Ryosuke Murai

The Effect of d-Aspartate on Spermatogenesis in Mouse Testis

ABSTRACT Spermatogenesis is controlled by hormonal secretions from the hypothalamus and pituitary gland, by factors produced locally in the testis, and by direct interaction between germ cells and Sertoli cells in seminiferous tubules. Although the mammalian testis contains high levels of d-aspartate (d-Asp), and d-Asp is known to stimulate the secretion of testosterone in cultured Leydig cells, its role in testis is unclear. We describe here biochemical, immunohistochemical, and flow cytometric studies designed to elucidate developmental changes in testicular d-Asp levels and the direct effect of d-Asp on germ cells. We found that the concentration of d-Asp in mouse testis increased with growth and that fluctuations in d-Asp levels were controlled in part by its degradative enzyme, d-aspartate oxidase expressed in Sertoli cells. In vitro sperm production studies showed that mitosis in premeiotic germ cells was strongly inhibited by the addition of d-Asp to the culture medium. Moreover, immunohistochemical analysis demonstrated that d-Asp accumulated in the differentiated spermatids, indicating either transport of d-Asp to spermatids or its de novo synthesis in these cells. Such compartmentation seems to prevent premeiotic germ cells in mouse testis from being exposed to the excess amount of d-Asp. In concert, our results indicate that in mouse testis, levels of d-Asp are regulated in a spatiotemporal manner and that d-Asp functions as a modulator of spermatogenesis.

Prediction of intravesical recurrence of non-muscle-invasive bladder cancer by evaluation of intratumoral Foxp3+ T cells in the primary transurethral resection of bladder tumor specimens

Patients with a history of non-muscle-invasive bladder cancer sometimes have recurrence of tumors after transurethral resection of bladder tumor treatment. To find factors related to the recurrence of non-muscle-invasive bladder cancer, we examined tissue specimens taken at transurethral resection of bladder tumor as an initial treatment. We revealed the association between prognosis of non-muscle-invasive bladder cancer and infiltration of Foxp3+ T cells that suppress anti-tumor immunity in 115 primary non-muscle-invasive bladder cancer patients retrospectively identified and followed for at least 3 months after primary transurethral resection. In immunohistological staining, we counted the number of cells positive for CD3 and positive for CD3 and Foxp3 together and calculated the percentage of Foxp3+ T cells among the CD3+ T cells. The recurrence-free survival rate was calculated by the Kaplan-Meier method, and a Cox regression analysis of recurrence factors was performed. The median (interquartile range) percentage of Foxp3+ T cells in all cases was 17.1% (11.9, 11.4–23.3%). Compared by risk stratification, it was 11.4% (10.4, 7.8–18.2%) in the low-risk group (n = 32), 16.8% (12.6, 11.6–24.2%) in the intermediate-risk group (n = 45), and 22.0% (9.7, 16.4–26.1%) in the high-risk group (n = 38). The Kaplan-Meier survival analysis indicated that the Foxp3+ T cell high group (≥ 17.1%) had a worse RFS rate than did the low group (< 17.1%) (P = 0.006). In multivariate analysis, the percentage of Foxp3+ T cells was an independent risk factor for intravesical recurrence (hazard ratio 2.25). Thus, peritumoral Foxp3+ T cell infiltration was correlated to risk stratification and recurrence-free survival. Therefore, the percentage of Foxp3+ T cells in tumor specimens may predict a risk for intravesical recurrence.

WORSENING RENAL FUNCTION AFTER ACUTE TYPE B AORTIC DISSECTION

Worsening renal function (WRF) after acute type B aortic dissection (ATBAD) occasionally occurs, but is not well studied.nnWe retrospectively reviewed 149 consecutive patients hospitalized for ATBAD between January 2014 and July 2017. Excluding patients with an unknown onset time, >14 days after the

Optical Coherence Tomography Predictors for Recurrent Restenosis After Paclitaxel-Coated Balloon Angioplasty for Drug-Eluting Stent Restenosis

BACKGROUNDnLittle is known of the relationship between optical coherence tomography (OCT) findings and recurrent restenosis after paclitaxel-coated balloon (PCB) angioplasty for drug-eluting stent in-stent restenosis (DES-ISR). To identify the predictors of recurrent restenosis after PCB angioplasty, we investigated quantitative and qualitative OCT findings during PCB angioplasty for DES-ISR. Methodsu2004andu2004Results: In all, 222 DES-ISR lesions treated by PCB angioplasty with OCT assessment and followed-up angiographically at 6 months were divided into restenotic and non-restenotic lesions on the basis of the presence or absence of restenosis at follow-up. There was a significantly higher proportion of the heterogeneous tissue pattern in restenotic than non-restenotic lesions (26.5% vs. 11.0%, respectively; P=0.02). The OCT-derived post-procedural minimal lumen and stent areas were significantly smaller in restenotic lesions, but the intima area was similar in both groups. Post-procedural stent underexpansion, defined as a stent diameter : size of the previous stent ratio <1.0, was more frequently observed in restenotic than non-restenotic lesions (33.3% vs. 17.4%, respectively; P=0.02). Multivariate analysis identified a heterogeneous tissue pattern (odds ratio [OR] 2.92; 95% confidence interval [CI] 1.32-6.47; P=0.006) and post-procedural stent underexpansion (OR 2.36; 95% CI 1.15-4.85; P=0.04) as independent predictors of recurrent restenosis.nnnCONCLUSIONSnThe heterogeneous tissue pattern and insufficient post-procedural minimal lumen area, caused primarily by stent underexpansion, may be associated with restenosis after PCB angioplasty for DES-ISR.

