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Biomedical subjects

S Okuno

Publications and source records attributed to S Okuno.

At least 253 records · Page 14Linked to original sources
PubMed1979

Differential effect of a microsomal deacetylase inhibition on the mutagenicity in Salmonella typhimurium of 2-acetylaminofluorene by liver homogenates of guinea pigs, mice and rats.

The effect of paraoxon, a microsomal deacetylase inhibitor, on the mutant genicity of 2-acetylaminofluorene (AAF) by liver homogenates was compared between the AAF carcinogenesis-resistant guinea pigs and the susceptible mice and rats. The mutagenicity of AAF was mostly abolished by paraoxon, not only in the 3 kinds of untreated animals but also in guinea pigs treated with a combination of phenobarbital and 5,6-benzoflavone, whereas about 50% of the mutagenicity was resistant to paraoxon in treated mice and rats. We suggest that microsomal deacetylase activity is crucially involved in the mutagenic activation of AAF by guinea pig liver homogenates, while the enzyme activity other than the deacetylase activity is also important in the activation by liver homogenates from treated mice or rats.

2-Acetylaminofluorene↗
PubMed1978

Mutational biosynthesis of butirosin analogs. I. Conversion of neamine analogs into butirosin analogs by mutants of Bacillus circulans.

By N-methyl-N'-nitro-N-nitrosoguanidine treatment, neamine-negative mutants which required neamine for biosynthesis of butirosins were obtained from a butirosin-producing organism Bacillus circulans. These mutants also produced butirosins from paromamine and could be divided into two types I and II. Mutants of type I could not produce butirosins from 2-deoxystreptamine, whereas those of type II could. Two typical mutants MCRL 5003 (type I) and MCRL 5004 (type II) could produce butirosin analogs, 3', 4'-dideoxybutirosins, 6'-N-methylbutirosins, 3', 4'-dideoxy-6'-N-methylbutirosins and 3', 4'-dideoxy-6'-C-methyl-butirosins from neamine analogs, gentamine Cla, 6'-N-methylneamine, 6'-N-methylgentamine Cla and gentamine C2, respectively.

Anti-Bacterial Agents↗
PubMed1978

Mutational biosynthesis of butirosin analogs. III. 6'-N-methylbutirosins and 3', 4'-dideoxy-6'-c-methylbutirosins, new semisynthetic aminoglycosides.

Two pairs of butirosin analogs were isolated from the fermentation broths obtained by cultivating a neamine-negative mutant of the butirosin-producing organism Bacillus circulans in the medium supplemented with 6'-N-methylneamine and gentamine C2, respectively. These amtibiotics were characterized as 6'-N-mentylbutirosins A and B (NMB-A & NMB-B), and 3', 4'-dideoxy-6'-C-methylbutirosins A and B (DCB-A & DCB-B), respectively, by chemical and spectroscopic studies. NMB-A and NMB-B exhibited broad-spectrum antibacterial activities with in vitro potency similar to or slightly less than that for butirosin A, but with greater activities against butirosin-resistant strain which contains acetylating enzyme AAC-(6')-I. The activities of NMB-A and NMB-B against Pseudomonas aeruginosa strains were relatively weak. DCB-B had broad-spectrum activity, and exhibited greatly improved activity against butirosin-resistant organisms which contain acetylating enzymes AAC(6')-I and AAC(6')-IV, and phosphorylating enzyme APH(3')-II. These new butirosin analogs were also active against some of the clinical isolates resistant to butirosins, dibekacin and/or gentamicin.

Anti-Bacterial Agents↗
PubMed1975

Innervation of hypothalamic and limbic areas by the cholinergic, the GABA-ergic and the catecholaminergic nerve fibers; a quantitative analysis.

