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Biomedical subjects

Y Eguchi

Publications and source records attributed to Y Eguchi.

At least 109 records · Page 6Linked to original sources

Localization of urokinase-type plasminogen activator, plasminogen activator inhibitor-1, 2 and plasminogen in colon cancer.

We examined the localization of urokinase-type plasminogen activator (u-PA), plasminogen activator inhibitors (PAI-1 and PAI-2) and plasminogen (plg) in 26 cases of colon cancer by immunohistochemical staining. The u-PA antigen was detected in the cytoplasm of cancer cells (18/26) and stromal cells adjacent to cancer tissues (9/26). The localization of u-PA mRNA examined by in situ hybridization was consistent with that of u-PA antigen. The PAI-1 antigen was detected in fibroblasts and endothelial cells (22/26), while PAI-2 antigen was found in cancer cells (20/26). The plg antigen was seen in the extracellular matrix of the cancer stroma. The u-PA expression in cancer cells was significantly more frequently detected in cases with lymph node metastasis than in cases without metastasis. In either PAI-1- or PAI-2-expressing cases, lymph node metastasis seemed to be restrained. These findings indicate that cancer cells themselves produce u-PA, and suggest that u-PA converts plg into plasmin, which dissolves the extracellular matrix surrounding cancer cells, resulting in cancer invasion and metastasis. PAI-1 and PAI-2 may have inhibitory actions on cancer invasion and metastasis mediated by u-PA.

Colonic Neoplasms↗

Seventeen alpha-hydroxylase deficiency with one base pair deletion of the cytochrome P450c17 (CYP17) gene.

Mutation of the cytochrome P450c17 (CYP17) gene causes 17 alpha-hydroxylase deficiency (17OHD). Recently, several researchers have elucidated the molecular basis of 17OHD by gene analysis. We experienced a case of 17OHD and intended to reveal the abnormality of the CYP17 gene in this Japanese female with 17OHD. Leukocytes were obtained from the patient, her mother and sister, and normal control subjects. We amplified the CYP17 gene using polymerase chain reaction and performed the sequence analysis using the dideoxy terminator method and restriction enzyme analysis. We found that the patient had one base-pair deletion at the position of amino acid 438. An identical result was obtained with restriction enzyme analysis. This G deletion altered the reading frame and resulted in a premature stop codon at position 443; the ligand of heme iron (Cys: cystine 442) was absent. This small mutation may account for the patient's clinical manifestations of 17OHD. This is the first case of 17OHD with only one base pair deletion of the CYP17 gene.

Adrenal Hyperplasia, Congenital↗

Protective effects of prostaglandin E2 on the paraquat-induced constriction of the fetal ductus arteriosus in the rat.

Pregnant rats on day 21 of gestation received a subcutaneous injection of paraquat (25 mg/kg). Two hr later, some fetuses of these rats received a subcutaneous injection of prostaglandin E2 (PGE2). The caliber of the ductus arteriosus (DA) of fetuses was measured 1 hr later. The DA of fetuses of paraquat-treated pregnant rats was significantly constricted compared with that of fetuses of control pregnant rats given physiological saline. However, the DA of PGE2-treated fetuses of paraquat-treated pregnant rats had a caliber comparable to that of control rats. The maternal plasma PGE2 level decreased following paraquat treatment. These results suggest that the decrease of maternal PGE2 level results in a constriction of the DA of fetuses.

Animals↗

Propranolol inhibits the spontaneous closure of the ductus arteriosus in newborn rats.

Newborn rats delivered by cesarean section were given subcutaneously propranolol (PRO), a beta-adrenergic blocker, (1) immediately or (2) 180 min after delivery. The diameter of the ductus arteriosus (DA) of the newborn pups was calibrated at 30, 60 and 90 min after the PRO-administration. The results were as follows: (1) the DA calibers of the pups given 0.2, 1.0., 5.0 mg/kg PRO immediately after cesarean delivery remained significantly larger than those of controls in a dose-dependent manner for 30 min after treatment. In the 5 mg/kg group, the enlargement of the DA was prolonged for 90 min after treatment. (2) In untreated pups, the DA completely closed by 180 min after cesarean delivery. The DA was not affected by the administration of 5 mg/kg PRO at 3 hr after delivery. It was concluded that, PRO inhibits the spontaneous constriction of the DA, suggesting an important role of beta-adrenergic stimulation on the spontaneous closure of the DA in newborn rats.

