anything else has contributed to reduced food intake and the near collapse of nutrition oriented health delivery services. Since the economic reforms may continue into the next decade and beyond, sustainable remedies for alleviation of the problem are urgently needed. Suggested remedial programmes include increased support for the rural farmers, strengthening of the rural credit schemes that are specifically targeted at the poor, distribution of vitamin A and iron supplements in rural health centres, encouraging production of low cost weaning diets and integrating nutrition education in primary health care schemes and in educational curricula. In Nigeria, the beginning of the structural adjustment program (SAP) in 1986 marked the beginning of a considerable decrease in real income and an unparalleled increase in food prices. This economic crisis stimulated reduced food consumption, particularly that of nutritious foods, and an increase in malnutrition. For example, in Borno/Yobe States in 1987, SAP contributed to an average decrease in energy and protein intake of 27% and 33%, respectively. SAP also contributed greatly to the almost complete destruction of nutrition oriented health delivery services. Different surveys of nutritional assessment in Nigeria reveal low intakes of protein, energy, iron, calcium, zinc, thiamin, and riboflavin in almost all age groups and in both sexes. Malnutrition and related diseases (diarrhea, measles, anemia, and gastroenteritis) are the cause of most deaths in infants and young children. The underlying causes of malnutrition in Nigeria are poverty, inadequate food production, inadequate food intake, ignorance and uneven distribution of food, poor food preservation techniques, improper preparation of foods, food restrictions and taboos, and poor sanitation. Economic reforms will likely continue into the first decade of the 21st century, so Nigeria really needs sustainable remedies to alleviate malnutrition. Recommended remedial programs are more support for rural farmers through input subsidies and high producer prices, improving rural credit schemes (e.g., the Peoples Bank) that target the poor, distribution of vitamin A and iron supplements in rural health centers, promoting production of low cost weaning diets, and integrating nutrition education in primary health care programs and in educational curricula."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I306,I306)","v":8212979},{"$f":"(LEN($J306) - LEN(SUBSTITUTE(LOWER($J306),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J306) - LEN(SUBSTITUTE(LOWER($J306),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J306) - LEN(SUBSTITUTE(LOWER($J306),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B306:D306)","v":0},1993,"[Alcohol, liver cirrhosis and disorders in sex hormone metabolism].","Van Steenbergen",8212979,"[Alcohol, liver cirrhosis and disorders in sex hormone metabolism].    Abstract:   Abnormalities in the metabolism of sex hormones are frequently observed in cirrhotic patients, especially in chronic alcoholics. Signs of hypogonadism with disturbed reproductive and endocrine gonadal functions are found in men as well as in women. Primary hypogonadism as well as hypothalamic-pituitary inhibition seem to play a role. Primary gonadal insufficiency is the result of a direct toxic effect of ethanol and of acetaldehyde on the gonads with inhibition of LH binding to the Leydig cells, with inhibition of the enzymes responsible for the formation of sex hormones, and with inhibition of the intratesticular activation of vitamin A. Hypothalamic-pituitary hypogonadism also results from a direct toxic effect of ethanol as well as from the increasing concentrations of oestrogens in the plasma. Men with alcoholic cirrhosis may also be characterized by signs of feminization, which mainly result from an increased peripheral conversion of androgens. In men who abstain from alcohol, a spontaneous recovery of sexual functions can occur, especially when no testicular atrophy is found and when the response of gonadotrophins after stimulation with LH-RH is normal. Therapeutically, only the administration of non-aromatizable androgens in high doses seems to lead to recovery of potency."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I307,I307)","v":1526926},{"$f":"(LEN($J307) - LEN(SUBSTITUTE(LOWER($J307),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J307) - LEN(SUBSTITUTE(LOWER($J307),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J307) - LEN(SUBSTITUTE(LOWER($J307),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B307:D307)","v":0},1992,"Effects of nutrient deficiencies and excesses on reproductive efficiency of livestock.","Dunn",1526926,"Effects of nutrient deficiencies and excesses on reproductive efficiency of livestock.    Abstract:   Successful reproduction is dependent on a host of macro- and micronutrients and ceases well before an animal expires from deficiency of a particular nutrient. This review focuses on the functional roles phosphorus, vitamin A and beta-carotene, protein, and energy play in reproductive processes. Although it is not known whether deficiencies of these nutrients limit reproduction through common or discrete mechanisms, appropriate quantities of these nutrients are required for optimal reproduction. Mechanisms through which nutritional status is perceived by the hypothalamic-pituitary-gonadal axis remain unclear but seem to impinge on hypothalamic regions that selectively regulate production and release of pituitary trophic hormones. Body condition, or degree of fatness, seems to be the most reliable indicator of well-being of an animal, and, when coupled with changes in BW, provides a useful method to assess reproductive potential."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I308,I308)","v":1313192},{"$f":"(LEN($J308) - LEN(SUBSTITUTE(LOWER($J308),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J308) - LEN(SUBSTITUTE(LOWER($J308),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J308) - LEN(SUBSTITUTE(LOWER($J308),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B308:D308)","v":0},1992,"The genetic and biologic aspects of treatment response and resistance in male germ cell cancer.","Kurie",1313192,"The genetic and biologic aspects of treatment response and resistance in male germ cell cancer.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I309,I309)","v":1289668},{"$f":"(LEN($J309) - LEN(SUBSTITUTE(LOWER($J309),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J309) - LEN(SUBSTITUTE(LOWER($J309),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J309) - LEN(SUBSTITUTE(LOWER($J309),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B309:D309)","v":0},1992,"Possible enhancement of prostate carcinogenesis by some chemopreventive agents.","Bosland",1289668,"Possible enhancement of prostate carcinogenesis by some chemopreventive agents.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I310,I310)","v":2244684},{"$f":"(LEN($J310) - LEN(SUBSTITUTE(LOWER($J310),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J310) - LEN(SUBSTITUTE(LOWER($J310),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J310) - LEN(SUBSTITUTE(LOWER($J310),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B310:D310)","v":0},1990,"Re-evaluation of fibroblasts and fibroblast-like cells.","Komuro",2244684,"Re-evaluation of fibroblasts and fibroblast-like cells.    