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Biomedical subjects

R Okamoto

Publications and source records attributed to R Okamoto.

At least 217 records · Page 12Linked to original sources

In vitro and in vivo antibacterial activities of ME1207, a new oral cephalosporin.

ME1207 (pivaloyloxymethyl ester of ME1206) is a new oral cephalosporin. ME1206 is (6R,7R)-7-[(Z)-2-(2-aminothiazol-4-yl)-2-(methoxyimino)- acetamido]-3-[(Z)-2-(4-methylthiazol-5-yl)-ethyl]-cephem-4-carboxy lic acid. The susceptibilities of about 1,600 clinical isolates to ME1206 were determined by the agar dilution method. ME1206 showed a broad spectrum of activity against gram-positive and gram-negative bacteria. ME1206 was more active than cefaclor, T-2525, and cefixime against Staphylococcus aureus and Staphylococcus epidermidis. Against gram-negative bacteria, the activity of ME1206 was comparable with that of T-2525, but ME1206 was less active than cefixime. Against Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria gonorrhoeae, ME1206 had high activity (MIC, less than or equal to 0.05 microgram/ml). ME1206 was stable against various beta-lactamases, except beta-lactamases from Providencia rettgeri, Pseudomonas cepacia, and Escherichia coli W3630 (Rms213). The 50% effective doses of ME1207 after oral administration against systemic infections in mice were comparable with those of T-2588 against gram-negative bacteria and about one-fourth that of T-2588 against Staphylococcus aureus Smith.

Administration, Oral↗

Effect of ba-wei-di-huang-wan (hachimi-jio-gan) on thymidine kinase and its isozyme activities in the prostate glands in rats.

Ba-wei-di-huang-wan (Hachimi-jio-gan, TJ-7) has been frequently used for the treatment of sterilitas virilis, prostatic disorders, etc. The hormonal effects of TJ-7 were studied using thymidine kinase (TK), an enzyme that catalyzes the phosphorylation of thymidine via the pyrimidine salvage pathway. TK isozyme activity increases in rapidly proliferating tissues. TJ-7 may act as a weak androgen and enhance prostatic TK and in particular, a specific TK isozyme activity, and also as an anti-androgen and reduce prostatic TK activity in the presence of androgen in immature rats.

Animals↗

[Effects of ACTH or hCG on corticosterone and progesterone secretion from adrenal glands of the rats at various ages].

Effects of ACTH or hCG on the secretion of corticosterone (CB) and progesterone (PRG) from adrenal glands of the female rats at various ages were studied. In in vitro experiment, adrenal gland cells were isolated from fetal, neonatal, immature and adult rats by the method described by us before and were incubated in MEM. We chose to designate the hormones in the medium as hormone secretion. In in vivo experiment, hormones in the serum were determined. In vitro experiment, in which ACTH was added to the medium, indicated that CB was low in the media containing the cells from fetal and neonatal glands compared to those from immature and adult. PRG was elevated by ACTH addition at all of the ages. hCG addition had no effects on both CB and PRG in the media of immature and adult rats. In vivo experiment, in which ACTH was injected s.c., indicated that the response of serum PRG was slightly earlier than the CB response and peaked with a subsequent decline in immature rats. The results suggest that adrenal gland responds to ACTH from fetal age and secrets PRG, but little of CB in fetal age.

Adrenal Glands↗

Relative activities of thymidylate synthetase and thymidine kinase in 1,2-dimethylhydrazine-induced colon carcinomas in rats.

Thymidylate synthetase (TS) and thymidine kinase (TK) are known to catalyse the methylation of dUMP for the de novo synthesis of dTMP and the phosphorylation of thymidine for the salvage synthesis of dTMP in the pyrimidine pathway, respectively. High TS and TK activities and the existence of TK isozymes have been observed in rapidly proliferating tissues. TS and TK activities in 1,2-dimethylhydrazine (DMH)-induced colon carcinomas in rats increased significantly to 331 and 207% of the activities in normal colon, respectively, and were well correlated inversely (y = -0.93x + 5.24), with a correlation coefficient of -0.787. The colonic TK isozymes were separated into two types by DEAE-cellulose column chromatography. The TK isozyme eluted from the column by the elution buffer alone without NaCl was markedly higher (23.6-fold) in activity in DMH-induced colon carcinoma than in normal control colon and was not affected by deoxycytidine triphosphate. This isozyme, whose mol. wt is 100,000 by h.p.l.c., is thought to be closely involved in rapid DNA replication. These results indicate that early biochemical changes in DMH-induced colon carcinoma in rats may serve as a useful model and provide valuable insight into the mechanisms involved in colonic carcinogenesis.

1,2-Dimethylhydrazine↗

New tylosin analogs produced by mutants of Streptomyces fradiae.

