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Biomedical subjects

K Kobashi

Publications and source records attributed to K Kobashi.

At least 127 records · Page 7Linked to original sources

Chemosensitivity study of urological malignancies using a novel dye-exclusion method.

The chemosensitivity of several urological malignancies was determined using a novel dye-exclusion method. The tests proved to be successful in 22 out of 33 urothelial transitional-cell carcinomas, 21 out of 29 renal-cell carcinomas, and in 8 out of 13 testicular tumors, but in 0 out of 4 Wilms' tumors. At 10% of the peak plasma concentration of anticancer drugs achievable after single bolus injection, the sensitivity rates of urothelial transitional-cell carcinomas for cis-platinum, adriamycin, and carboquone were 27.3%, 13.3%, and 5.6%, respectively. At the peak plasma level, urothelial transitional-cell carcinomas were 'susceptible' to cis-platinum, carboquone, and adriamycin, the sensitivity rates being 60%, 50%, and 30%, respectively. The number of these carcinomas susceptible at the peak plasma level was significantly larger than that at 10% of the peak plasma level (P less than 0.01). However, renal-cell carcinomas exhibited a low sensitivity rate of 38% even when exposed to the peak plasma level. A similar trend was observed when tumor chemosensitivity was determined using a modified human tumor clonogenic assay. These results suggest that urothelial transitional-cell carcinomas may show good responses when anticancer drugs are given at high concentrations using methods such as intra-arterial infusion and intravesical instillation.

Antineoplastic Agents↗

Immobilized arylsulfotransferase.

Arylsulfotransferase was stabilized for storage more markedly by covalent immobilization onto DEAE-cellulose or DEAE-Sephadex. The optimal pH, Km for sulfate donor and thermostability of covalently immobilized arylsulfotransferase were similar to those of the free enzyme. Tyrosine-containing peptides such as cholecystokinin-8-nonsulfate, tyrosine methylester and (Leu)enkephalin as acceptor substrates were effectively sulfated by the immobilized enzyme.

Arylsulfotransferase↗

Purification and characterization of 7 beta-hydroxysteroid dehydrogenase from Ruminococcus sp. of human intestine.

7 beta-Hydroxysteroid dehydrogenase (7 beta-HSD) was produced by Ruminococcus sp. PO1-3 obtained from among human intestinal bacteria. The enzyme was purified from a crude extract by ammonium sulfate fractionation, and Butyl-Toyopearl 650M, Sephadex G-150, Matrex Red A and Octyl-Sepharose chromatographies. The purified enzyme was obtained as a single band on polyacrylamide gel electrophoresis with enzyme activity staining and as one band corresponding to a molecular weight of 30,000 on SDS-polyacrylamide gel electrophoresis. On gel filtration, its apparent molecular weight was estimated to be 60,000. The enzyme had a sulfhydryl group(s) in its active site. Substrate specificity studies revealed that the enzyme showed absolute specificity for the beta-configuration of a hydroxyl group at the 7 position of bile acids, and required NADP+ and NADPH as cosubstrates. The Km values for ursodeoxycholic acid, 7-k etolithocholic acid, NADP+, and NADPH were 5.0, 8.5, 7.7, and 24 microM, respectively.

Bacterial Proteins↗

[An experience with nephrolithotomy under guidance of intraoperative ultrasonic scanning].

A 50-year-old male with small renal stones and ureteral stones underwent nephrolithotomy under guidance of electronic linear array ultrasound scanning. We used 5 MHz. and 7.5 MHz. ultrasound probes (Aloka model UST-587 T-5, UST-556 T-7.5). This intraoperative guidance was very useful to locate and remove small renal calculi which were impossible to remove by fibrin coagulum pyelolithotomy. The ultrasonogram of the 7.5 MHz. probe was clearer than that of the 5 MHz. one.

Humans↗

[An in vitro chemosensitivity study using the human tumor clonogenic assay in urological malignancies: a preliminary report].

