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Biomedical subjects

Y Ohba

Publications and source records attributed to Y Ohba.

At least 289 records · Page 16Linked to original sources

The interaction of H1 histone with nucleosome core.

The structural changes caused by H1 histone depletion of calf thymus chromatin or nucleosome monomer were studied by using the criterion of accessibility to micrococcal nuclease. When H1 histone was depleted from monomer, the DNS structure unfolded and became sensitive to the nuclease at a particular site on the nucleosome core, 105 base pairs from a chain terminus of core DNA. In reconstitution experiments with chromatin, this sensitive site on the core could be protected from the attack of the nuclease only when H1 histone was present. These results indicate that H1 histone interacts not only with the nucleosome linker region, but also with the core particle.

Animals↗

The hypotensive mechanisms of the new anti-anginal drug, N-(2-hydroxyethyl)nicotinamide nitrate (SG-75) in beagle dogs.

The hypotensive mechanisms of N-(2-hydroxyethyl) nicotinamide nitrate (SG-75, Nicorandil) were studied in anesthetized dogs. Intravenous injections of SG-75 (0.03-1 mg/kg) decreased systemic blood pressure (SBP) and increased peripheral (coronary, renal, mesenteric and femoral) blood flow (PBF) dose-dependently. The duration of the PBF increase, however, was much shorter than that of the SBP decrease. When peripheral vascular beds were perfused by means of a pump under a constant perfusion pressure near the SBP, the duration and magnitude of the SBP decrease and the PBF increase were equal. In doses of 0.03-0.3 mg/kg i.v., SG-75 did not significantly affect pulse pressure, heart rate, aortic blood flow, left ventricular pressure (LVP) and LVdP/dt max. Intra-arterial injections of SG-75 (0.003-1 mg) increased coronary, renal, mesenteric and femoral blood flow dose-dependently, without affecting SBP and cardiac function. In heart-lung preparations the drug (0.1-2 mg) did not cause cardiodepression. No hypotensive effect was observed following the administration of SG-75 (3 mg) into the cisterna magna. The results indicate that the hypotensive effect of SG-75 may be due mainly to its peripheral mechanisms, relating to vasodilation.

Animals↗

Clinical features and biochemical aspects of red blood cells in Hb Hirosaki.

Hb Hirosaki is a new unstable variant in which CE 1 phenylalanine of alpha-chain is substituted by leucine. Seven patients with hemolytic anemia were found in one family and Hb Hirosaki was detected in four of them. In clinical feature some differences of severity were observed between child and adult patients. The child cases showed relatively severe symptoms with repeated hemolytic crises and drug sensitivity. Otherwise most of adult cases had only mild hemolytic process throughout their past life. The variety of clinical severity suggests that the expression of abnormal gene may be various in this disorder. The mode of inheritance seemed to be autosomal dominant and all the cases in this report were heterozygous state. Macrocytic and hypochromic anemia was characteristic in most cases and red blood cells containing Heinz bodies were dominant in peripheral blood from the splenectomized patients. Accelerated glycolysis and enhanced ATPase activity were outstanding features in the metabolism of erythrocyte in this disorder. The instability of reduced glutathione was also found in three of five cases.

Adenine Nucleotides↗

Hemoglobin Tottori (alpha 59[E8] glycine replaced by valine).

A new electrophoretically silent, unstable hemoglobin was discovered in a Japanese family. Isolation of the abnormal chain and chemical analyses demonstrated a previously unreported amino acid substitution, alpha 59[E8] glycine replaced by Valine. The new variant has been named Hb Tottori.

Adult↗

Hemoglobin Miyashiro (beta 23[B5] val substituting for gly) an electrophoretically silent variant discovered by the isopropanol test.

A new unstable hemoglobin was discovered in a Japanese boy without any signs of hemolytic disease during screening of patients by the isopropanol test. The abnormal hemoglobin was found in three generations. This slightly unstable hemoglobin could not be separated from Hb A by electrophoresis. All carriers showed an increased whole blood oxygen affinity. Structural studies demonstrated a previously unreported amino acid substitution, beta 23[B5] valine substituting for glycine. This new unstable variant has been named Hb Miyashiro.

Adolescent↗

Survey of cord blood hemoglobin in Japan and identification of two new gamma chain variants.

