Carbachol-induced signaling through Thr696-phosphorylation of myosin phosphatase-targeting subunit 1 (MYPT1) in rat bladder smooth muscle cells.

Purpose: Lines of evidence suggest that Rho-associated protein kinase (ROCK)-mediated myosin phosphatase-targeting subunit 1 (MYPT1) phosphorylation plays a central role in smooth muscle contraction. However, the physiological significance of MYPT1 phosphorylation at Thr696 catalyzed by ROCK in bladder smooth muscle remains controversial. We attempt to directly observe the quantitative protein expression of Rho A/ROCK and phosphorylation of MYPT1 at Thr696 after carbachol administration in rat bladder smooth muscle cells (RBMSCs).

Urothelium-derived Sonic hedgehog promotes mesenchymal proliferation and induces bladder smooth muscle differentiation.

Induction of smooth muscle differentiation from bladder mesenchyme depends on signals that originate from the urothelium. We hypothesize Sonic hedgehog (Shh) is the urothelial signal that promotes bladder mesenchymal proliferation and induces bladder smooth muscle differentiation. Pregnant FVB mice were euthanized on embryonic day (E) 12.

Signalling molecules involved in mouse bladder smooth muscle cellular differentiation.

Mouse bladder mesenchyme differentiates into smooth muscle under the influence of urothelium at gestational day 13.5 (E13.5).

Estrogen effects on fetal penile and urethral development in organotypic mouse genital tubercle culture.

Purpose: We developed an organotypic genital tubercle culture system in vitro and used it to investigate the direct effects of the hyperestrogenic state on fetal mouse penile and urethral development.

Materials And Methods: Genital tubercles were dissected from embryonic day 14.5 C57B/L6 male mouse fetuses and cultured using an air-liquid interface on a microporous membrane support soaked in synthetic medium.

Differential expression of microRNAs in mouse embryonic bladder.

MicroRNAs (miRNAs) are involved in several biological processes including development, differentiation and proliferation. Analysis of miRNA expression patterns in the process of embryogenesis may have substantial value in determining the mechanism of embryonic bladder development as well as for eventual therapeutic intervention. The miRNA expression profiles are distinct among the cellular types and embryonic stages as demonstrated by microarray technology and validated by quantitative real-time RT-PCR approach.

Genomic variants of ATF3 in patients with hypospadias.

Purpose: ATF3, an estrogen responsive gene expressed during genital development, could be implicated in the etiology of hypospadias. ATF3 is up-regulated in the foreskin of patients with hypospadias and is implicated in suppression of the cell cycle, which may interfere with urethral cell growth. We sought to investigate the sequence of ATF3 in patients with hypospadias.

3-dimensional neuroanatomy of the human fetal pelvis: anatomical support for partial urogenital mobilization in the treatment of urogenital sinus.

Purpose: Retrospective reviews suggest that the functional outcomes of surgery of the urogenital sinus have often been unsatisfactory and to our knowledge the long-term results of newer surgical techniques have yet to be evaluated. A precise understanding of pelvic fetal neuroanatomy is germane for optimizing surgical correction of the urogenital sinus.

Materials And Methods: The pelves of 10 human female fetuses were serially sectioned.

Mutations of CXorf6 are associated with a range of severities of hypospadias.

Objective: Mutations in chromosome X open reading frame 6 (CXorf6), a recently described candidate gene involved in the development of male genitalia, have been found in patients with complex 46,XY disorders of sexual development (46,XY DSD) including micropenis, bifid scrotum, and penoscrotal hypospadias. The objective of this work was to identify genomic variants of CXorf6 in patients with isolated hypospadias, severe or non-severe.

Design And Methods: Forty-one patients with glandular to perineal hypospadias and thirty controls were studied.

Urothelium patterns bladder smooth muscle location.

Smooth muscle differentiation is induced in the embryonic bladder by the centrally located urothelium in the undifferentiated mesenchyme in the periphery adjacent to the serosa. We hypothesize that under the appropriate signal the entire undifferentiated bladder mesenchyme is capable of smooth muscle differentiation and that the urothelium patterns fibromuscular development. Embryonic bladders of wild-type and Green Fluorescent Protein mice were separated into urothelial and mesenchymal components before smooth muscle differentiation (E12.

Penile and scrotal Paget's disease: 130 Chinese patients with long-term follow-up.

Objectives: To report a retrospective series of 130 Chinese patients with penoscrotal extramammary Paget's diseases (EMPD), with a long-term follow-up, and thus improve the diagnosis and therapy of this disease.

Patients And Methods: The history, clinical presentation, pathology, treatment, and prognosis of 130 patients were analysed. All cases were confirmed by skin biopsy, and then the patients had local wide resection to remove the involved skin and subcutaneous tissue.