Adrenergic beta-Antagonists↗

Dilating effect of prostaglandin on the constricted ductus arteriosus in newborn rats.

The dilating effect of prostaglandin (PG) E1 and E2 on the once-constricted ductus arteriosus (DA) was examined in newborn rats. The animals were given subcutaneously PGs 3hr after caesarean delivery. The ratio of the DA to the pulmonary artery (PA) was determined 15, 30, 60, 90 and 180 min after injection. Both PGE1 and PGE2 dilated the DA for over 90 min. The maximal effect appeared 15 or 30 min after injection. The DA/PA ratio was significantly higher in PGE2 than in PGE1. In addition, another series of newborn rats were given subcutaneously PGE2 6 hr after caesarean delivery to examine the age-related changes in the DA-dilating effect. The DA/PA ratio was significantly decreased in 6-hr-old pups than in 3-hr-old pups. These findings indicate that both PGE1 and PGE2 have a dilating effect on the once-constricted DA and that the effect decreases with time.

Alprostadil↗

Amino acid sequence of alpha- and beta-polypeptide chains of turkey (Meleagris gallopavo) hemoglobin.

Two hemoglobin components are recognized in erythrocytes of the adult turkey (Meleagris gallopavo). We determined the amino acid sequences of turkey alpha A-, alpha D- and beta-globin from intact globin chains and chemical cleavage fragments. The sequences are highly similar to the hemoglobin of the Phasianidae, chicken, Japanese quail and pheasant. Turkey and pheasant beta-globin are identical. The amino acid sequence of turkey alpha A-globin differs by only one residue from chicken alpha A-globin. Phylogeny trees from alpha A-, alpha D- and beta-globin were constructed by the neighbor-joining method. Although the trees generated from alpha A- and beta-globin were similar, that from turkey alpha D-globin differed.

Amino Acid Sequence↗

Altered expression of plasminogen activator inhibitor type 1 in placentas from pregnant women with preeclampsia and/or intrauterine fetal growth retardation.

Elevated plasma levels of type 1 plasminogen activator inhibitor (PAI-1) have been implicated in mediating the fibrin deposition and occlusive lesions that occur within the placental vasculature in preeclampsia (PE) and intrauterine growth retardation (IUGR). In this report we identify the cells within the normal-appearing villous tissue that are responsible for the local production of PAI-1 in women with PE and IUGR. Levels for another fibrinolytic inhibitor (ie, type 2 plasminogen activator inhibitor [PAI-2]) were determined for comparative purposes. Elevated levels of PAI-1 were detected in placenta extracts from PE/IUGR patients (121 +/- 38 ng/mg, n = 8) when compared with the levels in placenta extracts from normal women (43 +/- 17 ng/mg, n = 10) or women with IUGR but not PE (51 +/- 22 ng/mg, n = 11). Immunohistochemical analysis of paraffin sections showed an increased immunoreactivity for PAI-1 in the placental villous syncytiotrophoblasts from PE/IUGR women compared with the immunostaining of placental samples from the normal or IUGR group. In contrast, antigen levels and immunostaining for PAI-2 were reduced in the placentas harvested from not only the PE/IUGR women (209 +/- 144 ng/mg) but also the IUGR group (169 +/- 106 ng/mg) in comparison with the PAI-2 levels in normal placentas (535 +/- 98 ng/mg). To document that the increased immunoreactivity for PAI-1 in PE/IUGR syncytiotrophoblasts was mediated by an increased production of PAI-1 within these cells, in situ hybridization analysis was performed. A strong positive signal for PAI-1 mRNA in villous syncytiotrophoblasts from PE patients (n = 5) was obtained after 2 weeks of exposure to the NTB2 emulsion in comparison with the weak signal for PAI-1 mRNA that required a 10-week exposure of the normal placenta sections (n = 10). Northern blotting for PAI-1 mRNA showed that both transcripts (ie, 3.2 and 2.3 kb) were elevated in samples of two PE patients in comparison with the PAI-1 mRNA transcripts present in a normal placenta and an IUGR placental sample. These results show increased PAI-1 and mRNA levels in placentas from PE patients and raise the possibility that localized elevated levels of PAI-1 may play a role in the initiation of placental damage, as well as in the thrombotic complications associated with this disease.

