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Biomedical subjects

M Zeniya

Publications and source records attributed to M Zeniya.

At least 37 records · Page 2Linked to original sources
PubMed1997

Induction of autoimmune-like hepatic and ductal lesions by administration of lipopolysaccharide in mice undergoing graft-versus-host reaction across MHC class I difference.

In this paper, we examined the induction of autoimmune-like histologic changes in the liver and other organs of mice undergoing graft-versus-host reaction (GVHR) with MHC class I disparity by the administration of bacterial lipopolysaccharide (LPS), on the assumption that stimulation with LPS could be an exacerbating factor. Spleen cells of C57BL/6 (B6) mice were injected twice into (B6 x bml) F1 recipient mice at an interval of 7 days to induce MHC class I GVHR and then challenged with 1 microg of LPS intravenously on the next day of the cell transfer. The hepatic lesions of the group of MHC class I GVHR mice challenged with LPS showed marked cellular infiltration at the portal area and focal necrosis was observed in the hepatic lobule. The major infiltrating cells were CD8+, and others including CD4+ cells being of minor populations. In addition, ductal lesions in extrahepatic organs, including the pancreas and salivary glands also showed marked cellular infiltration. Thus, we have demonstrated that LPS induced ductal lesions in mice with MHC class I disparity. CD8+ cells were detected at the destructive hepatic lesions, which might be effector cells. These findings indicate that LPS might be one of the potential factors which augment autoimmune-like lesions.

Alanine Transaminase↗
PubMed1997

Present status of autoimmune hepatitis in Japan--correlating the characteristics with international criteria in an area with a high rate of HCV infection. Japanese National Study Group of Autoimmune Hepatitis.

BACKGROUND/AIMS: A nationwide survey of autoimmune hepatitis (AIH) was carried out in Japan. METHODS: Four hundred and ninety-six patients were enrolled by questionnaires sent to 101 hospitals with hepatology specialists. RESULTS: The clinical features of Japanese AIH were as follows: most patients were middle-aged women; serum autoantibodies, especially antinuclear antibody, were frequently positive, serum IgG level was high, and HLA-DR4 was the major HLA allotype. Liver-kidney microsomal type 1 antibody was positive in nine of 79 patients tested. Eight of these antibody positive patients were also positive for antinuclear antibody and five for anti-smooth muscle antibody. Ninety-two percent of the patients showed piecemeal necrosis and 60% bridging necrosis; plasma cell infiltration in the portal areas was observed in 50% of the patients. Only 12.3% were diagnosed as having liver cirrhosis. A favorable effect of corticosteroid, normalization of serum transaminases, was observed in 89% of 317 patients, who were treated with an initial dose of over 30 mg/day. Sixty-two patients were positive for hepatitis C virus (HCV) markers. In these patients, however, only one patient was liver-kidney microsomal type 1 antibody positive. Corticosteroid was effective in 30 (81%) of 37 HCV-marker-positive patients treated with this agent. Thus the efficacy of corticosteroid did not differ from that in AIH patients without HCV infection (90%). Similarly, interferon treatment was used in 20 patients, all of whom were positive for HCV-RNA, and resulted in 50% efficacy as determined by normalization of the serum transaminase level 6 months after treatment. The International Diagnostic Scoring System for the diagnosis of AIH worked well in these patients, except for HCV-infected individuals, that is, approximately 10% of the total of AIH patients.

Adolescent↗
PubMed1996

Splenectomy-reduced hepatic injury induced by ischemia/reperfusion in the rat.

In the present study, we investigated the role of the spleen in experimental hepatic ischemia/reperfusion in the rat. After a 90-min period of ischemia in the left and middle hepatic lobes, the ischemia was released and the liver was reperfused for up to 24 h. Plasma alanine aminotransferase reached a peak 3 h after the onset of reperfusion, and gradually decreased thereafter. A histological examination revealed evidence of hepatocellular necrosis and degeneration, especially 24 h after the onset of reperfusion. In addition, there was a noticeable accumulation of polymorphonuclear cells in the liver following ischemia/reperfusion. A splenectomy performed just prior to ischemia/reperfusion reduced both biochemical and histological hepatocellular injury. The number of polymorphonuclear cells in the liver following ischemia/reperfusion was significantly reduced in rats subjected to splenectomy, suggesting that the increase in polymorphonuclear cells may contribute to liver injury. The number of mononuclear cells also increased in the marginal zones of the spleen following ischemia/reperfusion, and appeared to be derived from the splenic monocyte/macrophage population, based on immunohistochemical studies. The spleen plays an important role in the pathogenesis of hepatic ischemia/reperfusion injury and the splenic monocyte/ macrophage population contributes to liver damage.

Alanine Transaminase↗
PubMed1995

Genetic heterogeneity in the precore region of hepatitis B virus in hepatitis B e antigen-negative chronic hepatitis B patients: spontaneous seroconversion and interferon-induced seroconversion.

To elucidate the relationship between the clinical severity of chronic liver disease and the precore mutations in hepatitis B e antigen (HBeAg)-negative hepatitis B virus (HBV) carriers, mutations were investigated in the precore region of HBV DNA in 20 chronic hepatitis B patients who seroconverted either spontaneously or after the administration of alpha-interferon (IFN), and 5 asymptomatic carriers. The precore mutation with a stop codon at nucleotide 1896 was found in all patients, irrespective of the histology and in all asymptomatic carriers. The second mutation at nucleotide 1899 was found in 40% of cases studied but always followed by the first mutation at nucleotide 1896. The mixed viral infection of precore mutant and wild-type HBV virus was found in 40% of seroconverted cases after IFN treatment and in sera of HBV carriers obtained within a year after the spontaneous seroconversion. These data suggest that the precore mutants prevail over wild-type HBV in all HBeAg-negative HBV carriers within several years after the seroconversion, but their prevalence could not confine the clinical severity of chronic liver disease.

