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J Kumazawa

Publications and source records attributed to J Kumazawa.

At least 109 records · Page 6Linked to original sources

Prophylactic intravesical chemotherapy with adriamycin plus verapamil for primary superficial bladder cancer: preliminary results. The Kyushu University Urological Oncology Group.

A prospective randomized trial was conducted to compare the prophylactic effect of intravesical installation of Adriamycin (ADM) plus verapamil (VR) with that of ADM alone for recurrence of superficial bladder cancer. A total of 226 patients were enrolled and randomized into 2 groups. Group A received intravesical instillation of ADM (30 mg/30 ml physiological saline) on 19 occasions during a 1-year period after transurethral resection, whereas group B received intravesical instillation of ADM (30 mg/24 ml physiological saline) plus VR (15 mg/6 ml saline) according to the same schedule used for group A. Evaluation was possible in 157 of the 226 registered patients (group A, 76; group B, 81). There was no significant difference in the patients' characteristics between the two groups, and there was no significant difference in the overall nonrecurrence rate determined over a 24-month follow-up period. However, group B showed a significantly higher nonrecurrence rate than did group A for tumors measuring less than 1 cm in diameter (P < 0.05) and for histological grade 2 tumors (P < 0.01) in spite of there being no significant difference in the other characteristics of each subgroup of patients. The incidence and severity of side effects were similar in both groups, and VR caused no significant systemic toxicity. Although further follow-up is necessary, these results suggest that intravesical instillation of ADM plus VR is clinically safe and may be more effective than instillation of ADM alone in preventing the postoperative recurrence of superficial bladder cancer (less than 1 cm in diameter, histological grade 2).

Administration, Intravesical↗

Clinical significance of urinary enzymes and beta 2-microglobulin following ESWL.

To examine the renal damage caused by shock waves, urinary excretion of enzymes and beta 2-microglobulin were determined before and after ESWL. Urine samples were obtained from 35 patients with renal stone and 26 patients with ureteric stone treated with ESWL. Urinary lactate dehydrogenase (LDH) levels significantly increased on day 0, just after ESWL, in both groups. In the ureteric stone group the kidneys received less shock waves than in the renal stone group. Increased urinary lactate dehydrogenase was considered to have derived from erythrocytes in urine. Elevated urinary N-acetyl-beta-D-glucosaminidase (NAG) levels were also observed on day 0 after ESWL in both groups, due to unknown reasons. Indirect effect of ESWL through the sympathetic nervous system or humoral factors may contribute to increases in the urinary excretion of NAG. No significant increase was found in urinary gamma-glutamyl-transpeptidase (GGTP) levels for 5 days after ESWL. Urinary beta 2-microglobulin (BMG) levels increased on day 0 in the renal stone group alone. In our present study, the clinical significance of urinary enzymes and BMG was not well evaluated, because urinary excretion of these indicators following ESWL were transient and mild.

Acetylglucosaminidase↗

Clinical study of asymptomatic microscopic haematuria.

A clinical statistical survey was performed on 355 patients with asymptomatic microscopic haematuria. Urologic lesions were detected in 19.4% of the patients. Urologic lesions requiring surgical treatment were found in only two patients with bladder carcinoma and with renal calculus. With the exception of glomerulonephritis, the proportion of those over 40 years who had urologic lesions was higher. It is suggested that an initial evaluation based on excretory urography, cystoscopy and ultrasonography is more important for patients over 40 years.

Adolescent↗

Influence of hyperosmotic environment comparable to the renal medulla upon membrane NADPH oxidase of human polymorphonuclear leukocytes.

Hyperosmotic environment in the renal medulla seems important for bacterial pyelonephritis because it exerts inhibitory influences upon the function of polymorphonuclear leukocytes (PMN). Urea and NaCl primarily contribute to high osmolarity in the renal medulla. We previously reported that PMN function was actually suppressed in phagocytosis, intracellular bacterial killing and superoxide generation in the hyperosmotic solution of urea and NaCl. In the present report, to verify the mechanism of this inhibitory effect, a kinetic study for NADPH oxidase in the cell membrane, the key enzyme complex of superoxide generation, was carried out in the cell membrane-solubilizing system under the hyperosmotic condition caused by urea or NaCl. Urea directly denaturated NADPH oxidase, and its inhibitory mechanism was reversible and uncompetitive with a decrease in Vmax and Km, while NaCl had no effect upon it, maintaining Lineweaver-Burk plots in the same position as those of the control. This result suggests that urea at least produces an inhibitory effect upon PMN through the direct inactivation of NADPH oxidase, although NaCl was unable to do so.

