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Biomedical subjects

S Hashimoto

Publications and source records attributed to S Hashimoto.

At least 1,495 records · Page 83Linked to original sources
PubMed1977

Purification and properties of human serum dopamine-beta-hydroxylase.

1. Two different molecular forms of dopamine-beta-hydroxylase were isolated from human serum; a major component (Peak I enzyme) with a molecular weight of 368000 and with a higher specific activity and a minor component (Peak II enzyme) with a molecular weight of 188000 and with a lower specific activity. 2. Both forms require ascorbic acid for the activity, and are stimulated by fumarate. Addition of N-ethylmaleimide or copper also increased the activity. The optimal pH of both forms in the presence of 20mM tyramine as substrate is 5.0. 3. Km values toward tyramine of Peak I enzyme and Peak II enzyme were 1.67 mM and 14.2 mM respectively. 4. Both Peak I enzyme and Peak II enzyme are glycoprotein.

Animals↗
PubMed1977

Microbiological degradation of bile acids. The preparation of hexahydroindane derivatives as substrates for studying cholic acid degradation.

Relatively large amounts of 3-(3aalpha-hexahydro-7abeta-methyl-1,5-dioxoindan-4alpha-yl)propionic acid (IIb), which is believed to be one of the intermediates involved in the degradation of cholic acid (I), were needed to identify is further degradation products. A simple method for the preparation of this compound was then investigated. Arthrobacter simplex could degrade-3-oxoandrost-4-ene-17beta-carboxylic acid (IIIa) to 3-(1beta-carboxy-3aalpha-hexahydro-7abeta-methyl-5-oxoindan-4alpha-yl)propionic acid (IVa) in good yield, the structure of which was established by partial synthesis. It was therefore expected that, if a similar degradation by this organism occurred with 17alpha-hydroxy-3-oxoandrost-4-ene-17beta-carboxylic acid (IIIb), which is easily obtained by chemical oxidation of commercially availabe 17alpha-hydroxydeoxycorticosterone, the resulting product, 3-(1beta-carboxy-3aalpha-hexahydro-1alpha-hydroxy-7abeta-methyl-5-oxoindan-4alpha-yl)propionic acid (IVb), could be readily converted chemically into the required dioxocarboxylic acid, (IIb). Exposure of compound (IIIb) to A. simplex produced, as expected, compound (IVb) which was then oxidized with NaBiO3 to give a reasonable yield of compound (IIb).

Arthrobacter↗
PubMed1977

Microbiological degradation of bile acids. Metabolites formed from 3-(3a alpha-hexahydro-7a beta-methyl-1,5-dioxoindan-4 alpha-yl) propionic acid by Streptomyces rubescens.

1. The metabolism of 3-(3a alpha-hexahydro-7a beta-methyl-1,5-dioxoindan-4 alpha-yl)propionic acid (III), which is a possible precursor of 2,3,4,6,6a beta, 7,8,9,9a alpha,9b beta-decahydro-6a beta-methyl-1H-cyclopenta[f]quinoline-3,7-dione (II) formed from cholic acid (I) by streptomyces rubescens, was investigated by using the same organism. 2. This organism effected amide bond formation, reduction of the carbonyl groups, trans alpha beta-desaturation and R-oriented beta-hydroxylation of the propionic acid side chain and skeleton cleavage, and the following metabolites were isolated as these forms or their derivatives: compound (II), 1,2,3,4 a beta,-5,6,6a beta,7,8,9a alpha,9b beta-dodecahydro-6a beta -methylcyclopental[f][1]benzopyran-3,7-dione (IVa), (1R)-1,2,3,4a beta,5,6,6a beta,7,8,9.9a alpha,9b beta-dodecahydro-1-hydroxy-6a beta-methylcyclopenta[f][1]benzopyran-3,7-dione (IVb), (E)-3-(3aalpha-hexahydro-5 alpha-hydroxy-7a beta-methyl-l-oxo-indan-4 alpha-yl)prop-2-enoic acid (V), (+)-(5R)-5-methyl-4-oxo-octane-1,8-dioic acid (VI), 3-(4-hydroxy-5-methyl-2-oxo-2H-pyran-6-yl)propionic acid (VII) and 3-(3a alpha-hexahydro-1 beta-hydroxy-7a beta-methyl-5-oxoindan-4 alpha-yl)propionic acid (VIII). The metabolites (IVb), (V), (VI) and (VII) were new compounds, and their structures were established by chemical synthesis. 3. The question of whether these metabolites are true degradative intermediates is discussed, and a degradative pathway of compound (III) to the possible precursor of compound (VII), 7-carboxy-4-methyl-3,5-dioxoheptanoyl-CoA (IX), is tentatively proposed. The further degradation of compound (IX) to small fragments is also considered.

Bile Acids and Salts↗
PubMed1977

Comparative studies of coagulative and fibrinolytic faculties between the Japanese monkey and the human.

