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OBJECTIVE To evaluate the efficacy and safety of onabotulinumtoxinA (botulinum toxin type A) 100 U in patients with overactive bladder and urinary incontinence. METHODS This was a phase III, randomized, double-blind, placebo-controlled trial in Japanese patients who were inadequately managed with overactive bladder medications (anticholinergics and/or β3 -adrenergic receptor agonists). Eligible patients were randomized 1:1 to receive a single dose of either onabotulinumtoxinA or placebo into the detrusor muscle (n = 124 each). The primary end-point was the change in the number of daily urinary incontinence episodes at week 12 from baseline. Secondary end-points included volume voided per micturition, other symptomatic measures (urinary urgency incontinence, micturition, urgency and nocturia) and patient-reported outcomes. RESULTS In the onabotulinumtoxinA group, there was a significantly greater decrease from baseline in the mean number of daily urinary incontinence episodes compared with the placebo group (2.16; P

Androgen deprivation therapy is a standard of care for metastatic prostate cancer, however, eventually, all men relapse. A paradoxical approach utilizing high doses of testosterone in castration-resistant prostate cancer patients demonstrated clinical responses. Here we report on four heavily pretreated CRPC patients successfully treated with supra-physiological doses of testosterone.

Introduction Two percent of testicular germ cell tumors occur in family clusters. Here, we report metachronous testicular germ cell tumors in two brothers. Case presentation An elder brother was diagnosed at the age of 30 years old and the pathological diagnosis was mixed testicular germ cell tumor. A tumor in the younger brother was suspected during testicular self-examination. It was confirmed by ultrasound examination at the age of 30 years old, 3 years and 6 months after the diagnosis of the testicular tumor in elder brother. The pathological diagnosis was pure seminoma. Both brothers had stage 1 testicular germ cell tumors and no recurrence was observed during the follow-up period of 4 years and 4 months and 10 months, respectively. Conclusion Various histological types of tumor can occur in members of one family. Besides genetic predisposition, shared diet, environmental exposure and other factors can contribute to the familial testicular cancer. Testicular self-examination is recommended for family members of a person with testicular germ cell tumor.

Molecular-targeted therapy was recommended for the systemic therapy of renal cell cancer (RCC) in the RCC guidelines, but these guidelines do not address the order of administration of the multiple presently available agents. There are several aspects that remain unknown regarding the optimal administration order and combination of molecular-targeted drugs. Until the optimal treatment sequence is determined by clinical trials, treatment individualization is required for each patient based on patient and disease characteristics. We herein investigate 12 cases of RCC patients who received axitinib. Axitinib was used as the first-line drug in 4 cases, second-line in 5 cases, third-line in 1 case and as a fourth-line drug in 2 cases. Partial response (PR) was observed in 4 cases (30%) and stable disease in 4 cases (30%) during axitinib treatment, with an overall response rate of 60%. The duration of PR ranged from 6 to 19 months. Based on our cases, axitinib exhibited reasonable therapeutic efficacy as first- as well as second-line treatment. However, more cases are required to draw firm conclusions.

In recent years, abiraterone acetate (AA) and enzalutamide (EZL) have become available for the treatment of cancer. Prior clinical trials have demonstrated the benefits of these agents in males with castration-resistant prostate cancer (CRPC). The optimal sequencing of available therapies in the context of efficacy and known cross-resistance remains uncertain. Based on the mechanisms of action and accessible clinical data, AA and EZL may be indicated for the early stages of prostate cancer. Until clinical trials are conducted to determine the best treatment sequence, individualized therapy is required for each patient based on the clinicopathological characteristics. In the present study, 46 sequential patients (median age: 77, range 59-89; median serum PSA level: 56 ng/ml, range 1.5-3,211) with CRPC treated with EZL (160 mg/day) were retrospectively analyzed between June 2014 and July 2015 at the following institutions: Yamagata Prefectural Central Hospital (Yamagata, Japan); Yamagata Tokushukai Hospital (Yamagata, Japan); Ishinomaki Red Cross Hospital (Ishinomaki, Japan); Kan-etsu Hospital (Tsurugashima, Japan); Niigata Cancer Center Hospital (Niigata, Japan); Sakado Central Hospital (Sakado, Japan). A total of 18 patients were pre-treated with Docetaxel (DOC) and 28 patients were DOC-naïve. Once EZL therapy was initiated, increases in prostate specific antigen (PSA) levels were observed in 3/18 patients (17%) pre-treated with DOC and in 6/20 (30%) who were DOC-naïve. In total, 8/28 DOC-naïve patients were treated with AA without EZL. An increase in the PSA level was observed in only 1/8 (12%) cases following AA treatment in the DOC-naïve group. It was demonstrated that AA had a better efficacy in DOC-naïve patients. The efficacy of EZL was limited in AA-pre-treated patients following DOC administration.

