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Biomedical subjects

R Okamoto

Publications and source records attributed to R Okamoto.

At least 253 records · Page 14Linked to original sources

[Preparation of progesterone secreting cells from rat ovaries by a density gradient].

Isolation of progesterone secreting cells from the ovaries of immature rats pretreated with pregnant mare serum gonadotropin (PMS) was conducted by a simple procedure which combined the collagenase digestion with a density gradient method. After digestion of the ovarian tissue slices by the enzyme, the residue was gently pressed and placed on a sucrose density gradient. Three bands appearing in the tube after centrifugation were designated as S-1, S-2 and S-3 from the top to the bottom, respectively. The S-1 cells from the ovaries at 6 days after PMS secreted the greatest amount progesterone, i.e. approximately 430 ng per 10(5) cells during the 18th incubation. Progesterone secretion from the S-2 cells was less than 48% of that from the S-1 cells. A physiological interrelation between the S-1 and S-2 cells remains unexplained by the present experiment. The luteal cells were yellow, spheroidal and 15 to 40 mus in diameter. Many vesicle-like particles were found on the cell surfaces. Progesterone secretion from the prepared cells was stimulated significantly by hCG in vitro. This result indicates that progesterone secreting cells isolated by the collagenase-sucrose density gradient preserve their native function as luteal cells. The procedure for preparation of luteal cells in the present report may provide a suitable model for in vitro studies on the corpus luteum.

Animals↗

The effect of oxygen on the development of atherosclerosis in WHHL rabbits.

The effect of hyperoxic or hypoxic inhalation on blood lipid levels and on the development of atherosclerosis was studied in young male WHHL rabbits. They were exposed to ordinary room air containing different concentrations of oxygen: 6 animals were exposed to 40% oxygen (hyperoxia group) or 5-10% oxygen (hypoxia group) for 5 h a day, 5 days a week for 8 weeks. Four control rabbits inhaled ordinary room air. The following results were obtained. (1) The severity of aortic lesions significantly decreased in the hyperoxia group and increased in the hypoxia group, when these two groups were compared. However, both hypoxic and hyperoxic groups did not statistically differ from the control. (2) Plasma cholesterol levels were not changed either by hyperoxic or hypoxic inhalation. (3) Plasma triglyceride levels were elevated only in the hypoxia group, with significant differences from the values in both control and hyperoxia groups. (4) There was no significant correlation between mean plasma lipid level and severity of aortic lesions. From these results, we conclude that hyperoxic or hypoxic inhalation respectively regresses or aggravates the development of atherosclerotic lesions, not by an indirect action on blood lipid concentrations but by a direct action on the vascular wall.

Animals↗

[Estrogen receptors of the rat uterus during pregnancy and lactation].

Uterine estrogen receptors (ER) of the rat during pregnancy and postpartal lactation were assayed. Both the cytoplasmic and nuclear ER were determined by the controlled pore glass (CPG) method as previously described in detail. The cytoplasmic ER level slightly decreased as pregnancy advanced and then increased remarkably during postpartal lactation, with a tendency to decrease at 5 weeks of lactation when the estrous cycle could have recurred despite the nursing behavior of the rats. On the other hand, no remarkable difference in nuclear ER was noted during pregnancy and lactation. A high concentration of plasma progesterone could have reduced the translocation of the cytoplasmic ER to the nucleus and the replenishment of the cytoplasmic ER, despite a high concentration of plasma estrogen during pregnancy. In order to keep an environment of a high plasma concentration of estrogen similar to that of pregnancy, a long-acting estrogen (estradiol dipropionate) was injected in to the proestrous rats. The cytoplasmic ER rapidly translocated to the nucleus, followed by a prolonged maintenance of a low cytoplasmic and a high nuclear ER level until 7 days, with a gradual replenishment of the cytoplasmic Er and a gradual decline of the nuclear ER thereafter. A translocation of the cytoplasmic Er to the nucleus, similarly seen in the hysterectonized-adult rats treated with estradiol, was noted in the rats injected with estradiol at 3 weeks of lactation. In general, low estrogen and high prolactin may be held in plasma during lactation. These results indicate that the fluctuation of uterine ER simply depends on the plasma level of estrogen during pregnancy and postpartal lactation in rats.

Animals↗

Compensation techniques in NIRS proton beam radiotherapy.

Proton beam has the dose distribution advantage in radiation therapy, although it has little advantage in biological effects. One of the best advantages is its sharp fall off of dose after the peak. With proton beam, therefore, the dose can be given just to cover a target volume and potentially no dose is delivered thereafter in the beam direction. To utilize this advantage, bolus techniques in conjunction with CT scanning are employed in NIRS proton beam radiation therapy planning. A patient receives CT scanning first so that the target volume can be clearly marked and the radiation direction and fixation method can be determined. At the same time bolus dimensions are calculated. The bolus frames are made with dental paraffin sheets according to the dimensions. The paraffin frame is replaced with dental resin. Alginate (a dental impression material with favorable physical density and skin surface contact) is now employed for the bolus material. With fixation device and bolus on, which are constructed individually, the patient receives CT scanning again prior to a proton beam treatment in order to prove the devices are suitable. Alginate has to be poured into the frame right before each treatments. Further investigations are required to find better bolus materials and easier construction methods.

Aged↗

Studies of tylosin derivatives effective against macrolide-resistant strains: synthesis and structure-activity relationships.