Adult↗

Insulin autoimmune syndrome (Hirata disease): clinical features and epidemiology in Japan.

Since Hirata et al. first reported a patient with insulin autoimmune syndrome in 1970, 197 cases have been reported in Japan as of December, 1992. The clinical profiles of these 197 cases were as follows; the peak age at onset was 60-69 years and peak duration of hypoglycemic attacks was more than 1 and less than 3 months. There was no gender difference in the peak age of onset or duration of hypoglycemic attacks. Approximately 82% of the IAS patients had spontaneous remission without any positive treatment. Before diagnosis of IAS, 43% of the patients with IAS had been taking medication; methimazole (MTZ) for Graves' disease, alpha-mercaptopropionyl glycine (MPG) for cataracts, liver disease or rheumatoid arthritis, or glutathione for liver disease, all of which are sulfhydryl compounds. After such sulfhydryl compounds were discontinued, the hypoglycemic attacks subsided. Three patients with IAS experienced recurrence of the hypoglycemic attacks after re-administration of MTZ and MPG, although 6 patients who developed IAS without exposure to any drug had recurrent attacks without exposure to any drug around 1 year after the first hypoglycemic attacks had stopped. Thus, hypoglycemia in IAS is mainly transient and the development of IAS may be related to sulfhydryl compounds.

Age Factors↗

Modulation of the fibrinolytic system by major peripheral ischemia.

PURPOSE: A rat model was developed to investigate the effects of acute peripheral ischemia on the components of the fibrinolytic system. METHODS: Laparotomy was performed and ischemia was introduced by total aortic clamping at a subrenal position. Control animals underwent sham laparotomy alone. Plasma and tissue samples were collected for analysis at 30, 60, 90, and 120 minutes after operation. RESULTS: Functional assays of rat plasma revealed a dramatic and transient increase in tissue-type plasminogen activator (tPA) activity within 30 minutes of the onset of ischemia. A simultaneous decline in plasminogen activator inhibitor activity was observed. Immunohistochemical analysis suggested this initial increase in tPA activity resulted primarily from the release of stored tPA from ischemic vascular tissues. Northern blot analysis revealed that both tPA and plasminogen activator inhibitor-1 messenger RNA levels were elevated at 60 to 120 minutes in well-perfused tissues distant from the ischemic insult. CONCLUSIONS: Collectively, these data demonstrate that acute peripheral ischemia results in a rapid and transient increase in plasma fibrinolytic activity, concomitant with the early release of stored tPA from ischemic vascular tissues. In addition, peripheral ischemia appears to stimulate both tPA and plasminogen activator inhibitor-1 gene expression in well-perfused tissues at later time points, consistent with the existence of humoral mediators.

Adipose Tissue↗

Effects of cholesterol and cholesteryl oleate on lipolysis and liver uptake of triglyceride/phosphatidylcholine emulsions in rats.