Cell Membrane↗

Metallothionein expression is correlated with cisplatin resistance in transitional cell carcinoma of the urinary tract.

Metallothioneins (MTs) are small cysteine-rich, metal-binding proteins involved in resistance to heavy-metal toxicity, and are known to bind cisplatin. Several experiments suggest possible involvement of MT in cellular resistance to cisplatin. To investigate the relationship between MT expression and cisplatin resistance in urinary tract transitional cell carcinoma (TCC), immunohistochemical staining for MT was performed in 31 untreated TCCs of the urinary tract. The results were compared with the sensitivity of the tumors to cisplatin as assessed by the microtiter succinate dehydrogenase inhibition (mSDI) test. Variable MT expression was observed in all 31 TCCs, but there was no specific correlation between histopathological parameters and MT expression. Fourteen (87.5%) of the 16 TCCs with less than 10% of their tumor cells positive for MT were sensitive to cisplatin. On the other hand, 6 (75.0%) of the 8 TCCs with MT expression by more than 30% of their tumor cells were resistant to cisplatin, and there was a significant correlation between MT expression and cisplatin resistance (p < 0.01). These results suggest the possible involvement of MT in the intrinsic cisplatin resistance of urinary tract TCC and that immunohistochemical investigation of MT may be useful for predicting the response of these tumors to cisplatin therapy.

Adult↗

Suppression of renal scarring by prednisolone combined with ciprofloxacin in ascending pyelonephritis in rats.

To prevent renal scarring, which occurs at the end stage of chronic pyelonephritis due to vesicoureteral reflux of infected urine, immediate antimicrobial treatment is reported to be essential. When treatment is delayed, the antimicrobial agent is believed to be effective only in eliminating bacteria, not in preventing scar formation. Using the ascending pyelonephritis model in rats, we investigated the effect of immediate or delayed treatment with ciprofloxacin and that of delayed treatment with a combination of ciprofloxacin and prednisolone in preventing renal scarring following infection. An inoculum of 1 x 10(9) colony forming units (cfu)/0.1 ml. of the HM32 strain of Escherichia coli, which was isolated from a patient with a urinary tract infection, was injected directly into the rat bladder, and the urethra was clamped for 4 hours in each rat. Treatment by ciprofloxacin (15 mg./kg., twice a day for 5 days) alone or in combination with prednisolone (2 mg./kg., once a day for 4 days) was initiated 6 or 72 hours after bacterial inoculation. The kidneys of each rat were examined 6 weeks later. Immediate treatment by ciprofloxacin significantly inhibited renal scarring (no scarring was seen in any of the 8 rats), but delayed treatment had no effect on scarring (4 of 8 rats showed scarring) when compared with the untreated controls (7 of 8 rats showed scarring). However, the addition of prednisolone to the delayed treatment with ciprofloxacin significantly inhibited renal scarring (only 1 of 10 rats showed scarring) when compared with the untreated controls (7 of 8 rats showed scarring). These data suggest that prednisolone is effective in preventing renal scarring which occurs due to vesicoureteral reflux when the initiation of antimicrobial treatment is delayed.

Animals↗

[Fundamental and clinical studies on MIC breakpoint of SY5555 for Enterococcus faecalis in complicated urinary tract infections of moderate severity].