Abstract:   Scanning electron microscopic observations of connective tissue cells show a new aspect of the nature of fibroblasts, and the subsequent broad survey of references makes clear that fibroblasts of many tissues have various features which are regarded as atypical of fibroblasts, and at the same time that various connective tissue cells in different organs have features typical of fibroblasts. Both morphological and functional features of fibroblasts are more or less common to those of fibroblast-like cells, and differences among these cells are quantitative rather than qualitative. Therefore, it is almost impossible to set clear-cut criteria for distinguishing genuine fibroblasts from a large population of fibroblast-like cells. The majority of cells sharing features of fibroblasts, if not all, seem to belong to the same population of cells. They are probably adapted to special functional needs in their own micro-environment that are peculiar to local or pathological or experimental conditions. It is proposed to categorize these cells into subtypes depending on their main functions: 1, fibrogenesis; 2, tissue skeleton or barrier; 3, intercellular communication system; 4, gentle contractile machinery; 5, endocrine activity; and 6, vitamin A-storing. Re-evaluation of fibroblasts and fibroblast-like cells is required to facilitate their better understanding."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I311,I311)","v":2198038},{"$f":"(LEN($J311) - LEN(SUBSTITUTE(LOWER($J311),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J311) - LEN(SUBSTITUTE(LOWER($J311),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J311) - LEN(SUBSTITUTE(LOWER($J311),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B311:D311)","v":0},1990,"Ethanol-induced lipid peroxidation and oxidative stress in extrahepatic tissues.","Nordmann",2198038,"Ethanol-induced lipid peroxidation and oxidative stress in extrahepatic tissues.    Abstract:   An ethanol-induced oxidative stress is not restricted to the liver, where ethanol is actively oxidized, but can affect various extrahepatic tissues as shown by experimental data obtained in the rat during acute or chronic ethanol intoxication. Most of these data concern the central nervous system, the heart and the testes. An acute ethanol load has been reported to enhance lipid peroxidation in the cerebellum. This is accompanied by an increase in the cytosolic concentration of low-molecular-weight iron derivatives which may contribute to the generation of aggressive free radicals. The ethanol-induced decrease in the main antioxidant systems (superoxide dismutase, alpha-tocopherol, ascorbate and selenium) is a likely contributor to the cerebellar oxidative stress. Most of these disturbances can be prevented by allopurinol administration. Some experimental data support also the occurrence of pro- and anti-oxidant disturbances in the cerebellum and in other regions of the central nervous system after chronic ethanol administration. Chronic ethanol administration enhances lipid peroxidation in the heart. The increased conversion of xanthine dehydrogenase into xanthine oxidase as well as the activation of peroxisomal acyl CoA-oxidase linked to ethanol administration could contribute to the oxidative stress. Chronic ethanol administration elicits in the testes an enhancement in mitochondrial lipid peroxidation and a decrease in the glutathione level, which appear to be correlated to the gross testicular atrophy observed. Vitamin A supplementation attenuates the changes in lipid peroxidation, glutathione and testicular morphology. Whether the reported disturbances are involved in the pathogenesis of the tissue disorders observed in alcoholic patients remains unanswered.(ABSTRACT TRUNCATED AT 250 WORDS)"]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I312,I312)","v":2693225},{"$f":"(LEN($J312) - LEN(SUBSTITUTE(LOWER($J312),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J312) - LEN(SUBSTITUTE(LOWER($J312),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J312) - LEN(SUBSTITUTE(LOWER($J312),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B312:D312)","v":0},1989,"Lipid peroxidation: a mechanism for alcohol-induced testicular injury.","Rosenblum",2693225,"Lipid peroxidation: a mechanism for alcohol-induced testicular injury.    Abstract:   That alcohol abuse may lead to testicular lipid peroxidation is suggested by the fact that ethanol is a known testicular toxin and its chronic use leads to both endocrine and reproductive failure. Because testicular membranes are rich in polyenoic fatty acids that are prone to undergo peroxidative decomposition, it is reasonable to consider that lipid peroxidation may contribute to the membrane injury and gonadal dysfunction that occurs as a result of alcohol abuse and/or chronic use. The present report reviews the studies supporting the concept that testicular lipid peroxidation is a metabolic consequence of chronic alcohol administration to animals and that its presence correlates with the gonadal injury present in animals ingesting ethanol for prolonged periods. Consistent with such a mechanism for putative alcohol-associated testicular toxicity are the observed reductions in the testicular content of polyenoic fatty acids and glutathione (GSH) content of the testes of alcohol-fed animals as compared to isocalorically fed controls. The later finding demonstrates that ethanol modifies the precarious antioxidant balance of testicular tissue such that enhanced peroxidation can occur. It is well known that peroxidation injury can be attenuated when it occurs in association with dietary vitamin A supplementation. Thus, it is of interest to note that vitamin A, acting as an antioxidant, stabilizes testicular membranes by reducing lipid peroxidation and prevents the alcohol-induced atrophy that occurs in animals not receiving vitamin-A-enriched diets. Taken together, these observations suggest that the enhanced peroxidation of testicular lipids that occurs following ethanol exposure may be an important factor in the pathogenesis of alcohol-associated gonadal injury."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I313,I313)","v":3153130},{"$f":"(LEN($J313) - LEN(SUBSTITUTE(LOWER($J313),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J313) - LEN(SUBSTITUTE(LOWER($J313),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J313) - LEN(SUBSTITUTE(LOWER($J313),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B313:D313)","v":0},1988,"[Requirements of nutrients which participate in erythropoiesis].","Shalita",3153130,"[Requirements of nutrients which participate in erythropoiesis].    