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Biomedical subjects

M Oikawa

Publications and source records attributed to M Oikawa.

At least 91 records · Page 5Linked to original sources

Epidermal growth factor stimulates tissue plasminogen activator activity and messenger ribonucleic acid levels in cultured rat granulosa cells: mediation by pathways independent of protein kinases-A and -C.

Recent reports suggest that epidermal growth factor (EGF) or related peptides may act as local hormones to regulate granulosa cell differentiation. While FSH and GnRH are known to stimulate accumulation of tissue-type plasminogen activator (tPA) mRNA in granulosa cells, studies using nonovarian cells have shown stimulation of tPA by EGF. In this study, the effect of EGF and its structural analog transforming growth factor-alpha (TGF alpha) on ovarian tPA mRNA and activity was investigated. Granulosa cells obtained from immature estrogen-treated rats were cultured with FSH or increasing doses of EGF or TGF alpha before analysis of tPA activity using sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by a fibrin overlay technique. Like FSH and GnRH, EGF and TGF alpha stimulated the secretion of tPA activity in a dose- and time-dependent manner (onset, 12 h; maximum, 48 h). Northern blot hybridization of total RNA using a rat cRNA probe for tPA showed the accumulation of a 22S species mRNA in cells treated with EGF or TGF alpha, but not with nerve growth factor, suggesting increased expression of the tPA gene. Furthermore, slot blot hybridization of RNA from these cells confirmed a time-dependent increase in tPA mRNA preceding that in enzyme activity. Cotreatment of a saturating dose of EGF with phorbol myristate acetate (PMA) or GnRH resulted in additive increases in both tPA enzyme activity and mRNA levels. In addition, pretreatment with PMA desensitized the cells to subsequent treatment with PMA or GnRH, but did not diminish EGF-induced tPA mRNA, suggesting that EGF acts through a pathway independent of protein kinase-C. Also, extracellular cAMP levels did not increase with EGF treatment in the presence or absence of a phosphodiesterase inhibitor, suggesting the lack of involvement of the protein kinase-A pathway. Suppression of protein synthesis by cycloheximide inhibited the induction of tPA mRNA by EGF, whereas similar treatment resulted in the superinduction of tPA mRNA in FSH-treated cells, suggesting that EGF and FSH do not share the same pathway. These results suggest that EGF and TGF alpha induce tPA mRNA and activity in granulosa cells through a pathway independent of protein kinases-A (FSH) and -C (GnRH and phorbol ester), providing an interesting model for future elucidation of the molecular mechanism involved in tPA gene expression.

Animals↗

Beta-adrenergic agents stimulate tissue plasminogen activator activity and messenger ribonucleic acid levels in cultured rat granulosa cells.

Expression of tissue plasminogen activator (tPA) gene is stimulated by gonadotropins in granulosa cells. Because adrenergic agents interact with specific granulosa cell receptors to increase progesterone biosynthesis, the effects of these pounds on tPA activity and mRNA levels were also investigated. Cells obtained from immature estrogen-treated rats were initially cultured with FSH or medium alone for 2 days. They were then reincubated with various adrenergic agents before measurement of medium tPA activity using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, followed by a fibrin overlay technique. In addition, cellular RNA was extracted, and tPA mRNA levels were analyzed using a specific rat cRNA probe. Isoproterenol, a beta-adrenergic agonist, stimulated the secretion of tPA activity in a dose-dependent manner, with FSH-pretreated cells secreting higher levels of the enzyme than cells without FSH priming. Northern blot hybridization of total RNA showed the accumulation of a 22S species tPA message in cells treated with isoproterenol, suggesting increased expression of the tPA gene. Furthermore, slot blot hybridization of RNA from these cells indicated a time-dependent increase in tPA mRNA, with maximal induction between 1-3 h of incubation. A selective beta 2-adrenergic agonist, terbutaline, but not the beta 1-agonist dobutamine, stimulated tPA activity. Also, the stimulatory effect of isoproterenol was blocked by a beta 2-antagonist (ICI-118,551) but not by a beta 1-antagonist (practolol), suggesting the involvement of a beta 2-receptor. Like FSH and LH, isoproterenol increased extra- and intracellular cAMP levels. Cotreatment of a saturating dose of isoproterenol with FSH or LH did not further stimulate tPA activity. Similar to that in cells treated with FSH, inhibition of protein synthesis by cycloheximide resulted in the superinduction of tPA mRNA in isoproterenol-treated cells. Thus, activation of beta 2-adrenergic receptors in granulosa cells induces tPA mRNA and activity, presumably through the protein kinase-A pathway shared by gonadotropins. Adrenergic neurotransmitters may be potential intraovarian regulators of this important protease.

Actins↗

[A case of myocardial infarction due to the left main trunk lesion, in which percutaneous coronary recanalization and emergency coronary-aorto bypass graft, and subsequent percutaneous coronary angioplasty were effective not only from a viewpoint of survival but from comeback to social life].

