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Biomedical subjects

A Imai

Publications and source records attributed to A Imai.

At least 19 recordsLinked to original sources

Dehydroepiandrosterone sulfate-binding sites in plasma membrane from human uterine cervical fibroblasts.

Dehydroepiandrosterone sulfate (DHA-S) plays a critical role in cervical dilatation at labor. Incubation of cervical fibroblasts with [3H]DHA-S caused a rapid and saturable increase in cellular radioactivity: an apparent equilibrium was reached by 2 min. There was no detectable conversion of DHA-S into DHA or oestradiol. When the fibroblasts loaded with [3H]DHA-S were homogenized and fractionated, the specific radioactivity in the plasma membrane fraction was enriched approximately 8- to 9-fold compared with the whole homogenate; only low amounts of radioactivity were observed in the other subcellular fractions. The binding of DHA-S to plasma membrane preparations showed saturation kinetics with an apparent equilibrium dissociation constant (Kd) of 12 nM, and the binding capacity (Bmax) was calculated to be 1.25 fmol/mg protein. Neither DHA nor oestrone sulfate affected [3H]DHA-S binding to the plasma membrane. The plasma membranes of skin fibroblasts did not show specific binding sites for DHA-S. These findings demonstrate the presence of specific binding sites for DHA-S in the plasma membrane of cervical stroma cells. The fetal adrenal steroid may exert its action on cervical ripening at least in part through membrane-associated binding sites, or receptors.

Binding Sites

Juvenile granulosa cell tumor in a 2-year-old infant: report of a case complicated with ascites and acute respiratory distress.

A two-year-old girl with a juvenile granulosa cell tumor (JGCT) and with acutely progressive hydrothorax and ascites is presented. She had precocious pseudopuberty and an elevated level of serum estradiol. Sudden onset of respiratory distress, due to a pleural effusion and severe abdominal distention, led to an emergency laparatomy. Unilateral salpingo-oophorectomy induced a rapidly favorable course. Histological examination showed no evidence of invasion or peritoneal metastasis. This is the first case of JGCT associated with an acute respiratory emergency as a main clinical feature.

Child, Preschool

Evidence of a role for phosphatidylinositol synthesis in human amnion cell proliferation.

Phosphatidylinositol (PtdIns) is the key precursor of phosphoinositide-derived intracellular mediators. The effects of changing the rate of PtdIns synthesis on mitogenic activity of human amnion-derived WISH cells were investigated. Incubation of the cells with [3H]inositol caused a time- and dose-dependent PtdIns labeling. Exogenous Ca2+ inhibited [3H]inositol incorporation in a dose-dependent fashion; half-maximal inhibition occurred with 0.3-1.0 mM Ca2+. In contrast, removal of cytosolic Ca2+ by ionophore A23187 and 1 mM EGTA induced enhancement of the PtdIns labeling as a function of A23187 concentration, perhaps through release of inhibitory effects of endogenous Ca2+. The A23187-stimulated PtdIns labeling with [3H]inositol was not abolished by additional unlabeled inositol, suggesting that [3H]inositol labeling of PtdIns occurred mainly through de novo synthesis catalyzed by PtdIns synthase (EC 2.7.8.11). In cells with PtdIns synthase activity decreased by exogenous Ca2+, [3H]thymidine incorporation was also inhibited, while A23187 caused dose-dependent enhancement of thymidine incorporation. The changes in PtdIns synthase activity occurred in parallel with changes in mitogenic activity caused by increasing the dose of exogenous Ca2+ or A23187. A similar lowering of mitogenic activity was observed upon suppression of PtdIns synthase by pemirolast potassium (9-methyl-3-1H-tetrazol-5yl-4H-pyrido[1,2-a]pyridin-4-one potassium) via a Ca(2+)-independent mechanism. These data demonstrate that changes in PtdIns synthase activity by some agents acting via different mechanisms are associated with parallel changes in thymidine incorporation, and suggest that PtdIns production is tightly coupled to cell proliferation in human amnion cells.

Amnion

Tight coupling of gonadotropin-releasing hormone receptor to stimulated phosphoinositide turnover and antigonadotropic action in granulosa cells.

Gonadotropin-releasing hormone (Gn-RH) stimulates phosphoinositide turnover by binding to its specific receptor and suppresses gonadotropin-dependent maturation and steroidogenesis in granulosa cells. This study was undertaken to determine whether persistent receptor occupancy was necessary for Gn-RH to exert such actions on rat granulosa cells, or whether Gn-RH actions were continued by a first and transient stimulation by Gn-RH, using a competitive antagonist, antide. Gn-RH stimulated [32P]phosphate incorporation into phosphatidylinositol (PtdIns), which could be terminated by displacement of previously bound Gn-RH from its receptor by antide and restarted by reoccupying the receptors with Gn-RH. Antide could prevent Gn-RH-stimulated PtdIns radiolabelling whenever it was added to incubations. An identical effect of antide was observed also in the anti-follicle-stimulating hormone (FSH) action of Gn-RH. FSH markedly stimulated aromatase activity, and Gn-RH caused a time- and dose-dependent inhibition of FSH action. Estrogen production was quenched by Gn-RH and restarted at a time when Gn-RH was removed from its receptor by antide. These two responses associated with the occupancy of Gn-RH receptor provide the evidence in favor of a tight coupling of stimulated PtdIns turnover to suppression of aromatase activation. These data of required continued activation of receptor might exclude the possibility that hypothalamic Gn-RH participated in the control of steroidogenesis in the ovary.

