The Bladder Tissue Core (Core B) will be used by all three projects in the Urology Research Center.
The aim of the Bladder Tissue Core is to provide the program investigators with smooth muscle tissues from normal, obstructed and reversed rabbit bladders which have been characterized physiologically. It will also provide specimens from adult patients, with well-characterized symptoms of outlet obstruction, who are treated at the University of Pennsylvania Medical Center. In addition, protein extracts and RNA will be prepared from human and rabbit samples and distributed to various investigators for analyses. The Core will perform sham operations and surgery to produce partial outlet obstruction in rabbits, provide care for the animals postoperatively, obtain biopsies from bladders to monitor the degree of bladder smooth muscle hypertrophy and functional compensation, perform reversal surgery, sacrifice animals at appropriate time points, perform basic physiological characterization of the contractility of the bladder tissue, and distribute to the bladder tissues to the participating investigators. Physiological experiments will be performed with muscle strips to determine the ability of smooth muscle samples to produce force and with whole bladders to assess bladder emptying, since this property cannot be ascertained from isometric studies alone. Tissue samples will be either used immediately or frozen in liquid nitrogen for biochemical analysis or treatment with OCT for frozen sectioning for histology and immunohistochemistry and stored at -80 degrees Celsius for future use. All available information regarding the tissues at the time of distribution, or gathered subsequently from various projects in the Urology Research Center, will be logged onto a computer and made available to the investigators in the Center. Human detrusor smooth muscle tissues will be obtained from patients whose voiding dysfunction is clearly delineated based on urodynamic work-up and will be subdivided into those patients with low versus high post-void residual urine valves. Controls will be obtained from surgical specimens from non-cancerous regions of human bladder and from bladders of patient that have prostate cancers that did not produce an obstruction. Small muscle strips from human bladder tissue samples will be used for physiological studies to assess both the isometric force generating abilities as well as velocity of shortening. Additional human tissue will be frozen to allow for isolation of protein and RNA for correlation with physiologic studies. In studying a small number of well defined human bladder smooth muscle specimens, this core will help provide a crucial link between basic research findings and the clinical condition.
|Hypolite, Joseph A; Chang, Shaohua; Wein, Alan J et al. (2015) Protein kinase C modulates frequency of micturition and non-voiding contractions in the urinary bladder via neuronal and myogenic mechanisms. BMC Urol 15:34|
|Long, C J; Butler, S; Fesi, J et al. (2014) Genetic or pharmacologic disruption of the calcineurin-nuclear factor of activated T-cells axis prevents social stress-induced voiding dysfunction in a murine model. J Pediatr Urol 10:598-604|
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|Deng, Maoxian; Boopathi, Ettickan; Hypolite, Joseph A et al. (2013) Amino acid mutations in the caldesmon COOH-terminal functional domain increase force generation in bladder smooth muscle. Am J Physiol Renal Physiol 305:F1455-65|
|Eto, Masumi; Kirkbride, Jason A; Chugh, Rishika et al. (2013) Nuclear localization of CPI-17, a protein phosphatase-1 inhibitor protein, affects histone H3 phosphorylation and corresponds to proliferation of cancer and smooth muscle cells. Biochem Biophys Res Commun 434:137-42|
|Hypolite, Joseph A; Lei, Qi; Chang, Shaohua et al. (2013) Spontaneous and evoked contractions are regulated by PKC-mediated signaling in detrusor smooth muscle: involvement of BK channels. Am J Physiol Renal Physiol 304:F451-62|
|Boopathi, Ettickan; Hypolite, Joseph A; Zderic, Stephen A et al. (2013) GATA-6 and NF-ýýB activate CPI-17 gene transcription and regulate Ca2+ sensitization of smooth muscle contraction. Mol Cell Biol 33:1085-102|
|Basha, Maureen E; Chang, Shaohua; Burrows, Lara J et al. (2013) Effect of estrogen on molecular and functional characteristics of the rodent vaginal muscularis. J Sex Med 10:1219-30|
|Wei, Wenjie; Howard, Pamela S; Macarak, Edward J (2013) Recombinant insulin-like growth factor-1 activates satellite cells in the mouse urethral rhabdosphincter. BMC Urol 13:62|
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