Abstract:   Proteins, some minerals and vitamins, play important roles in erythropoiesis and the survival of the red blood cell. This article deals specifically with the physiological requirements and recommended intakes of iron, folate and vitamin B12. A comparison of the physiologic iron requirements according to age and sex, and the amount of iron which is actually absorbed from the diets consumed by the lower socioeconomic strata of the Venezuelan population; indicates that these diets do not satisfy the requirements at all ages. Such disparity is most marked in children below three years of age, in adolescents and in women during their reproductive age. Failure to do so leads to varying degrees of iron deficiency. This low bioavailability of the Venezuelan diet is also observed in other Latin American diets consumed by the same low socioeconomic strata, which explains the high prevalence of iron-deficiency anemia in the vulnerable groups. The low intake of fruits and vegetables by the lower socioeconomic strata of the Latin American population prevents these sectors from consuming an adequate intake of folate, failing to fulfill the daily recommended intake (3.3 - 3.6 micrograms/kg body weight). This situation is aggravated in pregnant and lactating women who require an additional intake of 300 micrograms and 100 micrograms, respectively. Prevalence of folate deficiency in the first stage may be in the order of 30% in some regions. In the second stage of deficiency, characterized by megaloblastic changes in the bone marrow and an erythrocyte folate concentration of less than 50 micrograms/lt, it could be as high as 40% in pregnant women. Nutritional vitamin B12 deficiency does not constitute a health problem in Latin America. Various surveys in the lower socioeconomic strata have reported normal or higher than normal serum B12 concentrations, compared to well-nourished populations."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I314,I314)","v":3153129},{"$f":"(LEN($J314) - LEN(SUBSTITUTE(LOWER($J314),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J314) - LEN(SUBSTITUTE(LOWER($J314),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J314) - LEN(SUBSTITUTE(LOWER($J314),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B314:D314)","v":0},1988,"[Abuse of megadoses of vitamins].","Arroyave",3153129,"[Abuse of megadoses of vitamins].    Abstract:   There is no evidence of any nutritional benefit derived from the consumption of vitamin supplements in excess of the daily intakes recommended by the various international and national expert committees. Furthermore, in the case of certain of the vitamins such as vitamin A and vitamin D, excessive intakes result in toxic effects. To a lesser extent this is also the case for vitamin C and nicotinic acid. In addition, the use of high supplements or megadoses of any vitamin results in a wasteful misuse of economic resources. This reduces the capacity to acquire foods which would have clear nutritional benefits for the whole family. Consequently, the indiscriminate use of these megadoses must be discouraged. Their application is exclusively justified in clinical situations under direct medical supervision."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I315,I315)","v":3153128},{"$f":"(LEN($J315) - LEN(SUBSTITUTE(LOWER($J315),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J315) - LEN(SUBSTITUTE(LOWER($J315),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J315) - LEN(SUBSTITUTE(LOWER($J315),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B315:D315)","v":0},1988,"[3 problem vitamins in Latin America].","Arroyave",3153128,"[3 problem vitamins in Latin America].    Abstract:   The list of vitamins recognized as essential in human nutrition is extensive. Only some of them, however, are attributed an important role in public health. The present paper deals with three of these selected because their deficiencies still prevail in important sectors of population in the Latin American Region: vitamin A, vitamin C and vitamin D. For each vitamin the paper discusses the scientific bases for their requirements, as well as pragmatic considerations to be taken into account for the derivation of recommended dietary intakes. Reference is made to the logic of applying the concepts of nutrient density when developing guidelines for the design of diets for the family and the community. Adequate nutrient density means that when a diet is consumed in sufficient amounts to satisfy energy requirements, the needs for essential nutrients are also being met. For the above reasons, the principle of expressing the recommended levels of intake of vitamin A and C per 1,000 kilocalories has been followed. This is not the case with vitamin D which, in view of its special feature of being synthesized endogenously, is not really a vitamin in the strict sense of the term and, therefore, a rational and consistent relationship with the energy of the diet cannot be established."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I316,I316)","v":3290396},{"$f":"(LEN($J316) - LEN(SUBSTITUTE(LOWER($J316),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J316) - LEN(SUBSTITUTE(LOWER($J316),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J316) - LEN(SUBSTITUTE(LOWER($J316),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B316:D316)","v":0},1988,"Serum cholesterol and risk of cancer in a cohort of 39,000 men and women.","Knekt",3290396,"Serum cholesterol and risk of cancer in a cohort of 39,000 men and women.    Abstract:   Serum cholesterol concentration was studied for its prediction of cancer in 39,268 men and women aged 15-99 years and initially free from cancer. During a median follow-up of 10 years 1381 cancer cases were diagnosed. Serum cholesterol level was inversely associated with cancer incidence among non-smokers. Age-adjusted relative risks of cancer in quintiles of serum cholesterol were in male non-smokers 1.0, 0.81, 0.73, 0.69, and 0.46 and in female non-smokers 1.0, 0.75, 0.84, 0.78, and 0.70. The associations were not found to be confounded by serum vitamins A or E, serum selenium or several other factors. The association between serum cholesterol level and risk of cancer varied from strongly negative to slightly positive according to subpopulation and site of cancer. The strongest negative associations were found to appear during the first years of follow-up, especially for rapidly developing cancers. Thus the increased occurrence of cancer at low cholesterol levels seems mainly to be due to preclinical cancer."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I317,I317)","v":3327234},{"$f":"(LEN($J317) - LEN(SUBSTITUTE(LOWER($J317),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J317) - LEN(SUBSTITUTE(LOWER($J317),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J317) - LEN(SUBSTITUTE(LOWER($J317),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B317:D317)","v":0},1987,"Nutrient utilization during pregnancy.","King",3327234,"Nutrient utilization during pregnancy.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I318,I318)","v":3006202},{"$f":"(LEN($J318) - LEN(SUBSTITUTE(LOWER($J318),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J318) - LEN(SUBSTITUTE(LOWER($J318),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J318) - LEN(SUBSTITUTE(LOWER($J318),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B318:D318)","v":0},1986,"Diet in the etiology of cancer.","Vaughan",3006202,"Diet in the etiology of cancer.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I319,I319)","v":3002865},{"$f":"(LEN($J319) - LEN(SUBSTITUTE(LOWER($J319),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J319) - LEN(SUBSTITUTE(LOWER($J319),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J319) - LEN(SUBSTITUTE(LOWER($J319),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B319:D319)","v":0},1986,"Nutritional factors in lung, colon, and prostate carcinogenesis in animal models.","Kroes",3002865,"Nutritional factors in lung, colon, and prostate carcinogenesis in animal models.    