The presence or absence of metastasis has critical implications for therapeutic decision-making in urothelial cancer (UC). Conventional magnetic resonance imaging (MRI) utilizing anatomic T1- and T2-weighted images has modest efficacy in detecting lymph node and distant metastases in UC. However, incorporation of functional techniques including diffusion weighted imaging and dynamic contrast-enhanced imaging, may improve the accuracy of lesion detection and staging. Multiparametric (mp)MRI is widely used in the imaging of prostate and breast cancers, though its usefulness in UC has yet to be fully elucidated. The present study reports on mpMRI in the context of two cases of bladder and ureteral cancer, and imaging results with pathological diagnosis.

We report a case of primary undifferentiated bladder carcinoma, which revealed a remarkable response to methotrexate, vinblastine, adriamycin, and cisplatin (MVAC) therapy. A 46-year-old Japanese woman presented at the hospital with the chief complaints of gross hematuria and pain during urination. Cystoscopy revealed a large smooth-surfaced tumor in the urinary bladder. The histopathological diagnosis was undifferentiated carcinoma. The patient then received 3 courses of MVAC over a 3-month period. Hydronephrosis disappeared after the first course, and the tumor shrank rapidly. After completion of the third MVAC course, radical cystectomy and ileal conduit surgery were performed. After 7 years, the patient has still had no recurrences or metastases. We retrospectively review the relative efficacy of the two popular chemotherapeutic regimens in the management of muscle-invasive bladder cancer in patients who had had radical cystectomy.

Several clinically approved recombinant erythropoietin (rEPO) preparations, such as epoetin-β, epoetin-δ and the epoetin-α derivative, darbepoetin-α, have been commercially produced. Since the expiration of patent protection, a number of novel rEPO biosimilars have been approved on the world market. In 2010, epoetin-κ, which is biosimilar to epoetin-α, was clinically approved. Epoetin-κ is a biopharmaceutical product that is based on serum-free media following master cell bank preparation. The present study analyzes the results obtained during a six-month observation period, in which the administration of epoetin-β was switched to that of epoetin-κ. In a cohort of patients receiving chronic dialysis, who were clinically in a state of relative calm and were in control of their renal anemia, it was possible to sustain good control of the anemia by reducing the frequency of the epoetin-β administration from the conventional and empirically determined three times a week to twice a week, and further to once a week. Furthermore, the good control was maintained upon changing from the administration of epoetin-β to that of epoetin-κ. Moreover, three months subsequent to this switch, the degree of instability observed among the patients had decreased. Despite the fact that the situation following the changeover requires further investigation, it may be concluded that the results obtained in this study are indicative of the clinical equivalence and efficacy of epoetin-κ.

Summary: Hormonal and ultrastructural examinations of the testis were performed in an XX-male. Plasma levels of testosterone and prolactin were within the normal range, but FSH and LH were higher than the normal range. The response of testosterone to the administration of HCG is within the normal range. In the interstitium marked hyperplasia of Leydig cells was observed. The presence of paracrystalline inclusions and the absence of Reinke's crystals were representative changes in Leydig cells. Seminiferous tubules were filled with Sertoli cells and spermatogenesis was completely abolished. Intermediate filaments were abundant and annulate lamellae were absent in Sertoli cells. Zusammenfassung: Bei einem XX-Mann wurden Hormonanalysen und eine Ultrastruk-tur-Untersuchung des Hodengewebes durchgefuhrt. Wahrend die Testosteron- und Prolak-tin-Werte normal ausfielen, lagen die Werte fur FSH und LH im erhohten Bereich. Nach HCG-Stimulierung ergab sich eine normale Testosteronreaktion. Histologisch lag eine deut-liche Leydig-Zell-Hyperplasie vor. Der Nachweis parakristalliner Einschlusse und das Feh-len von Reinke-Kristallen waren reprasentative Veranderungen in den Leydig-Zellen. Die Tubuli seminiferi waren mit Sertolizellen angefullt und die Spermatogenese fehlte voll-standig. Intermediare Filamente waren reichlich vorhanden und geringelte Lamellen fehl-ten in den Sertolizellen.

Background We have recently suggested that homozygosity for a specific 'AGATA' haplotype within a approximately 50 kb linkage disequilibrium (LD) block of the gene for estrogen receptor alpha (ESR1) may raise the susceptibility to cryptorchidism by enhancing estrogenic effects of environmental endocrine disruptors (EEDs). Methods Haplotype analysis of ESR1 was performed in 328 Japanese subjects, i.e. 70 patients with micropenis (MP), 43 patients with hypospadias (HS), 80 patients with spermatogenic failure (SF) and 135 control males. Genotyping was performed by the 5' nuclease assay. Results The LD block was identified in each of the patient groups and in the control males. The frequency of homozygotes for the specific 'AGATA' haplotype was markedly higher in the HS patients [P = 0.0000033, odds ratio [OR] = 11.26] and slightly higher in the MP patients (P = 0.034, OR = 3.64) than in the control males, and the 'AGATA' haplotype was strongly associated with HS (P = 0.0000022, OR = 11.26) and weakly associated with MP (P = 0.040, OR = 3.64) in a recessive mode. There was no significant difference between the SF patients and the control males. Conclusions Our results support the hypothesis that homozygosity for the specific ESR1 'AGATA' haplotype may increase the susceptibility to the development of male genital abnormalities in response to estrogenic EEDs.

