MED: Urology Papers
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Item Neurologic Factors in Female Sexual Function and Dysfunction(The Korean Urological Association, 2010-7-20) Azadzoi, Kazem M.; Siroky, Mike B.Sexual dysfunction affects both men and women, involving organic disorders, psychological problems, or both. Overall, the state of our knowledge is less advanced regarding female sexual physiology in comparison with male sexual function. Female sexual dysfunction has received little clinical and basic research attention and remains a largely untapped field in medicine. The epidemiology of female sexual dysfunction is poorly understood because relatively few studies have been done in community settings. In the United States, female sexual dysfunction has been estimated to affect 40% of women in the general population. Among the elderly, however, it has been reported that up to 87% of women complain of sexual dissatisfaction. Several studies have shown that the prevalence of female sexual arousal disorders correlates significantly with increasing age. These studies have shown that sexual arousal and frequency of coitus in the female decreases with increasing age. The pathophysiology of female sexual dysfunction appears more complex than that of males, involving multidimensional hormonal, neurological, vascular, psychological, and interpersonal aspects. Organic female sexual disorders may include a wide variety of vascular, neural, or neurovascular factors that lead to problems with libido, lubrication, and orgasm. However, the precise etiology and mechanistic pathways of age-related female sexual arousal disorders are yet to be determined. In the past two decades, some advances have been made in exploring the basic hemodynamics and neuroregulation of female sexual function and dysfunction in both animal models and in human studies. In this review, we summarize neural regulation of sexual function and neurological causes of sexual dysfunction in women.Item Microarray Gene Expression Profiling and Analysis in Renal Cell Carcinoma(BioMed Central, 2004-6-22) Liou, Louis S.; Shi, Ting; Duan, Zhong-Hui; Sadhukhan, Provash; Der, Sandy D.; Novick, Andrew A.; Hissong, John; Skacel, Marek; Almasan, Alexandru; DiDonato, Joseph A.BACKGROUND. Renal cell carcinoma (RCC) is the most common cancer in adult kidney. The accuracy of current diagnosis and prognosis of the disease and the effectiveness of the treatment for the disease are limited by the poor understanding of the disease at the molecular level. To better understand the genetics and biology of RCC, we profiled the expression of 7,129 genes in both clear cell RCC tissue and cell lines using oligonucleotide arrays. METHODS. Total RNAs isolated from renal cell tumors, adjacent normal tissue and metastatic RCC cell lines were hybridized to affymatrix HuFL oligonucleotide arrays. Genes were categorized into different functional groups based on the description of the Gene Ontology Consortium and analyzed based on the gene expression levels. Gene expression profiles of the tissue and cell line samples were visualized and classified by singular value decomposition. Reverse transcription polymerase chain reaction was performed to confirm the expression alterations of selected genes in RCC. RESULTS. Selected genes were annotated based on biological processes and clustered into functional groups. The expression levels of genes in each group were also analyzed. Seventy-four commonly differentially expressed genes with more than five-fold changes in RCC tissues were identified. The expression alterations of selected genes from these seventy-four genes were further verified using reverse transcription polymerase chain reaction (RT-PCR). Detailed comparison of gene expression patterns in RCC tissue and RCC cell lines shows significant differences between the two types of samples, but many important expression patterns were preserved. CONCLUSIONS. This is one of the initial studies that examine the functional ontology of a large number of genes in RCC. Extensive annotation, clustering and analysis of a large number of genes based on the gene functional ontology revealed many interesting gene expression patterns in RCC. Most notably, genes involved in cell adhesion were dominantly up-regulated whereas genes involved in transport were dominantly down-regulated. This study reveals significant gene expression alterations in key biological pathways and provides potential insights into understanding the molecular mechanism of renal cell carcinogenesis.Item Effects of tamoxifen on vaginal blood flow and epithelial morphology in the rat(BioMed Central, 2006-9-13) Kim, Noel N.; Stankovic, Miljan; Armagan, Abdullah; Cushman, Tulay T.; Goldstein, Irwin; Traish, Abdulmaged M.BACKGROUND. Tamoxifen, a selective estrogen receptor modulator with both estrogenic and anti-estrogenic activity, is widely used as adjuvant therapy in breast cancer patients. Treatment with tamoxifen is associated with sexual side effects, such as increased vaginal dryness and pain/discomfort during sexual activity. There have been limited investigations of the effect of tamoxifen on estrogen-dependent peripheral genital arousal responses. The objective of this study was to investigate the effects of tamoxifen on vaginal physiology in the rat. METHODS. Female Sprague-Dawley rats were subjected to sham surgery or bilateral ovariectomy. After 2 weeks, sham-operated rats were implanted with subcutaneous osmotic infusion pumps containing vehicle (control) or tamoxifen (150 μg/day). Ovariectomized rats were similarly infused with vehicle. After an additional 2 weeks, vaginal blood flow responses to pelvic nerve stimulation were measured by laser Doppler flowmetry and vaginal