Abstract:   Dietary factors are now considered to be among the most important environmental risk determinants for cancer. In addition to epidemiological studies, experimental animal studies are an important tool to investigate dietary modulation in carcinogenesis. Results of recent experimental studies on the effect of some nutrients indicate that vitamin A did show an inverse relation with the occurrence of preneoplastic respiratory lesions but not with respiratory tract tumors in benzo[a]pyrene-induced respiratory carcinogenesis. Dietary fat increases respiratory tract tumors and preneoplastic lesions. In colon carcinogenesis, a fat-fiber interrelation was noticed in 1,2-dimethyl-hydrazine- and N-methyl-N-nitro-N-nitrosoguanidine-induced tumors. Preliminary results in prostate carcinogenesis indicate that dietary fat did not influence the incidence of prostate cancer in a recently developed rat model. Some possible mechanisms in colon and prostate carcinogenesis are discussed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I320,I320)","v":3900157},{"$f":"(LEN($J320) - LEN(SUBSTITUTE(LOWER($J320),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J320) - LEN(SUBSTITUTE(LOWER($J320),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J320) - LEN(SUBSTITUTE(LOWER($J320),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B320:D320)","v":0},1985,"Hereditary epidermolysis bullosa.","Haber",3900157,"Hereditary epidermolysis bullosa.    Abstract:   Hereditary epidermolysis bullosa (EB) is a group of disorders of skin characterized by formation of blisters following minor trauma. There are at least sixteen types of hereditary EB. These types are reviewed in this article. There are several classifications of hereditary EB, and they are discussed, as well as current ideas on pathogenesis. Last, the treatment of this often recalcitrant group of diseases is discussed."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I321,I321)","v":2995885},{"$f":"(LEN($J321) - LEN(SUBSTITUTE(LOWER($J321),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J321) - LEN(SUBSTITUTE(LOWER($J321),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J321) - LEN(SUBSTITUTE(LOWER($J321),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B321:D321)","v":0},1985,"Vitamin A-binding proteins.","Ong",2995885,"Vitamin A-binding proteins.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I322,I322)","v":2862747},{"$f":"(LEN($J322) - LEN(SUBSTITUTE(LOWER($J322),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J322) - LEN(SUBSTITUTE(LOWER($J322),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J322) - LEN(SUBSTITUTE(LOWER($J322),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B322:D322)","v":0},1985,"[Side effects of drugs on male fertility].","Schill",2862747,"[Side effects of drugs on male fertility].    Abstract:   Side effects of drugs on male fertility occur more often than they are expected to. In general, they are not recognized till during andrological examination on account of a barren marriage. A transient or permanent inhibition of male fertility by drugs is possible, if one of the following functions interferes: spermatogenesis, sperm maturation within the epididymis, sperm transport, sperm metabolism and motility, semen liquefaction, capacitation, acrosomal reaction, or ovum penetration. Best known is the impairment of spermatogenesis by direct inhibition of the germinal epithelium (antispermatogenic agents: cytostatics, immunosuppressive agents, psychopharmacological compounds, antibiotics) or indirectly by influencing the axis between hypothalamus, pituitary gland, and gonads (hormones: estrogens, gestagens, androgens, anabolics, antiandrogens). Sperm transport may be impaired by neuroleptic drugs, tricyclic antidepressants, antihypertensive drugs like guanethidine, and ganglionic blocking agents. Inhibition of sperm motility is possible by antibiotics, psychopharmacological agents, anthelmintics, and beta receptor blockers. In future, it will therefore be necessary to pay more attention to side effects of drugs on male fertility, particularly with regard to patients at the age of reproductiveness."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I323,I323)","v":3911268},{"$f":"(LEN($J323) - LEN(SUBSTITUTE(LOWER($J323),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J323) - LEN(SUBSTITUTE(LOWER($J323),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J323) - LEN(SUBSTITUTE(LOWER($J323),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B323:D323)","v":0},1985,"Functional consequences of zinc deficiency.","McClain",3911268,"Functional consequences of zinc deficiency.    Abstract:   Zinc is an essential trace element necessary for over 200 zinc metalloenzymes and required for normal nucleic acid, protein, and membrane metabolism. During the past two decades there has been a rapid expansion of knowledge concerning zinc metabolism in both normal and disease situations, including mechanisms for zinc absorption, excretion and internal redistribution of zinc after stress or trauma. Acrodermatitis enteropathica has been recognized to be a disease of impaired zinc absorption in man. A host of disease processes now are recognized to be complicated by zinc deficiency including alcoholic liver disease, sickle cell anemia, protein calorie malnutrition, and a variety of intestinal diseases including Crohns disease, sprue, short bowel syndrome and after jejunal ileal bypass. Zinc has proved to be an extremely interesting mineral to nutritionists and physicians because of its importance in normal physiology and biochemistry and because of the diverse presenting features of zinc deficiency. This paper reviews ten functional consequences of zinc deficiency and emphasizes certain consequences in which there have been new discoveries concerning their mechanism (e.g., anorexia) or their clinical importance (e.g., immune dysfunction)."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I324,I324)","v":3896272},{"$f":"(LEN($J324) - LEN(SUBSTITUTE(LOWER($J324),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J324) - LEN(SUBSTITUTE(LOWER($J324),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J324) - LEN(SUBSTITUTE(LOWER($J324),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B324:D324)","v":0},1985,"Zinc and reproduction.","Apgar",3896272,"Zinc and reproduction.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I325,I325)","v":3887778},{"$f":"(LEN($J325) - LEN(SUBSTITUTE(LOWER($J325),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J325) - LEN(SUBSTITUTE(LOWER($J325),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J325) - LEN(SUBSTITUTE(LOWER($J325),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B325:D325)","v":0},1985,"Vitamins and immunocompetence.","Panush",3887778,"Vitamins and immunocompetence.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I326,I326)","v":6428773},{"$f":"(LEN($J326) - LEN(SUBSTITUTE(LOWER($J326),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J326) - LEN(SUBSTITUTE(LOWER($J326),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J326) - LEN(SUBSTITUTE(LOWER($J326),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B326:D326)","v":0},1984,"Implications of nutritional status on human biochemistry, physiology, and health.","Sauberlich",6428773,"Implications of nutritional status on human biochemistry, physiology, and health.    