A multicenter clinical study was carried out to investigate the clinical efficacy of SY5555 from viewpoint of its MIC breakpoint for Enterococcus faecalis. SY5555 was administered in dosages of 150 mg x 3/day and 300 mg x 3/day, for 7 days, to patients with complicated urinary tract infections of moderate severity (no indwelling catheter). Based primarily on the bacteriological efficacy (eradication) as the criterion for evaluation, the MIC breakpoint of SY5555 was investigated. SY5555 showed potent antimicrobial activity towards E. faecalis, and its MIC80 value for the clinical isolates of this bacterial species was 1.56 micrograms/ml. Analysis was carried out to determine the extent to which this in vitro activity is corroborated by the drug's clinical efficacy in eradicating E. faecalis. 1. Experimental study In a study employing an experimental model of complicated bladder infections of moderate severity, it was judged that the MIC breakpoints of SY5555 administered at 150 mg x 3/day and 300 mg x 3/day were 2 micrograms/ml and 8 micrograms/ml. 2. Clinical study SY5555 was administered at 150 mg x 3/day (7 days) to six patients and at 300 mg x 3/day (7 days) to 32 patients, and the clinical efficacy of these treatments was investigated. 2.1. Investigation of the clinical MIC breakpoint showed it to be 12.5 micrograms/ml for both the 150 mg x 3/day and 300 mg x 3/day regimens. However, since the number of cases in this study was small, analysis was performed of the data from a large number of cases by including the cases registered in a nation-wide Phase II study of SY5555. That analysis showed the clinical MIC breakpoint for the two dosages to be 3.13 micrograms/ml and 6.25 micrograms/ml. Thus, this analysis of large number of cases yielded clinical MIC breakpoint that are in agreement with the abovementioned experimental MIC breakpoints. 2.2. In the evaluation of the efficacy rate using the UTI drug efficacy evaluation criteria, cases rated as "good" or "excellent" numbered five of the six patients in the 150 mg x 3/day treatment group and 25 of the 32 (78.1%) patients in the 300 mg x 3/day treatment group, or 30/33 (78.9%) cases overall. These efficacy rates are about the same as the 82.0% reported for the nation-wide Phase II study. 2.3. Each of the strains of E. faecalis isolated from the patients was found to be eradicated by the SY5555 treatment: four strains in the 150 mg dosage group (the MIC of each was 3.13 micrograms/ml or less) and 18 strains in the 300 mg dosage group (the MIC of each was 6.25 micrograms/ml or less). Moreover, in both dosage groups, E. faecalis was not found to recur after the SY5555 treatment. 3. Conclusions In consideration of the above findings in the investigations of treatment of patients with complicated urinary tract infections of moderate severity, the following conclusions can be drawn. 3.1. In antimicrobial treatment employing SY5555 in a regimen consisting of 300 mg x 3/day for 7 days, the clinical breakpoint is in the range of 6.25-12.5 micrograms/ml. 3.2. In particular, as would be surmised from the fact that the MIC80 value of SY5555 for E. faecalis isolated is 1.56 micrograms/ml, this drug shows quite strong efficacy in the eradication of E. faecalis from cases of complicated urinary tract infection.

Adult↗

High prevalence of Neisseria gonorrhoeae strains with reduced susceptibility to fluoroquinolones in Japan.

OBJECTIVE: To study the antibiotic susceptibility of Neisseria gonorrhoeae strains isolated in Japan and, in particular, to examine the possibility of emerging fluoroquinolone resistance. MATERIALS AND METHODS: Sixty-nine strains of Neisseria gonorrhoeae isolated in 1992 were tested for susceptibility to 15 antibiotics including fluoroquinolones and were seroclassified. Twenty-seven strains isolated from 1981 to 1984 were also evaluated as controls. RESULTS: The MIC90 values of norfloxacin, ofloxacin, and ciprofloxacin against the isolates from 1992 were 2.0, 1.0, and 0.5 microgram/ml, respectively. The MIC90 values of norfloxacin, ofloxacin, and ciprofloxacin against the isolates from 1981-84 (controls) were 0.25, 0.125, and 0.063 microgram/ml, respectively. These results indicate that the MIC90 values of norfloxacin, ofloxacin, and ciprofloxacin against the strains from 1992 were 8-fold higher than those against the strains from 1981-84. However, there were no significant differences in susceptibility to beta-lactams, tetracyclines, macrolides, and spectinomycin between the isolates from 1992 and those from 1981-84. The majority of the isolates belonged to the WII/WIII serogroup. There was no relationship between fluoroquinolone resistance and serogroup. CONCLUSIONS: Fluoroquinolones have been used frequently as first-line therapy and have provided excellent clinical efficacy for gonococcal infections for the last several years in Japan. However, our data indicate that a rapid decrease in the susceptibility of Neisseria gonorrhoeae to fluoroquinolones is occurring in our country.

