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Biomedical subjects

J Kumazawa

Publications and source records attributed to J Kumazawa.

At least 91 records · Page 5Linked to original sources
PubMed1995

Expression of multidrug resistance-associated protein (MRP), MDR1 and DNA topoisomerase II in human multidrug-resistant bladder cancer cell lines.

The acquisition of the multidrug resistance phenotype in human tumours is associated with an overexpression of the 170 kDa P-glycoprotein encoded by the multidrug resistance 1 (MDR1) gene, and also with a 190 kDa membrane ATP-binding protein encoded by a multidrug resistance-associated protein (MRP) gene. Human bladder cancer is a highly malignant neoplasm which is refractory to anti-cancer chemotherapy. In order to understand the mechanism underlying multidrug resistance in bladder cancer, we established three doxorubicin-resistant cell lines, T24/ADM-1, T24/ADM-2 and KK47/ADM, and one vincristine-resistant cell line, T24/VCR, from human bladder cancer T24 and KK47 cells respectively. Both T24/ADM-1 and T24/ADM-2 cells which had elevated MRP mRNA levels showed both a cross-resistance to etoposide and a decreased intracellular accumulation of etoposide. T24/VCR cells which had elevated levels of MDR1 mRNA and P-glycoprotein but not of MRP mRNA, showed cross-resistance to doxorubicin. On the other hand, KK47/ADM cells, which had elevated levels of both MRP and MDR1 mRNA and a decreased level of topoisomerase II mRNA, were found to be cross-resistant to etoposide, vincristine and a camptothecin derivative, CPT-11. Our present study demonstrates a concomitant induction of increased levels of MRP mRNA, decreased levels of topoisomerase II mRNA and decreased drug accumulation during development of multidrug resistance in human bladder cancer cells. The enhanced expression of the MRP gene is herein discussed in a possible correlation with the decreased expression of the topoisomerase II gene.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Laparoscopic adrenalectomy: review of 14 cases and comparison with open adrenalectomy.

We reviewed 14 cases of laparoscopic adrenalectomy and compared the results with those of a recent series of 15 consecutive patients undergoing a traditional open adrenalectomy for a benign tumor. The laparoscopic adrenalectomy group included nine patients with primary aldosteronism, three with Cushing's syndrome, one with pheochromocytoma, and one with a nonfunctioning incidentaloma. In the patient with pheochromocytoma, a good operative field was safely obtained by a combination of pneumoperitoneum at less than 6 mm Hg insufflation pressure and the abdominal wall-lift method. In both groups, the tumors were removed successfully in all cases. Laparoscopic adrenalectomy, which required neither a large skin and muscle incision nor any resection of the ribs, offered a lower morbidity and earlier recovery in spite of the longer operation time. The most important complication observed in laparoscopic adrenalectomy was that of pneumothorax secondary to an injury of the diaphragm and pleura during the dissection of the left adrenal gland using electrocautery. However, the injury wound was small, and the pneumothorax was resolved by suturing the tear under laparoscopy. These results suggest that laparoscopic adrenalectomy is a minimally invasive alternative to traditional open adrenalectomy and thus has the potential soon to become a standard procedure for the treatment of benign adrenal tumors.

Adrenal Gland Diseases↗
PubMed1995

Non-P-glycoprotein-mediated atypical multidrug resistance in a human bladder cancer cell line.

A human bladder cancer cell line resistant to adriamycin (ADM), T24/ADM9 has been established in vitro by exposing T24 parent cells to progressively higher concentrations of the drug over a period of 12 months. The T24/ADM9 cells were found to be 9 times more resistant to ADM than the T24 parent, and showed various degrees of cross-resistance to an ADM derivative, vinea alkaloids and a DNA topoisomerase II (Topo II)-targeting agent, etoposide. No significant differences was observed in the cellular accumulation of ADM between the T24/ADM9 and T24 parent cells. A Northern blot analysis showed an overexpression of multidrug resistance-associated protein (MRP) mRNA, but no overexpression of multidrug resistance-1 (MDR1) mRNA was observed in the T24/ADM9 cells. A flow cytometric analysis showed that the MDR1 gene product, P-glycoprotein (Pgp), is not expressed on the T24/ADM9 cells. T24/ADM9 showed approximately the parental level of DNA Topo II catalytic activity. In Western blot and Northern blot analyses, however, the cellular level of DNA topo II was apparently much lower in T24/ADM9 than in the T24 parent. Thus, these results suggest that a decreased cellular level of DNA Topo II and an overexpression of MRP gene may be responsible for the expression of an MDR phenotype in the T24/ADM9 cells and that such non-Pgp-mediated, atypical MDR may develop in bladder cancer treated with chemotherapy including ADM.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

[A nation-wide surveillance of pathogen in elderly patients with urinary tract infections. 1st Report: Distribution of pathogen].