Standard lymphadenectomy for prostate cancer is limited to the obturator lymph nodes (LNs), although the internal and external iliac LNs represent the primary landing zone for prostatic lymphatic drainage. We performed anatomically semi-extended pelvic lymph node dissection (PLND) to assess the incidence of LN metastasis in cases of clinically localized prostate cancer. A total of 730 consecutive patients underwent radical prostatectomy with either semi-extended PLND, comprising 6 selective fields, namely the external iliac, internal iliac and obturator LNs bilaterally, or standard LND (obturator LNs alone). A total of 131 patients undergoing semi-extended PLND were compared with 599 patients undergoing standard LND. The patients were stratified into high-risk [prostate-specific antigen (PSA)>20 ng/ml, Gleason score (GS)≥8], intermediate-risk (PSA 10-20 ng/ml, GS=4+3) and low-risk (PSA

Background/Aims: Although insulin-like factor 3 (INSL3) and its receptor leucine-rich repeat-containing G protein-coupled receptor 8/G protein-coupled receptor affecting testis descent (LGR8/GREAT) are essential for the gubernacular development, mutations of INSL3 and LGR8/GREAT are infrequent in patients with cryptorchidism (CO), and there is no report documenting a positive association of CO with a polymorphism in INSL3 or LGR8/GREAT. Here, we further examined the relevance of INSL3 and LGR8/GREAT mutations and polymorphisms to the development of CO. Methods: Sixty-two Japanese CO patients and 60 fertile males were studied. INSL3 was analyzed by direct sequencing and restriction enzyme digestion, and LGR8/GREAT was examined by denaturing high-performance liquid chromatography followed by direct sequencing for exons with abnormal chromatogram patterns. Results: No definitive mutation was identified in both genes. Six polymorphisms were detected in INSL3 or LGR8/GREAT and Thr/Thr genotype of Ala60Thr polymorphism in INSL3 was strongly associated with CO (p = 0.0024, odds ratio = 5.3, 95% confidence interval = 1.7–17). Conclusion: The results, in conjunction with the previous data, suggest that mutations of INSL3 and LGR8/GREAT remain rare, and that the Thr/Thr genotype of Ala60Thr polymorphism in INSL3 may constitute a susceptibility factor for the development of CO.

Genotyping analysis was performed for Gly146Ala polymorphism in the gene for steroidogenic factor-1 (SF-1), which is known to reduce the transactivation function by approximately 20%, in 72 cryptorchid patients and 136 control males, revealing that the Ala allele, the Ala/Gly genotype, and the Ala/Ala plus Ala/Gly genotype frequencies were significantly higher in the patients than in the control males. The results suggest that the Gly146Ala polymorphism may be a susceptibility factor for the development of cryptorchidism (CO).

Context: The prevalence of cryptorchidism (CO) has increased during the past few decades in several countries, and this event has primarily been ascribed to the estrogenic effects of environmental endocrine disruptors (EEDs). Little is known, however, about the role of genetic susceptibility to EEDs in this phenomenon.Objective: The objective of this study was to determine whether CO is associated with a specific haplotype of the gene for estrogen receptor α (ESR1) that mediates the estrogenic effects of EEDs.Design: This was a case-control study.Setting: The study was performed at the National Research Institute and University Hospitals.Subjects: Sixty-three cryptorchid males, aged 1–13 yr, and 47 control males, aged 4–12 yr, were studied.Intervention: After genotyping 15 single nucleotide polymorphisms widely distributed in the greater than 300-kb genomic sequences of ESR1, haplotype analysis was performed.Main Outcome Measure: Identification of a specific ESR1 haplotype associated with CO was the main outcome measure.Results: A haplotype block was identified for an approximately 50-kb region encompassing single nucleotide polymorphisms 10–14 in the 3′ region of ESR1 in both groups. The frequency of the estimated AGATA haplotype within the block was higher in the patients than in the control males (34.0% vs. 21.3%; P = 0.037), and the association of this haplotype with CO phenotype was significant in a recessive mode (P = 0.0060). The homozygosity for this haplotype was identified only in the patients, and the frequency of the homozygotes was significantly different between the two groups (10 of 63 vs. zero of 47; P = 0.0042).Conclusions: The association of CO with homozygosity for the specific ESR1 haplotype suggests the relevance of genetic susceptibility to EEDs in the development of CO.