In the present study, the coagulative and the fibrinolytic faculties of the Japanese monkey (Macaca fuscata) were investigated and compared with those of the human. Regarding the coagulative faculty, the plasmic fibrinogen level, prothrombin times, and partial thromboplastin times of the Japanese monkey were similar to those of the human, but the antithrombin level in the monkey was higher than that in the human. Regarding the fibrinolytic faculty, the simian plasminogen level was significantly higher than the human, but the simian, plasma clot and the euglobulin clot lysis times were extremely prolonged, which means that the Japanese monkey has a great fibrinolytic potential, but that it is difficult to activate. In addition, the human and simian reactivities of plasminogen to streptokinase were also investigated and compared.

Animals↗
PubMed1977

Studies of the mechanism of augmented synthesis of cholesteryl ester in atherosclerotic rabbit aortic microsomes.

A study was undertaken to test the hypothesis that an abnormally high concentration of acyl-CoA:cholesterol acyltransferase in atherosclerotic microsomes is partly responsible for augmented esterification of cholesterol. We approached the problem indirectly by measuring the incorporation of radioactivity into cholesteryl ester from [1-14C]palmityl-CoA in normal microsomes after enrichment of their concentration of microsomal free cholesterol to levels characteristic of atherosclerotic microsomes. Elevation of free cholesterol content induced increased cholesterol esterification approximately linearly over the range studied. The cholesterol-esterifying activity of atherosclerotic microsomes was not greater than that of normal microsomes having the same concentration of cholesterol. The results suggest that, with acyl-CoA constant, augmented cholesterol esterification in atherosclerotic microsomes is an effect of high microsomal cholesterol concentrations and not due to an increase in the concentration of the enzyme.

Acyl Coenzyme A↗
PubMed1977

Influence of dietary status and diabetes on aortic acyl-CoA hydrolase activity.

We have postulated that the accelerated snythesis of cholesteryl ester in atherosclerotic microsomes may result in part from decreased acyl-CoA hydrolase activity in arterial tissue, because acyl-CoA is a common substrate for both reactions. We have now investigated the influence of nutritional status, type of diet, and diabetes on the acyl-CoA hydrolase activity of otherwise normal aortic microsomes. Fasting rabbits for 16 hr diminished the acyl-CoA hydrolase activity approximately 30%. The activity of this aortic microsomal enzyme in rats maintained on a high-carbohydrate diet for 5 weeks was comparable to the activity observed on a high fat (olive oil) diet. The type of fat in the diet influences the acyl-CoA hydrolase activity: oils containing 77% oleic acid (high-oleic safflower oil) and containing 70% linoleic acid (conventional safflower oil) lowered the aortic microsomal acyl-CoA hydrolase activity in comparison to a more saturated fat (cocoa butter). Aortic preparations of rats made diabetic by streptozotocin exhibited higher acyl-CoA hydrolase activity than the normal. The results show that conditions associated with human atherogenesis (diabetes and saturated fat diet) increase rather than suppress the activity of this arterial enzyme in normal arterial tissues of the rat.

Animals↗
PubMed1977

Studies of antitumor agents. 1. Resolution of racemic 1-(tetrahydro-2-furanyl)-k-fluorouracil into the R and S isomers and examination of the biological activities of the isomers.

1-(Tetrahydro-2-furanyl)-5-fluorouracil (Thf-FU), which is named Ftorafur or FT-207 and is used clinically as an antitumor agent, was conveniently synthesized by condensation of the trimethylsilyl derivative of 5-fluorouracil with 2-acetoxytetrahydrofuran using NaI as a catalyst. This optically inactive Thf-FU was resolved into optically active (R)-(+)- and (S)-(-)-Thf-FU in high optical purity and excellent yield by formation of diastereoisomers with brucine. 13C NMR data were obtained on Thf-FU and related compounds and the antibacterial activities and in vivo antitumor activities of these isomers were tested. The degradations of these isomers to 5-fluorouracil by liver microsomes were also examined. No significant differences were found in any of these properties of these isomers.

Animals↗
PubMed1977

Effect of high-oleic and high-linoleic safflower oils on mammary tumors induced in rats by 7,12-dimethylbenz(alpha)anthracene.

A mutant safflower oil, rich in oleic acid, was used for a critical test of the hypothesis that polyunsaturated fats act as co-carcinogens. Weanling female rats were each given 5 mg of 7,12-dimethylbenz(alpha)anthracene. They were then pair-fed diets containing 20%, by weight, of conventional high-linoleic safflower oil; a mutant high-oleic safflower oil; or coconut oil. Half of each group received supplementary DL-alpha-tocopherol. Tumors were identified by two observers, by palpation. Data on incidence of tumors and on numbers of tumors per affected rat led to similar conclusions. At 16 weeks, there were significant differences when supplementary tocopherol was included in the diet: the group fed high-oleic safflower oil had more tumors than the group fed coconut oil. This difference was not seen in the absence of supplementary tocopherol. When the data for tocopherol-supplemented and unsupplemented subgroups were combined, the high-oleic safflower oil group had significantly more tumors than did the coconut oil group. The high-linoleic safflower oil group was not significantly different from either of the other groups. In all groups, histologic examination of the largest tumor in each rat revealed more benign tumors, mostly duct papillomas, than carcinomas.

9,10-Dimethyl-1,2-benzanthracene↗