[Origins of the vagus nerve fibers to the rat intestine: tracing study with cholera-toxin B subunit as a retrograde tracer].
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Biomedical subjects
Publications and source records attributed to H Okamura.
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Vascular responsiveness to angiotensin II in pregnant rats with a normal or a low calcium diet were examined. From day 6 of pregnancy, Wistar rats were separated into two groups. One group was fed a normal diet containing 1.2% calcium (control group) and the other group was fed a low calcium diet containing 0.02% calcium (low Ca group). Using a tail cuff method, the systolic blood pressure in the low Ca group was found to be significantly higher than that in the control group on day 18 of pregnancy. On days 12 and 18 of pregnancy using the hindquarters perfusion technique, the vascular response to bolus angiotensin II (30, 100, 300, and 1000 ng/kg of rat body weight) in the low Ca group increased significantly more than that in the control group. However, the pressor response to norepinephrine and the depressor response to acetylcholine did not differ between the low Ca group and the control group. Urinary sodium excretion in the low Ca group was lower than that in the control group on days 12 and 18 of pregnancy, and decreased toward term, whereas urinary phosphorus excretion in the low Ca group was higher than that in the control group on days 12 and 18 of pregnancy. These data indicate that low calcium intake during pregnancy increases sensitivity to the pressor effects of angiotensin II and increases systolic blood pressure in normotensive pregnant rats.
The abdominal aorta of 20 pregnant rabbits was surgically constricted below the renal arteries on the 21st day of pregnancy, producing a stricture that decreased the blood flow by 60%. Four pregnant rabbits underwent sham operation and served as control. The pressor response to angiotensin II (A-II) was assessed by measuring the systolic blood pressure in the ear of rabbits. We intravenously administered 20 mg/kg of OKY-046, a thromboxane A2 (TXA2) synthetase inhibitor (OKY group: n = 13) or saline (n = 7) daily from the 23rd day of pregnancy until the day of delivery. After stricture of the abdominal aorta, the "effective pressor dose" (EPD:nanograms of A-II/kg/min necessary to cause a 20 mmHg rise in systolic pressure) was significantly lower in the saline group than in the control group. On the 27th and 29th day of pregnancy, the EPD in the OKY group was significantly higher than that in the control group. The plasma thromboxane B2 (TXB2) level in the OKY group was significantly lower than that in the saline group on the 27th day. The fetal birth weight in the saline group was significantly lower than that in the control group. These finding suggest that OKY-046 restores the vascular refractoriness induced by A II and suppresses TXA2 synthesis in pregnant rabbits with aortic constriction.
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OBJECTIVE: We examined the effects of norethisterone and/or mestranol on the pressor response to angiotensin II in 20 healthy men. METHODS: Four study protocols were used: I) mestranol 0.08 mg/day for 6 days followed by mestranol plus norethisterone 20 mg/day for 6 days, II) mestranol 0.16 mg/day for 6 days followed by norethisterone alone 10 mg/day for 6 days, III) mestranol 0.24 mg/day followed by norethisterone 20 mg/day for 6 days, and IV) norethisterone 20 mg/day for 6 days. The angiotensin II dose to elicit a 20-mmHg rise in diastolic blood pressure was considered the effective pressor dose. This was determined before each protocol, at the end of the mestranol-alone portion, and at the end of the norethisterone portion. Subjects in study III also underwent measurement of plasma prostanoid levels, plasma renin activity and concentration, and estradiol and progesterone just before each angiotensin II infusion. Subjects in studies I and III underwent measurement of mean platelet volume, complete blood counts, liver function tests, and coagulation factors before each angiotensin II infusion. RESULTS: Whereas mestranol had no apparent effect on angiotensin II pressor response, norethisterone at a dose of 20 mg/day (with or without concurrent mestranol administration) caused a significant decrease in pressor responsiveness to angiotensin II. No changes in plasma prostanoids or renin could be found that would account for the change in pressor response. CONCLUSION: These findings indicate that the refractoriness to angiotensin II induced by norethisterone was related to its progestogenic properties.
6-Hydroxydopamine (6-OHDA) was injected into the rat striatum unilaterally. After 2-4 weeks, a marked decrease in the number of tyrosine hydroxylase-immunoreactive neuronal perikarya and dendrites was observed in the substantia nigra (SN) ipsilateral to the injection. Nissl staining showed a severe cell loss in the same region and electron microscopy revealed neuronal perikarya under degenerating process in the SN. The results showed a retrograde cytotoxic effect of 6-OHDA from the striatal terminals to their dopaminergic neuronal perikarya in the SN, and suggest the possibility that the striatum may be a primary locus in the degeneration process in Parkinson's disease.
