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Biomedical subjects

S Hatanaka

Publications and source records attributed to S Hatanaka.

At least 37 records · Page 2Linked to original sources

Protective effect of DM-9384, a novel pyrrolidone derivative, against experimental cerebral anoxia.

The protective effects of DM-9384 [N-(2,6-dimethylphenyl)-2-(2-oxo- 1-pyrrolidinyl) acetamide] against cerebral anoxia were investigated using various animal models. Oral administration of DM-9384 resulted in a significant prolongation of survival time in mice and rats subjected to the normobaric hypoxia; its minimal effective doses were 30 and 10 mg/kg, respectively. A significant protection by this drug against hypobaric hypoxia, histotoxic anoxia and cerebral ischemia also occurred in mice at a dose of 100 mg/kg, p.o. Bifemelane (100-300 mg/kg, p.o.) was protective against these models except for hypobaric hypoxia, and the effects of piracetam, aniracetam and pramiracetam (1000 mg/kg, p.o.) were variable depending on the type of anoxia model used. DM-9384 (100 mg/kg and lower) attenuated the hypolocomotion and the disturbance of cerebral energy metabolism such as a decrease in ATP, an increase in lactate and lactate/pyruvate ratio induced by hypoxia in rats. The spontaneous motor activity, uptake and utilization of brain glucose in normal animals, however, were not influenced by this drug. Based on these results, DM-9384 is characterized as a broad spectrum anti-anoxic drug with negligible CNS depression, and the cerebral protective effect of this drug may be, at least in part, attributable to its ability to improve the cerebral energy metabolic disturbance.

Animals↗

[Effects of gestrinone on serum lipid and lipoprotein levels in women with endometriosis].

Gestrinone (G) was given to 12 females with endometriosis in weekly doses of 5 or 10mg for 4 to 6 months, and the change in serum lipids and lipoproteins was analysed. G decreased total cholesterol by 20% (p less than 0.05), triglycerides by 36% (p less than 0.05), phospholipids by 28% (p less than 0.01) and lipid peroxides by 34% (p less than 0.05), among which reductions in them were statistically significant when compared with the pretreatment levels. Levels of high density lipoproteins (HDL) also fell: HDL-cholesterol by 41% (p less than 0.01), HDL-triglycerides by 49% (p less than 0.05) and HDL-phospholipids by 38% (p less than 0.01) which were significant. Concurrently apolipoproteins (Apo) and lecithin-cholesterol acyltransferase activity (LCAT) decreased: Apo A-I by 31% (p less than 0.01), Apo A-II by 13% (p less than 0.05) and LCAT by 53% (p less than 0.05), which were significant. In contrast, there were few changes in the levels of low density lipoproteins (LDL) and Apo B. There was also little effect on very low density lipoproteins (VLDL) except VLDL-triglycerides which decreased by 52% (p less than 0.05). Meanwhile free fatty acids increased by 61% (p less than 0.05). Therefore, the atherogenic index defined as the ratio of LDL-cholesterol to HDL-cholesterol rose as much as 92% (p less than 0.01) of the initial value in 24 weeks of medication. When these results were examined with respect to the 5 and 10mg administration group, dose-dependent effects were observed, but these were not marked.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoproteins↗

Partial purification and properties of gamma-glutamyltranspeptidase from mycelia of Morchella esculenta.

Three gamma-glutamyltranspeptidase (enzymes I, II and III) were partially purified from the cell free extracts of the cultured mycelia of Morchella esculenta Fr. The molecular masses of enzymes were 155,000 (I), 219,000 (II) and 102,000 (III). All of them catalyzed both hydrolysis and transpeptidation of various gamma-glutamyl compounds. gamma-L-Glutamyl-cis-3-amino-L-proline occurring in the cultured mycelia of this fungus was a good substrate for both reactions. Km values for hydrolysis were in the order of 10(-4) to 10(-5) M, and those for transpeptidation were in the order of 10(-2) to 10(-4) M. The enzymes were inhibited by a gamma-glutamyltranspeptidase inhibitor, L-serine plus borate.

Ascomycota↗

Kinetic studies of ox-liver glutamate dehydrogenase oxidative deamination of two glutamate analogues, L-threo-gamma-methylglutamate and L-alpha-amino-gamma-nitraminobutyrate, in the presence of the allosteric effector ADP.

