Yoshitada Ohi

Correlation between thymidine phosphorylase expression and prognosis in human renal cell carcinoma.

PURPOSEThymidine phosphorylase (TP) is identical to platelet-derived endothelial cell growth factor (PD-ECGF) and has angiogenic activity. We examined whether TP expression in renal cell carcinoma (RCC) is associated with microvessel density as a marker of angiogenesis, clinicopathologic characteristics, and outcome.PATIENTS AND METHODSThe enzymatic activity and expression of TP were examined in 18 RCCs and 19 kidney tissues not grossly involved with tumor from 24 patients with 13 paired samples and 11 unpaired samples by spectrophotometry and immunoblotting. The relationship between TP expression and microvessel density was assessed by immunohistochemistry in 133 RCCs.RESULTSThe median enzymatic activity of TP in RCCs was nine fold higher than that in nonneoplastic kidney tissues (P < .001). Similar results were obtained by immunoblot analysis. According to the TP staining profile, tumors were classified as no or low, intermediate, or high TP-expressing tumors. TP positivity was significantly correlated ...

Expression of a carbohydrate signal, sialyl dimeric Lex antigen, is associated with metastatic potential of transitional cell carcinoma of the human urinary bladder

Sialyl dimeric Le(x) antigen was expressed in significant portion of transitional cell carcinoma of the human urinary bladder, but not in the normal uroepithelial tissue. Primary tumors with weak or no expression of the antigen scarcely metastasized to lymph nodes, whereas tumors with high levels of antigen expression metastasized frequently. Metastatic lymph nodes expressed the antigen in most cases. Sialyl dimeric Le(x) antigen was mainly located on 60 and 42 KDa glycoproteins. Since a group of cell adhesion molecules, called LECCAMs, recognize a portion of the antigen, the above results strongly suggest that a LECCAM on the surface of host cells recognizes the carbohydrate structure on the glycoprotein, leading to promotion of metastasis.

Bacterial biofilms and catheters in experimental urinary tract infection

Employing in vitro and in vivo models of catheter-associated infection, biofilm formation of Pseudomonas aeruginosa in artificial urine and bactericidal activity of several classes alone or in combination with a macrolide antibiotic were investigated. In the course of continuous urine flow, bacteria adherent to a Teflon catheter formed microcolonies at 6 h and a biofilm at 24 h. Following 24 h of urine flow, the thickness and the density of the biofilm increased to about 20 microm and 10(8) cfu/mm3, respectively. Of the antibiotics examined, the fluoroquinolones showed the most potent bactericidal activity against the P. aeruginosa biofilms. However, those antibiotics were not always potentiated by the combination with a macrolide antibiotic.

Sphingosine induces apoptosis in androgen‐independent human prostatic carcinoma DU‐145 cells by suppression of bcl‐XL gene expression

Our recent studies have suggested that sphingosine, an endogenous protein kinase C (PKC) inhibitor, may mediate apoptosis induced by a phorbol ester (PMA) in human promyelocytic leukemia HL‐60 cells [Ohta et al. Cancer Res. 1995;55:691–697], and that the apoptotic induction by both PMA and sphingosine is accompanied by down‐regulation of bcl‐2, a gene which acts to prevent apoptotic cell death [Sakakura et al. FEBS Lett. 1996;397:177–180]. In this study, we examined the sphingosine‐induced apoptosis of the androgen‐independent human prostatic carcinoma cell line DU‐145, which expresses bcl‐XL and Bax but not bcl‐2, and found that treatment of DU‐145 cells with sphingosine suppressed bcl‐XL in both mRNA and protein levels but did not change bax expression at all. In contrast, in apoptotic cells treated with a PKC inhibitor, staurosporine, no effect on bcl‐XL or bax expression was observed. The initial metabolites of sphingosine in the cells, ceramide and sphingosine 1‐phosphate, failed to induce apoptosis. These results indicate that, in DU‐145 cells, sphingosine, but not its metabolites, induces apoptosis through down‐regulation of bcl‐XL, independently of PKC inhibition. Our present results, together with previous observations, strongly suggest that apoptosis regulatory genes differ according to cell type and apoptosis induction through sphingosine is accompanied by inhibition of either bcl‐2 or bcl‐XL activity in these cells.

In vitro bactericidal activities of beta-lactamases, amikacin, and fluoroquinolones against pseudomonas aeruginosa biofilm in artificial urine

OBJECTIVES To compare bactericidal activities of antimicrobial agents against Pseudomonas aeruginosa biofilms by employing an in vitro model of catheter-associated infection because such infections are refractory to antimicrobial treatment. METHODS Bactericidal activities of piperacillin (PIPC), ceftazidime (CAZ), panipenem (PAPM), amikacin (AMK), ciprofloxacin (CPFX), and levofloxacin (LVFX) were examined against a P. aeruginosa biofilm generated on a Teflon catheter in artificial urine. The colony-forming activities of biofilm bacteria were determined for 48 hours during the treatment with each drug at concentrations of 1 up to 128 times the minimal bactericidal concentration (MBC), and time-kill curves were constructed by plotting the viable cell counts against time. RESULTS Although CAZ was more bactericidal to the biofilm bacteria than PIPC, the biofilm bacteria still remained on the catheter during CAZ treatment at a concentration 128 times the MBC for 48 hours. Biofilm bacteria were completely eradicated within 48 hours by treatment with PAPM and AMK at a concentration 64 and 128 times the MBC, respectively. Both CPFX and LVFX eradicated biofilm bacteria completely by 24 hours at a concentration 32 times the MBC. CONCLUSIONS These results indicate that fluoroquinolones have the most potent bactericidal activity against the P. aeruginosa biofilm generated in urine.