A nation-wide surveillance of causative organisms was conducted on 1,699 elderly patients with UTIs aged more than 65 in 190 private clinics and 73 hospitals in August and September, 1993, in order to investigate the distribution of causative bacteria and the relationship between isolates and the background of those patients. From 1,233 of the 1699 patients, 1,636 strains were isolated. E. coli was isolated most frequently (30%). in male and older patients, less E. coli were isolated, while more attenuated Gram negative rods such as NFGNR including P. aeruginosa were found. A similar trend was observed in uncomplicated UTIs isolates in this study. More E. coli were isolated from patients with stronger subjective symptoms while more bacteria other than E. coli were isolated in those with weaker subjective symptoms. From the above findings, it was confirmed that a high recovery rate of opportunistic pathogen which is less susceptible to various antibacterials is one the refractory factors in elderly patients with UTIs. Therefore, it is necessary to select a suitable antibacterial that can be used for complicated UTIs in elderly patients even when diagnosed as uncomplicated UTIs. Regardless of the size of the clinic or hospital, when treating elderly patients, with unsatisfactory results in initial treatment and with less subjective symptoms the physician must bear this in mind.

Aged↗
PubMed1995

[A nation-wide surveillance of pathogen in elderly patients with urinary tract infections. 2nd Report: Sensitivities of pathogen for oral antibacterial agents].

A nation-wide surveillance of sensitivities of bacteria, which were isolated from elderly patients with UTIs aged more than 65 in 190 private clinics and 73 hospitals, for oral antibacterials, CPFX, OFLX, NFLX, CPDX and CCL, was conducted in August and September in 1993. Antibacterial activities of 5 agents against all 1,511 strains were intensified in CPFX, OFLX, NFLX, CPDX and CCL in that order. Major pathogens such as Enterobacteriaceae, E. faecalis, Staphylococcus spp. and P. aeruginosa were more susceptible to fluoroquinolones than cephems. The rate of resistant strains to antibacterials was higher in isolates from older patients, patients with complicated UTIs and with indwelling catheter. The representative of resistant strains was P. aeruginosa, and about 50% of the strains of P. aeruginosa were resistant to even CPFX which had the most superior antibacterial activity among the 5 agents. About 40% of the S. aureus were MRSA, which were almost resistant to the 5 agents. From the above findings, it was confirmed that a high recovery rate of strains which is less susceptible to various antibacterials is one of the refractory factors in elderly patients with UTIs, particularly in complicated UTIs and with indwelling catheter. Regardless of the size of the clinic or hospital, Fluoroquinolones are more suitable for the treatment of elderly patients with UTIs than cephems.

Aged↗
PubMed1995

Emergence of in vitro resistance to fluoroquinolones in Neisseria gonorrhoeae isolated in Japan.

To investigate emerging fluoroquinolone resistance in Neisseria gonorrhoeae isolated in Japan, we compared the in vitro antimicrobial susceptibilities of 79 gonococcal isolates from 1992 through 1993 to 14 fluoroquinolones and 14 other antibiotics with those of 27 isolates from between 1981 and 1984. The MICs at which 90% of the isolates were inhibited by nine fluroquinolones, including norfloxacin, enoxacin, ofloxacin, ciprofloxacin, tosufloxacin, lomefloxacin, fleroxacin, levofloxacin, and sparfloxacin, for isolates from 1992 to 1993 were 8- or 16-fold higher than those for isolates from 1981 to 1984. Furthermore, the MICs at which 90% of the isolates were inhibited by five fluroquinolones, including OPC-17116, T-3761, DU-6859a, AM-1155, and Q-35, that have recently been synthesized but have not yet been introduced for clinical use in Japan for isolates from 1992 to 1993 were also 2- to 16-fold higher than those for isolates from 1981 to 1984. The gonococcal isolates from 1992 to 1993 showed no significant decreases in susceptibility to beta-lactams, tetracyclines, macrolides, and spectinomycin, compared with those for isolates from 1981 to 1984. Our data indicate that the incidence of gonococcal strains with decreased susceptibilities to fluoroquinolones is increasing in Japan.

Anti-Bacterial Agents↗
PubMed1995

Preventive effect of ulinastatin on renal scarring in rat model of pyelonephritis induced by direct or ascending infection with Serratia marcescens or Escherichia coli.

