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Biomedical subjects

C Sekiya

Publications and source records attributed to C Sekiya.

At least 55 records · Page 3Linked to original sources
PubMed1990

Flow cytometric and functional analysis of mononuclear cells infiltrating the liver in experimental autoimmune hepatitis.

Experimental autoimmune hepatitis was produced by immunizing Wistar rats with syngeneic liver proteins. Mononuclear cells infiltrating the liver tissue were identified by immunohistochemical techniques using monoclonal antibodies specific for subpopulations of rat lymphocytes. The strong infiltration of CD8+ cytotoxic T lymphocytes (CTL) were found in the portal areas. Subpopulations of mononuclear cells infiltrating the liver, spleen cells and peripheral blood lymphocytes were identified by flow cytometry. Flow cytometric analysis revealed the presence of CD5- and CD8+ lymphocytes in the liver tissues. Mononuclear cells infiltrating the liver were isolated from Wistar rats having autoimmune hepatitis to determine whether those exhibit cytotoxicity against syngeneic hepatocytes; they exhibited cytotoxicity against isolated syngeneic hepatocytes, but failed to lyse K562 cells, syngeneic concanavalin A-activated splenocytes and allogeneic hepatocytes. Depletion of CD8+ T cells significantly reduced the cytotoxic ability of mononuclear cells infiltrating into the liver against syngeneic hepatocytes. These findings support the idea that liver cell injury in experimental autoimmune hepatitis may at least in part be mediated by CTL.

Animals↗
PubMed1990

Measurement of immunoreactive prothrombin precursor and vitamin-K-dependent gamma-carboxylation in human hepatocellular carcinoma tissues: decreased carboxylation of prothrombin precursor as a cause of des-gamma-carboxyprothrombin synthesis.

Des-gamma-carboxyprothrombin is an abnormal prothrombin which is drastically increased in the plasma of patients with hepatocellular carcinoma. To investigate the process of the abnormal prothrombin synthesis, the amount of prothrombin precursor was measured with an enzyme-linked immunosorbent assay using a specific antibody directed to human prothrombin; the vitamin-K-dependent gamma-carboxylation of prothrombin precursor was determined in human liver tissues. The tissue content of prothrombin precursor was increased in hepatoma tissues compared with noncancerous liver tissues, while the vitamin-K-dependent carboxylation of prothrombin precursor was markedly decreased in hepatoma tissues of the patients with increased plasma des-gamma-carboxyprothrombin. The present study indicates that in hepatocellular carcinoma an increase in prothrombin precursor concentration does not induce vitamin-K-dependent carboxylase activity, which is ordinarily observed in normal liver; probably an overproduction of prothrombin precursor with reduced gamma-carboxylation causes an increase in plasma des-gamma-carboxyprothrombin in patients with hepatocellular carcinoma.

Adult↗
PubMed1990

Measurement of immunoreactive prothrombin, des-gamma-carboxy prothrombin, and vitamin K in human liver tissues: overproduction of immunoreactive prothrombin in hepatocellular carcinoma.

Des-gamma-carboxy prothrombin is an abnormal prothrombin which increases in the plasma of patients with hepatocellular carcinoma. To clarify the process of des-gamma-carboxy prothrombin synthesis, immunoreactive prothrombin, des-gamma-carboxy prothrombin, and vitamin K (phylloquinone and menaquinone) concentrations were determined in human liver tissue, including hepatocellular carcinoma. In the patients with elevated plasma des-gamma-carboxy prothrombin levels, both immunoreactive prothrombin and des-gamma-carboxy prothrombin significantly increased in hepatoma tissues compared with non-cancerous liver tissue. On the other hand, no significant difference was observed in the endogenous vitamin K (K1, MK-4, MK7) concentrations between hepatoma and noncancerous portions, in either the cases with or without increase of plasma des-gamma-carboxy prothrombin. These data strongly suggested that in the patients with an increase of plasma des-gamma-carboxy prothrombin, overproduction of prothrombin in hepatoma plays in important role in the synthesis of des-gamma-carboxy prothrombin.

Analysis of Variance↗
PubMed1989

Indomethacin blocks the anorexic action of interleukin-1.

It has been reported recently that the central nervous system actions of interleukin-1 are mediated by the prostaglandin system in the brain. The present study was therefore performed in order to examine the hypothesis that indomethacin, an inhibitor of prostaglandin biosynthesis, might alleviate the interleukin-1-induced suppression of food intake in rats. The i.p. injection of interleukin-1 (2 micrograms/rat) resulted in a significant decrease in food intake. The pre-injection of indomethacin (0.5 mg/rat), however, completely blocked the anorexic action of the monokine, while indomethacin on its own did not affect food intake. These results suggested that indomethacin might be clinically useful for improvement of the anorexic state of patients with acute infectious diseases.