Animals

Enhancement of growth-promoting activity in extract from uterine cancers by protein kinase C in human endometrial fibroblasts.

Uterine cervical and corpus cancers have been reported to synthesize and secrete a putative peptide mitogen, which elicits a potent proliferative response in fibroblasts by a mechanism independent of phosphoinositide turnover. The extract from human uterine cervical cancer stimulated [3H]thymidine incorporation into human endometrial fibroblasts in a dose-dependent manner. Concomitant exposure of the fibroblasts to thrombin or fibroblast growth factor (FGF) led to synergistic enhancement of the extract-stimulated [3H]thymidine incorporation into fibroblasts. An apparent maximal activity of the extract in the presence of thrombin or FGF was 2-fold higher than that in the absence of them, implying that thrombin or FGF acted at a stage after the interaction of the mitogen in the extract with its specific receptor. Insulin or epidermal growth factor failed to augment the growth-promoting activity in the extract. The stimulatory action of thrombin or FGF was mimicked by protein kinase C activators, phorbol-12-myristate-13-acetate (PMA) or 1-oleoyl-2-acetyl glycerol, but not by Ca2+ ionophore A23187. When the fibroblasts were first exposed to the extract for 4 h and then to PMA, PMA succeeded to augment the mitogenic activity in the same manner. The identical effects of protein kinase C activators with thrombin or FGF suggested that both types of ligand share a similar signaling cascade of action, activation of protein kinase C. These results demonstrated that the growth-promoting activity in uterine cancer extract could be enhanced by the agents which promote phosphoinositide metabolism through activation of protein kinase C. These findings could give a new insight into pathophysiology of the interaction between malignant cells and their stromal cells, fibroblasts.

Endometrium

Successful outcomes of pregnancy complicated with dermatomyositis. Case reports.

There are few reports in the literature of pregnancy in dermatomyositis (DM), in contrast with those of other connective tissue diseases. We describe 2 patients who had an established diagnosis of DM and then became pregnant. In these cases, both the fetal and maternal outcome were good, and differed from those in previously reported cases.

Adult

Incomplete testicular feminization syndrome: studies of 17 beta-oestradiol-binding activity and aromatase activity in cultured genital fibroblasts showing impaired dihydrotestosterone-binding.

Dihydrotestosterone (DHT) and 17 beta-oestradiol binding, and aromatase activity were measured in cultured genital skin fibroblasts from two siblings with the incomplete testicular feminization syndrome. Whole-cell and nuclear DHT binding in the cells from both patients were reduced to 80% and 60%, respectively of those in a normal male subject. The nuclear oestradiol binding was not impaired in the fibroblasts from the patients whose plasma oestradiol was normal or a little elevated. Although gonadectomy led to a decrease in plasma testosterone concentration, the concentration of testosterone-binding globulin showed no change suggesting no apparent effect on testosterone-binding globulin synthesis by testicular steroids. There was no significant difference in aromatase activity of the fibroblasts between the patients and the normal male subjects. The relatively increased oestrogen concentration in the syndrome might result from oestrogen production in testes, but is unlikely to be from peripheral tissues such as fibroblasts. This is the first report to examine oestradiol binding and aromatase activity in the cells from the incomplete testicular feminization associated with impaired DHT binding. These findings may give new insight into the pathogenesis of abnormal male sexual differentiation in the patients with testicular feminization syndrome.

Adult

Role of the sympathetic system in impairment of the cerebrovascular CO2 responsiveness during moderate hypoglycemia.

We examined the mechanism of impairment of the cerebrovascular CO2 responsiveness in moderate hypoglycemia. Twelve fasted cats were used. The brain-PO2, brain-PCO2 and brain-pH were measured continuously with electrodes placed on the brain surface. Hypoglycemia was induced with insulin. Intravenous injection of hexamethonium (a sympathetic ganglion blocker, C6; 0.1 mg/kg) was performed at the following stages: Control, hypoglycemia and recovery. Before and after the C6 administration, 5% CO2 in air was inhaled for 3 min at the respective stages. The CO2 responsiveness (cerebrovascular dilatory response to increased PaCO2) at the control stage was not altered after the ganglionic blockade. At the hypoglycemic stage, the increase in BrPO2 by CO2 inhalation was significantly less than that at the control stage. This reduction of delta BrPO2 was significantly improved after the administration of C6. At the recovery stage, the CO2 responsiveness before and after the administration of C6 was not significantly different. An impaired CO2 responsiveness in the hypoglycemic state was improved by sympathetic ganglion blockade with C6 which did not alter the reactivity during normoglycemia. It is suggested that the sympathetic activity plays an important role in impairment of the cerebrovascular CO2 responsiveness during moderate hypoglycemia.