Abstract:   Optimum nutrition is the level of intake that should promote the highest level of health. Although excess caloric intake will lead to obesity, a deficit in nutrition may result in a tissue depletion of essential nutrients that can lead to biochemical changes and eventually to clinical signs and symptoms. Nutrition requirements may differ according to sex, age, activity, or physiological state and can be influenced by drugs, smoking, alcohol, and other factors. With ever-increasing sedentary life styles and less physically demanding jobs, the resulting reduced caloric requirements have made it more difficult to make nutritionally sound food choices. Nutrition is the single most important component of preventive health care. Diet has been associated with cancer, heart disease, diabetes, stroke and hypertension, arteriosclerosis, and cirrhosis of the liver. The ability of the human to respond to stresses, such as altitude, heat, trauma, surgery, and infection can be influenced by nutritional status. Nutritional status is reflected in a variety of metabolic processes that provide the basis for a number of methods for its assessment."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I327,I327)","v":6338505},{"$f":"(LEN($J327) - LEN(SUBSTITUTE(LOWER($J327),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J327) - LEN(SUBSTITUTE(LOWER($J327),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J327) - LEN(SUBSTITUTE(LOWER($J327),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B327:D327)","v":0},1983,"The function of vitamin A: current concepts.","Zile",6338505,"The function of vitamin A: current concepts.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I328,I328)","v":6340124},{"$f":"(LEN($J328) - LEN(SUBSTITUTE(LOWER($J328),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J328) - LEN(SUBSTITUTE(LOWER($J328),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J328) - LEN(SUBSTITUTE(LOWER($J328),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B328:D328)","v":0},1983,"Vitamin A in pregnancy and lactation.","Bates",6340124,"Vitamin A in pregnancy and lactation.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I329,I329)","v":6340122},{"$f":"(LEN($J329) - LEN(SUBSTITUTE(LOWER($J329),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J329) - LEN(SUBSTITUTE(LOWER($J329),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J329) - LEN(SUBSTITUTE(LOWER($J329),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B329:D329)","v":0},1983,"Biochemical mechanisms of vitamin A action.","Weber",6340122,"Biochemical mechanisms of vitamin A action.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I330,I330)","v":6300915},{"$f":"(LEN($J330) - LEN(SUBSTITUTE(LOWER($J330),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J330) - LEN(SUBSTITUTE(LOWER($J330),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J330) - LEN(SUBSTITUTE(LOWER($J330),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B330:D330)","v":0},1983,"Chemical structure and the changing concept of vitamin A activity.","Pitt",6300915,"Chemical structure and the changing concept of vitamin A activity.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I331,I331)","v":7050193},{"$f":"(LEN($J331) - LEN(SUBSTITUTE(LOWER($J331),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J331) - LEN(SUBSTITUTE(LOWER($J331),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J331) - LEN(SUBSTITUTE(LOWER($J331),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B331:D331)","v":0},1982,"Possible role of beta-carotene in improving fertility in dairy cattle.","Hemken",7050193,"Possible role of beta-carotene in improving fertility in dairy cattle.    Abstract:   Recent interest in beta-carotene has been stimulated by reports that reproductive performance in cattle was improved with dietary supplementation of beta-carotene even when the diet was supplemented with vitamin A. Vitamin A requirements for cattle are based on studies with beta-carotene as the vitamin A source and with studies with vitamin A in the ester or alcohol form. Most of the studies with cattle that demonstrate the need for vitamin A for optimum reproduction were when beta-carotene was the source of vitamin A. Recent German reports show an improvement in conception rate, intensity of estrus, and changes in luteinizing hormone patterns when cattle received beta-carotene supplementation of low carotene diets. These diets were supplemented with vitamin A. A similar study from Israel did not detect benefits of beta-carotene. The active form of vitamin A for reproduction in rats and other species has not been determined; however, vitamin A does meet the reproductive requirements. The ruminant animal does have differences in carotene metabolism from the rat. Before the role of beta-carotene for reproduction in cattle can be clarified, the specific function of carotene or the specific form of vitamin A for reproduction needs to be determined."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I332,I332)","v":6177111},{"$f":"(LEN($J332) - LEN(SUBSTITUTE(LOWER($J332),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J332) - LEN(SUBSTITUTE(LOWER($J332),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J332) - LEN(SUBSTITUTE(LOWER($J332),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B332:D332)","v":0},1981,"[Recent findings on the importance of vitamin A and its metabolism in man and laboratory animals].","Kolb",6177111,"[Recent findings on the importance of vitamin A and its metabolism in man and laboratory animals].    Abstract:   A survey is given concerning recent realizations of importance and metabolism of vitamin A in man and experimental animals. The transport of vitamin A from the small intestine takes place in form of esters by inclusion in chylomicrons and lipoproteins. A higher content in the blood plasma over a longer period evokes toxic effects. In the liver one part of the vitamin A in form of an ester with binding to lipoproteins is accumulated, one part is - according to the need - associated with a vitamin-A-binding protein, which forms complexes with prealbumin molecules and transports the vitamin to the various places of effect. With the help of the receptor proteins the vitamin A is included in the cells, in which it is effective and is transported into the vitamin-A-aldehyde and the vitamin-A-acid. The vitamin A and the vitamin-A-acid are transported into the cell nuclei with the help of receptor-proteins and play a role in the differentiation of the tissues and in the regulation of the synthesis of RNA. When a deficit or an abundance of vitamin A is present in the early phase of pregnancy malformations in the fetuses appear. The vitamin A and structure-similar connections have an inhibiting effect on the development of tumours."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I333,I333)","v":7031395},{"$f":"(LEN($J333) - LEN(SUBSTITUTE(LOWER($J333),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J333) - LEN(SUBSTITUTE(LOWER($J333),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J333) - LEN(SUBSTITUTE(LOWER($J333),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B333:D333)","v":0},1981,"The curly-tail mouse: an experimental model for human neural tube defects.","Seller",7031395,"The curly-tail mouse: an experimental model for human neural tube defects.