2'''-Demethoxytylosin (component IIIc), 2'''-demethoxy-4'''-epi-tylosin (component IIId) and 2'''-O-demethyltylosin (component Vb) were produced by blocked mutant strains of Streptomyces fradiae. Fermentation, isolation, structure determination and biosynthetic considerations of these tylosin analogs are described.

Chemical Phenomena↗

Nifedipine suppressed atherosclerosis in cholesterol-fed rabbits but not in Watanabe heritable hyperlipidemic rabbits.

We studied the effects of nifedipine, a calcium antagonist, on atherosclerosis in cholesterol-fed rabbits and Watanabe heritable hyperlipidemic rabbits (WHHL rabbits). Japanese White rabbits were fed 120g of 2% cholesterol rabbit chow daily, and WHHL rabbits were fed standard rabbit chow. In each experiment, the rabbits were divided into two groups. Twenty milligrams of nifedipine was given orally twice a day to the nifedipine group, and the control group was given a placebo in the same way. The rabbits were sacrificed at the end of the 12th week in the case of cholesterol-fed rabbits, and the 20th week in the case of WHHL rabbits. Among the cholesterol-fed rabbits, the percentage of aortic intimal surface area covered by atherosclerotic lesions (AS%) was 25.9 +/- 7.6% (mean +/- S.D.) in the nifedipine group (n = 7), and 55.6 +/- 22.8% in the placebo group (n = 8) (p less than 0.01). The cholesterol content of thoracic and abdominal aorta in the nifedipine group was lower than those in the placebo group (p less than 0.05). Among the WHHL rabbits, the AS% was 33.4 +/- 14.1% in the nifedipine group (n = 5), and 27.0 +/- 11.7% in the placebo group (n =6) (n.s.). The aortic cholesterol and calcium contents also showed no significant differences between the two groups. We concluded that nifedipine suppressed atherosclerosis in cholesterol-fed rabbits but not in WHHL rabbits. The different responses suggest that the effect of nifedipine could be mediated by low density lipoprotein receptors or that the early exposure to hyperlipidemic serum from birth might affect cell functions of WHHL rabbits.

Administration, Oral↗

Absence of argininosuccinate lyase protein in the liver of two patients with argininosuccinic aciduria.

The enzyme defects in two cases of argininosuccinic aciduria were examined at the molecular level by enzymatic and immunological methods. No argininosuccinate lyase activity was detected in the liver or erythrocytes of either patient nor in the kidney or brain of one of the patients even in the presence of high concentrations of the substrate. The titration curve of antiserum to human argininosuccinate lyase with the liver extract from a control subject was not affected by the addition of the liver extracts from one of the patients. Double immunodiffusion analysis revealed a single precipitin line between the purified antiserum and the liver extract from a control, but no precipitin lines between the antisera and the liver extracts from the two patients. These results indicate a complete or almost complete defect of an immunologically cross-reactive material in the liver of the patients.

Amino Acid Metabolism, Inborn Errors↗

Increased activities of thymidine kinase isozymes in human mammary tumours.

Thymidine kinase, the enzyme in the pyrimidine salvage pathway, and its isozymes were examined in 10 specimens of normal mammary gland, 10 fibroadenomas and 11 adenocarcinomas in human breasts. The average thymidine kinase activities in fibroadenomas and adenocarcinomas were about 3 and 8 times that in normal mammary gland. The mammary thymidine kinase isozymes were separated into two types by diethylaminoethyl (DEAE) cellulose column chromatography. The activity of the thymidine kinase isozyme eluted with 0.1 M sodium chloride in buffer was twofold higher in fibroadenomas and fourfold higher in adenocarcinomas than that in normal tissue. In adenocarcinomas, but not fibroadenomas, the activity of the other isozyme eluted with buffer alone was increased to 22-fold that in normal tissues. As the activity of the latter isozyme was not affected by deoxycytidine triphosphate, it may be involved closely in DNA replication.

Adenocarcinoma↗

Priming procedure and cell isolation for study on luteal cell response to peptide hormone in the rat.

The objective of this study was to develop a method of isolating luteal cells from the ovaries of immature rats pretreated with pregnant mare serum gonadotrophin (PMSG). After the ovaries were digested by collagenase and trypsin, the corpora lutea were obtained from the tissues, gently pressed in a test tube, and then placed on a sucrose density gradient. The two bands that appeared in the tube after centrifugation were designated S1 (top band) and S2 (bottom band). Progesterone and 20 alpha-dihydroprogesterone (20 alpha-DHP) secreted by the isolated cells during short-term incubation were measured by radioimmunoassay (RIA). A larger amount of progesterone, i.e., 60 to 260 ng/10(5) cells, was secreted by S1 cells than by S2 cells during the 18-h incubation. These results suggest that this simple procedure for isolation of luteal cells may provide a suitable model for in vitro studies of the luteal function.

20-alpha-Dihydroprogesterone↗