Animals

[Cricoarytenoid joint involvement in rheumatoid arthritis].

The cricoarytenoid (CA) joint, which controls the vocal cords, is diarthrodial; it is composed of two cartilages with a ligamentous capsule lined by synovial membrane. It has been known that inflammation of CA joint occurs sometimes in patients with rheumatoid arthritis (RA). Yet, so far, no detailed full-report on this subject has ever been made in this country. Here we report four RA cases with CA joint ankylosis or abduction disturbance due to progression of CA arthritis. Episodes of inspiratory dyspnea were observed in all cases and tracheostomy was performed in case 1 and case 2. Further surgical intervention i.e., tracheoplasty was necessary in case 2. Case 3 and case 4 have been followed conservatively thus far. Clinical surgical interventions were necessitated mainly with joint replacement, 3) there exists severe destruction of cervical spines as well as temporomandibular joints. Rheumatologist must be fully aware of how urgent this clinical entity is and not miss-diagnose+ these patients.

Arthritis, Rheumatoid

Direct action of gonadotropin-releasing hormone (LH-RH) analogue on ovary: an alternative acting mechanism of buserelin.

The mechanisms by which gonadotropin-releasing hormone (LH-RH) analogue buserelin exerts direct action on the ovary was investigated. The analogue inhibited the luteinizing hormone (LH)-induced increase of steroidogenesis by rat ovarian granulosa cells in a dose-dependent manner. The LH-RH analogue did not alter binding capacity and affinity of 125I-LH to granulosa cells, suggesting the involvement of post-receptor mechanism. Likewise, the analogue caused inositol trisphosphate (IP3) formation as a result of stimulated inositol-phospholipid turnover. Half maximal effects of both steroidogenesis suppression and IP3 production occurred at 10 nM buserelin. These findings indicate that the inhibitory action of buserelin on granulosa cell function is mediated by IP3 (or calcium)-dependent mechanisms. Buserelin, in addition to its well-known action at pituitary level, exerts a direct inhibition of ovarian steroidogenesis at gonadal level without changes in gonadotropin receptors.

Animals

The use of peritoneum for vaginoplasty in 24 patients with congenital absence of the vagina.

Vaginoplasty using pelvic peritoneum (Rothman's method) was used in 24 patients with congenital absence of the vagina. The results are presented. Rothman (1972) described vaginoplasty using pelvic peritoneum. We have operated on 24 patients with the anomaly. In this report, the better technique for this operation and the results of treatment are evaluated using data from these 24 cases.

Adolescent

A dermoid cyst of the paravaginal space.

We describes a patient with a dermoid cyst in the paravaginal space. The cyst recurred after repeated drainage procedures and became infected. The cyst was ultimately excised.

Adult

Sex steroids enhance endotoxin-stimulated phospholipase A2 activity in hum endometrial cells.

Growing evidence suggests an association between intra-amniotic infection and preterm labor. We recently demonstrated that some factor(s) including endotoxin produced by the organism stimulated endogenous phospholipase A2 resulting in liberation of arachidonic acid and prostaglandin formation (Takahashi et al. 1988). The studies presented in this report were designed to evaluate whether ovarian steroids alter activity of the phospholipase A2 responsive to endotoxin. Exposure of human endometrial proliferative- or secretory-phases epithelium to endotoxin from Escherichia coli increased the level of lysophosphatidylcholine (lyso-PC) by 15- and 25-fold, respectively. When the endometrial cells were preincubated with progesterone alone or progesterone and estradiol-17 beta for 16 h, the increase of lyso-PC by endotoxin was enhanced by approximately 1.5-fold. Progesterone showed a stimulatory effect on the response of phospholipase A2 to bacterial endotoxin in endometrial cells. These observations may explain the mechanism(s) by which preterm or term labor associated with intra-amniotic infection is initiated.

Amniotic Fluid

Estriol binding in uterine corpus cancer and in normal uterine tissues.

1. The specific bindings of estriol (E3) and estradiol-17 beta (E2) to their specific receptors were investigated in endometrial carcinoma from 7 patients and normal tissues from their respective organs or from other patients. 2. In both cytosolic and KCl-extracted fractions from them, specific binding sites for E3 and E2 were detected, demonstrating the presence of their separate receptors in human uterus-associated tissues. 3. In certain cases (6 cases) of well-differentiated adenocarcinoma, the ratio of concentration of E3 receptor to that of E2 receptor was almost equal to or higher than in other normal tissues. 4. These findings of unique localization of E3 receptor distribution may offer new insight into identification of endometrial carcinoma more likely to respond to hormonal influence or therapy.

Adenocarcinoma