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Biomedical subjects

M Hirata

Publications and source records attributed to M Hirata.

At least 631 records · Page 35Linked to original sources
PubMed1983

Effect of diltiazem on the release of calcium from the canine fragmented cardiac sarcoplasmic reticulum.

Fragmented sarcoplasmic reticulum fraction (SR) was prepared from the ventricle of canine heart, and the effect of diltiazem on its Ca2+ binding and Ca2+ release was examined by centrifugation and filtration methods using 45Ca. Cardiac SR bound 45-55 nmoles/mg of Ca ions in the presence of Mg-ATP. Diltiazem in concentrations up to 10(-4) M had little effect on the Ca2+ binding of SR. The membrane of cardiac SR was "depolarized" by either changing propionate to chloride (anionic) or potassium to Tris (hydroxymethyl) aminomethane (Tris) (cationic). About 12% of the maximum Ca2+ bound to the SR was released by cationic "depolarization", but no Ca2+ was released by anionic "depolarization". The Ca2+ release induced by the cationic "depolarization" was inhibited by diltiazem, and the inhibitory effect of diltiazem on the Ca2+ release was dependent on the incubation time. Incubation of the SR with 3 X 10(-6) M diltiazem for 30 sec almost completely inhibited the release of Ca2+, while incubation with 3 X 10(-7) M diltiazem incompletely inhibited the Ca2+ release. About 20% of the maximum Ca2+ bound to the SR was released by the addition of 5.1 mM caffeine. The Ca2+ release induced by caffeine was inhibited by increasing the concentration of MgCl2 from 5 to 10 mM, but was not inhibited by 10 mM procaine. An increase of ATP concentration accelerated the time course of the caffeine-induced release of Ca2+ from the SR and subsequent rebinding of Ca2+. Diltiazem up to 10(-5) M had no effect on the caffeine-induced Ca2+ release.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

[Phase II study with methyl-6[[[2-chloroethyl) nitrosoamino] carbonyl] amino]-6-deoxy-alpha-D-glucopyranoside (MCNU) in hematological malignancies].

A total of 117 cases with hematological malignancies were treated with MCNU at doses of 70-100 mg/m2. Following are the results obtained. 1. MCNU showed a marked depression of cells in the cases with CML, polycythemia vera and thrombocythemia. The low level of cells was maintained for 2 to 7 months. 2. A good response was observed in several cases with blastic crises of CML. 3. No response was observed in two cases with acute leukemia. 4. Although a fair response was observed in several cases with malignant lymphoma or multiple myeloma, moderate bone marrow suppression was observed in a majority of the cases.

Adult↗
PubMed1983

[Phase I study on oral administration of methyl-6-[[[(2-chloroethyl) nitrosoamino] carbonyl] amino]-6-deoxy-alpha-D-glucopyranoside (MCNU)].

A total of 48 patients with various malignant disorders, mostly from hemopoietic organs, entered to phase I study of MCNU given orally. Fifty-six percent of the patients given MCNU at the doses of 50-125 mg/m2 complained of gastrointestinal symptoms including nausea and vomiting, which were however mild and well tolerated. In the following study employing administration of 50 mg/day of MCNU for consecutive 2-6 days, the gastrointestinal toxicities were reduced to 26.1%, and hematological toxicities of delayed leukopenia and thrombocytopenia were derived 4-6 weeks after oral intake of the drug. The hematological recovery required 1-2 weeks after the nadir of leukocyte and thrombocyte count. A recommended dose for phase II study of MCNU by the route of oral administration was 50 mg/body/day for consecutive 4-6 days in every 8 weeks interval. The peak value of blood concentration of MCNU was obtained 60-120 minutes after p.o. administration at the doses of 50-100 mg. Elimination half-life was estimated to be 40-45 minutes. No concentration of the drug was detected in blood 24 hours after the administration.

Administration, Oral↗
PubMed1982

Studies of isoniazid metabolism in isolated rat hepatocytes by mass fragmentography.

Isoniazid metabolism in isolated rat hepatocytes was studied by mass fragmentography using single ion monitoring. Isoniazid and its metabolites were determined as the trimethylsilylated derivatives of acetylisoniazid and diacetylhydrazine and of the benzaldehyde hydrazones of isoniazid and acetylhydrazine. Deuterated analogues served as internal standards. Hydrazine was quantitated as benzalazine using 15N-labeled hydrazine as an internal standard. The method is well suited for the microanalysis of isoniazid metabolism, from which it was clarified that the greater part of hydrazine, a hazardous metabolite of isoniazid, was formed through the direct hydrolysis of isoniazid itself as expected.

Acetylation↗
PubMed1982

Hepatic bile acid elution by albumin and bile acid content in isolated rat hepatocytes.

Bile acid contents were determined for isolated rat hepatocytes. During the course of isolating the hepatocytes, perfusion of rat liver with buffer containing 2% albumin eluted a significant amount of bile acids. The elution was proportional to the volume of the buffer and attributable to albumin in the buffer. The isolated hepatocytes prepared by perfusion with 0.1% albumin buffer, which eluted a negligible amount of bile acids, contained 95 +/- 12 micrograms/10(8) cells of bile acids. The major bile acids were cholic acid (22%), beta-muricholic acid (34%) and hyodeoxycholic acid (10%). Levels of the other bile acids were less than 3%. Peak 8, unidentified but presumed to be a trihydroxycholanoic acid, accounted for 19%.

Animals↗
PubMed1982

Morphological changes of isolated rat hepatocytes induced by imipramine.

Effect of imipramine on freshly isolated rat hepatocytes was investigated by scanning and transmission electron microscopy. Soon after the treatment of the cell with imipramine, marked changes in plasma membrane and mitochondria were found. Amitriptyrine, a structurally related drug, produced similar changes in the hepatocytes. On the other hand, Triton X-100, a nonionic surfactant, damaged the cell surface but little influence the features of the organelles.

Animals↗
PubMed1982

Coronary circulatory failure and thromboxane A2 release during coronary occlusion and reperfusion in anaesthetised dogs.

Attempts were made to demonstrate release of vasoactive substances from the heart during coronary occlusion (for 60 min) and reperfusion (for 60 min), and to clarify the pathophysiological significance of them. Vasoactive substances were detected by superfusion of rabbit aortic and dog coronary arterial strips with great coronary venous blood. Plasma thromboxane (TX) B2 was radioimmunologically assayed. Gradually developing, sustained contraction of both vascular strips was noted during coronary occlusion and reperfusion, while a transient contraction in rabbit aortic and relaxation in dog coronary arterial strips were seen immediately after reperfusion. The TXB2 released into the great coronary venous blood significantly increased during occlusion and reperfusion. Indomethacin treatment of the dog abolished the sustained contraction of both vascular strips and TXB2 release. The transient contraction of rabbit aorta after reperfusion was inhibited by phenoxybenzamine. Reactive hyperaemia following a 60 min occlusion was significantly depressed, as compared with that following 30 s to 30 min occlusion, and the depression was alleviated by indomethacin and imidazole. These results suggest that catecholamine(s) and TXA2 are released during coronary occlusion and reperfusion, and that the latter might be responsible for the coronary circulatory failure during reperfusion of irreversibly damaged myocardium.

Animals↗