Ox-liver glutamate dehydrogenase is known to utilise a wide range of amino acid substrates. Kinetic studies are presented here for L-threo-gamma-methylglutamate and L-alpha-amino-gamma-nitraminobutyrate in the presence of the allosteric effector ADP. The results presented are considered in the light of similar studies presented elsewhere in which the cofactor was systematically replaced by a variety of analogues. These amino acid analogues share the same pH optimum as glutamate, unlike the monocarboxylic amino acids including alanine and norvaline, and give linear double-reciprocal plots under the conditions used here. Studies with the alternative coenzymes have suggested an ordered addition of glutamate before coenzyme in the presence of ADP. The present results obtained under identical conditions support this conclusion.

Adenosine Diphosphate↗

Detection of tumor-inducing plasmid DNA sequence in Agrobacterium tumefaciens by DNA-DNA hybridization.

Absence of plasmid DNA sequences in non-tumorigenic (crown gall tumor) strains of Agrobacterium tumefaciens was confirmed by DNA-DNA hybridization between purified tumor-inducing (Ti) plasmid DNAs isolated from the progenitor tumorigenic strains and 3H-labeled whole cell DNAs from tumorigenic strains and their non-tumorigenic derivatives. The genes controlling tumorigenicity in plant and utilizability of nopaline as their sole nitrogen source were confirmed to locate on Ti-plasmids.

Arginine↗

Beef liver glutamate dehydrogenase: a study of the oxidation of various alternative amino acid substrates retaining the correct spacing of the two carboxylate groups.

1. Several glutamate analogues substituted at the beta- or gamma-carbon atoms have been tested as substrates for glutamate dehydrogenase. 2. The two gamma-methyl derivatives and DL-beta-methylglutamate give the same pH optimum (8.7) as L-glutamate, but show inhibition by ADP and activation by GTP as pH 8, unlike glutamate and like the monocarboxylic substrate L-norvaline, which gives a pH optimum of 10. 3. L-gamma-methyleneglutamate, the poorest substrate tested (0.28% of rate with glutamate) gives a high pH optimum (10), like norvaline, but shows marked activation by both ADP (13-fold) and GTP (27-fold). 4. Despite the correct dicarboxylate spacing, all the analogues were much poorer substrates than L-norvaline.

Amino Acids↗

Transplantability of granulosa cell tumors induced in mice by intrasplenic ovarian grafting.

The nature, in particular the transplantability of granulosa cell tumors induced in mice by intrasplenic ovarian grafting was investigated. Female mice were ovariectomized and received autoplastic ovarian grafts into the spleens. The animals were killed at various periods from 2 to 12 months after grafting and the size of intrasplenic ovarian nodules was measured. There was an approximate liner increase in the size of intrasplenic ovarian grafts with passage of time. Intrasplenic ovarian tumors were transplanted subcutaneously into intact male mice. About two-thirds or more intrasplenic ovarian tumors over 1.0 cm in diameter were transplantable. The larger the intrasplenic ovarian grafts, the greater was the estrous reaction in the vaginal smears. All animals bearing the grafts over 1.0 cm in diameter showed reaction. Once intrasplenic ovarian grafts grow to the extent that estrogen is released with no complete inactivation by the liver, estrogens would escape into the general circulation. Inhibiting excessive release of pituitary gonadotropins. It is considered that intrasplenic ovarian tumors become transplantable when they grow autonomously, even if the excessive release of pituitary gonadotropins is inhibited.

Animals↗

Effect of hormonal milieu on the growth of transplantable granulosa cell tumors in mice.

Two transplantable granulosa cell tumor lines (designated as T and M lines) induced in mice by intrasplenic ovarian grafting were established. The hormonal milieu which promotes the growth of transplantable granulosa cell tumors was investigated in the present work. The inoculation of the T line tumors into host animals led to tumor formation in intact and gonadectomized animals, but not in hypophysectomized animals.Subcutaneous grafts in intact male hosts were significantly large than those in gonadectomized male hosts, whereas tumors of approximately equal size were formed in androgen-treated gonadectomized male hosts. These results indicate that both androgens and gonadotropins promote the tumor growth in vivo. The behavior of the M line tumors was similar to that of the T line tumors. When the cell growth of the M line tumors was examined in culture, steroid hormone depletion in medium did not affect the growth of the tumor cells, nor did androgen have a growth-promoting effect in serum-free medium or in medium supplemented with charcoal-extracted male mouse serum. It was concluded that the growth-promoting effect of androgens is not direct, and that androgens themselves or their derivative estrogens may produce specific growth factors, which in turn promote the tumor growth in vivo.

Animals↗