Quantitative determination of forphenicinol and its metabolites in human serum and urine by gas chromatography/mass spectrometry with selected ion monitoring.
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Biomedical subjects
Publications and source records attributed to H Morikawa.
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The ontogenesis of specific binding of 125I-hPL and 125I-insulin was determined in rat liver cell membranes (10(5) X g pellets), and the regulatory mechanisms of these binding sites were also examined. There were striking differences in the mode of ontogenesis between binding sites of hPL and insulin in rats. HPL binding sites were very few in liver cell membranes from fetal and immature rats. They began to increase after puberty, and markedly increased in late pregnancy. On the other hand, insulin binding sites, which decreased in late pregnancy, were dominant in fetal liver and placenta. Consequently, the lipolytic and glycogenolytic activities of hPL in maternal liver were accentuated, whereas the effects of insulin on maternal liver were suppressed. In contrast, in fetal liver and placenta only the anabolic effects of insulin seemed conspicuous. According to the results of experiments on in vivo administration of estradiol-17 beta, progesterone, hydrocortisone or hPL to intact or hypox-rats, and the measurement of serum rat chorionic mammotropin (rCM), rPRL, estradiol-17 beta, and insulin during pregnancy in rats, the increase in hepatic hPL binding sites observed in late pregnancy might be, at least in part, due to rCM secreted from placenta, and the decrease in insulin binding sites due to the increase in serum insulin itself in rats.(ABSTRACT TRUNCATED AT 250 WORDS)
The responses of plasma renin activity (PRA), plasma bradykinin (BK) and urinary kallikrein like activity (UK) associated with the infusion of angiotensin II (AII) before and after NaCl loading were investigated in pregnancy induced hypertension (PIH). AII was infused step by step (2-10 ng/kg/min) into pregnant women (1st AII infusion). About 10 minutes later 100ml of physiological saline was rapidly infused, and the AII infusion was repeated (2nd AII infusion). PRA decreased dose dependently after the 1st AII infusion in normal pregnancy. But the decreasing pattern of PRA was not observed after the 2nd AII infusion in some cases of normal pregnancy, and was also not observed in many cases of PIH after the 1st or 2nd AII infusion. BK significantly increased after the 1st AII infusion and more remarkably after the 2nd AII infusion in normal pregnancy. In PIH, BK levels before the 1st AII infusion were higher than in normal pregnancy, but after the AII infusion increased less than in normal pregnancy. There was no difference between the rate of increase in UK output in normal pregnancy and in PIH. These data suggest that in PIH the mechanism for control of renin secretion is altered, and the vasodepressor system is stimulated in an in-situ condition, but its reserve function against the AII may be weaker than in normal pregnancy.
Insulin receptors in fat cell membranes (10(5)g pellets) were investigated by a conventional incubation method in pregnant and nonpregnant rats or women. Insulin binding in pregnant L20 rats was 8.1 +/- 2.1% (M +/- SD) less than that in nonpregnant rats (14.5 +/- 3.5%) in peripheral adipose tissues (p less than 0.05). In the former a reciprocal rise in the serum insulin level was observed. In pregnant women, insulin binding was determined in subcutaneous fat tissues obtained at cesarean section or other laparotomy. Insulin binding was 29.3 +/- 8.9% in nonpregnant women, and it did not change in early pregnancy (34.3 +/- 6.2%, NS). However, it decreased obviously in late pregnancy (20.4 +/- 6.4%) (p less than 0.05). Scatchard analysis indicated that the decrease in insulin binding was due to the changes in the number of insulin receptors in fat cell membranes. Their Kd values were indistinguishable from each other in rats and women. In addition, insulin binding correlated significantly with Insulin Sum, Glucose Sum at 75g OGTT, TG and FFA in serum. These results suggested that insulin receptors in adipose tissues were suppressed in late pregnancy, and this might be the cause of the "insulin resistance" observed in the maternal body in late pregnancy.
The dynamics of insulin receptors was investigated in the feto-placenta-maternal system of DM-onset pregnant nonobese diabetic (NOD) mice. Insulin binding experiments were carried out by conventional incubation methods using cell membrane fractions (10(5) X g pellets). The results were as follows. In the case of JCL-ICR mice, used as the control, insulin specific binding in liver cell membranes, which was 26.6 +/- 3.2% in the nonpregnant state, decreased in late pregnancy (20.7 +/- 2.7%). On the other hand, in pregnant NOD mice hepatic insulin binding was 24.3 +/- 1.0%, more than that of JCL-ICR pregnant mice. By Scatchard analyses, these changes were found to be due to the changes in the number of receptors especially in high affinity sites. The serum insulin level was 6.3 +/- 4.2 microU/ml in pregnant NOD mice, which was much lower than that in other mice (nonpregnant JCL-ICR: 14.8 +/- 6.4, pregnant JCL-ICR: 37.3 +/- 18.3). In fetal liver and carcasses of NOD fetuses, insulin binding was also much greater than that in JCL-ICR fetuses. In conclusion, the hormone sensitivity to insulin was accentuated in pregnant DM-onset NOD mice not only in the maternal body but also in the fetus. This is regarded as a metabolic adaptation to the environment in the insulin deficient state of these mice. And it is speculated that insulin receptors are also down-regulated in fetal liver as well as in adult mice.