Spermatogenic cells are susceptible to heat stress and undergo apoptosis. Although a variety of factors appear to be involved in the apoptotic process, the nature of the intracellular signaling pathway is ambiguous. To clarify the process, we chose a simple model in which testes of mice were exposed to mild heating by immersion in hot water at 42 degrees C for 15 min. In situ DNA fragmentation was detected by a TUNEL method. The release of cytochrome c into the cytoplasm was observed by Western blotting both in heat-treated testis and in isolated spermatogenic cells that had been incubated at 42 degrees C for 1h, but not in Sertoli cells. Minocycline, a semisynthetic tetracycline, is known to reach the brain by permeating the blood-brain barrier and suppresses apoptosis in neuronal cells. Since the testis also has a similar barrier, minocycline was examined as a possible agent to inhibit heat stress-induced apoptosis. The results indicate that minocycline suppressed the release of cytochrome c from mitochondria both in vivo and in vitro and significantly decreased the number of TUNEL-positive cells. These findings suggest that heat stress of testes triggers the release of cytochrome c from mitochondria in spermatogenic cells, leading to the activation of an apoptotic pathway.

Objectives: We evaluated posterior retroperitoneoscopic partial adrenalectomy with regard to operative complications, operation time, intraoperative blood loss. Patients and Methods: Between January 1997 and April 2002, we performed 47 posterior retroperitoneoscopic partial adrenalectomies. There were 18 males and 29 females with a mean age of 48 years (range 28–82 years). The average adrenal tumor size was 26 mm (range 10–50 mm). All procedures required three trocars. Results: There was no mortality and conversion rate to open surgery was 2.1%. Average operative time and average blood loss was 198.0 ml (range 71–420 ml) and 40.8 ml (range 0–1100 ml), respectively. There was a significant correlation of operative time with the number of procedures performed. However, no significant correlation was observed between intraoperative blood loss and the number of procedures. Tumor size did not correlate with intraoperative blood loss and operative time. No significant correlation was found between body mass index and operative time. The operative time in the initial 20 cases was significantly longer than that in the subsequent 26 cases. Conclusion: Posterior retroperitoneoscopic partial adrenalectomy is a safe and less invasive method for treatment of adrenal tumors. With improved operative technique, the time required for this procedure has been decreased.

Translation of a number of mRNAs is under strict regulation via RNA-binding proteins in the spermatogenic cells of testes. A family of Y-box binding proteins represents promising candidates for these presently uncharacterized RNA-binding proteins. The effects of heat stress on the expression of a Y-box binding protein, YB2/RYB-a, and mouse protamine 2 (mP2) were investigated in cultured spermatogenic cells and mouse testes by immunoblot and Northern blot analyses. Localization and alterations in the expression of the YB2/RYB-a protein and the mP2 mRNA in heat-stressed testes were examined by immunohistochemistry and in situ hybridization, respectively. Levels of the YB2/RYB-a protein in spermatogenic cells decreased rapidly as the result of exposure to higher temperature, 378 Co r 438C, compared with the scrotal temperature, 32.58C, under the culture conditions used. In experimental cryptorchidism, levels of the YB2/RYB-a protein were decreased after Day 10, while the mRNA levels were affected only slightly. The levels of the mP2 mRNA were also decreased and about comparable with those of the YB2/RYB-a protein. Exposure of the lower abdomen to a high temperature, 438C for 15 min, also damaged the testis and led to a decrease in YB2/RYB-a protein and the mP2 mRNA levels in a coordinated manner. Because YB2/RYB-a is proposed to function as a stabilizer of mP2 mRNA, the perturbation of YB2/RYB-a by heat stress could account for the decline of the mP2 mRNA in elongated spermatids. gene regulation, spermatid, spermatogenesis, stress

The laparoscopic Palomo varicocelectomy were performed in 38 males with left-sided varicocele. The mean operation time was 37 (25-56) min. There were no intra-abdominal visceral or vascular complications during operation. Neither testicular atrophy nor recurrence was observed postoperatively. However, hydrocele formation was found in two (5.3%) patients. These findings suggest that laparoscopic Palomo varicocelectony is a safe and effective procedure for patients with varicocele.

Objective: To evaluate the occurrence of mutations of 5α-reductase type 2 gene in patients with cryptorchidism or idiopathic azoospermia. Design: Controlled clinical study. Setting: Yamagata University Hospital, Yamagata and Tokyo Electric Power Company Hospital, Tokyo, Japan. Patient(s): Patients with isolated cryptorchidism (n = 48) or idiopathic azoospermia (n = 33) and a control group of males with proven fertility (n = 51). Intervention(s): Collection and analysis of blood, leukocytic DNA, semen, and testicular biopsy. Main Outcome Measure(s): Semen analysis, screening of the 5α-reductase type 2 gene within exon 1 using direct sequencing and exons 2–5 using single strand conformational polymorphism analysis. Result(s): No mutations were detected in isolated cryptorchid men, idiopathic azoospermic men, or controls within the 5 exons of the 5α-reductase type 2 gene. Conclusion(s): 5α-Reductase type 2 gene abnormalities do not constitute a major factor in the development of cryptorchidism or idiopathic azoospermia.