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I334,I334)","v":7044701},{"$f":"(LEN($J334) - LEN(SUBSTITUTE(LOWER($J334),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J334) - LEN(SUBSTITUTE(LOWER($J334),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J334) - LEN(SUBSTITUTE(LOWER($J334),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B334:D334)","v":0},1981,"Hypogonadism and feminization in alcoholic men: the past, present and future.","Van Thiel",7044701,"Hypogonadism and feminization in alcoholic men: the past, present and future.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I335,I335)","v":6445537},{"$f":"(LEN($J335) - LEN(SUBSTITUTE(LOWER($J335),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J335) - LEN(SUBSTITUTE(LOWER($J335),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J335) - LEN(SUBSTITUTE(LOWER($J335),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B335:D335)","v":0},1980,"Nutritional concerns during adolescence.","Marino",6445537,"Nutritional concerns during adolescence.    Abstract:   Adolescent food habits often run counter to the special nutritional needs of this age group. Suggestions for nutrient supplements are offered, with particular emphasis on fulfilling the unique needs of the obese, athletic, or pregnant teenager. Selected aspects of adolescent nutrition are reviewed. Focus is on adolescent nutrient requirements, food habits, and the special nutritional needs of obese, athletic, or pregnant teenagers. The nutritional implications of alcohol abuse, oral contraceptive (OC) use, and acne during the adolescent period are discussed. Although the critical role of nutrition in pubertal growth and development actually begins before adolescence--during childhood, total nutrient needs are higher during adolescence than at any other time in the life cycle. A failure to consume an adequate diet at this time can potentially retard growth and delay sexual maturity. The weight gain of both adolescent males and females is appreciable, but the rate, amount, and composition of tissue generated differs between the 2 sexes. Based on nutrient needs for growth, recommended dietary allowances have been made for adolescents by the Food and Nutrition Board of the National Research Council. The recommendations for protein and all vitamins and minerals, presented here in table form, include a safety factor so that the needs of quot;practically all healthyquot; adolescents are met. The skipping of meals is a common phenomenon among adolescents. Because of busy schedules during and after school, the teenager may eat sparingly of poor quality foods and then quot;catch upquot; on food intake during the late evening. Snacking is definitely part of adolescent food behavior. 1 health concern is the prevalence of adolescent obesity and its associated problems. Supportive dietary counseling is mandatory in a weight reduction program for the adolescent. A program of physical activity is another component of any successful weight reduction program."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I336,I336)","v":6182689},{"$f":"(LEN($J336) - LEN(SUBSTITUTE(LOWER($J336),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J336) - LEN(SUBSTITUTE(LOWER($J336),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J336) - LEN(SUBSTITUTE(LOWER($J336),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B336:D336)","v":0},1980,"Systemic mode of action of vitamin A.","Ganguly",6182689,"Systemic mode of action of vitamin A.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I337,I337)","v":6155672},{"$f":"(LEN($J337) - LEN(SUBSTITUTE(LOWER($J337),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J337) - LEN(SUBSTITUTE(LOWER($J337),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J337) - LEN(SUBSTITUTE(LOWER($J337),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B337:D337)","v":0},1980,"Regulation of prostate growth in organ culture.","Sandberg",6155672,"Regulation of prostate growth in organ culture.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I338,I338)","v":793396},{"$f":"(LEN($J338) - LEN(SUBSTITUTE(LOWER($J338),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J338) - LEN(SUBSTITUTE(LOWER($J338),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J338) - LEN(SUBSTITUTE(LOWER($J338),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B338:D338)","v":0},1976,"Evaluation of emotional reactions to oral contraceptive use.","Kane",793396,"Evaluation of emotional reactions to oral contraceptive use.    Abstract:   A review of available clinical studies indicates that 10 to 40 per cent of oral contraceptive users may suffer mild to moderate depression syndromes. Clinical and animal data indicate that a variety of mechanisms may be involved, including alterations in folate, pyridoxine, and vitamine B12 metabolism, as well as related effects on biogenic amine metabolism. Interactive effects may result, such as impairment of usual coping mechnisms and psychological defenses by altered central nervous system function. Literature on the association of oral contraceptives (OCs) with psychological disturbances is reviewed. The data from available clinical studies indicate that perhaps 10-40% of OC users may experience mild to moderate depression syndromes characterized by tiredness, lethargy, sadness and, in some cases, loss of libido. These psychological alterations may involve numerous mechanisms including changes in folate, pyridoxine, and Vitamin-B12 metabolism, and related effects on biogenic amine metabolism. The interaction of these impaired mechanisms may disturb usual coping functions and psychological defenses by altered central nervous system activity."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I339,I339)","v":780184},{"$f":"(LEN($J339) - LEN(SUBSTITUTE(LOWER($J339),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J339) - LEN(SUBSTITUTE(LOWER($J339),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J339) - LEN(SUBSTITUTE(LOWER($J339),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B339:D339)","v":0},1976,"Alcoholism: its effect on hypothalamic pituitary gonadal function.","Van Thiel",780184,"Alcoholism: its effect on hypothalamic pituitary gonadal function.    Abstract:   Both as the result of liver disease and of alcoholism per se, chronic alcoholics develop infertility, sterility, gonadal atrophy, hypoandrogenization, and feminization. The hypothalamic-pituitary abnormalities associated with alcoholism include hyperprolactenemia-increased estrogen-stimulated neurophysin levels, suppressed secretion of plasma gonadotropins, and loss of gonadotropin reserve. Several of the possible mechanisms potentially responsible for the development of these endocrine abnormalities have been discussed. The rational for suspecting that alcohol might interfere with either vitamin A metabolism of alter the redox state of the testes, thus affecting germ cell proliferation and steroidogenesis, has been presented. A possible mechanism for the sexual changes observed in chronic alcoholic men has been proposed. Much work remains to be done in this area before a complete understanding of the pathogenesis of these phenomena is obtained. The omission of any consideration of the effects of alcohol on sexual function in women is an admission of gross ignorance greatly in need of rectification. The necessity for couching a description of even the natural history of the syndrome in alcoholic men in conditional terms is a reflection of the limited state of the art. Nevertheless, it behooves the gastroenterologist, who is frequently called upon to be the primary physician for alcoholic men, to keep abreast of the nongastrointestinal medical consequences of alcohol addiction so that they can be recognized early and incorporated into long range medical planning designed to care for the chronic alcoholic patient."