We detected a diurnal change of vasoactive intestinal peptide (VIP) messenger RNA (mRNA) in the rat suprachiasmatic nucleus (SCN) using the in situ hybridization technique combined with computed image analysis. The amount of VIP mRNA was greatest at 02.00 h, the next largest level was seen at 20.00 h during the dark phase and smallest at 14.00 h during the light phase. We also confirmed that the onset of the fluctuation of mRNA occurred 2-6 h prior to the diurnal variation of the content of VIP-like immunoreactivity by semiquantitative immunocytochemistry. These findings suggest that light stimulus from the retina is a primarily influence on the transcription of VIP mRNA and induces a diurnal variation of VIP synthesis.
Swallowing function was studied in three patients following the pectoralis major musculocutaneous reconstruction of the hypopharynx and cervical esophagus after extensive resection for hypopharyngeal cancer. Fluoroscopy and endoscopy revealed the formation of a sphincter-like ring at the proximal end of the remaining intact esophagus. This ring may act to prevent reflux from the lower esophagus, although its sphincteric power is weak. Manometric testing showed that no swallowing pressure was produced in the reconstructed gullet; therefore, bolus propulsion at the pharyngeal stage occurs mainly by gravity. Follow-up studies on swallowing indicate a minimum length of the suture line of 11 cm in order to prevent esophageal stenosis due to anastomotic stricture at the distal mucocutaneous junction.
Hydroxyeicosatetraenoic acid methyl esters (HETEs) are lipoxygenase products of arachidonic acid that are generated along with prostaglandins (PGs) during acute inflammatory reactions. Whereas it is well known that ovarian PG levels increase during the ovulatory process, little is known about ovarian HETEs. This report compares the ovarian changes in 5-, 12-, and 15-HETE with ovarian PGE and PGF, along with progesterone, 17 alpha-hydroxyprogesterone, 4-androstene-3,17-dione, testosterone, and 17 beta-estradiol. Ovulation was induced in immature Wistar rats by sequential treatment with pregnant mare's serum gonadotropin and human chorionic gonadotropin (hCG). Follicles began rupturing 10 h after hCG treatment. The greatest correlation was among 12-HETE, 15-HETE, and progesterone, which increased to peak levels at 10 h after hCG. In contrast, the ovarian levels of 5-HETE, 17 alpha-hydroxyprogesterone, testosterone, and 17 beta-estradiol all declined sharply beginning 4 h after hCG. 2 alpha,4 alpha,7-4,5-Epoxy-17-hydroxy-4,17-dimethyl-3-oxo-androstane-2- carbonitrile (epostane), a potent inhibitor of steroid synthesis and ovulation, sharply reduced the synthesis of all five steroids within 30 min after its injection at 3 h after hCG. Among the five eicosanoids, epostane mainly inhibited 15-HETE. The results suggest that 15-HETE, along with progesterone, may have an important role in ovulation.
Indomethacin, an inhibitor of cyclooxygenase that generates prostaglandins (PGs) from arachidonic acid, and 2 alpha,4 alpha,7-4,5-epoxy-17-hydroxy-4,17-dimethyl-3-oxoandrostane- 2-carbonitrile (epostane), an inhibitor of 3 beta-hydroxysteroid dehydrogenase that generates progesterone from pregnenolone, are both potent inhibitors of ovulation. This report compares the dose-dependent effects of these two inhibitors on ovarian levels of 5-, 12-, and 15-hydroxyeicosatetraenoic acid methyl ester (HETEs), prostaglandin E2 (PGE), prostaglandin F2 alpha (PGF), progesterone, 17 alpha-hydroxyprogesterone, 17 beta-estradiol, 4-androstene-3,17-dione, and testosterone during ovulation in 25-day-old immature Wistar rats. The ovulatory process was initiated by 10 IU of human chorionic gonadotropin (hCG). Indomethacin was given at 3 h after hCG in doses ranging from 0.0316 to 10.0 mg/rat. A dose of 0.1 mg/rat was the lowest dose to significantly reduce the ovulation rate from the control level of 70.5 +/- 5.8 ova/rat. This dose also reduced 15-HETE, but not 5-HETE, 12-HETE, or the steroids. PGE and PGF were strongly inhibited by an even lower dose of indomethacin (0.0316 mg/rat), but this dose did not affect the ovulation rate. Epostane was given at 3 h after hCG in doses ranging from 0.1 to 5.0 mg/rat. A dose of 1.0 mg/rat was the lowest dose to significantly inhibit ovulation. This dose also reduced the ovarian levels of 15-HETE and progesterone but not 5-HETE, 12-HETE, PGE, PGF, or the other steroids. The results indicate that the ovulation rate is most closely correlated to ovarian 15-HETE levels.