Animals↗
PubMed1989

Interleukin-1 inhibits the secretion of gastric acid in rats: possible involvement of prostaglandin.

To examine the hypothesis that interleukin-1 may inhibit the secretion of gastric acid, the present study was carried out using pylorusligated rats. Based upon three lines of evidence, we report here that interleukin-1, both endogenously released and exogenously administered, suppresses gastric acid secretion and that the interleukin-1-induced inhibition of acid output is possibly mediated by prostaglandin. First, lipopolysaccharide, a potent stimulant of the release and production of endogenous interleukin-1, caused the suppression of gastric acid, and this response was dose-related. Second, the intraperitoneal injection of interleukin-1 resulted in a dose-related inhibition of gastric acid output. Third, the administration of indomethacin completely blocked the suppression of gastric acid secretion induced by interleukin-1. These results demonstrated for the first time that IL-1 might be involved in the regulation of gastric secretion.

Animals↗
PubMed1989

Cooperative study on arterial regional chemotherapy for primary liver cancer in Hokkaido.

The Liver Study Group of Hokkaido analyzed a total of 57 patients with non-resectable primary liver cancers, which were treated by intra-arterial adriamycin infusion chemotherapy combined with lipiodol and/or the Gelform embolization of the hepatic arteries. Of the ten patients considered clinical responders, three complete response patients and seven partial response cases were obtained. The overall response rate was 17.5%. The median survival period at each clinical stage was as follows: stage I: 13.0 months, stage II: 16.0 months, stage III: 11.5 months and stage IV: 4.7 months. The common side-effects of this treatment were nausea, vomiting and anorexia. Hematological toxicities were also found, but there was no patient who suffered from severe complications.

Adult↗
PubMed1989

Measurement of immunoreactive gamma-glutamyl transpeptidase in human sera and liver tissues of patients with various liver diseases.

Immunoreactive gamma-glutamyl transpeptidase in human serum and liver tissue was measured by a solid phase enzyme-linked immunosorbent assay. The immunoreactive gamma-glutamyl transpeptidase was significantly elevated in the sera of patient with hepatocellular carcinoma. On the other hand, in sera of patients with non-neoplastic diseases, including chronic hepatitis, acute hepatitis, fatty liver and hemangioma, the immunoreactive gamma-glutamyl transpeptidase was not elevated. In hepatocellular carcinoma and metastatic liver tumor tissues, the immunoreactive gamma-glutamyl transpeptidase content was also elevated, showing good correlation with the enzyme protein content in sera. However, no correlation was found between the activity of gamma-glutamyl transpeptidase determined by an enzymatic assay and the content determined by an enzyme-linked immunosorbent assay. On immunohistochemical examination, the immunoreactive enzyme protein without enzymatic activity was detected only in the cytoplasm of cancer cells. This suggested that there is an increased level of the immunologically active but enzymatically inactive form of gamma-glutamyl transpeptidase in hepatoma tissues.

Carcinoma, Hepatocellular↗
PubMed1989

Increased ACTH response to corticotropin-releasing factor in cold-adapted rats in vivo.

We have recently reported that chronically repeated restraint stress results in improved cold tolerance in rats via an increased activity of nonshivering thermogenesis, a characteristic metabolic change observed during cold adaptation, suggesting the presence of cross-adaptation between cold and stress. It is well established that the hypothalamic-pituitary-adrenal (HPA) axis is activated in various stress responses. In the present study, therefore, we examined whether cold adaptation would alter the adrenocorticotropic hormone (ACTH)-releasing state in vivo using freely moving, conscious rats chronically implanted with intra-atrial cannulas. There was no difference in the basal levels of plasma ACTH between warm control and cold-adapted rats. On the other hand, the ACTH response to the intravenous administration of corticotropin-releasing factor (CRF; 2 micrograms/animal) was significantly elevated in cold-adapted rats. However, the injection of 10 micrograms of CRF, which was considered as a dose to elicit the maximal ACTH response, resulted in similar ACTH release patterns between the two groups. These changes in the responsiveness of ACTH secretion have been observed in rats chronically exposed to stressful conditions. The results demonstrated in the present study, therefore, provide further evidence for our hypothesis that there may exist cross-adaptation between cold and nonthermal stress.

Adaptation, Physiological↗
PubMed1989

Anorexia induced by interleukin 1: involvement of corticotropin-releasing factor.