tissue was collected for histological and biochemical assay. RESULTS. Tamoxifen treatment did not change plasma estradiol concentrations relative to control animals, while ovariectomized rats exhibited a 60% decrease in plasma estradiol. Tamoxifen treatment caused a significant decrease in mean uterine weight, but did not alter mean vaginal weight. Vaginal blood flow was significantly decreased in tamoxifen-infused rats compared to controls. Similar to ovariectomized animals, estrogen receptor binding was increased and arginase enzyme activity was decreased in tamoxifen-infused rats. However, different from control and ovariectomized animals, the vaginal epithelium in tamoxifen-infused rats appeared highly mucified. Periodic acid-Schiff staining confirmed a greater production of carbohydrate-rich compounds (e.g. mucin, glycogen) by the vaginal epithelium of tamoxifen-infused rats. CONCLUSION. The observations suggest that tamoxifen exerts both anti-estrogenic and pro-estrogenic effects in the vagina. These physiological alterations may eventually lead to vaginal atrophy and compromise sexual function.Item Streptozotocin-induced diabetes in the rat is associated with changes in vaginal hemodynamics, morphology and biochemical markers(BioMed Central, 2006-5-30) Kim, Noel N.; Stankovic, Miljan; Cushman, Tulay T.; Goldstein, Irwin; Munarriz, Ricardo; Traish, Abdulmaged M.BACKGROUND. Diabetes is associated with declining sexual function in women. However, the effects of diabetes on genital tissue structure, innervation and function remains poorly characterized. In control and streptozotocin-treated female rats, we investigated the effects of diabetes on vaginal blood flow, tissue morphology, and expression of arginase I, endothelial nitric oxide synthase (eNOS) and cGMP-dependent protein kinase (PKG), key enzymes that regulate smooth muscle relaxation. We further related these changes with estrogen receptor alpha (ERα) and androgen receptor (AR) expression. RESULTS. In addition to significantly elevated blood glucose levels, diabetic rats had decreased mean body weight, lower levels of plasma estradiol, and higher plasma testosterone concentration, compared to age-matched controls. Eight weeks after administration of buffer (control) or 65 mg/kg of streptozotocin (diabetic), the vaginal blood flow response to pelvic nerve stimulation was significantly reduced in diabetic rats. Histological examination of vaginal tissue from diabetic animals showed reduced epithelial thickness and atrophy of the muscularis layer. Diabetic animals also had reduced vaginal levels of eNOS and arginase I, but elevated levels of PKG, as assessed by Western blot analyses. These alterations were accompanied by a reduction in both ERα and AR in nuclear extracts of vaginal tissue from diabetic animals. CONCLUSION. In ovariectomized (estrogen deficient) animals, previous reports from our lab and others have documented changes in blood flow, tissue structure, ERα, arginase I and eNOS that parallel those observed in diabetic rats. We hypothesize that diabetes may lead to multiple disruptions in sex steroid hormone synthesis, metabolism and action. These pathological events may cause dramatic changes in tissue structure and key enzymes that regulate cell growth and smooth muscle contractility, ultimately affecting the genital response during sexual arousal.Item Previously Unidentified Changes in Renal Cell Carcinoma Gene Expression Identified by Parametric Analysis of Microarray Data(BioMed Central, 2003-11-27) Lenburg, Marc E.; Liou, Louis S.; Gerry, Norman P.; Frampton, Garrett M.; Cohen, Herbert T.; Christman, Michael F.BACKGROUND. Renal cell carcinoma is a common malignancy that often presents as a metastatic-disease for which there are no effective treatments. To gain insights into the mechanism of renal cell carcinogenesis, a number of genome-wide expression profiling studies have been performed. Surprisingly, there is very poor agreement among these studies as to which genes are differentially regulated. To better understand this lack of agreement we profiled renal cell tumor gene expression using genome-wide microarrays (45,000 probe sets) and compare our analysis to previous microarray studies. METHODS. We hybridized total RNA isolated from renal cell tumors and adjacent normal tissue to Affymetrix U133A and U133B arrays. We removed samples with technical defects and removed probesets that failed to exhibit sequence-specific hybridization in any of the samples. We detected differential gene expression in the resulting dataset with parametric methods and identified keywords that are overrepresented in the differentially expressed genes with the Fisher-exact test. RESULTS. We identify 1,234 genes that are more than three-fold changed in renal tumors by t-test, 800 of which have not been previously reported to be altered in renal cell tumors. Of the only 37 genes that have been identified as being differentially expressed in three or more of five previous microarray studies of renal tumor gene expression, our analysis finds 33 of these genes (89%). A key to the sensitivity and power of our analysis is filtering out defective samples and genes that are not reliably detected. CONCLUSIONS. The widespread use of sample-wise voting schemes for detecting differential expression that do not control for false positives likely account for the poor overlap among previous studies. Among the many genes we identified using parametric methods that were not previously reported as being differentially expressed in renal cell tumors are several oncogenes and tumor suppressor genes that likely play important roles in renal cell carcinogenesis. This highlights the need for rigorous statistical approaches in microarray studies.