Chi-Square Distribution↗

Reduced uptake and accumulation of norfloxacin in resistant strains of Neisseria gonorrhoeae isolated in Japan.

OBJECTIVE: To investigate the alteration of cell permeability toward fluoroquinolones in Neisseria gonorrhoeae, which is a major quinolone-resistance mechanism along with the alteration of DNA gyrase in gram-negative bacteria. The prevalence of fluoroquinolone-resistant N gonorrhoeae strains is rapidly increasing in Japan. MATERIALS AND METHODS: The uptake and accumulation of norfloxacin by gonococcal cells, including six clinical and five World Health Organization (WHO) reference strains, were measured. Of the six clinical strains, two were highly resistant to norfloxacin (MIC 8.0 and 4.0 micrograms/ml), two were moderately resistant (MIC 1.0 and 0.5 microgram/ml), and two were sensitive (MIC 0.063 and 0.004 microgram/ml). All five WHO reference strains were sensitive to norfloxacin (MIC < or = 0.001 to 0.063 microgram/ml). RESULTS: Mean initial norfloxacin uptake in the four resistant strains (104 ng/mg of dry cells) was significantly lower than that in the seven sensitive strains (158 ng/mg of dry cells) (p < 0.05). The mean uptake after 20 minutes was also significantly lower in the four resistant strains (130 ng/mg of dry cells) than in the seven sensitive strains (194 ng/mg of dry cells) (p < 0.05). However, there was no significant difference in mean norfloxacin accumulation after 20 minutes between the four resistant strains (26 ng/mg of dry cells) and the seven sensitive strains (36 ng/mg of dry cells). The accumulation of norfloxacin after 20 minutes was almost zero in two of the four resistant strains, while the remaining two strains accumulated norfloxacin as well as the sensitive strains. CONCLUSIONS: These findings suggest that alteration of bacterial cell permeability is a quinolone-resistance mechanism in N gonorrhoeae isolated in Japan, and that this bacteria may exhibit other mechanisms such as alteration of DNA gyrase.

Cell Membrane Permeability↗

Renal scarring.

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Bibliography, Descriptive↗

Proliferating cell nuclear antigen in needle biopsy specimens of prostatic carcinoma.

The expression of proliferating cell nuclear antigen (PCNA) was immunohistochemically determined using a monoclonal antibody PC10 in 54 prostatic carcinoma samples. The samples were taken from needle biopsy specimens which had been paraffin-embedded after routine fixation with 10% formaldehyde solution (formalin) for less than 24 h. The PCNA index was calculated as the percentage of positive tumor cell nuclei. There was a significant difference in the PCNA index according to the growth pattern (p < 0.001), nuclear anaplasia (p < 0.001) and T stage (p < 0.01). Regarding the growth pattern, solid carcinomas showed a significantly higher PCNA index than did either separate gland carcinomas (p < 0.05) or trabecular/fused gland carcinomas (p < 0.05). The PCNA index correlated closely with either the nuclear anaplasia or T stage, and increased in conjunction with the increased nuclear anaplasia (rs = 0.641; p < 0.001) or T stage (rs = 0.435; p < 0.01). The patients in the high PCNA index (> or = 15%) group showed a significantly worse survival than did those in the lower PCNA index group (p < 0.01), and multivariate analyses indicated that the PCNA index had an independent prognostic significance. These results suggest that the PCNA index, as determined by PC 10 on needle biopsy specimens of prostatic carcinoma, can thus be an objective and quantitative means for evaluating the biological malignancy of prostatic carcinoma.

Adenocarcinoma↗

Laparoscopic adrenalectomy: comparison with open adrenalectomy.