Background and Purpose: Laparoscopic partial nephrectomy remains surgically challenging because of the potential for excessive blood loss, infection, and the development of urinary fistulas. In addition, posterior retroperitoneoscopic partial nephrectomy is not popular because of the limited space for surgical manipulation. We evaluated the usefulness of a microwave tissue coagulator in posterior retroperitoneoscopic partial nephrectomy for small posterior renal tumor. Patients and Methods: Posterior retroperitoneoscopic partial nephrectomy was performed without renal pedicle clamping using a microwave tissue coagulator in six patients with small posterior renal tumors. Results: The mean operative time was 136 minutes (range 78-180 minutes), and the blood loss was

Objective: To investigate molecular mechanisms of germ cell apoptosis induced by heat exposure in mice. Design: Controlled laboratory study. Setting: Departments of Urology and Biochemistry, Yamagata University School of Medicine, Yamagata, Japan. Animal(s): Forty-four male B6D2F1 mice. Intervention(s): Heat exposure, 43°C for 15 minutes. Main Outcome Measure(s): Testicular germ cell apoptosis (percentages of apoptotic tubules and apoptotic cells) was assessed by using DNA nick-end labeling, and expression of Bcl-2 family, Fas-FasL system, and p53 was evaluated by using Western analysis. Result(s): Bilateral testicular weights decreased significantly from 3 days after heat exposure. Percentages of apoptotic tubules and apoptotic germ cells increased significantly from 1 day after heat exposure. There were no significant changes in the levels of Bcl-xl, Bad, and Bax after heat exposure. However, Bcl-2 expression level decreased significantly 7 days after heat exposure. In contrast, the expression level of Fas and p53 increased significantly from 1 day to 3 days after heat exposure, respectively. Expression level of FasL elevated significantly at days 1 and 2 but declined from day 3. Conlusion(s): Germ cell apoptosis induced by heat exposure is mainly mediated by the Fas-FasL system.

Unilateral or bilateral cryptorchidism is found in 80-100% of male patients with Prader-Willi syndrome (PWS). Recently, the relationship between Yq deletions and cryptorchidism has been assessed. However, the relationship between Yq deletions and PWS patients with cryptorchidism remains unclear. Polymerase chain reaction (PCR) amplification of 51 DNA loci encompassing all of the regions for azoospermia factor (AZF) of the Y chromosome, including the deleted in azoospermia (DAZ) and ribonucleic acid-binding motif (RBM) genes, were examined for microdeletions in 10 PWS males with cryptorchidism and 20 healthy control male subjects. No microdeletions of 51 loci were found in any of the PWS males. The present study therefore suggests that microdeletions in the AZF regions of the Y chromosome do not relate to the occurrence of cryptorchidism in PWS patients.

Male sexual differentiation, testicular descent, and spermatogenesis require androgens. Their action is mediated through the androgen receptor (AR), which binds to the androgen responsive element on DNA and regulates gene transcription. No mutations in any of the AR gene exons 1-8 are detected in males with isolated cryptorchidism, hypospadias, micropenis, or idiopathic male infertility. In addition, the CAG repeat length in exon 1 of the AR gene does not expand in males with isolated cryptorchidism, hypospadias, micropenis, or idiopathic male infertility. These facts indicate that an alteration of the AR gene is rare in these males. However, further studies will permit a better clarification on the relevance of the AR gene abnormalities to the development of isolated cryptorchidism, hypospadias, micropenis, or impaired spermatogenesis.

Background Liposarcoma is one of the most common soft tissue sarcomas found in adults. It has a predilection for retroperitoneal space. Renal cell carcinoma is the most common tumor of the kidney. Case presentation Concurrent retroperitoneal liposarcoma and renal cell carcinoma were found in a 34-year-old Japanese man. The renal tumor was first detected by ultrasonography, it was confirmed by computed tomography, which also identified a presumptive retroperitoneal liposarcoma, and the tumors were further assessed with magnetic resonance imaging. The patient was treated by surgical resection of retroperitoneal liposarcoma and left nephrectomy and has been disease-free for 10 years. Conclusions The concomitant occurrence of a renal tumor and a primary primary liposarcoma is rare. The major factors promoting a good prognosis in this case were the favorable histology and the small size of the tumors.