By measuring activities of enzymes involved in synthesis of acetylcholine, gamma-aminobutyric acid (GABA), dopamine or noradrenaline, extent of innervation of cholinergic, GABA-ergic, dopaminergic and noradrenergic fibers were analysed in discrete brain areas and subareas of the baboon and the rabbit with a special reference to the hypothalamus and the preoptic ares. In the latter area, cholinergic and dopaminergic innervation increases medio-lateraly on the one hand, and noradrenergic innervation reversed on the other hand. GABA-ergic innervation is almost evenly distributed in this structure. By placing electrical lesions in the lateral hypothalamus, an analysis was made of inputs of these innervations.

Acetylcholinesterase↗
PubMedDate not supplied

Biological activity of neurotensin and its C-terminal partial sequences.

A hypothalamic tridecapeptide, neurotensin, and its C-terminal partial sequences down to the dipeptide were synthesized. These peptides were assayed for smooth muscle contracting and blood pressure lowering properties using preparations of isolated stomach fundus, uterus and duodenum of the rat, isolated guinea pig ileum and rabbit carotid artery. Sequences of 6 or more terminal amino acids produced a strong stomach fundus contracting effect, the potencies of the fragments being approximately equivalent to or slightly more than that of the parent tridecapeptide. These fragments also elicited the ileum contracting activity, but the potencies were only one fifth to one tenth that of neurotensin. The tetra- or dipeptide hardly stimulated either the fundus or the ileum. The stimulating effect on the uterus or relaxing effect on the duodenum of neurotensin was not consistent. Rabbit blood pressure was lowered markedly by neurotensin and weakly by its dodecapeptide. From these results, the arginine or arginine-arginine residue down to the C-terminal leucine appears to be essential for the smooth muscle contracting activity of neurotensin. The full length sequence may be needed for the hypotensive effect.

Amino Acid Sequence↗
PubMedDate not supplied

Regional and subcellular distribution of gold in brain of gold thioglucose obese mouse.

By employing neutron activation analysis, endogenous content of gold was estimated quantitatively in discrete brain areas and in subcellular fractions of the hypothalamus of gold thioglucose (GTG) induced obese mice. The highest concentration of gold was obtained in the ventromedial hypothalamus (VMH) reaching approximately 100 ng/mg wet tissue. Significantly higher concentrations were observed in other hypothalamic subareas followed by certain limbic areas and the thalamus, while in the cerebral and the cerebellar cortex the gold concentration was very low. Subcellularly, the hypothalamic gold was principally recovered in the supernatant fraction particularly after a hyposmotic shock treatment of the crude mitochondrial fraction. Contrary to GTG, treatment with gold thiomalate (GTM) did not induce obesity in the mouse, although considerable amount of gold was observed in the VMH, a finding suggesting the existence in the VMH of at least a two step mechanisms for inducing GTG obesity. To identify the satiety neuron transmitter, an analysis of certain enzyme activities involved in the synthesis of known transmitters, such as acetylcholine or gamma-aminobutyric acid (GABA), was made in the GTG-obese mice. There were no significant changes in any of the areas functionally related to the VMH.

Animals↗
PubMedDate not supplied

Single-allele correction of the Dmo1 locus in congenic animals substantially attenuates obesity, dyslipidaemia and diabetes phenotypes of the OLETF rat.

1. Whole-genome scans have identified Dmo1 as a major quantitative trait locus for dyslipidaemia and obesity in the Otsuka Long Evans Tokushima Fatty (OLETF) rat. 2. We have produced congenic rats for the Dmo1 locus through successive back-cross breeding with diabetic OLETF rats. Marker-assisted speed congenic protocols were applied to efficiently transfer chromosomal segments from non-diabetic Brown Norway (BN) rats into the OLETF background. 3. In the fourth generation of congenic animals, we observed a substantial therapeutic effect of the Dmo1 locus on lipid metabolism, obesity control and plasma glucose homeostasis. 4. We have concluded that Dmo1 primarily affects lipid homeostasis, obesity control and/or glucose homeostasis at fasting and is secondarily involved in glucose homeostasis after loading. 5. The results of the present study show that single-allele correction of a genetic defect of the Dmo1 locus can generate a substantial therapeutic effect, despite the complex polygenic nature of type II diabetic syndromes.

Alleles↗