Estradiol upregulates activating transcription factor 3, a candidate gene in the etiology of hypospadias.

Hypospadias is a penile developmental abnormality that may partly result from in utero exposure to estrogenic compounds. Expression of activating transcription factor 3 (ATF3) is elevated in human foreskin tissue from hypospadic patients, and in utero exposure to ethinyl estradiol (17-EE) causes ATF3 upregulation in a hypospadias mouse model. We investigated the effects of in vitro exposure to EE on ATF3 expression and promoter activity in human foreskin fibroblasts using immunocytochemistry, quantitative polymerase chain reaction (PCR), western blot, and the luciferase activity assay.

In utero exposure to benzophenone-2 causes hypospadias through an estrogen receptor dependent mechanism.

Purpose: Additives such as benzophenone-2 are commonly used in cosmetic products and food container plastics to filter out ultraviolet light. In pregnant women exposure may result in transplacental transfer of benzophenone-2 to fetuses. Benzophenone-2 is estrogenic in vitro and in the rat uterotropic assay.

Urothelial sonic hedgehog signaling plays an important role in bladder smooth muscle formation.

During bladder development, primitive mesenchyme differentiates into smooth muscle (SM) under the influence of urothelium. The gene(s) responsible for this process have not been elucidated. We propose that the Sonic hedgehog (Shh) signaling pathway is critical in bladder SM formation.

Ontogeny of androgen receptor and disruption of its mRNA expression by exogenous estrogens during morphogenesis of the genital tubercle.

Purpose: The ontogeny of androgen receptor expression in male and female mouse genital tubercles, and the effects of in utero ethinyl estradiol exposure on androgen receptor mRNA expression in the hypospadias model were studied.

Materials And Methods: Androgen receptor mRNA expression was measured in mouse genital tubercles from fetuses and pups collected on gestational days 12, 14, 16 and 18, and from newborns using immunohistochemistry and real-time quantitative polymerase chain reaction. Pregnant dams were exposed to ethinyl estradiol or corn oil as controls from gestational days 12 to 17.

Activating transcription factor 3 is estrogen-responsive in utero and upregulated during sexual differentiation.

Background/aims: Synthetic estrogens induce hypospadias, an anomaly of genital tubercle/urethral development. Activating transcription factor 3 (ATF3), which is estrogen-responsive in vitro, is upregulated in hypospadiac human tissue. We used a mouse model of steroid-dependent genital tubercle development to elucidate the ontogeny of ATF3 expression and the developmental response of ATF3 in vivo to estrogen exposure.

Randomized study of single instillation of epirubicin for superficial bladder carcinoma: long-term clinical outcomes.

Purpose: Intravesical instillation of epirubicin (EPI) is one of the most effective adjuvant therapies for nonmuscle-invasive bladder cancer postoperation. We evaluated the long-term efficacy of single dose intravesical epirubicin for superficial bladder carcinoma recurrence.

Methods: Between June 1997 and May 1998, a total of 47 patients with resectable superficial bladder carcinoma (Ta-1, Grade 1-2), primary or recurrent with no recurrence during last one year, were enrolled in this study.

Activating transcription factor 3 is up-regulated in patients with hypospadias.

Hypospadias is a congenital anomaly of the genitalia characterized by abnormalities of the urethra and foreskin, with the urethral meatus located in an abnormal position anywhere from the distal ventral penile shaft to the perineum. Because the incidence of hypospadias is approximately 1/200-1/300 live male births, it is one of the most common congenital malformations, but its etiology is largely uncharacterized. Genomic analysis of hypospadic tissue indicated a potential role for activating transcription factor 3 (ATF3) in the development of this anomaly.

Identification of potential biomarkers of Peyronie's disease.

Aim: To identify proteins that are differentially expressed in cells derived from normal and diseased tunica albuginea (TA) as related to Peyronie's disease (PD).

Methods: Cells with characteristics of fibroblasts were isolated from two tissue sources. Those from the plaque of patients with PD were designated as PT cells, and those from the normally-appearing TA of the same patients were designated as NT cells.

[Single instillation of epirubicin for the prophylaxis of recurrent primary superficial bladder carcinoma].

Objective: To determine the feasibility of single dose intravesical epirubicin in the prevention of recurrent superficial bladder carcinoma.

Methods: We compared the effect of intravesical epirubicin or mitomycin C on tumor recurrence and disease free interval and their side effects after treatment of superficial bladder tumor. 47 postoperative patients with stages Ta to T1 primary superficial bladder carcinoma of grades 1 or 2 were randomized into groups A: single 80 mg epirubicin; B: 40 mg consecutive epirubicin; C: 40 mg consecutive mitomycin C.