The efficacy and safety of degarelix, a luteinizing hormone-releasing hormone(LH-RH)antagonist, in patients with prostate cancer(PCa)were evaluated in a phase II, open-label, multicenter clinical trial. In this trial, a total of 13 patients were accrued at the Yamagata Prefectural Central Hospital from 2007 to 2008. The median age was 80 years(range, 65-85 years), and clinical stages were T1c, T2, T3, and T4 in 1, 4, 6, and 2 patients, respectively. Nodal(N)status was N0 in 9 patients and N1 in 4 patients. Distant metastases were absent(M0)in 12 patients and present(M1b)in 1 patient. The median prostate- specific antigen(PSA)level was 29.1 ng/mL(range, 6.3-427 ng/mL). All but one patient, who died of an unrelated cause, received a monthly dose(80 or 160mg)of degarelix for 12 months and were followed-up for 3 years. The PSA level declined in all patients. One patient died of an unrelated cause during the phase II trial. After completion of the phase II trial, 5 patients were treated with combined and rogen blockade(CAB)(leuprolide plus anti-androgen therapy), 2 patients were treated with single-agent leuprolide, 2 patients received single-agent bicalutamide, and 1 patient was followed-up without additional treatment. Radical prostatectomy was performed in 2 patients. Among the 5 patients treated with CAB, 2 died of metastatic cancer. CAB was effective in suppressing PSA levels in 3 patients. In 1 patient with T3aN1M1b PCa, colon cancer with lung metastases was detected during the follow-up period. Treatment with chemotherapy for colon cancer was effective in suppressing PSA levels for 12 months. In 1 patient with cT3aN1M0 PCa, the PSA level declined to0.02 ng/mL, and a reduction in size of the prostate gland and metastatic lymph nodes was observed. This effect persisted for 3.5 years after the completion of the 12-month degarelix regimen, and no additional treatment was required.

BACKGROUND Mutations of the androgen receptor (AR) gene give rise to a wide array of phenotypic abnormalities. A systematic analysis of the AR gene in patients with 47,XXY has not previously been performed. METHODS Mutations of the AR gene and expansion of the CAG repeats in exon 1 of the AR gene were studied in 13 patients with Klinefelter's syndrome either with (n = 1) or without (n = 12) spermatogenesis. RESULTS No abnormalities in the AR gene were detected by single strand conformational polymorphism analysis. The CAG lengths ranged from 17 to 27 (mean +/- SD 22.8 +/- 3.3, median 23) for Klinefelter patients or from 17 to 28 (mean +/- SD 23.2 +/- 2.6, median 23) for control subjects. X-inactivation analysis for the methylation status of the AR gene was performed in seven patients who were heterozygous for CAG repeats of different length, showing that the longer CAG repeat alleles underwent random but more frequent inactivation in five patients and skewed inactivation in two. CONCLUSIONS An AR gene abnormality does not constitute an important factor for impaired spermatogenesis in patients with Klinefelter's syndrome.

We report an 11-year-old boy with undermasculinized genitalia and an abnormally expanded CAG repeat length at exon 1 of the androgen receptor (AR) gene. He had microphallus and scrotal hypospadias with chordee, and underwent urethroplasty at 4 years of age. At 11 years of age, a gonadotropin releasing hormone (GnRH) test yielded a relatively high leutinizing hormone (LH) response (0.7-->20.4 IU/l) and a relatively low follicle-stimulating hormone (FSH) response (1.7-->4.8 IU/l), and an human chorionic gonadotropin (hCG) test showed sufficient responses of testosterone (0.7-->23.0 nmol/l) and dihydrotestosterone (0.38-->2.95 nmol/l). The CAG repeat length was 44 for the boy and ranged from 12 to 32 for 100 control males. The DNA sequences of the AR gene were normal for the exons 1-8 and for the splice donor, splice acceptor and branch sites. The markedly expanded CAG repeat length appears to be relevant to the undermasculinized genitalia of this boy, because such an expandsion, which has previously been reported only in spinal and bulbar muscular atrophy, is known to reduce AR function.

Peroxiredoxins are novel peroxidases that exhibit divergent biological functions. The fourth member, Prx4, is synthesized with a signal sequence and, after processing, secreted as a 27-kDa form in most tissues. A 31-kDa Prx4 which corresponds to the unprocessed, membrane-bound form is found only in testis. This study was undertaken in order to investigate the role of the membrane-bound Prx4 during spermiogenesis in rats. The Prx4 transcript was observed in testes at 14 days of age, the age before puberty, and its level increased only slightly during aging. Only the secretable form of Prx4 was present before 30 days of age, but the membrane-bound Prx4 became detectable in adult testes, although sum of the two forms appeared to be the same after 21 days old. While weak immunoreactivity to the Prx4 antibody was detected in spermatogenic cells for all ages, a strong immunoreactivity was observed in the elongating spermatid and residual body of adult testis. Prx4 was present in the lumen of the endoplasmic reticulum, Golgi bodies, and the perinuclear space in young rat testes. However, the localization of Prx4 was restricted to membranes of the acrosomal vesicle of the elongated spermatid and was not detected in spermatozoon. Once spermiogenesis is accomplished, vesicles containing the membrane-bound Prx4 were released into the residual body, along with residual membranous components. Thus the conversion of the soluble form to the membrane-bound form may have a role in the acrosome formation during vesicular reorganization during spermiogenesis.

