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Biomedical subjects

G Toda

Publications and source records attributed to G Toda.

At least 109 records · Page 6Linked to original sources
PubMed1995

Polymorphisms in alcohol metabolizing enzyme genes and alcoholic cirrhosis in Japanese patients: a multivariate analysis.

Alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), and P450IIE1 are the primary enzymes that catalyze the conversion of ethanol to acetaldehyde and then to acetate. Genetic polymorphisms have been reported in ADH2, ADH3, ALDH2, and the 5'-flanking region of P450IIEI. In this study, we used multivariate analysis to determine which genetic polymorphisms in alcohol metabolizing enzymes were independently associated with the development of alcoholic cirrhosis. Thirty-four noncirrhotic alcoholic patients, including 27 with fatty liver and 7 with nonspecific changes, and 46 patients with alcoholic liver cirrhosis were studied. Restriction fragment length polymorphisms (RFLPs) in the ADH2 and P450IIE1 genes were detected by digestion of polymerase chain reaction (PCR)-amplified DNA with MaeIII and RsaI, respectively. In the ALDH2 gene, RFLPs were detected by differences in the MboII site after PCR amplification. By multivariate analysis of four significant factors including total alcohol intake, ADH, ALDH, and P450IIE1 using the multiple logistic regression model, genotype ADH2(2)/ADH2(2) (P = .029) and genotype c1/c1 of P450IIE1 (P = .013) were found to be independently associated with alcoholic cirrhosis. The odds ratios for ADH2(2)/ADH2(2) genotype and the type A genotype of P450IIE1 (c1/c1) were 4.600 and 4.006, respectively. These results suggest that ADH2 and P450IIE1 gene polymorphisms may be independently associated with the development of alcoholic liver cirrhosis in Japan.

Adult↗
PubMed1995

Thrombomodulin expression of sinusoidal endothelial cells in chronic viral hepatitis.

The expression of thrombomodulin on sinusoidal endothelial cells was studied using the immuno-peroxidase method and both light and electron microscopy in patients with chronic viral hepatitis (type B: four cases; type C: 28 cases). Thrombomodulin was found on sinusoidal endothelial cells, especially on the surface in both type B and type C chronic hepatitis. There was no correlation between the level of thrombomodulin expression and clinical data including serum level of transaminase, and coagulating factors. The supernatant of liver tissue homogenate obtained from the patients showed a clear 80 kDa single band by western blotting. We concluded that the expression of thrombomodulin might be related to hepatic inflammatory responses in chronic viral hepatitis.

Blotting, Western↗
PubMed1995

Alcohol-metabolizing enzyme polymorphisms and alcoholism in Japan.

The liver enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), which are responsible for the oxidative metabolism of ethanol, are polymorphic in humans. Cytochrome P450IIE1, an ethanol-inducible isozyme of liver microsomal P450, is also important in ethanol metabolism. Genetic polymorphisms in the 5'-flanking region of the human cytochrome P450IIE1 gene have recently been reported. We hypothesized that the polymorphisms of ADH, ALDH, and P450IIE1 modify the susceptibility to development of alcoholism. We determined the genotypes of the ADH2, ALDH2, and P450IIE1 loci of 96 Japanese alcoholics and 60 healthy male subjects, using leukocyte DNA by the restriction fragment-length polymorphism by polymerase chain reaction. The alcoholics had significantly higher frequencies of the ADH2(1) and ALDH2(1) alleles than did the healthy subjects. No significant difference in the frequency of the P450IIE1 genotype was observed between the alcoholics and the healthy subjects. In conclusion, genetic polymorphisms of the ADH and ALDH genes, but not of the P450IIE1 gene, influence the risk of developing alcoholism in Japanese.

Adult↗
PubMed1995

Prostanoid secretion by rat hepatic sinusoidal endothelial cells and its regulation by exogenous adenosine triphosphate.

We investigated the secretory profiles of prostanoids in two types of nonparenchymal cell from the rat liver, sinusoidal endothelial cells and Kupffer cells, in primary culture both under basal conditions and after stimulation with adenine nucleotides. Prostaglandin (PG) E2 was the main prostanoid secreted by both types of hepatic nonparenchymal cell in the basal and adenosine triphosphate (ATP)-stimulated states. Time- and concentration-dependent effects of ATP-mediated PGE2 secretion were noted in sinusoidal endothelial cells, whereas the profile of the relative potencies of individual nucleotides was consistent with the presence of P2y and P1 purinergic receptors. In Kupffer cells, the regulation of prostanoid secretion by adenine nucleotides was essentially the same as that in sinusoidal endothelial cells except that adenosine did not stimulate prostanoid secretion and that prostanoid secretion differed somewhat; Kupffer cells secreted relatively more PGF2 alpha and less 6-keto-PGF1 alpha than sinusoidal endothelial cells in the presence of ATP, suggesting the presence of only P2y receptors. In summary, PGE2 is the main prostanoid secreted by hepatic nonparenchymal cells and its secretion may be stimulated by adenine nucleotides and adenosine.

Adenine Nucleotides↗