The results of the first 6 cases of laparoscopic adrenalectomy were compared with the most recent 11 consecutive cases of traditional open adrenalectomy for the treatment of benign adrenal tumor. In both groups, all the tumors were less than 4 cm in diameter and were removed successfully with no significant complications. The weight of the resected specimen and estimated blood loss were not significantly different in the two groups, and none of the patients needed a blood transfusion. Although laparoscopic adrenalectomy required a significantly longer operation time (median 230 min vs. 165 min for an open operation), the postoperative recovery estimated by the duration of restricted oral intake or walking was shorter, and the incidence of patients requiring postoperative parenteral analgesics was also significantly lower in laparoscopic adrenalectomy. Although the number of patients treated with the laparoscopic procedure is still small, these results suggest that laparoscopic adrenalectomy is a minimally invasive alternative to open adrenalectomy and, with further improvement of the operative technique and equipment, may become a more reliable and standard procedure for the treatment of benign adrenal tumor.

Adrenal Gland Neoplasms↗

Suppressive effect of cyclosporin A on delayed-type hypersensitivity to syngeneic testicular cells.

We have investigated the immunosuppressive effect of cyclosporin A (CsA) on delayed-type hypersensitivity (DTH) to syngeneic testicular cells (TC). DTH to syngeneic TC was induced by subcutaneous (sc) immunization with viable syngeneic TC and was augmented by a high dose of cyclophosphamide (CY)-pretreatment. DTH was suppressed by administration of CsA in a dose-dependent manner. When the mice were immunized alone or with 100 mg/kg of CY-pretreatment, 30 mg/kg or more of CsA suppressed DTH to TC. In mice immunized with 200 mg/kg of CY-pretreatment, 50 mg/kg of CsA was needed to suppress DTH. DTH is thought to play a key role in the induction and/or maintenance of experimental autoimmune orchitis (EAO). Our data show that DTH to syngeneic TC induced by immunization is suppressed by administration of CsA. Pretreatment of mice with immunization and administration of CsA suppressed DTH significantly when the mice were challenged with immunization with CY-pretreatment. However, DTH was rather enhanced significantly in mice pretreated with administration of CsA alone without preimmunization. Therefore, even though administration of CsA with immunization suppresses DTH, administration of CsA alone might rather eliminate suppressive mechanism resulting in augmentation of DTH.

Animals↗

Inhibition of allograft rejection by anti-T-cell receptor-alpha beta monoclonal antibodies preserving resistance to bacterial infection.

Anti-CD3 monoclonal antibody (mAb) has been administered in clinical organ transplantation to reverse acute allograft rejection; however, severe immunodeficiency can result from such mAb treatment and cause an increased incidence of opportunistic infections. Therefore, new model systems are required in order to establish better methods for suppressing allograft rejection while preserving resistance to opportunistic infections. In this study, we compared the effects of the in vivo administration of anti-T-cell receptor-alpha beta (TcR alpha beta) mAb, H57-597, with those of anti-CD3 mAb, 145-2C11. Much to our surprise, the in vivo administration of anti-TcR alpha beta mAb prior to skin grafting led to a longer allograft survival than that of anti-CD3 mAb at any of the comparable dosages examined. In the lymphoid organs of mice treated with anti-TcR alpha beta mAb, TcR alpha beta-bearing cells were almost completely depleted, while TcR gamma delta-bearing cells remained at a relatively increased level on day 14 after anti-TcR alpha beta mAb treatment. The in vitro stimulation by anti-TcR gamma delta mAb clearly showed that such TcR gamma delta-bearing cells were functionally intact. Furthermore, the mice treated with anti-TcR alpha beta mAb, but not anti-CD3 mAb, were observed to be resistant to infection with Listeria monocytogenes. Finally, treatment with H57-597, but not with 145-2C11, led to a marked prolongation of skin allograft survival in the thymectomized mice. These results strongly suggest that anti-TcR alpha beta mAb, which partially preserved anti-bacterial resistance, may be more effective in preventing graft rejection than anti-CD3 mAb in the periphery, and indicate that anti-TcR alpha beta mAb may thus be potentially applicable for human transplantation. In addition, these results also indicate that the TcR gamma delta-bearing cells alone, at least in the absence of TcR alpha beta-bearing cells, do not contribute to allograft rejection in vivo.

Animals↗