To investigate whether LH/human CG (hCG) or progesterone acts as a regulator of estrogen receptors (ER) and progesterone receptors (PR) in granulosa cells, we studied the immunohistochemical expression of both ER and PR in the ovary and the uterus of mature rabbits, during the induction of ovulation by FSH followed by administration of hCG, progesterone, or a progesterone antagonist (RU486) and hCG. Granulosa cells pretreated with FSH for 3 days showed ER staining, but negligible PR staining. The staining pattern for ER and PR changed in animals pretreated with FSH followed by hCG injection; by 6 h after hCG injection, we observed the disappearance of ER and the appearance of PR, and by 3 days after hCG injection, we observed the reappearance of ER and the disappearance of PR. However, the expression of ER and PR in the granulosa cells of animals pretreated with FSH followed by progesterone administration instead of hCG was almost the same as that of animals pretreated with FSH alone. In addition, the expression of ER and PR in the granulosa cells of animals pretreated with FSH followed by RU486 and hCG was almost the same as that of animals pretreated with FSH followed by hCG administration. The uterine glandular epithelium, in contrast, began to show decreased appearance of ER and PR by 48 h after hCG injection, and we observed the disappearance of both receptors by 3 days after hCG administration. These results suggest that the expression of ER and PR in granulosa cells is not regulated by the action of progesterone, but by that of LH/hCG.
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Changes in interstitial collagenase activity in the rat uterine cervix during ripening were clarified in a time-dependent manner. Premature delivery was induced by an antiprogesterone agent, RU486, for rats in late pregnancy. The presence of interstitial collagenase in the extract from the rat cervical tissue was demonstrated, by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis using the natural and unaffected collagen as a substrate. The collagenase activity was determined as the release of digested peptides from the radio-labeled collagen. Our experiments with RU486 were performed in rats on the 18th day of pregnancy. A single administration of RU486 (15 mg/kg) resulted in the premature delivery of all treated rats within 30 h after the injection (average time was 23.9 h). The marked increase in cervical wet weight was observed up to the time to premature delivery along with a significant acceleration from 18 h after the administration of RU486. In this state, the cervical collagenase activity was enhanced, the highest levels being recorded at 21 h after the administration. The interstitial collagenase in the uterine cervix appears to play a significant role in the regulation mechanisms of cervical ripening in late pregnant rats.
A 73-year-old woman, whose medical history reported radical hysterectomy and radiotherapy for squamous cell carcinoma of the cervix uteri 20 years earlier, was found to have an angiosarcoma of the vagina. The histological diagnosis was confirmed by immunohistochemical staining of tumor cells for factor VIII-related antigen and ultrastructurally defined vasoformative structures. Primary angiosarcoma of the vagina is quite rare and reported in only two published cases. The present case is a third in general, and the first report confirmed by light microscopy, immunohistochemical, and electronmicroscopy studies.
A case is reported of aqueductal stenosis caused by an abnormal draining vein and demonstrated by computerized tomography and magnetic resonance imaging. Placement of a ventriculoperitoneal shunt relieved the patient's progressive headaches.
The preovulatory surge of gonadotropins causes resumption of oocyte meiosis, rupture of follicle wall and release of a fertilizable ovum, and luteinization. In the present lecture, current studies of the biochemical mechanism of follicle rupture are discussed. Over the past decade the cyclooxygenase pathway of arachidonic acid metabolism, namely prostaglandins (PGs), has received considerable attention in ovulation studies. We studied the changes in ovarian levels of eicosanoids during ovulation and the effects of indomethacin or lipoxygenase inhibitors on ovulation and ovarian eicosanoids in PMSG/hCG primed immature rats. Our data demonstrate that lipoxygenase products, especially 15-hydroxyeicosatetraenoic acid (HETE), is more essential for the ovulatory process than PGs. Ovarian steroidogenesis shifts from estradiol to progesterone after LH surge. It is not yet clarified how progesterone participates in the ovulatory process. We studied the effects of epostane and RU486 on ovulation rate, ovarian levels of steroids and eicosanoids, ovarian 3 beta-HSD activity, and ovarian proteolytic enzymes (collagenase, plasminogen activator and kallikrein) activities in the rats. The results show that progesterone plays an important role in the initial 4 hours of the ovulatory process by regulating proteolytic enzyme activities, and that an autocrine regulation may take place in progesterone production during ovulation. Morphological studies have demonstrated dilation and increased permeability of follicle vasculature during ovulation. We investigated the relation between ovarian blood volume and progesterone, and the role of active oxygen in ovarian vascular permeability by using SM-SOD.(ABSTRACT TRUNCATED AT 250 WORDS)
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