The 4"-O-substituted tylosin derivatives were prepared by selective esterification of the 4"-OH, and relationships between the substituent groups and antimicrobial activity against macrolide-resistant strains were examined. Introduction of branched-chain aliphatic acyl groups such as 2-methoxyisovaleryl or 4-methylvaleryl group afforded derivatives with good antibacterial activity; MIC values were 12.5 microgram/ml against Staphylococcus aureus MS-8710. MIC values of tylosin, erythromycin and josamycin against this strain were 800 microgram/ml or more. Further improved activity was obtained by introduction of aromatic groups such as phenylthioacetyl, phenylsulfonylacetyl, 4-nitrophenylacetyl, 4-nitrophenylsulfonyl and phenylethanesulfonyl groups; MIC values were 6.25 microgram/ml. These derivatives had also an improved antimycoplasmal activity; MIC values were 0.08 microgram/ml against macrolide-resistant strains of Mycoplasma gallisepticum. MIC values of tylosin against these strains were from 2.5 to 10 microgram/ml. Introduction of the groups described above into the 4"-OH was confirmed to increase the uptake by a resistant strain.

Anti-Bacterial Agents↗

Binding of 3-O-acetyl-4"-O-isovaleryltylosin to ribosomes from a macrolide-resistant strain of Staphylococcus aureus.

The resistance of Staphylococcus aureus MS-9610 to tylosin and 3-O-acetyltylosin was due to the decreased affinity of its ribosome system to these macrolides. However, 3-O-acetyl-4"-O-isovaleryltylosin was found to bind to ribosomes of the strain about three times more than 3-O-acetyltylosin. This binding was not interfered by tylosin and 3-O-acetyltylosin. The 4"-O-acyl group and the mycinose moiety were suggested to have an important role in the binding of tylosin derivatives to ribosomes of resistant strains.

Anti-Bacterial Agents↗

Bacteriological evaluation of midecamycin acetate and its metabolites.

In vitro midecamycin acetate was shown to have broad spectrum of antibacterial activities similar to those of other macrolides (midecamycin, josamycin, 9-propionyl josamycin and 2'-ethylsuccinyl erythromycin), which include Gram-positive organisms, a part of Gram-negative organisms and anaerobes. Metabolites of midecamycin acetate also showed certain degree of antibacterial activities although they gave higher MIC values than midecamycin acetate. The antibacterial activities of midecamycin acetate were potentiated in the medium with pH 7 or pH 8 and little affected by inoculum size or addition of human serum into the medium. Both midecamycin acetate and its metabolites were found to have relatively high protein binding rates. In vivo therapeutic experiments in experimental infections in mice, midecamycin acetate was shown to be much superior to other drugs tested in the therapeutic efficacy against intraperitoneal infections caused by Staph. aureus, Strept. pyogenes, Strept. pneumoniae and Cl. perfringens. In infections transnasally induced by Strept. pneumoniae, midecamycin acetate showed therapeutic efficacy 2 or 5 times greater than that of josamycin or midecamycin, despite that MICs of midecamycin acetate were equal to josamycin or midecamycin. Moreover, midecamycin acetate showed high therapeutic efficacy for subcutaneous infections due to Staph. aureus, suggesting that it exerts pronounced antibacterial activities against not only systemic infections but also local infections.

Ampicillin↗

[Estrogen and progesterone interactions on the estrogen receptor and thymidine kinase in the immature rat uterus].

In medical clinics or experiments, progesterone (P) has been used for treatment of adenomatous hyperplasia or cancer of the endometrium. In the present paper, effects of P in combination with or without estradiol-17 beta (E2) on the estrogen receptor (ER) and thymidine kinase (TK) activity in immature rat uterus are described. P has been reported to interfere with the replenishment of the cytoplasmic ER of the rat uterus. In the present study, no translocation of the cytoplasmic ER to the nucleus was found after the injection of P, whereas P slightly enhanced the wet weight and the TK activity of the uterus. The TK activity increased 20 to 30 times the control level at 30 hours after the injection of E2. However, the enzyme activity induced by E2 was inhibited by P which was approximately 1,000-fold or more dose of E2. This enzyme was separated into isozymes by DEAE-cellulose column chromatography. Induction of the specific TK isozyme, which was induced by E2 in immature rat uterus and closely related to DNA synthesis, was found to be inhibited by P.

Animals↗

Studies on the preventive method of lowered ventricular fibrillation threshold during experimental acute myocardial infarctions. A comparison between disopyramide phosphate and lidocaine.

This study was performed to investigate the prophylactic effect of disopyramide phosphate on ventricular fibrillation in acute myocardial infarction. Lidocaine and disopyramide phosphate were compared in terms of their effects on the lowered ventricular fibrillation threshold in experimental myocardial infarction produced by coronary ligation in dogs. The following results were obtained: 1) The effect of lidocaine i.v. + infusion appeared promptly and the ventricular fibrillation threshold exceeded control levels from 45 min onwards (p less than 0.01). 2) The i.m. injection of lidocaine was effective in a dose of 10 mg/Kg. The minimally effective blood level was 1.7 mcg/ml. 3) Disopyramide phosphate 5 mg/Kg i.v. produced a tendency towards recovery from 15 min onwards. After 30 min, the ventricular fibrillation threshold was significantly higher than control (p less than 0.01). 4) Disopyramide phosphate 5 mg/Kg i.m. was initially effective after 45 min. The effect was significant from 1 hour and 30 min onwards, compared with control (p less than 0.01). The minimally effective blood level was 2.4 mcg/ml. 5) Disopyramide phosphate 2 mg/Kg i.m. produced a tendency towards recovery but the difference from the control was not significant. 6) In equivalent i.m. doses, disopyramide phosphate tended to be more potent than lidocaine in increasing the ventricular fibrillation threshold. 7) In the aforementioned doses, disopyramide phosphate did not cause any marked changes in PQ interval or QT time in ECG. These results suggest that the intramuscular injection of disopyramide phosphate is a hopeful clinical treatment to prevent ventricular fibrillation in the very early stages of acute myocardial infarction.

Animals↗