Two gamma chain variants were discovered during a survey of 2,569 cord bloods of Japanese. One was the first case with mutation of the T-gamma chain, i. e. Hb F Yamaguchi or gamma 80 (EF 4) Asp leads to Asn (75 Thr, 136 Ala). It comprised 33.6% of Hb F, an unusually high percentage for a gamma chain variant. The other concerned with the first report of substitution at E 16, i. e. Hb F Iwata or gamma 72 (E 16) Gly leads to Arg (75 Ile, 136 Ala). It comprised 11.0% which is comparable to the values usually reported in an A-gamma chain variant. No clinical consequences have been observed in association with the hemoglobin variants.

Amino Acid Sequence↗

Hb Toyoake: beta 142 (H20) Ala replaced by Pro. A new unstable hemoglobin with high oxygen affinity.

A new unstable hemoglobin with high oxygen affinity, Hb Toyoake: beta 142 (H20) Ala replaced by Pro, was found in Japanese male with a normal blood hemoglobin level, shortened red cell survival, and increased plasma erythropoietin. Hemoglobin studies showed heat and isopropanol instability, and an increased tendency to heme loss and to subunit dissociation. Electrophoresis of whole hemolysate showed inconstant abnormal bands with reduced mobilities due to progressive heme loss during the in vitro procedure. Isolated Hb Toyoake with normal heme content migrated slightly faster than HbA. Oxygen affinity of red cells was elevated with P50 of 17.0 mm Hg at pH 7.4 and 37 degrees C (normal 25.0 mm Hg). Studies on hemolysate implied that Hb Toyoake had an almost normal Bohr effect, a diminished cooperativity, and a reduced response to inositol hexaphosphate. These multiple abnormalities are associated with a substitution of Pro for beta 142 Ala, resulting in disruption of the H-helix and the adjacent C-terminal portion of beta chain, which contain residues crucial for normal oxygen binding.

Adult↗

Serum glutathione S-transferase activity in liver diseases.

Assay conditions of human liver glutathione S-transferase and its activity in human serum from liver disease patients were investigated. One mmol/l reduced glutathione, and 1 mmol/l-1-chloro-2,4-dinitrobenzene, pH 6.5, were used for the measurement, because of the very low non-enzymatic conjugation. Glutathione S-transferase activity was inhibited by bilirubin, but this inhibition was counteracted by the presence of a low concentration of albumin. The normal human serum glutathione S-transferase activity was 5.2 +/- 2.4 I.U./l (mean +/- S.D.), and was not influenced by any differences of age, sex or leukocyte count. A significant increase in serum enzyme activity was noted in cases of acute hepatitis with GPT exceeding 200 I.U./l, primary hepatoma and metastatic liver cancer. Some of the cases with fulminant hepatitis showed extremely high values. The degree of correlation between serum glutathione S-transferase and GOT or GPT was high in acute hepatitis, with GOT or GPT exceeding 200 I.U./l, in fulminant hepatitis, primary hepatoma and gall stones, while in chronic hepatitis and liver cirrhosis it was low. In cases of acute hepatitis and fulminant hepatitis, the disappearance of serum glutathione S-transferase from the blood was much faster than that of GOT and GPT. Serum glutathione S-transferase measurements will provide new and unique information for the diagnosis of acute liver diseases.

Adult↗

Pharmacodynamic and metabolism studies on a new coronary vasodilator, N-(2-hydroxyethyl) nicotinamide nitrate (SG-75).

Pharmacodynamics and metabolism of N-(2-hydroxyethyl) nicotinamide nitrate (SG-75) were investigated in rats in relation to its main metabolic product. When SG-75 was orally administered, SG-75 and SG-86, a denitrate compound of SG-75, appeared in the blood. Within 7 yr, approximately 60% of the administered SG-75 were recovered in the urine as SG-86. When administered intraduodenally, SG-75 was rapidly absorbed and transferred in an unaltered form into the portal vein. SG-75 possessed hypotensive and coronary vasodilating actions, while SG-86 had little effect on the cardiovascular system. The coronary vasodilating effects of SG-75 k(0.3-20 micrograms i.a.) were unaffected by the continuous infusion of SG-86 into the coronary perfusion system, even in large doses (50 micrograms/min, or 500 micrograms/min).

Animals↗