A case of acute myocardial infarction due to the lesion in the left main coronary artery was reported. A 50-year male was referred to our department for suspected acute myocardial infarction. Physical examination on admission revealed slight cyanosis with cold sweating due to severe chest pain. Pulse was irregular and heart rate was 78 beats/min. Blood pressure was 100/80 mmHg. A series of electrocardiograms (ECG) and laboratory data provided the diagnosis of wide-ranged anterolateral infarction in the left ventricle. Emergency coronary angiograms taken without delay showed a subtotal occlusion (99% stenosis) of the left main coronary trunk (LMT) before the initiation of intracoronary thrombolysis (PTCR). Following the intracoronary infusion of urokinase of 1,200,000 units, symptoms and ECG changes transiently improved but worsened later, and LMT stenotic lesion and delayed filling of myocardium were similar with before PTCR. Emergency coronary-aorto bypass graft (CABG) was undertaken without a significant delay to both the left anterior descending artery (LAD) and left circumflex coronary artery (LCX). With these treatments, the patient could survive despite the wide area of infarction due to LMT lesion. Coronary angiograms performed 37 days after the CABG showed that the graft to LAD was completely occluded and the LCX graft was patent with partial stenosis. Treadmill test at this time induced an anginal episode with ischemic ECG changes on moderate exercise, indicating the presence of significant area of ischemic myocardium. For salvage of the ischemic myocardium, percutaneous transluminal coronary angioplasty (PTCA) was successfully performed for the LMT stenosis, resulting in no episode of angina nor ischemic ECG changes during exercise loading.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon, Coronary↗

Cardiopathology of sudden cardiac death in the race horse.

Twenty thoroughbred race horses were selected for postmortem cardiopathological study of sudden cardiac death; ten of the twenty horses died suddenly. In order to define accurately the morphological changes observed in these ten hearts, ten other thoroughbred race horses considered to have normal hearts were selected as a control group and studied by postmortem coronary angiography. Of the ten horses that died suddenly, eight were witnessed to have died either during or shortly after training or racing. The death was instantaneous except in one horse, which showed ventricular tachycardia and died 4.5 h after a race. The other two died unexpectedly in the stable at night. Pathologically, the horses that died suddenly generally showed multifocal myocardial lesions that were ischemic and fibrotic. These lesions were found in the atrial tissue close to the sinoatrial (SA) node and in the atrioventricular (AV) junction, including the upper portion of the interventricular septum. Such myocardial lesions were often associated with vascular changes including arterio- and/or arteriolosclerosis. Angiographically, the SA node appeared to be perfused by atrial branches of the left and right coronary arteries. One branch originating from the left coronary artery gave off a few branches into the AV junction. These pathological findings, mainly consisting of both atrial lesions and lesions in the AV junction, were similar to those observed in horses with either atrial fibrillation, SA block, or paroxysmal ventricular tachycardia. A finding of particular interest was the angiographic demonstration that the blood supply to the AV junction partly came from the SA node artery.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Effects of ovarian wedge resection (WR) and spironolactone administration on pulsatile LH release and serum steroid hormone levels in women with polycystic ovarian disease].

The exact mechanism(s) by which WR induces ovulation in women with PCOD is still uncertain. The aim of this study is to observe the change in sex steroids and pulsatile LH release (pul-LH-R) after WR. Before and either 7-8 days after the surgery (n = 8) or after 30 days of spironolactone treatment (n = 4), serum LH levels were measured every 15 min for 2-4 hours in PCOD women. Sex steroids were radioimmunoassayed before, and 3-4 and 7-8 days after WR. Testosterone (T) and androstenedione (A) in 7 women in whom spontaneous ovulation occurred after WR decreased significantly either 3-4 or 7-8 days after the surgery (p less than 0.001). Estrone decreased significantly (p less than 0.001) 7-8 days after the operation. The mean level of LH after WR in the 7 women decreased significantly (p less than 0.001). Furthermore, significant decreases both in the mean values of LH pulse amplitude (p less than 0.001) and frequency (p less than 0.01) were observed after WR. Ovulation occurred after 45 and 58 days of spironolactone administration in 2 PCOD women who showed changes in pul-LH-R and a drop in serum testosterone levels after 30 days of treatment. The data suggested that changes in pul-LH-R and decreased sex steroids after WR seemed to play key roles in the mechanism(s) by which WR induces ovulation.

Adult↗

Serial changes in sonographic appearance after transcatheter hepatic arterial embolization.

Serial changes in sonographic appearance after transcatheter hepatic arterial embolization (TAE) were studied in 22 patients who had hepatoma and one patient who had a hepatoblastoma. These changes were classified into three types. In cases of type 1, the internal echo of the entire tumor became remarkably echogenic with or without an acoustic shadow. In cases of type 2, echogenic areas or scattered echogenic spots with or without acoustic shadows were observed. In Type 3 cases, no changes in sonographic appearance were observed. Tumor diameters in all of the type 1 cases were less than 4.9 cm. Various size tumors were observed in the cases of type 2 and type 3. Transcatheter arterial embolization was completely effective or effective in 89 per cent of the type 1 and type 2 cases, but was not effective in 75 per cent of the type 3 cases. The sonographic changes correlated well with the effectiveness of TAE.

Adult↗