Objective To clarify the role of Rho small GTP-binding protein (Rho) in the progression of testicular germ cell tumour (GCT), by examining the expression levels of mRNAs of Rho genes in testicular GCT. Patients and methods The mRNA levels of the RhoA, RhoB and RhoC genes were analysed in the surgical specimens of testicular GCT tissues from 45 consecutive Japanese patients, and in the corresponding unaffected tissue originating from the same patient, using reverse transcription-polymerase chain reaction. The expression levels in tumour tissues were compared with those in unaffected tissues and the relationship between their expression levels in tumours and tumour stage evaluated. The expression levels of mRNAs of the Rho genes were also evaluated between tumours with seminoma only, and mixed tumours with seminoma and nonseminoma.Results The mRNA levels of RhoA were greater in tumour tissues than in unaffected tissues of the resected testis (P<0.01); the mRNAs of RhoB and RhoC were not detected in either tissue. The increase in RhoA mRNA levels was related to tumour stage (P<0.05). The mRNA levels of RhoA in seminomatous and nonseminomatous areas where both were present were higher than those in tumours with seminoma only (P<0.05). Conclusions These results suggest that RhoA is involved in testicular germinal epithelial carcinogenesis and progression in testicular GCT, indicating that RhoA may be a useful prognostic marker for progression in testicular GCT.

Pituitary adenylate cyclase-activating polypeptide-38 (PACAP38) is a neuropeptide related to vasoactive intestinal peptide-secretin-glucagon which stimulates adenylate cyclase in cultured rat pituitary cells and stimulates LH and FSH release in vitro and in vivo. Because the cAMP-protein kinase-A pathway regulates the gonadotropin subunit messenger RNAs (mRNAs) and modulates GnRH-stimulated gonadotropin secretion in vitro, we examined the effects of PACAP38 on gonadotropin secretion and subunit mRNA levels. Anterior pituitary cells were prepared from 7-week-old male rats castrated at 5 weeks of age. In monolayer cultures stimulated with GnRH, 0.1-10 nM PACAP38 decreased (P < 0.05) the EC50 for GnRH dose-dependently without affecting the maximum LH secretory response. Cells were next stimulated with 1-min pulses of 2.5 nM GnRH every hour for 9 h in the absence or presence of 10 nM PACAP38, which was perifused continuously. The amplitude of GnRH-induced LH, FSH, and alpha-subunit secretory episodes from PACAP38-treated cells rose (P < 0.01) gradually to 233 +/- 54%, 197 +/- 44%, and 378 +/- 104%, respectively (mean +/- SEM; n = 5 experiments), of the value for control cells lacking PACAP38. This enhancement was sustained for at least 3 h after PACAP38 was removed from the perifusion medium. With PACAP treatment, interpulse secretion of LH and alpha-subunit increased gradually (P < 0.01) to 174 +/- 21% and 212 +/- 64% of the value for chambers stimulated with GnRH alone (control), respectively, whereas interpulse secretion of FSH declined (P < 0.001) to 75 +/- 7% of the control value. In contrast to the gradual effect of PACAP38 to enhance GnRH-induced hormone secretion, PACAP38 alone produced a transient burst of gonadotropin secretion. At the completion of the perifusions, total RNA was extracted and gonadotropin subunit mRNA levels were determined by Northern analysis. GnRH increased (P < 0.01) FSH beta mRNA to 438 +/- 52% of the level in cells stimulated with medium alone (control). Adding PACAP38 to the perifusion medium partially blocked (P < 0.01) the effect of GnRH (178 +/- 20% of the control value), and PACAP38 alone reduced (P < 0.01) FSH beta mRNA levels to 31 +/- 3% of the control value. By contrast, alpha-subunit mRNA levels were increased by both PACAP38 (143 +/- 4% of the control value; P < 0.01) and GnRH (121 +/- 2% of the control value; P < 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