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I340,I340)","v":781682},{"$f":"(LEN($J340) - LEN(SUBSTITUTE(LOWER($J340),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J340) - LEN(SUBSTITUTE(LOWER($J340),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J340) - LEN(SUBSTITUTE(LOWER($J340),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B340:D340)","v":0},1976,"Vitamins in Western diets.","Morton",781682,"Vitamins in Western diets.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I341,I341)","v":824857},{"$f":"(LEN($J341) - LEN(SUBSTITUTE(LOWER($J341),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J341) - LEN(SUBSTITUTE(LOWER($J341),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J341) - LEN(SUBSTITUTE(LOWER($J341),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B341:D341)","v":0},1976,"Xerophthalmia.","Oomen",824857,"Xerophthalmia.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I342,I342)","v":824850},{"$f":"(LEN($J342) - LEN(SUBSTITUTE(LOWER($J342),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J342) - LEN(SUBSTITUTE(LOWER($J342),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J342) - LEN(SUBSTITUTE(LOWER($J342),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B342:D342)","v":0},1976,"Physiological and practical considerations of nutrient function and requirements.","Beaton",824850,"Physiological and practical considerations of nutrient function and requirements.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I343,I343)","v":822591},{"$f":"(LEN($J343) - LEN(SUBSTITUTE(LOWER($J343),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J343) - LEN(SUBSTITUTE(LOWER($J343),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J343) - LEN(SUBSTITUTE(LOWER($J343),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B343:D343)","v":0},1976,"Vitamin A deficiency and xerophthalmia. Report of a Joint WHO/USAID Meeting.","Beaton",822591,"Vitamin A deficiency and xerophthalmia. Report of a Joint WHO/USAID Meeting.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I344,I344)","v":798418},{"$f":"(LEN($J344) - LEN(SUBSTITUTE(LOWER($J344),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J344) - LEN(SUBSTITUTE(LOWER($J344),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J344) - LEN(SUBSTITUTE(LOWER($J344),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B344:D344)","v":0},1976,"Recommended nutrient allowances.","Masek",798418,"Recommended nutrient allowances.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I345,I345)","v":790782},{"$f":"(LEN($J345) - LEN(SUBSTITUTE(LOWER($J345),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J345) - LEN(SUBSTITUTE(LOWER($J345),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J345) - LEN(SUBSTITUTE(LOWER($J345),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B345:D345)","v":0},1976,"Vitamin A deficiency in Indian children.","Pereira",790782,"Vitamin A deficiency in Indian children.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I346,I346)","v":812958},{"$f":"(LEN($J346) - LEN(SUBSTITUTE(LOWER($J346),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J346) - LEN(SUBSTITUTE(LOWER($J346),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J346) - LEN(SUBSTITUTE(LOWER($J346),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B346:D346)","v":0},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."]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I347,I347)","v":805504},{"$f":"(LEN($J347) - LEN(SUBSTITUTE(LOWER($J347),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J347) - LEN(SUBSTITUTE(LOWER($J347),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J347) - LEN(SUBSTITUTE(LOWER($J347),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B347:D347)","v":0},1975,"Human vitamin A deficiency.","Srikantia",805504,"Human vitamin A deficiency.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I348,I348)","v":788039},{"$f":"(LEN($J348) - LEN(SUBSTITUTE(LOWER($J348),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J348) - LEN(SUBSTITUTE(LOWER($J348),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J348) - LEN(SUBSTITUTE(LOWER($J348),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B348:D348)","v":0},1975,"Vitamin A.","McLaren",788039,"Vitamin A.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I349,I349)","v":4617396},{"$f":"(LEN($J349) - LEN(SUBSTITUTE(LOWER($J349),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J349) - LEN(SUBSTITUTE(LOWER($J349),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J349) - LEN(SUBSTITUTE(LOWER($J349),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B349:D349)","v":0},1974,"The fat-soluble vitamins in modern medicine.","Marks",4617396,"The fat-soluble vitamins in modern medicine.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I350,I350)","v":4616468},{"$f":"(LEN($J350) - LEN(SUBSTITUTE(LOWER($J350),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J350) - LEN(SUBSTITUTE(LOWER($J350),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J350) - LEN(SUBSTITUTE(LOWER($J350),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B350:D350)","v":0},1974,"The determination of vitamin A and some aspects of its distribution, mobilization and transport in health and disease.","Underwood",4616468,"The determination of vitamin A and some aspects of its distribution, mobilization and transport in health and disease.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I351,I351)","v":4569986},{"$f":"(LEN($J351) - LEN(SUBSTITUTE(LOWER($J351),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J351) - LEN(SUBSTITUTE(LOWER($J351),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J351) - LEN(SUBSTITUTE(LOWER($J351),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B351:D351)","v":0},1973,"Progress in swine nutrition for the veterinarian.","Bowland",4569986,"Progress in swine nutrition for the veterinarian.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I352,I352)","v":4566403},{"$f":"(LEN($J352) - LEN(SUBSTITUTE(LOWER($J352),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J352) - LEN(SUBSTITUTE(LOWER($J352),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J352) - LEN(SUBSTITUTE(LOWER($J352),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B352:D352)","v":0},1973,"Recommended intakes of vitamins for normal growth and development.","Kodicek",4566403,"Recommended intakes of vitamins for normal growth and development.