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↗
PubMed1994

Cloning and functional expression of human inducible nitric oxide synthase (NOS) cDNA from a glioblastoma cell line A-172.

Nitric oxide (NO) is a messenger molecule with diverse functions throughout the body. The inducible type of nitric oxide synthase (NOS) is considered to be a key molecule in the immune responses to bacteria, parasites, and tumors, and its gene expression is regulated by cytokines. We isolated 3 overlapping partial inducible NOS cDNA clones from a human glioblastoma cell line A-172 induced by IL-1, TNF-alpha, and IFN-gamma. The 3,963-bp human glioblastoma inducible NOS cDNA contained the longest open reading frame of 3,459 bp, which encoded a polypeptide of 1,153 amino acids with a calculated molecular mass of 131 kDa. This human inducible NOS possessed consensus recognition sites for the cofactors FMN, FAD, and NADPH and calmodulin recognition sites, and displayed 48.1% sequence identity with the endothelial type, 43.1% with the neuronal type, and 99.3% with the inducible type from hepatocytes, and 99.9% with the inducible type from chondrocytes and adenocarcinoma. An expression plasmid consisting of pSG5 expression vector and cDNA containing the entire putative coding sequence was constructed and transfected into COS-1 cells. COS-1 cells showed nitric oxide synthase activity together with a 130 kDa immunoreactive band on Western blot analysis.

Amino Acid Oxidoreductases↗
PubMed1994

HCV-marker-positive autoimmune-type chronic active hepatitis: a possible relation between HCV infection and liver autoreaction.

This study focused on 32 patients who were diagnosed as having autoimmune hepatitis based upon clinical and histological factors. Fifteen of these patients were positive for HCV-RNA and for one of the HCV-related markers tested, including anti-C100, ELISA II, and RIBA 2 (Group 2). The remaining 17 patients were negative for all HCV-related markers (Group 1). Clinical factors in the two groups, including the frequency of autoantibodies, serum levels of aminotransferase and gammaglobulin, HLA phenotypes, and the response to corticosteroid treatments, were compared. The titer of serum anti-nuclear antibodies and the level of serum aminotransferase at initial diagnosis were significantly higher in Group 1 than in Group 2. Furthermore, the genetic background of the two groups, as indicated by HLA phenotypes, differed. All cases in Group 1 were HLA-DR4-positive, whereas only 60% of those in Group 2 cases had HLA-DR4. Also, all cases in Group 1 but only 66.7% of the cases in Group 2 showed good clinical responses to corticosteroid treatment. Finally, no cases of HCV-related-marker-positive autoimmune hepatitis (Group 2) had antibodies for LKM, suggesting that these cases were clinically different from type II autoimmune hepatitis. These data indicated that immunosuppressive treatment might be the preferred initial treatment in patients who either satisfy the criteria for AIH or who are sero-positive for an HCV-marker.

Autoantibodies↗
PubMed1993

Immunogenetic background of hepatitis B virus infection and autoimmune hepatitis in Japan.

Human leucocyte antigen (HLA)-typing was studied in 82 hepatitis B carriers and 15 cases of autoimmune hepatitis (AIH) to elucidate the genetic factors which may associated with the etio-pathogenesis of chronic hepatitis in Japan. There were two types of HLA phenotypes: HLA A2 was associated with the progression of the disease induced by HBV infection, and HLA A26 and DR5 were related to the retardation of the disease. A family study confirmed the strong association of these HLA phenotypes with the disease induced by HBV infection. In the analysis of AIH, HLA DR4 is a risk factor related to susceptibility of Japanese AIH which shows different clinical manifestations compared to HLA-DR3-positive AIH, dominantly observed in Western countries. These results suggest that genetic background as expressed by HLA, is an important factor in restricting the development of type B hepatitis and AIH, and can explain racial differences of disease susceptibility.

Autoimmune Diseases↗
PubMed1993

[Association of pre-core defective HBV mutant with anti-HBe positive chronic hepatitis].

Precore defective HBV mutant has been suggested to be responsible for the pathogenesis of fulminant hepatitis. This variant is unable to produce HBeAg because of the presence of a novel translational stop codon at the end of the precore region of the genome. We examined the precore region of the HBV nucleotide sequence in 12 Japanese anti-HBe positive chronic hepatitis patients in order to ascertain whether the genome has stop-codon mutation in the precore region. Precore defective HBV mutant was found in most of the examined cases. A few cases had a mixture of strains, wild type and precore defective HBV mutant. The variety of precore genome concerned with the pathogenesis of chronic hepatitis still needs to be clarified.

Adult↗
PubMed1992

Establishment of the human BSMZ breast cancer cell line, which overexpresses the erbB-2 and c-myc genes.

A new cell line, designated BSMZ, was established from a malignant pleural effusion from a woman with breast cancer. This line has a doubling time of 27 h and has now been cultured for over 120 passages. The large, rounded BSMZ cells grow as both a monolayer and as aggregations in suspension. Intracytoplasmic lumen, a finding consistent with results from cells derived from mammary tissue, was detected on ultrastructural analysis. Injection of BSMZ cells into nude mice resulted in the growth of solid tumors 4 weeks after inoculation. The solid tumor was identical to the original BSMZ cells in microscopic and electron microscopic studies. These cells possess an average of 80 chromosomes. Expression of erbB-2 and c-myc genes was increased by 10-fold, while there was no detectable overexpression of the N-ras and c-myb genes. Southern analysis has revealed amplification of the erbB-2 and c-myc loci. The BSMZ cell line may therefore provide a useful model for the study of human breast cancer and overexpression of the erbB-2 gene.

Adult↗