Aim: The aim of the present study was to compare the effectiveness of a cholinergic drug, an ablocker and combinations of the two for the treatment of underactive detrusor. Methods: One hundred and nineteen patients with underactive bladder were assigned to three groups: the cholinergic group, consisting of 40 patients taking bethanechol chloride (60 mg/day) or distigmine bromide (15 mg/day); the a-blocker group, consisting of 38 patients taking urapidil (60 mg/ day); and the combination group, consisting of 41 patients taking both a cholinergic drug and an ablocker. The effectiveness of each therapy was assessed 4 weeks after initialization of the therapy. Results: Total urinary symptom scores (International Prostate Symptom Score, IPSS) remained unchanged after the cholinergic therapy, but were significantly lower after the a-blocker treatment (P = 0.0001) and the combination therapy (P = 0.0001). With regard to the total IPSS, there were significant differences between the cholinergic and the a-blocker groups (P = 0.0008), and also between the cholinergic and combination groups (P = 0.0033), in favor of the latter. The average and maximum flow rates did not increase significantly after monotherapy with either the cholinergic drug or the a-blocker, but they significantly increased after combination therapy compared to baseline values (P = 0.0033 and P = 0.0004, respectively). Postvoid residual volume did not decrease significantly after the cholinergic drug therapy, but decreased significantly after the a-blocker (P = 0.0043) and the combination therapies (P = 0.0008). The percentage of residual urine decreased significantly after therapy in all groups (P = 0.0005, P = 0.0176 and P = 0.0001, respectively). Conclusion: Combination therapy with a cholinergic drug and an a-blocker appears to be more useful than monotherapy for the treatment of underactive detrusor.

Abbreviations & AcronymsAbstract: Although percutaneous nephrolithotomy has been recommended as the first-line treatment for renal stones larger than 2 cm, its major complication rate is not negligible and less invasive approaches are to be explored. Thanks to the recent advances in endoscopic technology, flexible ureteroscopy has become another option in this setting. Herein we report our most recent experience with flexible ureteroscopy for large renal stones. Between September 2008 and May 2011, 20 patients with renal stones Ն2 cm underwent a total of 28 procedures of ureteroscopy with holmium laser lithotripsy, using the Olympus URF-P5 and a ureteral access sheath. The number of procedures, operative time, stone-free rates, stone compositions and complications were evaluated. Stone-free status was defined as the absence of fragments or fragments of Յ4 mm. Mean stone size was 3.1 cm (range 2.0-5.0). The average number of procedures was 1.4. One, two and three procedures were required in 13, six and one patients, respectively. Overall, the stone-free rate was 90%. The stone-free rate for preoperative stone size of 2 to Յ4 cm and >4 cm was 100% (14/14) and 67% (4/6), respectively. No major intraoperative complications were identified. Postoperative high-grade fever was observed in three patients, including one patient who developed sepsis. All these patients were successfully treated conservatively. Our findings suggest that ureteroscopy represents a favorable option for selected patients with renal stones, especially those 2 to Յ4 cm in size.

OBJECTIVE To assess the roles of RhoA small GTPase (RhoA) in upper urinary tract cancer by analysing the mRNA and protein levels of RhoA. PATIENTS AND METHODS The mRNA and protein levels of RhoA in matched sets of tumour, non‐tumour and metastatic lymph node tissues of surgical specimens were analysed in 47 consecutive patients with renal pelvic/ureteric cancer, using the polymerase chain reaction after reverse transcription and Western blotting. The relationship between mRNA and protein levels of RhoA in tumour tissues and the clinicopathological features of the patients was also assessed. RESULTS The mRNA levels of RhoA and RhoA protein were greater in tumour and metastatic lymph node tissues than in non‐tumour tissues (all P < 0.001). The expression levels of RhoA mRNA and protein levels in primary tumours was related to poorly differentiated grade (both P < 0.05) and muscle invasion (P < 0.01 and < 0.001, respectively). Kaplan‐Meier plots of survival in patients with low or high RhoA showed that high mRNA and protein levels were associated with a shorter disease‐free (P < 0.01) and overall survival (P < 0.001). Multivariate analysis using the Cox proportional hazards model showed that a high RhoA protein level was an independent prognostic factor, second to stage, in disease‐free and overall survival (both P < 0.05). CONCLUSIONS These findings suggest that RhoA is involved in the invasion and metastasis of upper urinary tract cancer, indicating that RhoA may be a useful prognostic factor in this disease.