It has recently been demonstrated by three independent research groups including ours that interleukin 1 (IL-1), a polypeptide hormone produced by activated monocytes or macrophages, or both, stimulates the release of hypothalamic corticotropin-releasing factor (CRF). Since CRF acts centrally in the brain to reduce food intake, we hypothesized that IL-1 might induce anorexia through this central action of CRF. The present study was carried out to examine the hypothesis, using male Wistar rats. Based on three lines of evidence, we report here that IL-1, both endogenously released and exogenously administered, induces the suppression of food intake in rats and that endogenous CRF in the brain is involved in the IL-1-induced anorexia. First, lipopolysaccharide (LPS), a potent stimulant of the release and production of endogenous IL-1, caused anorexia in a dose-related manner, and this effect was significantly blocked by pretreatment with glucocorticoid hormones, which have been shown to inhibit the production of endogenous IL-1 by LPS. Second, intraperitoneal injection of IL-1 resulted in a dose-related suppression of food intake. Third, anorexia induced by IL-1 was diminished by the immunoneutralization of endogenous CRF in the brain. These results provide further evidence of the existence of bidirectional communication between the immune and neuroendocrine systems. Furthermore, this connection between IL-1 and CRF may represent a mechanism by which anorexia results from the activation of the immune system by such immunological challenges as acute infectious diseases.

Animals↗
PubMed1989

Effects of exercise, cold, and immobilization stresses on gamma-glutamyltransferase activity in rat kidney.

Effects of acute and chronic stresses (exercise, cold, and immobilization) on gamma-glutamyltransferase (gamma GT) activity in the rat kidney were investigated. In the extramicrosomal fraction there were significant decreases in acute-exercised rats but significant increases in cold-adapted and immobilized rats. In the microsomal fraction, on the other hand, the gamma GT activity of acute-exercised rats increased definitely. The results suggest that different types of stresses have different effects on gamma GT activity in the rat kidney.

Animals↗
PubMed1988

Phosphorylation of beta-glucuronidases from human normal liver and hepatoma by cAMP-dependent protein kinase.

beta-Glucuronidases purified from human hepatoma and from normal liver could serve as a substrate for a cAMP-dependent protein kinase. The rate of phosphorylation reaction of the hepatoma beta-glucuronidase was rapid, whereas that of the normal liver beta-glucuronidase was slow and much lower. Stoichiometry of phosphorylation was 4.3 and 0.46 mol of phosphate/mol of the beta-glucuronidase from the hepatoma and normal liver, respectively. Tryptic peptide mapping of 32P-labeled beta-glucuronidase from hepatoma identified two distinct phosphopeptides (X and Y). The peptide from hepatoma hydrolase was phosphorylated predominantly at the X, while the peptide Y was the major phosphopeptide in the hydrolase of normal liver. Analysis of phosphoamino acids revealed two sites, phosphoserine and phosphothreonine. beta-Glucuronidase from hepatoma consisted of a major subunit with molecular mass of 64,000 (64 kDa) and a minor subunit with 76 kDa, whereas the hydrolase from normal liver had almost exclusively 64 kDa subunit. 32P-labeled beta-glucuronidase indicated that the 64 kDa subunit was phosphorylated both in hepatoma and normal liver beta-glucuronidases.

Amino Acids↗
PubMed1988

[A case of subacute thyroiditis associated with acute hepatitis].

We report one case of subacute thyroiditis associated with acute hepatitis, which is histopathologically diagnosed. A 43-year-old woman visited our hospital with chief complaints of fever, sore throat and anterior neck pain. Thyroid gland was found to be swollen and tender. Laboratory findings gave high ESR and positive test for CRP. High values of T3, T4 and RT3U indicated that the patient had hyperthyroidism. However no autoantibodies against thyroglobulin and microsome were found. High activities of serum AIP, LAP and gamma-GTP were observed. Serum GOT and GPT activities increased moderately. AIP type 2 was dominant in zymograms. Histopathological findings of liver specimen obtained by needle biopsy showed ballooning degeneration of hepatocytes with a slight focal necrosis and hyaline bodies. In addition bile plugs were observed in some biliary tubules. These findings were consistent with those of acute hepatitis. After three months all laboratory data were found to be within normal ranges and no recurrence has been observed. Subacute hepatitis associated with liver dysfunction is considered to be relatively frequent. However very few reports have been published on the case in which histopathological evidence for acute hepatitis was presented.

Acute Disease↗
PubMed1986

[Hepatic GOT and GPT activities in patients with various liver diseases--especially alcoholic liver disease].

GOT and GPT activities were measured in percutaneous needle biopsy specimens of human liver tissue from 98 cases including normal subjects and patients with various liver diseases. Hepatic GOT activity was markedly decreased in liver tissue of patients with nonalcoholic liver cirrhosis. Hepatic GPT activity was markedly decreased in liver tissue of patients with alcoholic liver cirrhosis. The GOT/GPT ratio in liver tissue was increased in patients with alcoholic liver cirrhosis (5.32 +/- 2.03) and alcoholic liver disease (4.78 +/- 2.43). The increased SGOT/SGPT ratio in patients with alcoholic liver disease is due to primarily to the increased LGOT/LGPT ratio.

Alanine Transaminase↗