Objective: To evaluate the effect of dexamethasone, a potent synthetic glucocorticoid hormone, on apoptosis of testicular germ cells and vascular neutrophil adhesion after repair of testicular torsion in rats. Design: Controlled laboratory study. Setting: Department of Urology, Yamagata University School of Medicine, Yamagata, Japan. Animal(s): Fifty-one male Sprague-Dawley rats. Intervention(s): Dexamethasone, 10 mg/kg of body weight. Main Outcome Measure(s): Testicular germ-cell apoptosis (percentages of apoptotic tubules and apoptotic cells) and vascular neutrophil adhesion were assessed by using DNA nick-end labeling and the endothelial-neutrophil adhesion score, respectively. Result(s): Intravenous administration of dexamethasone at repair of 90-minute testicular torsion significantly inhibited testicular germ-cell apoptosis and vascular neutrophil adhesion. This inhibition was suppressed by intravenous injection of mifepristone, a glucocorticoid-receptor antagonist. Conclusion(s): Glucocorticoids can be administered for torsion in addition to conventional torsion repair.

Objective To determine the expression of CD34 (to evaluate vascularity) and Ki-67 (as a proliferative index) in a variety of phaeochromocytomas and thus assess the utility of these markers as possible predictors of malignancy. Patients and methods Deparaffinized tissue sections from 21 patients with benign and four with malignant phaeochromocytoma were assessed immunohistochemically to evaluate microvascular counts (using CD34 antigen) and the proliferative index (Ki-67 antigen, monoclonal antibody MIB-1). Results There was no statistical association between high microvascular counts and malignancy, but there was between the MIB-1 score and malignancy (P

The effect of testosterone replacement therapy on serum prostate-specific antigen (PSA) was investigated in 11 patients with Klinefelter syndrome. Significant increases in serum testosterone level and prostate volume were observed after testosterone replacement therapy. However, serum PSA level did not change after testosterone replacement therapy. It would appear that serum PSA is not influenced by exogenous testosterone in patients with Klinefelter syndrome.

Prostate cancer has become one of the most common malignancies in the world. The incidence of prostate cancer has rapidly increasing over the last decade in East Asia. In Japan, age-adjusted death rates due to prostate cancer rose from 4.4 to 8.6 per 100,000 between 1980 and 1998. Recent research has focused on age, race-related differences, patterns of familial aggregation, genetic factors, hormones, and diet. Epidemiological approach has identified several possible risk factors that may be useful for the prevention of prostate cancer and targeting high-risk individuals for early detection.

To evaluate the efficacy of sutureless vasovasostomy using vascular closure staples, 20 male Sprague-Dawley rats were used for the study. In each rat, a sutureless vasovasostomy using vascular closure staples was performed on a randomly selected side, and a conventional end-to-end microsutured anastomosis was performed on the opposite side. Operation time was significantly shorter for sutureless vasovasostomy using vascular staples (p < .001). Four weeks after the surgery, however, patency rate and granuloma formation were not different for conventional end-to-end vasovasostomy vs. sutureless vasovasostomy. These findings suggest that sutureless vasovasostomy is simple to perform and requires fewer special technical skills. This procedure may provide an alternative to the conventional vasovasostomy.

Genetic evidence for a novel gene(s) involved in urogenital development on 10q26. Background Although the frequent association between distal 10q monosomy and urogenital anomalies suggests the presence of a gene(s) for urogenital development on distal 10q, molecular deletion mapping has not been performed for the putative gene(s). In this study, we examined genotype-phenotype correlations in patients with distal 10q monosomy. Methods This study consisted of six karyotypic males (cases 1 through 6) and four karyotypic females (cases 7 through 10) with 10q26 monosomy. Cases 3 through 5 and 7 through 10 had urinary anomalies such as vesicoureteral reflux and hypoplastic kidney, and cases 1 through 6, 8, and 9 exhibited genital anomalies such as micropenis, hypospadias, cryptorchidism, and hypoplastic labia majora. Fluorescence in situ hybridization (FISH) for 10q telomere, whole chromosome 10 painting, and microsatellite analysis for 35 loci on distal 10q were performed in cases 1 through 8. Results FISH and whole chromosome painting confirmed distal 10q monosomy in cases 1 through 8. Microsatellite analysis revealed that hemizygosity for the region distal to D10S186 was shared by cases with urinary anomalies and that for the region distal to D10S1248 was common to cases with genital anomalies. Furthermore, it was indicated that PAX2, GFRA1, and EMX2 on distal 10q, in which the deletions could affect urinary and/or genital development, were present in two copies in cases 1 through 8. Conclusions The results suggest that a novel gene(s) for urinary development and that for genital development reside in the approximately 20cm region distal to D10S186 and in the approximately 10cm region distal to D10S1248, respectively, although it remains to be determined whether the two types of genes are identical or different.