Renal scarring is considered to be a characteristic of reflux nephropathy. The effects of ulinastatin, a strong inhibitor of polymorphonuclear leukocyte elastase, on renal scarring following direct parenchymal or intravesical ascending infection by Serratia marcescens or Escherichia coli were determined. Four days of treatment with ulinastatin initiated 2 or 5 days after infection prevented renal scarring. Doses of 1,000-4,000 units/kg inhibited renal scar formation, but 8,000 units/kg did not. These results suggest that it may be possible to limit renal scar formation in pyelonephritis by the use of an appropriate pharmacologic agent.

Animals↗
PubMed1995

Effect of MPL 9000 extracorporeal shock wave lithotripsy on renal hemodynamics and urine flow: assessment by 99mTc-DTPA renal scintigraphy.

The effect of extracorporeal shock wave lithotripsy (ESWL) with an MPL9000 lithotriptor on renal hemodynamics and urine flow was investigated by 99mTc-DTPA renal scintigraphy. In the first-pass scintigrams obtained within 1 min after injection of 99mTc-DTPA, there was no significant change in the time to the maximum radioactivity level and the maximum radioactivity ratio at 1 day before ESWL and 1 day or 1 month after ESWL. However, analysis of 30-min scintigrams showed that urinary clearance of radioactivity was delayed in the treated kidney 1 day after ESWL, particularly in the region targeted by shock waves, despite the absence of overt urinary tract obstruction by residual stone fragments. This change was reversible and was no longer noted 1 month after ESWL. These results suggest that ESWL with the MPL9000 lithotriptor induces a focal and temporary decrease in urine flow in the treated kidney, but has little or no effect on renal hemodynamics.

Adult↗
PubMed1995

[Treatment of advanced renal cell carcinoma with a combination of interferon alpha and gamma].

A total of 29 patients with advanced renal cell carcinoma entered a pilot study of combination therapy with interferon alpha (IFN-alpha) and interferon gamma (IFN-gamma). IFN-alpha (HLBI: 3 x 10(6) IU, BALL 1:5 x 10(6) IU, IFN-alpha-2a: 9 x 10(6) IU or IFN-alpha-2b: 6 x 10(6) IU) was given intramuscularly every day and IFN-gamma (IFN-gamma-1a: 3 x 10(6) JRU) was given intravenously by drip infusion 3 times a week (every 2-3 days). The treatment was continued for 3 months as the induction therapy, and then the tumor response was evaluated. Of the 22 evaluable patients, 4 achieved a partial response (PR), 10 showed no change (NC), and in 8 the disease had progressed (PD) during the therapy. Thus, the overall response rate was 18.2% [95% confidence interval (CI) 2.1-34.3%]. A favorable response tended to be obtained in patients with good performance status or small pulmonary metastases, or in those who had no prior therapy with IFN-alpha, who received this treatment immediately subsequent to radical nephrectomy, or who received IFN-gamma as much as possible according to this regimen. Toxicity was evaluated in 28 patients: fever, general fatigue, anorexia, leukocytopenia and impaired liver function were frequently noted, and 3 patients were withdrawn from the study because of such adverse effects. In patients who had a PR or NC, the same dosage of IFN-alpha was continued to be given intramuscularly 2-3 times a week (every 2-4 days) as the maintenance therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

[Murine "sympathetic orchitis" induced by unilateral testicular injury and autoimmune response].

BACKGROUND: Experimental autoimmune orchitis (EAO) has been studied as an animal model for human male immunological infertility. Most EAO models have been induced by immunization with testis antigens in artificial adjuvants. In this paper, we report a more clinical EAO model. METHODS: Ten to 20 needle punctures were made to the unilateral testis of mice and it was crushed by a needle-holder. RESULTS: Contralateral EAO (so-called "sympathetic orchitis") was gradually induced starting on Day 28. Delayed type hypersensitivity (DTH), one of the cell-mediated immunities, to autologous testicular cells (TC) as well as anti-TC antibodies, humoral immunity, were both detected in those mice. Repeated crush(es) of the ipsilateral testis two weeks later (and four weeks later) as a booster did not enhance the contralateral lesion or autoimmune responses. CONCLUSION: Our present injury model mimics clinical testicular trauma; therefore, this testicular injury model can be very useful in studying the immunological mechanism of EAO and of human immunological male infertility.

Animals↗
PubMed1995

Combination chemotherapy with intra-arterial cisplatin and doxorubicin plus intravenous methotrexate and vincristine for locally advanced bladder cancer. Kyushu University Urological and Radiological Oncology Group.

