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Biomedical subjects

Y Mizoguchi

Publications and source records attributed to Y Mizoguchi.

At least 253 records · Page 14Linked to original sources

Studies on the mechanism of liver injury by antibody-dependent cell-mediated cytotoxicity (ADCC)--partial purification of cytotoxic factor detected in the culture supernatant of ADCC reaction.

Liver cell damage is inducible when isolated liver cells coated with the specific antibody against the liver cell membrane are cultured with peripheral blood mononuclear cells. Moreover, a cytotoxic material (or materials) causing an inhibition of protein synthesis in liver cells was detected in culture supernatant of these antibody-dependent cell-mediated cytotoxicity (ADCC) reactions. By gel filtration using a Sephadex C-75 column, the active material (materials) was recovered in a definitive fraction and was further fractionated into two portions by DEAE-cellulose column chromatography. These active principles were shown by isoelectric focusing electrophoresis to be different substances from each other. These results suggest that some cytotoxic or cytostatic materials are produced in consequence of ADCC reaction and these may cause liver injury.

Antibody-Dependent Cell Cytotoxicity↗

Participation of the cholestatic factor in the pathogenesis of intrahepatic cholestasis, found in various liver diseases.

The possible involvement of lymphokine, cholestatic factor, in the pathogenesis of intrahepatic cholestasis was investigated in nine patients with different types of liver diseases; two cases with acute viral hepatitis (nonA and nonB type), five patients with alcoholic hepatitis and two cases with liver cirrhosis. All patients showed the typical clinical features of intrahepatic cholestasis. The production of the cholestatic factor from the sensitized lymphocytes was demonstrated by antigenic stimulation in vitro and the existence of the factor was detected in seven out of nine patients in patients' own serum. These results strongly suggest that the cholestatic factor may be partially involved in the induction of intrahepatic cholestasis in various types of liver disease.

Acute Disease↗

The possible involvement of Kupffer cell-mediated hepatocytotoxicity in the pathogenesis of liver injuries.

The possible involvement of cell-mediated immune response to liver specific lipoprotein (LSP) in the pathogenesis of liver injury was investigated. The subjects were consisted of one patient with acute hepatitis, five cases with chronic active hepatitis and one case with chronic failure inactive hepatitis. When peripheral blood lymphocytes from these patients were cultured in the presence of LSP and lymphocyte transformation was determined by measuring the uptake of [3H]-thymidine into the acid-insoluble materials, positive blastogenesis was seen in three cases with chronic active hepatitis. Furthermore, when peripheral blood lymphocytes from halothane-induced cholestatic hepatitis were cultured with offending drug in the presence of LSP and lymphocyte transformation was determined, a positive blastogenesis was seen. The factor which activated Kupffer cells (KCAF), a kind of lymphokine, was also detectable in the culture medium of activated lymphocytes from four patients who showed positive blastogenesis by estimating [3H]-glucosamine incorporation into Kupffer cells. The macrophage activating factor (MAF) was detectable in culture medium of activated lymphocytes from three patients who showed positive blastogenesis by estimating [3H]-glucosamine incorporation into macrophages. Furthermore, the KCAF-activated Kupffer cells and MAF-activated macrophages were shown to be cytotoxic for the isolated liver cells causing marked inhibition of albumin synthesis. The observations suggest that Kupffer cell-mediated cytotoxicity and macrophage-mediated cytotoxicity play a role in the pathogenesis of liver disease.

Cytotoxicity, Immunologic↗

Immunological studies on the drug-induced allergic hepatitis.

The possible involvement of cell-mediated immunity in the pathogenesis of drug-induced allergic hepatitis was investigated in 21 patients; 6 patients with cholestasis, two cases with the hepatitis resembling viral hepatitis and 13 cholestatic hepatitis. The peripheral blood lymphocytes from all these patients showed the positive lymphocyte transformation and MIF production when stimulated by the offending drug in the presence of liver specific lipoprotein. By injection of the culture medium prepared from activated lymphocytes into mesenteric vein of rat, a marked reduction of bile flow and bile acid secretion was observed in 12 cases among 17 patients tested. Active material which caused the reduction of bile flow was fractionated by a gel filtration and was identified to have similar molecular size to MIF. Morphologically, a dilated bile canaliculus with diminution of microvilli and vesicles around the dilated bile canaliculus were observed by an electron microscopy after injection of culture supernatant or their fractionated material into mesenteric vein of rat. No such changes could be seen in rats by administering the supernatant of lymphocytes from normal individuals prepared as above. Macrophage activating factor (MAF), a kind of lymphokines, was also detected in the culture medium of activated lymphocytes from seven patients among eight cases tested. The MAF-activated macrophages were shown to exhibit a cytotoxic effect on the separated liver cells by judging from the inhibition of albumin biosynthesis. Moreover, the antibody-dependent cell-mediated cytotoxic reaction as well as lymphocyte-mediated cytotoxicity were also demonstrated in three cases among nine patients tested. These observations suggest that diverse immune reactions were possible correlated to the pathogenesis of the drug-induced allergic hepatitis although their exact participation or relative significances are remained to be elucidated.

Bile Acids and Salts↗