Surgical tumor specimens from 67 urological malignancy patients were subjected to a human tumor clonogenic assay (HTCA) developed by Hamberger and Salmon. Appreciable growth of colonies was obtained in 20 of the 33 renal cancers, 20 of the 30 urothelial cancers and 1 of the 4 testicular cancers examined. Using HTCA, a plating efficiency ranging from 0.01 to 0.5% was obtained in these urologic malignancies. However, colonial growth adequate for chemosensitivity was obtained in 30 of these 67 patients. According to Von Hoff's definition, more than a 70% decrease in the plating efficiency after anticancer drug exposure was defined as susceptible. Susceptibility to vinblastine (VBL) was seen in 4 of the 11 patients with renal cancer. Susceptibility to cis-dichlorodiamine platinum (CDDP) was seen in 4 of the 15 patients with urothelial cancer, 1 of the 4 patients with renal cancer, and that to adriamycin (ADM) was seen in 3 of the 15 patients with urothelial cancer, 2 of the 10 patients with renal cancer and 1 patient with testicular cancer. For comparison, the ratio of IC90 to the peak plasma concentration of the drug tested was used as the "in vivo-in vitro therapeutic index (TI)". According to TI, susceptibility to VBL was seen in 3 of the 7 patients with renal cancer, and that to CDDP was seen in 2 of the 12 patients with urothelial cancer, and 1 of the 2 patients with renal cancer. Susceptibility to ADM was seen in 3 of the 15 patients with urothelial cancer, and 1 of the 6 patients with renal cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Agents↗

[A combined treatment of interferon-alpha, 8 MHz radiofrequency hyperthermia and/or irradiation in a patient with advanced renal cancer].

A combined treatment of alpha interferon (INF), 8 MHz radiofrequency (RF) hyperthermia using Thermotron-RF Model 8 and/or irradiation was performed on a patient with advanced renal cancer. The patient was a 52-year-old male, who had received arterial embolization with a gelatin sponge and 60 mg of adriamycin for the right renal tumor in January, 1985. He was referred to our clinic in April, 1985. Computed tomography showed a right renal tumor, 120 x 105 x 80 mm. Histological examination revealed clear cell carcinoma of the right kidney. The tumor was unresectable because of the huge tumor size, invasion into the right lobe of the liver, multiple pulmonary metastases and severe dysproteinemia. From the beginning of May, 1985, administration of 3 x 10(6) units interferon-alpha (INF) daily and radiofrequency (RF)hyperthermia for one hour twice a week were started. By June 11, 1985, 10 sessions of RF-hyperthermia were performed. Thereafter, hyperthermia for the renal tumor was maintained once a week until June, 1986. From the middle of June, 1985, a gradual improvement of dysproteinemia and appetite loss, and a decrease of the right renal tumor size as well as disappearance of febrile attacks were attained. In November, 1985, mediastinal lymph node swelling developed. A combined therapy of RF-hyperthermia twice a week and irradiation with 2.0 Gy daily 5 times a week was started. A total of 14 sessions of RF-hyperthermia and 30 Gy of irradiation were delivered until January, 1986. Intratumoral temperature of the renal tumor reached 44.0 degrees C during the heating.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinoma, Renal Cell↗

[Successful percutaneous drainage for infected cysts in polycystic kidney disease in a case of chronic hemodialysis].

A 60-year-old woman, who had been receiving chronic hemodialysis for chronic renal failure due to polycystic disease for 7 years, was admitted to our hospital with the chief complaints of right flank pain and high-grade fever on February 3, 1986. She had a family history of polycystic kidney disease and her elder sister has been undergoing chronic hemodialysis. The patient has had repeated episodes of urinary tract infection. The right markedly distended kidney was palpated with severe tenderness, and the performance status was poor. Computerized tomography showed the right kidney enlarging beyond the median line, but localization of the infected cysts was not clear. The 7-day intensive antibiotic therapy had no beneficial effect. On the 8th hospital day, percutaneous drainage, which was carried out for a large cyst with low-level echoes using ultrasonic guidance, yielded 600 ml of hemopurulent fluid. Bacterial culture of the aspirated fluid was positive for Escherichia coli. As the clinical symptoms did not improve after the 8th day, 10 Fr. catheter placement, percutaneous drainage and catheter placement were added for other cysts containing hemopurulent fluid. Although hematopyuria persisted, the patient became afebrile and the right kidney became smaller and softer. Both catheters were removed on the 30th hospital day. Repeated computerized tomography or ultrasonography revealed a few hyperdense or hyperechoic cysts in the right kidney. However, no recurrence of high-grade fever or right flank pain has been seen for 3 months. Ultrasonic-guided percutaneous drainage has a great potential for patient care of infected cysts in polycystic kidney disease.

