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Biomedical subjects

Kenya Iyoda

Publications and source records attributed to Kenya Iyoda.

6 recordsLinked to original sources
PubMed2004

Circulating soluble Fas levels in patients with hepatitis C virus infection and interferon therapy.

BACKGROUND: The clinical relevance of the circulating soluble form of the Fas-Receptor (sFas) was investigated in patients with hepatitis C receiving type 1 interferon (IFN) therapy. METHODS: sFas was quantified by enzyme-linked immunosorbent assay in 66 hepatitis C virus (HCV) carriers and 30 HCV-naive or previously infected controls. The levels were then monitored during enhanced treatment with type 1 IFNs in 15 chronic hepatitis C patients. RESULTS: The HCV carriers had high levels of sFas compared with controls (3.8+/-1.3 vs 2.7+/-0.8 ng/ml; P<0.001). sFas levels in patients with chronic HCV infection were directly related to serum alanine aminotransferase levels (r=0.440; P<0.001) and the histological grade (r=0.403; P=0.019). Among necroinflammatory reactions, only piecemeal necrosis showed a correlation with sFas levels (r=0.556; P=0.001). Pretreatment sFas levels, however, were not predictive of therapeutic outcomes. A sustained virological response to enhanced IFN therapy showed a relation to only the pretreatment HCV load. Interestingly, circulating sFas was upregulated when IFN-beta was administered at short intervals (3 MU/every 12 h). This upregulation was accompanied by parallel aminotransferase elevation, which was observed regardless of a virological response. CONCLUSIONS: sFas elevation, in parallel with the severity of liver injury, suggests the possible upregulation of hepatic Fas expression and the Fas-mediated pathway in both HCV- and type 1 IFN-induced liver injury. The essential function of sFas to protect hepatocytes against Fas-mediated liver injury was not evident in these clinical settings.

Adult↗
PubMed2004

Ninjurin1 increases p21 expression and induces cellular senescence in human hepatoma cells.

BACKGROUND/AIMS: Ninjurin1 is a novel adhesion molecule that has a role in promoting nerve regeneration. Although ninjurin1 is ubiquitously expressed in various human tissues, including the liver, the biologic functions of ninjurin1 in tissues other than the nervous system remain unknown. The aim of this study was to investigate the function of ninjurin1 in hepatocytes. METHODS: The effect of ninjurin1 overexpression was examined in Huh-7 hepatoma cells. Ninjurin1 expression was examined by Western blot in human hepatocellular carcinoma tissues as well as their adjacent liver tissues. RESULTS: Ninjurin1-overexpressing clones exhibited strong growth inhibition due to G1 cell cycle arrest, which is associated with a posttranscriptional increase in p21WAF1/Cip1, a decrease of cyclin-dependent kinase 2 activity and the hypophosphorylation of Rb. The ninjurin1-overexpressing clones had increased senescence-associated beta-galactosidase activity and autofluorescent pigment, characteristic features of cellular senescence. The levels of ninjurin1 expression were higher in hepatocellular carcinoma tissues than those in adjacent liver tissues. CONCLUSIONS: The present study provides the first evidence that ninjurin1 is able to induce the senescence program. Ninjurin1 may be involved in the regulation of cellular senescence in the liver during carcinogenesis.

Carcinoma, Hepatocellular↗
PubMed2003

Involvement of the p38 mitogen-activated protein kinase cascade in hepatocellular carcinoma.

BACKGROUND: The mitogen-activated protein kinase (MAPK) cascade is activated in response to various extracellular stimuli. The authors investigated the involvement of the p38 MAPK, a member of the MAPK superfamily, cascade in hepatoma cell lines and in human hepatocellular carcinoma (HCC) tissue specimens. METHODS: Constitutively active mutant of MAPK kinase 6 (MKK6), which is upstream of p38 MAPK, was transfected into the HepG2 and HuH7 human hepatoma cell lines. The constitutive active mutant was constructed by replacing Ser-189 and Thr-193 with Glu. The growth and death of mutant MKK6-transfected hepatoma cells were analyzed by the WST-1 and sub-G1 assays. The surgically resected livers of 20 HCC patients were divided histologically into tumorous (T) and nontumorous (NT) lesions. p38 MAPK activity was analyzed using in vitro kinase assay and MKK6 activity was measured using Western blot analysis. RESULTS: Mutant MKK6 transfection increased p38 MAPK activity, cytochrome c release from the mitochondria to the cytosol, and caspase-3 activity, accompanied by apoptosis. In contrast, SB203580, a p38 MAPK-specific inhibitor, prevented MKK6-induced apoptosis in hepatoma cell lines. In the T lesions of 20 HCC parients, p38 MAPK and MKK6 activities were significantly lower compared with NT lesions (P < 0.05). There was a significant positive correlation between p38 MAPK and MKK6 activity (r = 0.507, P < 0.05). Larger tumors (> 20 mm) exhibited lower levels of p38 MAPK and MKK6 activity than did smaller tumors (P < 0.05). CONCLUSIONS: These findings suggested that reduction of the p38 MAPK cascade may account, in part, for the resistance to apoptosis, leading to the unrestricted cell growth of human HCC.

Apoptosis↗
PubMed2003

Histological improvement of chronic liver disease after spontaneous serum hepatitis C virus clearance.

The long-term histological and virological outcomes of spontaneous circulating hepatitis C virus (HCV) clearance were studied in chronic liver disease. Between 1979 and 1984, three patients underwent laparoscopy for chronic non-A, non-B liver disease, and two were found to have cirrhosis and one with chronic active hepatitis. After HCV assays became available in 1990, they were positive persistently for HCV antibody without serum HCV RNA. Reductions of antibody levels to HCV core and/or nonstructural proteins were observed, and liver biopsies were undertaken between 1995 and 2000. Liver biopsies at 11-19 years after laparoscopy disclosed marked alleviation of liver inflammation and fibrosis in each case although a low grade of inflammation remained. The two patients with cirrhosis no longer showed histological features of cirrhosis, and the poor liver function in one patient had been ameliorated. Liver specimens from two patients were subjected to polymerase chain reaction to detect positive and negative HCV RNA strands and hepatitis B virus DNA. Only the positive HCV RNA strand was detected for one patient who had previously cirrhosis. Liver specimens were examined from another six nonviremic HCV-seropositive individuals without chronic liver disease. Five patients displayed low-grade liver inflammation without evident fibrosis, but none had any viral genome in the liver. These findings suggest that spontaneous circulating HCV clearance in chronic liver disease confers favorable liver histological outcome, although occult HCV infection persists. J. Med. Virol. 69:41-49, 2003.

Female↗