The location of the bladder neck in postoperative cystography predicts continence convalescence after radical prostatectomy

BackgroundThis study was conducted to determine whether the location of the bladder neck in postoperative cystography predicts recovery of continence after radical prostatectomy.MethodsBetween 2008 and 2015, 203 patients who underwent laparoscopic radical prostatectomy (LRP, nu2009=u200999) and robot assisted radical prostatectomy (RARP, nu2009=u2009104) were analyzed. The location of the bladder neck was visualized by postoperative routine cystography, and quantitative evaluation of the bladder neck position was performed according to the bladder neck to pubic symphysis (BNPS) ratio proposed by Olgin et al. (J Endourol, 2014). Recovery of continence was defined as no pad use or one security pad per day. To determine the predictive factors for recovery of continence at 1, 3, 6 and 12xa0months, several parameters were analyzed using logistic regression analysis, including age (≤68 vs. >u200968, BMI (≤23.4 vs. >u200923.4xa0kg/m2), surgical procedure (LRP vs. RARP), prostate volume (≤38 vs. >u200938xa0mL), nerve-sparing technique, vesico-urethral anastomosis leakage, and BNPS ratio (≤0.59 vs. >u20090.59).ResultsThe mean postoperative follow-up was 1131xa0days (79–2880). At 1, 3, 6 and 12xa0months after surgery, continence recovery rates were 25, 53, 68 and 81%, respectively. Although older age (>u200968) and RARP were significant risk factors for incontinence within 3xa0months, neither was significant after 6xa0months. A high BNPS ratio (>u20090.59) was the only significant risk factor for the persistence of incontinence at all observation points, up to 12xa0months.ConclusionsA lower bladder neck position after prostatectomy predicts prolonged incontinence.

Evaluations for Hydronephrosis After the Establishment of Tubeless Cutaneous Ureterostomy

Purpose To investigate hydronephrosis after the establishment of tubeless cutaneous ureterostomy by using our definition of the tubeless condition and our indications for catheter insertion. Materials and Methods Twenty-eight (54 renal units) patients with both establishment of tubeless cutaneous ureterostomy 3 months after surgery and at least 12 months of follow-up were investigated in this study. The 4-grade system was used to evaluate the hydronephrosis. The definition of the tubeless condition in cutaneous ureterostomy was as follows: 1) the catheter stent is not placed in the renal pelvis through the stoma, 2) the grade of hydronephrosis is less than 3, and 3) the kidney is functioning. Indications for catheter insertion after the establishment of tubeless cutaneous ureterostomy were as follows: 1) difficulty in curing acute pyelonephritis by drug treatments, 2) flank pain due to hydronephrosis, or 3) increase in the grade of hydronephrosis. Results The follow-up period was 12 to 78 months (average, 40.5±22.1 months). After the establishment of tubeless cutaneous ureterostomy, 6 of 54 renal units (11.1%) were eligible for catheter insertion. The catheter insertion was performed in 4 renal units. Another 2 renal units were followed up without intervention, and they gradually became atrophic. The renal functions were preserved in the other 52 renal units. Conclusions Our results suggest that our definition of the tubeless condition and our indications for catheter insertion would be useful for the evaluation and management of hydronephrosis after establishment of tubeless cutaneous ureterostomy.

Diagnostic Criteria for Stomal Obstruction of Tubeless Cutaneous Ureterostomy by Use of 99mTc-Mercaptoacetyltriglycine Diuretic Renography

Purpose To evaluate 99mTc-mercaptoacetyltriglycine diuretic renograms for diagnosing stomal obstruction in tubeless cutaneous ureterostomy. Materials and Methods Cutaneous ureterostomy was performed in 29 patients (56 renal units) with a minimum follow-up period of 12 months. Stomal obstruction was evaluated with 99mTc-mercaptoacetyltriglycine diuretic renography 3 months after surgery. Regions of interest were drawn that completely encircled and snugly fit the kidney, renal pelvis, and ureter. The data analyses were performed with half-times to tracer clearance following furosemide (0.5 mg/kg) administration. Results The mean half-times to tracer clearance were 6.90±6.30, 5.25±4.29, and 8.75±7.63 minutes in the total, ipsilateral, and contralateral kidneys, respectively, in side relationships between the ureter and the stoma. There were significant differences between the ipsilateral and contralateral kidneys in the mean half-time to tracer clearance (p=0.038). Forty-eight renal units (85.7%) had a half-time to tracer clearance of less than 15 minutes, and all 48 renal units had no hydronephrosis. On the other hand, 5 renal units (8.9%) had a half-time to tracer clearance of more than 20 minutes, and these 5 renal units required the insertion of stent catheters or became atrophic. Conclusions 99mTc-mercaptoacetyltriglycine diuretic renography was very useful for diagnosing stomal obstruction of tubeless cutaneous ureterostomy. The upper limit of the half-time to tracer clearance for unobstructed systems was 15 minutes, which allowed for the confident exclusion of stomal obstruction in tubeless cutaneous ureterostomy.