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I353,I353)","v":4644266},{"$f":"(LEN($J353) - LEN(SUBSTITUTE(LOWER($J353),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J353) - LEN(SUBSTITUTE(LOWER($J353),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J353) - LEN(SUBSTITUTE(LOWER($J353),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B353:D353)","v":0},1972,"A review of teenage nutrition in the United States.","Huenemann",4644266,"A review of teenage nutrition in the United States.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I354,I354)","v":4556123},{"$f":"(LEN($J354) - LEN(SUBSTITUTE(LOWER($J354),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J354) - LEN(SUBSTITUTE(LOWER($J354),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J354) - LEN(SUBSTITUTE(LOWER($J354),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B354:D354)","v":0},1972,"A conspectus of research on vitamin A requirements of man.","Rodriguez",4556123,"A conspectus of research on vitamin A requirements of man.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I355,I355)","v":4616082},{"$f":"(LEN($J355) - LEN(SUBSTITUTE(LOWER($J355),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J355) - LEN(SUBSTITUTE(LOWER($J355),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J355) - LEN(SUBSTITUTE(LOWER($J355),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B355:D355)","v":0},1972,"Nutrition and reproduction in sheep.","Cloete",4616082,"Nutrition and reproduction in sheep.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I356,I356)","v":4343258},{"$f":"(LEN($J356) - LEN(SUBSTITUTE(LOWER($J356),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J356) - LEN(SUBSTITUTE(LOWER($J356),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J356) - LEN(SUBSTITUTE(LOWER($J356),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B356:D356)","v":0},1972,"Vitamin A and spermatogenesis in the rat.","Cloete",4343258,"Vitamin A and spermatogenesis in the rat.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I357,I357)","v":4942864},{"$f":"(LEN($J357) - LEN(SUBSTITUTE(LOWER($J357),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J357) - LEN(SUBSTITUTE(LOWER($J357),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J357) - LEN(SUBSTITUTE(LOWER($J357),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B357:D357)","v":0},1971,"Nutritive influences upon reproduction.","Moustgaard",4942864,"Nutritive influences upon reproduction.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I358,I358)","v":4916225},{"$f":"(LEN($J358) - LEN(SUBSTITUTE(LOWER($J358),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J358) - LEN(SUBSTITUTE(LOWER($J358),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J358) - LEN(SUBSTITUTE(LOWER($J358),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B358:D358)","v":0},1970,"Nutritional diseases of exotic animals.","Wallach",4916225,"Nutritional diseases of exotic animals.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I359,I359)","v":4930376},{"$f":"(LEN($J359) - LEN(SUBSTITUTE(LOWER($J359),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J359) - LEN(SUBSTITUTE(LOWER($J359),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J359) - LEN(SUBSTITUTE(LOWER($J359),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B359:D359)","v":0},1970,"[Dehydrogenation and enzymatic isomerization of delta 5-3 beta-hydroxysteroids].","Grangaud",4930376,"[Dehydrogenation and enzymatic isomerization of delta 5-3 beta-hydroxysteroids].    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I360,I360)","v":4922143},{"$f":"(LEN($J360) - LEN(SUBSTITUTE(LOWER($J360),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J360) - LEN(SUBSTITUTE(LOWER($J360),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J360) - LEN(SUBSTITUTE(LOWER($J360),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B360:D360)","v":0},1970,"Hypervitaminosis A of the cat.","Seawright",4922143,"Hypervitaminosis A of the cat.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I361,I361)","v":4259238},{"$f":"(LEN($J361) - LEN(SUBSTITUTE(LOWER($J361),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J361) - LEN(SUBSTITUTE(LOWER($J361),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J361) - LEN(SUBSTITUTE(LOWER($J361),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B361:D361)","v":0},1970,"[Vitamin A, steroid hormones and nutrition].","Grangaud",4259238,"[Vitamin A, steroid hormones and nutrition].    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I362,I362)","v":4916873},{"$f":"(LEN($J362) - LEN(SUBSTITUTE(LOWER($J362),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J362) - LEN(SUBSTITUTE(LOWER($J362),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J362) - LEN(SUBSTITUTE(LOWER($J362),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B362:D362)","v":0},1969,"A review of the causes of reproductive failure in swine.","Rasbech",4916873,"A review of the causes of reproductive failure in swine.    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I363,I363)","v":4318822},{"$f":"(LEN($J363) - LEN(SUBSTITUTE(LOWER($J363),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J363) - LEN(SUBSTITUTE(LOWER($J363),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J363) - LEN(SUBSTITUTE(LOWER($J363),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B363:D363)","v":0},1968,"[Kidney and vitamin E].","Arvy",4318822,"[Kidney and vitamin E].    Abstract:  "]
[{"$f":"HYPERLINK(\"http://www.ncbi.nlm.nih.gov/pubmed/\" & I364,I364)","v":4229758},{"$f":"(LEN($J364) - LEN(SUBSTITUTE(LOWER($J364),LOWER(B$3),\"\")))/LEN(B$3)","v":0},{"$f":"(LEN($J364) - LEN(SUBSTITUTE(LOWER($J364),LOWER(C$3),\"\")))/LEN(C$3)","v":0},{"$f":"(LEN($J364) - LEN(SUBSTITUTE(LOWER($J364),LOWER(D$3),\"\")))/LEN(D$3)","v":0},{"$f":"SUM(B364:D364)","v":0},1966,"Recent advances in the physiology of vitamin A.","Pitt",4229758,"Recent advances in the physiology of vitamin A.    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":2974796},2974796,"Pub Yr: 1988"]
[]
["Title:","Isotretinoin revisited.",null,"Fauthor: Shalita"]
["Title and Abstract:","Isotretinoin revisited.    Abstract:   Isotretinoin (13-cis-retinoic acid) remains the drug of choice for treatment of severe, recalcitrant nodulocystic acne that is unresponsive to conventional therapy, including oral antibiotics. The drug has been shown to produce dramatic clearing of lesions and prolonged remissions. The length of remission may be dependent on both the dosage used and the duration of therapy. Since fetal malformations have been observed in infants born of mothers taking isotretinoin during pregnancy, it is mandatory to prevent women who are pregnant or may become pregnant during treatment from taking isotretinoin. Because the half-life of isotretinoin is ten to twenty hours, and because it is eliminated from the body rapidly enough, women may become pregnant one month after discontinuation of therapy without an increased risk of birth defects. Common side effects of the drug include mucocutaneous reactions, serum lipid alterations, eye irritation, and myalgias. Less commonly observed are hyperostoses and exuberant granulation tissue, and rarely, pseudotumor cerebri. Recommendations for substantially reducing or eliminating these effects are made."]

{"sheet":"Notes","index":2,"n_rows":3,"n_cols":8,"rows_kept":3,"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":15203181},null,"GABA and cp; picrotoxin and 3-mercaptopropionic acid","Cleft palate by picrotoxin or 3-MP and palatal shelf elevation in GABA-deficient mice.",null,15203181]