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Biomedical subjects

Keisuke Hino

Publications and source records attributed to Keisuke Hino.

23 records · Page 2Linked to original sources

Hepatitis C virus infection upregulates expression of the type I interferon receptor in human peripheral blood mononuclear cells.

To assess whether hepatitis C virus infection (HCV) affects type I interferon (IFN) receptor expression, the expression levels of two subunits of this receptor, IFNAR1 and IFNAR2, in peripheral blood mononuclear cells (PBMCs) were determined by flow-cytometric assay in 68 anti-HCV antibody-positive patients (47 positive for HCV RNA and 21 negative for HCV RNA) and 14 healthy controls. The percentages of IFNAR1- and IFNAR2-expressing cells were significantly higher in HCV RNA-positive patients than in HCV RNA-negative patients or healthy controls. In multiple regression analysis, the presence of HCV RNA in serum was independently associated with the expression of both IFNAR1 and IFNAR2 in PBMCs (P=0.007 for IFNAR1 and P=0.003 for IFNAR2). The frequency of IFN-gamma-producing peripheral CD4(+) and CD8(+) cells was also significantly higher in HCV RNA-positive patients than in HCV RNA-negative patients or healthy controls and there was a significant correlation between IFN receptor expression and the frequency of IFN-gamma-producing cells. These results suggest that HCV infection upregulates the expression of the type I IFN receptor in PBMCs through enhanced IFN-gamma production by peripheral CD4(+) and CD8(+) cells as one of mechanisms that regulate the expression of the type I IFN receptor.

Journal Article↗

Expression of type I interferon receptor in liver and peripheral blood mononuclear cells in chronic hepatitis C patients.

To assess whether peripheral blood mononuclear cells (PBMCs) can be substituted for liver tissue in monitoring the hepatic expression of interferon receptors (IFNAR1 and/or IFNAR2) in chronic hepatitis C, we quantified the mRNA of both subunits, using the competitive polymerase chain reaction, in the liver specimens from 37 chronic hepatitis C patients and in PBMCs from 29 of 37 patients. PBMCs from 10 healthy subjects were also quantified for both subunits. Hepatic expression of IFNAR1 and IFNAR2 were more frequent than PBMCs: IFNAR1, 23/27 (85%) vs 7/19 (37%), P = 0.0021, IFNAR2, 34/37 (92%) vs 19/29 (66%), P = 0.0182. Neither subunits was detected in PBMCs from control subjects. The expression level of IFNAR2 in the liver was related to that in PBMCs (r = 0.613, P = 0.0052). These results suggest that hepatitis C virus infection may up-regulate the expression of the type I interferon receptor and that the measurement of IFNAR2 expression in PBMCs may be useful for monitoring its expression in liver.

Adult↗

Constrained genomic and conformational variability of the hypervariable region 1 of hepatitis C virus in chronically infected patients.

We analysed the genomic and conformational variability of the hypervariable region 1 (HVR1) of the hepatitis C virus (HCV) to evaluate the importance of its biological role. A total of 865 genotype 1b HVR1 subclones were collected from serially sampled sera in 11 patients with chronic hepatitis C, four of whom received interferon therapy. Consequently, 169 distinct sequences were examined for amino acid substitutions as well as hydrophilic or hydrophobic profile at each amino acid position within HVR1. Secondary structure of HVR1 was also predicted by the method of Robson in 90 distinct sequences from eight patients, including three interferon-treated patients. Some positions within the HVR1 were invariable or nearly so as to amino acid substitution. Hydrophilic or hydrophobic residues exclusively predominated at several positions. These constrained amino acid replacement and hydrophilic or hydrophobic profiles were conserved irrespective of interferon therapy, though the frequency of amino acid replacement was greater at almost all amino acid positions within the HVR1 in interferon-treated patients. The quasispecies of HCV showed various secondary structures of HVR1, but many sequences seemed to have common characteristics. beta sheet conformations around both the N-terminus and position 20 (numbered from the NH2 terminus of E2 envelope glycoprotein), and/or coil structures around the C-terminus of HVR1 could be identified. These results suggest that HVR1 amino acid replacements are strongly constrained by a well-ordered structure, in spite of being tolerant to amino acid substitutions, and imply an important biological role of the HVR1 protein in HCV replication.

Adult↗

Current strategies for chemoprevention of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) develops frequently in the liver of patients with chronic hepatitis and cirrhosis caused by persistent infection with hepatitis B virus or hepatitis C virus in Asia. Several studies including ours have revealed that the risk of HCC increases in parallel with the progression of hepatic fibrosis associated with chronic hepatitis and liver cirrhosis. It may be delineated reasonably, therefore, that suppression of fibrosis by chemical (or biological) agents would be able to decrease the risk of HCC. We have demonstrated that antifibrotic agents, such as HOE 077, TJ-9 and interferon, can reduce the risk of HCC. Accordingly, antifibrotic agents are promising candidates for chemoprevention of HCC. The results of our study are discussed within the scope of the current state of the art as regards chemopreventing HCC.

Animals↗