Bacterial Infections↗

[Successful chemotherapy with adriamycin and methotrexate in a case of advanced transitional cell carcinoma of the ureter--a clinical application of subrenal capsule assay].

A case of advanced transitional cell carcinoma of the left ureter was treated with a combination of adriamycin and methotrexate. These drugs were selected using the subrenal capsule assay for which tumor tissues were obtained from a biopsy specimen of the left supraclavicular lymph node. Complete regression of left supraclavicular lymph node metastasis and 90% regression of para-aortic lymph node metastasis were obtained after four courses of the combination therapy. Subsequently, left total nephro-uretrectomy and retroperitoneal lymph node dissection were carried out. Pathological examination revealed the remains of tumor cells in the primary lesion and in the para-aortic lymph node. The tumor tissues obtained from the para-aortic lymph node were not susceptible to adriamycin and methotrexate. However, the tendency of the regression rates in the drug-treated groups was the same as that apparent before chemotherapy. Three courses of the same regimen as that given before surgery were then prescribed. The patient is currently alive with no evidence of disease. We therefore suggest the usefulness of the subrenal capsule assay for predictive chemosensitivity testing.

Antineoplastic Combined Chemotherapy Protocols↗

A novel sulfotransferase sulfates tyrosine-containing peptides and proteins.

The novel sulfotransferase (M.W. 315 kDa) obtained from Eubacterium A-44 catalyzed the sulfation of tyrosine residues of peptides and proteins such as kyotorphin, enkephalin, cholecystokinin-8 (non-sulfated form), trypsin inhibitor and insulin. Also, the enzyme sulfated tyrosine residues of protein fractions purified from Eubacterium A-44.

Eubacterium↗

The role of intestinal flora in metabolism of phenolic sulfate esters.

Arylsulfotransferase activity was found in the feces of human (14.74 +/- 2.674) and rat (7.37 +/- 1.126 mumol/hr/g wet feces). In the case of the rat, arylsulfotransferase activity was markedly and rapidly decreased by the treatment with antibiotics mixture, but restored to the original activity 3 weeks after stopping the administration of antibiotics. The excretion of the sulfate esters derived from p-nitrophenylsulfate was enhanced by the administration of acetaminophen but not by the treatment with antibiotics. Furthermore, in rats treated with antibiotics, inorganic sulfate excretion was severely decreased. When only acetaminophen was administered, the excretion of acetaminophen-O-sulfate showed a 10-15% decrease in rats treated with antibiotics compared with conventional rat.

Acetaminophen↗

Purification, characterization and reaction mechanism of novel arylsulfotransferase obtained from an anaerobic bacterium of human intestine.

A novel type of arylsulfotransferase was purified from Eubacterium A-44, one of the predominant bacteria of human intestine. The enzyme (Mr 315 000) was composed of four identical subunits (Mr 80 000) whose N-terminal amino acids were arginine. pI and optimal pH of the enzyme were 3.9 and 8-9, respectively. The apparent Km for p-nitrophenylsulfate using tyramine as an acceptor substrate and that for tyramine using p-nitrophenylsulfate as a donor substrate were determined to be 0.104 mM and 3.5 mM, respectively. The reaction mechanism of the enzyme was proposed as follows: a donor substrate, p-nitrophenyl [35S]sulfate, combines a histidine residue of the enzyme active site with concomitant release of a phenolic compound, p-nitrophenol. The sulfate group of the histidine residue transfers to a tyrosine group, and then to an acceptor with the binding of another donor to the histidine residue.

Arginine↗

A novel type of aryl sulfotransferase obtained from an anaerobic bacterium of human intestine.

A novel type of aryl sulfotransferase is produced by an anaerobic bacterium of human intestine, Eubacterium A-44. Aryl sulfotransferase separated from this bacterium differs from the sulfotransferase which uses 3'-phosphoadenosine 5'-phosphosulfate as a donor. The enzyme catalyzes stoichiometric transfer of a sulfate group from a phenol sulfate ester to other phenolic compounds, with strict specificity. The optimal pH and molecular weight were 8-9 and 315,000, respectively.

Arylsulfotransferase↗