Expression of the multidrug transporter, P‐glycoprotein, in renal and transitional cell carcinomas

Background. Renal cell carcinomas (RCC) respond poorly to anthracyclines, Vinca alkaloids, and other agents. P‐glycoprotein is overproduced in multidrug‐resistant cells and thought to function as an energy‐dependent drug efflux pump. The authors thus examined the expression level of P‐glycoprotein in RCC and transitional cell carcinomas (TCC).

Recent Distribution and Treatment of Filarial Chyluria in Japan

Since 1975 parasitism by the filarial worm has not existed in Japan. However, patients still present with filarial chyluria because the condition is one of the late manifestations of filariasis. From 1952 to 1973 renal pelvic instillation therapy, and surgical stripping and interruption of renal pedicle lymphatics were done in 217 and 383 patients, respectively, in the urology clinic of our and affiliated hospitals. Chyluria ceased immediately after instillation therapy in 129 of the 217 patients (59.4 per cent) but recurred in half of the cases. The short-term results of the surgical procedure were excellent. Chyluria ceased in 375 of the 383 patients (97.9 per cent) and diminished in 5 (1.3 per cent). Of 160 operated patients followed for more than 2 years recurrence of chyluria at contralateral and undetermined sites was observed in 41 (25.6 per cent).

Diffusion of Piperacillin, Cefotiam, Minocycline, Amikacin and Ofloxacin into the Prostate

Background: The successful treatment of bacterial prostatitis depends on an effective antimicrobial concentration in prostatic tissue against the infecting organism. In this study we compared the diffusion of 5 types of antimicrobials into the prostate.

Long-term results of intravesical chemoprophylaxis of superficial bladder cancer: experience of the Japanese Urological Cancer Research Group for Adriamycin.

SummaryLong-term results were analyzed in terms of tumor progression and survival in patients with superficial bladder cancer who were enrolled in the second intravesical chemoprophylactic study of the Japanese Urological Cancer Research Group for Adriamycin, which was started in July 1982. This study was a prospective, randomized, controlled trial conducted on primary tumors treated with a long-term instillation regimen that involved control versus intravesical instillations of Adriamycin or mitomycin C given once a week for the first 2 weeks, once every other week for 14 weeks, once a month for 8 months, and once every 3 months for 1 year, for a total of 21 instillations in 2 years. An analysis of the prophylactic effects of such treatment on bladder tumors after TUR has previously been performed, and the results have been published elsewhere. The present study represents a follow-up of the above trial. Of the 671 cases previously analyzed with regard to tumor prophylaxis, 158 cases (23.5%) were eligible to be followed for tumor progression and survival. A detailed comparison of the background factors between these 158 patients and the other 513 cases revealed no statistically significant difference. Thus, the 158 evaluable cases might reasonably be considered to represent all patients enrolled in the second study, and the results were thought to be reasonable enough to reflect the long-term efficacy of the long-term instillation regimen adopted in this study. The median follow-up for these 158 cases was 6.6 years. Tumor progression in terms of the disease stage and/or grade occurred in 43 of 127 patients who received prophylactic instillations and in 12 of 31 control cases. No significant difference in the incidence of tumor progression was found between the treatment and the control groups. In addition, no difference in survival was observed between the treatment group and the control group. Survival was also compared between patients who showed tumor progression and those who did not. All patients whose tumors did not progress survived, whereas the 7-year survival of those exhibiting tumor progression was <90%.

Diagnosis and treatment of priapism: experience with 5 cases

OBJECTIVES Priapism is a rare disease, but needs early intervention and appropriate management. We present 5 cases, 2 of nonischemic high-flow priapism and 3 of ischemic low-flow priapism. METHODS Focusing on the differential diagnosis of priapism between the nonischemic high-flow type and the ischemic low-flow type, we reviewed the medical records of 5 patients. RESULTS Of the examinations carried out, cavernosography, blood gas analysis of cavernosal blood, color Doppler ultrasound, and internal pudendal arteriography were useful in differentiating the type of priapism. Complete detumescence of the penis in 2 cases of high-flow priapism and 3 cases of low-flow priapism was achieved by selective embolization with gelform and by glandular-cavernosal shunting, respectively. No recurrence was observed in any patient, and postoperative erectile function was preserved in 4 patients and is unknown in 1. CONCLUSIONS These results indicate that angiographic studies provide the most reliable information for the differentiation of the type of priapism. However, color flow Doppler ultrasound and cavernosal blood gas determination can obviate the need for angiographic studies and are noninvasive. Although conservative treatment or even expectant management may be feasible with high-flow priapism, aggressive treatment should be carried out for low-flow priapism immediately after initial treatment fails to achieve detumescence of the penis. Selective embolization of the internal pudendal artery may be the treatment of choice for patients with high-flow priapism.