The first case of a dermoid cyst arising from the unilateral adrenal gland is reported with special reference to its embryonal development and imaging analysis.

Recent advances are provided in assisted reproductive technology and application of ICSI as treatment for infertile patients with previous cryptorchidism. Fertility rates were 25-81% and 8-48% in patients with unilateral and bilateral cryptorchidism, respectively. With the advent of assisted reproductive technology, pregnancy was not possible without sperm. Research in humans has resulted in pregnancy and live births after the injection of haploid germ cells (round spermatids) into the oocytes. In the mouse tetraploid germ cells (primary spermatocytes), nuclei have been injected into oocytes, which undergo meiosis, forming an embryo and live young. In animal models, round spermatids from both cryptorchid and previously cryptorchid testes can initiate normal embryo development when injected into mature oocytes. These cells may be used as substitutes for mature sperm. However, cryptorchidism in humans is often associated with inherent defects of spermatogenesis. With successive breakthroughs in treatment of impaired fertility associated with cryptorchidism, there is an increased risk of genetic abnormalities in the progeny. It is incumbent on clinicians who are involved in reproductive medicine to proceed cautiously with the development and application of assisted reproductive techniques to avoid creating future generations of genetically abnormal individuals.

Localization of the sex-determining region Y (SRY) was investigated in 2 XX males. Metaphase chromosomes from peripheral lymphocytes were stained by fluorescence in situ hybridization using DXZ1 and SRY probes. An identical hybridization signal with the SRY probe was found on an X chromosome in both cases. The karyotype of the 2 cases was 46,XX, t(X;Y)(p22.3;p11.3). It would appear that XX male is the presence of a Y-chromosome fragment transferred to the X-chromosome short arm by unequal interchange between homologous regions in the short arms of sex chromosomes.

The presence or absence of 33 DNA loci was investigated with a focus on the long arm of Y chromosome (Yq) interval 6 involving the DAZ and RBM genes, by means of a polymerase chain reaction strategy, in 10 patients with hypospadias. All patients did not show any of the 33 DNA loci. It would appear that chordee without hypospadias does not involve interval 6 of the Y chromosome.

Acute effects of tumor necrosis factor-alpha (TNF-alpha) on testicular germ cell apoptosis and vascular neutrophil adhesion were investigated in rats. Acute administration of TNF-alpha did not show a significant increase in percentage of apoptotic tubules and apoptotic germ cells. TNF-alpha administration did not enhance neutrophil adhesion score in the intertubular and subtunical vein. TNF-alpha does not acutely influence testicular germ cell apoptosis and vascular neutrophil adhesion in rats.

The effect of mast cell blocker (ebastine) on semen quality was evaluated in 15 idiopathic oligozoospermic males. Ten milligrams/day of ebastine was administered orally for 3 months. Nine cases (66.7%) showed definite improvement in the semen quality. The wives of 3 patients (20%) became pregnant within 6 months of the initial treatment. It would appear that mast cell blocker (ebastine) significantly improves semen quality in men with idiopathic oligozoospermia.

The influence of immobilization stress on testicular germ cell apoptosis was investigated in rats. A transient increase in serum corticosterone and a transient decrease in serum testosterone were observed during each period of immobilization stress. Twenty-four hours after the last immobilization session, the testicular weight and serum concentrations of corticosterone and testosterone were the same between the immobilization stress and control groups. However, the percentages of apoptotic tubules and apoptotic cells in the stress group were significantly higher than those in controls (P < 0.001). These facts suggest that immobilization stress can enhance testicular germ cell apoptosis in rats.

In benign prostatic hyperplasia (BPH), bladder outlet obstruction is caused by mechanical blockage resulting from an enlarged prostate, and by the increased tone of prostatic smooth muscle. In patients with obstructive BPH, the prostatic urethra urodynamically corresponds to the flow-controlling zone (FCZ). We sought to investigate the relation between the obstruction and elastic properties of the FCZ and the histologic composition of the prostate in symptomatic patients with BPH.The grade of infravesical obstruction was classified according to preoperative pressure-flow data from 30 men with symptomatic BPH, and the elastic properties of the FCZ were evaluated as the mean elastance, which was calculated using the three-parameter model. The area densities of smooth muscle, fibrous tissue, epithelium, and lumen were determined by quantitative morphometry, using BPH tissue obtained by transurethral resection.The area density of smooth muscle had a negative correlation with mean elastance (p = -0.50, P0.01), the linear passive urethral resistance relation (p = -0.43, P0.05), and the group-specific urethral resistance factor (p = -0.39, P0.05). No other histologic element was correlated with these variables.Our results suggest that urethral elasticity and bladder outlet obstruction grade are influenced by the relative content of smooth muscle within the prostate in patients with BPH.