Emulsions composed of soy bean triglyceride (TG), egg yolk phosphatidylcholine (PC), cholesterol (Chol) or cholesteryl-oleate (CO), labeled with a cholesteryl ether (3H-CHE) and a triglyceride (14C-TO), were injected into rats. 14C-TO was removed from plasma faster than 3H-CHE. The 14C-labeled moiety is cleaved by digestion of the TG in the emulsion in plasma and is removed to the endothelial cells (lipolysis). In contrast, the 3H-label remains stably associated and represents circulating emulsion particles. The majority (90%) of the 3H-label disappearing from the plasma accumulated in the liver for all types of emulsions. On the basis of these observations, the lipolysis and the removal of emulsion particles to organs (mainly liver) were determined: 30 mole percent of cholesterol (Chol) at the TG-PC emulsion surface markedly retarded organ uptake, but the effect on lipolysis was rather small; 20 mole percent of cholesteryl oleate (CO) in the TG-PC emulsion cores delayed both organ uptake and lipolysis, and induced a rapid increase in organ uptake rate after the initial delay accompanying the gradual progress of lipolysis. Lipolysis led to the enrichment of the cores with CO. Replacement of the core TG by CO, however, induced strong suppression of the liver uptake. These results show that the lipid composition at both surface and core of emulsion particles is a crucial factor in metabolism in the rat.

Animals↗

Suppressive effect of fetal testes on development of fetal ovaries transplanted into adult males in the rat.

The age-related testicular effect on the ovarian primordia was studied by combined transplantation of fetal testes and ovaries in adult male hosts. First, ovarian primordia of 14-day fetal rats were transplanted into a renal subcapsular position of castrated or intact adult male rats. In both the castrated and the intact hosts, most of the ovarian transplants developed normally with only 3 of them having in part seminiferous tubule-like structures in addition to normal ovarian structure. Second, a 14-day ovary was combined with a fetal testis the age of which varied from 13- to 18-day, and the combination was transplanted. In the combination of a 14-day ovary and a 13-day testis, the results varied in such a way that the ovary or the testis alone developed or otherwise, both gonads developed well. In union with 15- to 18-day testes, the ovaries did not develop, although the testes developed well. These results suggest that the 14-day ovarian primordia have a slight reactiveness to androgens of host rats and that the 13-day fetal testes begin to inhibit the development of the 14-day ovaries co-transplanted with them.

Animals↗

Effect of maternal paraquat administration on the fetal ductus arteriosus in the rat.

The ductus arteriosus (DA) in the fetal rat was calibrated using a whole-body freezing method, 3 hr after maternal treatment with paraquat at a dose of 25 mg/kg of body weight on days 19-21 of gestation. On days 20 and 21, the DA was significantly constricted. The DA was also significantly constricted on day 19 2/3 but not on day 19 1/2. It is concluded that paraquat has a constrictive effect on the DA and that the onset of this effect occurs in the first half of day 19 of gestation.

Animals↗

Inhibitory effect of enalapril on the constriction of the ductus arteriosus in newborn rats.

Caesarean newborn rats were given subcutaneously enalapril maleate (EM), an angiotensin-converting enzyme inhibitor, (1) immediately or (2) 180 min after delivery. The ductus arteriosus (DA) in these newborn pups was calibrated 30, 60 and 90 min after the EM-treatment. The results were as follows: (1) DA calibers of the pups given 10 or 50 mg/kg EM just at caesarean delivery remained significantly larger than those of the controls thereafter until 90 min. (2) The DA was completely closed 180 min after caesarean delivery. However, with 50 mg/kg EM given at this time, the DA was temporarily re-opened and then constricted. It is concluded that, in newborn rats, EM has the direct inhibitory action on the constriction of the DA, and that it also has the re-opening action on the once-constricted DA.

Animals↗

In vitro study of teratogenic effects of caffeine on cultured rat embryos and embryonic cells.

The teratogenic potential of caffeine was examined in vitro by a whole embryo culture system (WECS) and an embryonic cell culture system (micromas teratogen assay: MTA) in the rat. In the WECS, hyperemia of the tail, and a reduction of the placental size was induced by caffeine at concentrations higher than 50 micrograms/ml; hypoplasia of the forelimb bud was induced at concentrations higher than 100 micrograms/ml; hematoma in the yolk sac and dysmorphogenesis of the fore- and hind-limb buds, prosencephalon and tail were induced by 200 micrograms/ml caffeine. In the MTA, even with 200 micrograms/ml caffeine, the toxicological parameters obtained by proliferation and differentiation assays of the midbrain and limb bud cells were almost the same as in the control. In conclusion, caffeine induced various morphological anomalies, but did not affect proliferation or differentiation of cells in these experimental systems.