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Histochemical and in vitro investigations of the autonomic innervation in the human mesotubarium ovarica (MTO) are described here in the course of our studying its physiologic role in the capture of released oocytes at ovulation. The present results imply that the muscle activity of MTO is under the excitatory control of cholinergic nerves and under a reciprocal (predominantly excitatory) control of adrenergic nerves, and that both adrenergic and cholinergic neural factors (at least postsynaptic ones) are related in the enhancement of the muscle activity of MTO around the time of ovulation.
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To elucidate the mechanism of follicular rupture at ovulation in human, ultrastructural changes of stromal tissue of the follicular apex during follicular growth and ovulation were studied by focusing on the collagen and fibroblasts in the stroma. Sixteen ovaries were obtained from women at their thirties who underwent the abdominal hysterectomy for gynecologic diseases. From follicles at various stages of development, apical portions were excised and processed for electronmicroscopy. At the apex of growing follicles, fibroblasts with poor cytoplasm and abundant collagen fibers among them were observed in the layers of tunica albuginea and theca externa. At the preovulatory follicles, fibroblasts had rich cytoplasm containing lysosomal granules and multivesicular structures and intercellular collagen fibers were rather sparse. These lysosomal granules and multivesicular structures in the fibroblasts were much conspicuous in the theca external layer of preovulatory and post-ruptured follicles and collagen fibers among these fibroblasts were almost disappeared. It seems that these intercellular collagen fibers and ground substance were digested by the content of lysosomal granules and multivesicular structures.
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The human mesotubarium ovarica has been shown to contain bundles of smooth muscle cells. Its contractility at various phases of the menstrual cycle was studied in vitro in 51 tissue strips obtained at laparotomy. The strips obtained at the ovulatory phase showed the greatest spontaneous contractile activity as well as the greatest contractile response to norepinephrine, acetylcholine, and prostaglandin F2 alpha. This corresponds to the increased contractility of the ovary at this phase of the cycle. It is suggested that these contractile actions may, under the influence of chemical transmitters, play a role in ovum pick-up by the tubal fimbria at ovulation.
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Dehydroepiandrosterone sulfate (DHAS) is now used for a dynamic test of placental function by many obstetricians. While practicing this test, the authors found that DHAS markedly promoted so-called "cervical ripening". To study this problem, DHAS of 50 or 100 mg in multiple doses were injected into 132 Japanese pregnant women in their 38th--42nd week of gestation. The change in Bishop score was carefully recorded. Bishop score in the injected groups of primiparae (100 mg) began to rise much sooner than the control groups (p less than 0.01 on seventh day and 14th day). However, such significant difference in the rise of Bishop score was not noted in the multiparae and primiparae with 50 mg. Although the rise of score is not significant, the duration (day) from injection to delivery was shorter in the injected group than the control group (t=2.1529, p less than 0.05 in primiparae with 50 mg, t=3.8829, p less than 0.01 with 100 mg, t=2.1029, p less than 0.05 in multiparae with 50 mg). In some of these cases, labor began or delivery was finished within 24 hrs. Among the factors of Bishop score, mainly the effacement, consistency and dilatation of the cervix were remarkably improved by DHAS injection (p less than 0.01 and less than 0.05). Side effects of any type were not seen in the mothers and foetuses. As a conclusion, DHAS injection in considered to produce favorable conditions for delivery in women with "unripe cervix" by softening the soft birth canal. Furthermore, it is suggested that DHAS might play an important role in triggering labor.
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In order to clarify the mechanisms by which the egg is transported from the ruptured follicle into the fimbrial end of the Fallopian tube in the human being, the mesotubarium ovarica (MTO), the unique anatomical structure which connects the tubal fimbriae and the ovary, was studied in seven human adnexal specimens histochemically and electron microscopically. The results demonstrated clearly the presence of smooth muscle cells in the MTO, and failed to demonstrate the presence of cilia in the lining epithelial cells of the MTO. Based on these morphological results, contractility of the MTO was studied in vitro by using a muscle chamber and a pressure transducer with 26 human adnexal specimens. Spontaneous contractile activites of regular frequency and moderate intensity were observed in the MTOs of all specimens examined. A possible role of the MTO in the mechanisms of ovum pickup at the time of ovulation is discussed.
In order to clarify the mechanisms by which the egg is transported from the ruptured follicle into the fimbrial end of the fallopian tube in the human, the mesotubarium ovarica (MTO), the unique anatomic structure which connects the tubal fimbriae and the ovary, was studied in seven human adnexal specimens histochemically and electronmicroscopically. The results demonstrated clearly the presence of smooth muscle cells in the MTO, and failed to demonstrate the presence of cilia in the lining epithelial cells of the MTO. A possible role of the MTO in the mechanisms of ovum pick-up at the time of ovulation is discussed.