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T Kuno

Publications and source records attributed to T Kuno.

186 records · Page 11Linked to original sources

Acute and subacute toxicity of 10B-paraboronophenylalanine.

The acute and subacute toxicities of 10B-paraboronophenylalanine (10B-BPA) were investigated in the rat, according to the Good Laboratory Practice Standard for safety studies on drugs in Japan. In the acute toxicity test of 10B-BPA, LD50 values of acidic 10B-BPA for intraperitoneal and subcutaneous injections were 640 mg/kg for male and 710 mg/kg for female rats, and more than 1,000 mg/kg for male and female rats, respectively. The LD50 values of neutral 10B-BPA for intraperitoneal and subcutaneous injections were more than 3,000 mg/kg for male and female rats. The difference in LD50 values between acidic and neutral 10B-BPA may be attributed to the acidity of material. From the subacute toxicity test, in which the rats were injected daily subcutaneously for 28 days, the following toxic effects of 10B-BPA were observed. Increase in ketone level in the urine was induced in all rats treated with 10B-BPA. High dose of 10B-BPA (1,500 mg/kg) induced increase in spleen weight and reticulocyte count, and decrease in hemoglobin count, thereby suggesting that 10B-BPA causes hemolysis. Increases in the leukocyte count and the ratio of neutrophils and lymphocytes were also observed in rats treated with a high dose of 10B-BPA. This may be attributed to local reactions at the injection site. There were no significant differences in the findings between control rats and rats treated with a low dose of 10B-BPA (300 mg/kg). Thus, low doses of neutral 10B-BPA may be available for use as a drug.

Animals↗

Expression of the multidrug-resistant gene in human musculoskeletal tumors.

We measured the levels of messenger RNA of the human multidrug-resistant (MDR) gene in 15 human musculoskeletal tumors. In metastatic tumors and those which did not respond to combination chemotherapy, there was an increased expression of this gene. No evidence of expressions of the MDR gene was found in the benign tumors. The high expression of the MDR gene from musculoskeletal tumors apparently induced a multidrug resistance, and this acquired resistance may be due to outgrowth of the P-glycoprotein-expressing MDR tumor. Elucidation of expression of the MDR gene is an important step in malignant musculoskeletal tumors research.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Phosphate removal during hemodialysis, hemodiafiltration, and hemofiltration. A reappraisal.

Kinetics of phosphate removal, based on hourly collection of used dialysate or filtrate and hourly changes of phosphate plasma concentration, were studied in hemodialysis (QB 300; QD 500 ml/min), hemodiafiltration (QB 300; QD 500; QSF 25 ml/min), and hemofiltration (QB 250; QSF 70 ml/min) for six 5-hour sessions in each mode of therapy. Whatever the pretreatment phosphate concentration (1.5-2.0 mmol/L range), and whatever the treatment modality used, final plasma phosphate concentration was in the narrow range of 0.8-0.9 mmol/L, and about 50% of the total mass transfer occurred during the first 2 hours. At the third hour, a steady state is reached, suggesting that removal of phosphate is limited by the rate of phosphate transfer from body compartments to extracellular fluid, which was on the average about 362 mumol/kg.hr. Consequently, total phosphate mass transfer accounts only for 20 to 28 mmol per session. Control of pretreatment phosphatemia in the range of 1.5 to 2.0 mmol/L depends on daily phosphate binder prescription, calcitriol supplementation, and control of metabolic acidosis; one cannot rely on intermittent phosphate removal during the dialysis session.

Hemofiltration↗