PURPOSE: We evaluate the usefulness of neoadjuvant chemotherapy for bladder cancer. MATERIALS AND METHODS: The usefulness of neoadjuvant, modified methotrexate, vinblastine, doxorubicin and cisplatin chemotherapy was evaluated in 36 patients with locally advanced bladder cancer. RESULTS: Of 36 patients 12 achieved a clinical complete response and 17 had a partial response. Of the 12 patients who achieved a clinical complete response the bladder was preserved in 11 and all patients were disease-free at a median of 33 months. No significant toxicity was observed. CONCLUSIONS: This chemotherapy is useful for locally advanced bladder cancer and the feasibility of bladder preservation in patients with a clinical complete response was suggested.

Adult↗
PubMed1995

Effect of pili of Serratia marcescens on superoxide production and phagocytosis of human polymorphonuclear leukocytes.

PURPOSE: To determine the role played by superoxide in renal scar formation following renal infection. MATERIALS AND METHODS: The piliation of bacteria was assessed for its capacity to interact with human polymorphonuclear leukocytes (PMNs). Two recombinant strains having either MS or MR pili of Serratia marcescens were constructed. RESULTS: The MS-piliated strain stimulated superoxide production of PMNs twice as much as the MR- or nonpiliated strains did. The MS-piliated strain was more susceptible to phagocytosis than was the MR- or nonpiliated strain. CONCLUSION: These data suggest that the MS-piliated strain stimulates superoxide production of PMNs associated with phagocytosis, which leads to tissue damage in infected organs.

Drug Resistance, Microbial↗
PubMed1995

Testicular injury induces cell-mediated autoimmune response to testis.

Studies on testis autoimmunity are needed for a better understanding of immunological male infertility. Evidence has accumulated that the delayed type hypersensitivity (DTH) response plays a key role in the induction and/or maintenance of experimental autoimmune orchitis (EAO), an animal model for human immunological male infertility or aspermatogenesis. We report here that an antigen-specific DTH response to autologous testicular cells (TC) could be induced by bilateral testicular injury (trauma) in mice. Pretreatment of traumatized mice with a high dose of cyclophosphamide (CY) enhances the DTH response in a dose-dependent manner. The DTH response induced by testicular injury reaches its peak on the ninth day. We have shown that the local passive transfer of the footpad reaction to normal recipients by T cells further defines the DTH reaction. These characteristics resemble those of the previously reported DTH response to syngeneic TC induced by subcutaneous immunization with viable syngeneic crude TC. Our present injury model mimics clinical testicular trauma; therefore, this testicular injury model can be very useful in studying the immunological mechanism of EAO and of human immunological male infertility.

Animals↗
PubMed1994

Increased expression of DNA topoisomerase I gene and collateral sensitivity to camptothecin in human cisplatin-resistant bladder cancer cells.

We established three cis-diamminedichloroplatinum(II) (cisplatin)-resistant cell lines, T24/DDP5, T24/DDP7, and T24/DDP10, by the stepwise exposure of T24 human bladder cancer cells to increasing concentrations of cisplatin. The resistance to cisplatin of T24/DDP5, T24/DDP7, and T24/DDP10 cells was 2.2-, 5.2-, and 8.4-fold that of the parental T24 cells, respectively. The cisplatin-resistant cell lines also showed an increased resistance to vincristine, although their sensitivities to Adriamycin and etoposide resembled that of T24. In contrast, the cisplatin-resistant cells developed a collateral sensitivity to (4s)-4,11-diethyl-4-hydroxy-9-[(4-piperidinopiperidino)carbonyl oxy]dione hydrochloride trithydrate, a camptothecin derivative, and its active metabolite, 7-ethyl-10-hydroxy-camptothecin, that targets DNA topoisomerase I. Both a Northern blot analysis and an immunoblot analysis demonstrated increased cellular levels of DNA topoisomerase I mRNA in the resistant cell lines. However, the expression of DNA topoisomerase II in the three resistant cell lines did not differ significantly from that in the T24 cells. No significant differences in the glutathione S-transferase pi levels were observed, although the intracellular content of glutathione in the T24/DDP7 cells was slightly but significantly increased. In addition, the intracellular platinum concentration correlated negatively with the degree of cisplatin resistance and was found to be significantly decreased in T24/DDP10 at an external cisplatin concentration of 20 micrograms/ml. These results suggest that the increased levels of DNA topoisomerase I mRNA thus play an important role in cisplatin resistance and produce a collateral sensitivity to (4s)-4,11-diethyl-4-hydroxy-9[(4-piperidinopiperidino)carbonylo xy]dione hydrochloride trithydrate and 7-ethyl-10-hydroxycamptothecin in these cisplatin-resistant bladder cancer cell lines. In addition, the presence of decreased intracellular cisplatin accumulation may also contribute to the acquisition of resistance to cisplatin in these cell lines.

Blotting, Northern↗