Abnormalities, Drug-Induced↗

Amino acid sequence of the alpha A- and beta-polypeptide chains of the Ryukyu rufous turtle dove (Streptopelia orientalis Stimpsoni) hemoglobin.

Only one hemoglobin component is recognized in the erythrocytes of the adult Ryukyu rufous turtle dove. We have determined the amino acid sequence of the alpha A-globin and the beta-globin by conventional protein sequence analysis. The sequences of both the alpha A- and the beta-globins were highly similar to domestic pigeon hemoglobin. The alpha A-globin has 6 exchanges and beta-globin has 4 exchanges compared with the corresponding domestic pigeon chains.

Amino Acid Sequence↗

Longitudinal changes of serum insulin concentration and insulin antibody features in persistent insulin autoimmune syndrome (Hirata's disease).

In a 56-year-old woman with granulomas of gold thioglucose in her hips, who developed insulin autoimmune syndrome, the relationships among the frequency or severity of hypoglycemic attacks, serum insulin (IRI) concentration, and characteristics of insulin antibodies were investigated during the clinical course with steroid treatment and two resection operations for the gold-thioglucose granulomas. When hypoglycemia was severe, the total IRI level was elevated, and Scatchard analysis showed that a high-affinity (k1), low-capacity (b1) population of antibodies had a relatively low affinity constant and very high binding capacity compared with the same population of antibodies in insulin-treated diabetic patients. When the attacks were relieved by steroid treatment and/or granuloma resection operation, the total IRI level was decreased and the high-affinity (k1), low-capacity (b1) population of antibodies showed a higher affinity constant and a lower binding capacity than those during the attacks. This indicated that the antibodies changed their characteristics to release insulin into the serum. The k1/b1 population of insulin antibodies with the lower affinity constant and higher binding capacity may easily release human insulin into the serum, leading to hypoglycemia. The longitudinal change of the k1/b1 population suggests a clonal change of the B cells producing the insulin antibody in insulin autoimmune syndrome.

Aurothioglucose↗

Experimental studies on perinatal development of adrenal and thyroid glands in the rat.

In the rat, as regards the adrenal gland, (1) during the fetal period, the adrenal cortex first begins to develop autonomically, (2) subsequently, the cortex comes under the control of the hypophysis, (3) later, the hypophysial-adrenal system comes under hypothalamic regulation, (4) after birth, the adrenal gland becomes shrunken temporarily, accompanied by an abrupt rise and a subsequent decline of the plasma corticosterone concentrations (PCC) just before and after birth. The rise and decline of PCC is probably responsible for the temporary hiatus of the hypothalamic-hypophysial activity, and (5) a preventive therapy of the abrupt rise of PCC allows the adrenal gland to escape neonatal shrinkage. As to the thyroid gland, (1) the initial formation of thyroid follicles is independent of thyroid-stimulating hormone (TSH), (2) follicles, once developed, are capable of responding to TSH, (3) the fetal hypophysial-thyroid function is independent of the hypothalamic regulation, (4) the early neonatal thyroid gland does not seem to undergo hyperfunctioning, and (5) hypothalamic regulation of the thyroid gland seems to begin 5 or more days after birth.

Adrenal Cortex↗

A case of tachycardia-induced cardiomyopathy due to chronic ectopic atrial tachycardia.

Only a few reports exist that chronic supraventricular tachycardia causes ventricular dilation and poor left ventricular contraction--so-called "tachycardia-induced cardiomyopathy." Clinical and electrophysiologic features of chronic supraventricular tachycardia including chronic persistent ectopic atrial tachycardia (EAT) in adults have also been described by a few investigators. We report a rare case of long follow-up of chronic EAT-induced severe cardiomyopathy and mitral regurgitation that was well controlled after medical treatment.

Cardiac Catheterization↗