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Biomedical subjects

H Fusamoto

Publications and source records attributed to H Fusamoto.

At least 37 records · Page 2Linked to original sources
PubMed1996

Hepatitis C biochemical remission and viral replication in haemodialysis patients.

The natural course of non-A, non-B (type C) hepatitis was studied in 62 haemodialysis patients. From the onset of the disease, serum alanine aminotransferase levels were monitored monthly for 9-218 mon (median 115). After fluctuation of aminotransferase levels for 1-206 mon (median 39), 57 (92%) patients showed normalization of these levels lasting until the end of the follow-up, which was for > 2 yr in 31 (50%) cases and for > 5 yr in 15 (24%) cases. At the end of follow-up, hepatitis C viraemia was assessed by reverse transcription-polymerase chain reaction (RT-PCR) and branched DNA (bDNA) assay. Viraemic levels were significantly lower in the 15 patients with normal aminotransferase for > 5 yr (median RT-PCR + ve/bDNA-ve, range RT-PCR-ve to 10(6.7) Eq/mL) than in the 47 cases with normal levels for < 5 yr (median 10(6.6), range RT-PCR + ve/bDNA-ve to 10(7.6) Eq/mL) (P < 0.01). Moreover, a significant inverse relation was observed between viraemic levels and the duration of aminotransferase normalization (r = -0.46, P < 0.01). These findings indicate that biochemical remission of hepatitis C may be frequent in haemodialysis patients and may be related to viral attenuation.

Adult↗
PubMed1996

Low expression of erythrocyte complement receptor type 1 in chronic hepatitis C patients.

Primate erythrocyte complement receptor type 1 (CR1) plays an essential role in complement-associated immune complex clearance by transporting complexes to macrophages in the liver and/or spleen. Antibody-bound hepatitis C virus, which consists of immune complexes, is observed in patients with chronic hepatitis C. The aim of this study was to clarify the pathophysiological roles of erythrocyte CR1 in hepatitis C virus-infected individuals. We quantified the expression of erythrocyte CR1 with a fluorescence-activated cell sorter system in 57 chronic hepatitis C and 37 chronic hepatitis B cases and 20 normal volunteers. Complement-bound immune complexes were quantified by means of an enzyme-linked immunosorbent assay using anti-C1q and anti-C3d antibodies. Hepatitis C virus-infected patients showed lower erythrocyte CR1 and higher C3d immune complex levels than volunteers (P < 0.01 and P < 0.05, respectively). An inverse correlation was observed between the erythrocyte CR1 and C3d immune complex levels in hepatitis C virus infection (r = -0.300, P = 0.032). The erythrocyte CR1 levels in hepatitis C virus infection were lower in patients with severe liver inflammation, cirrhosis, or hepatocellular carcinoma than in those with mild inflammation, whereas the levels did not differ regardless of the disease stage in hepatitis B virus infection. These findings demonstrate that the expression of erythrocyte CR1 is related to immune complex quantity and the severity of liver disease in hepatitis C virus infection.

Adult↗
PubMed1996

Long-term biochemical and virological response to natural interferon-alpha in patients with chronic hepatitis C.

To determine the long-term response to interferon-alpha, 134 patients with chronic hepatitis C were followed for more than a year after therapy. Follow-up was stopped for 14 patients and 43 patients received retreatment. The remaining 77 patients were followed for 26-46 months, and 39 of them achieved long-term sustained alanine aminotransferase (ALT) normality. This normality was achieved in 35/38 short-term sustained responders, which was significantly higher (P < 0.001) than in the short-term relapsers (2/38) and the short-term nonresponders (2/44). Hepatitis C virus (HCV) RNA remained negative in 27 (73%) of 37 patients in the long-term sustained ALT normality group. However, only one (1.6%) of 63 long-term responders was negative for HCV RNA. The results of HCV RNA testing for the long-term period agreed with those at three to six months after therapy. Serum ALT levels during the first six months after therapy and HCV RNA testing at three to six months after therapy are important for predicting long-term sustained ALT normality and HCV RNA negativity.

Adult↗
PubMed1996

Fas antigen expression in liver tissues of patients with chronic hepatitis B.

BACKGROUND: Hepatitis B virus-infected cells can be eliminated by the cytotoxic T cell-mediated immune reaction. Fas ligand, recently detected on the surface of cytotoxic T cell, is thought to induce cells to apoptosis by adhering to Fas antigen. AIMS/METHODS: To evaluate the role of Fas antigen and apoptosis in chronic hepatitis B, we immunohistochemically studied Fas antigen and HBsAg expression in liver samples from patients with hepatitis B virus infection. RESULTS: In samples from 56 HBV patients, Fas antigen was mainly expressed in the cytoplasm (partly at the membrane) of hepatocytes, and these positive cells were detected especially at the periportal region near "piecemeal necrosis". According to Knodell's HAI scoring system, the scores of periportal inflammation and necrosis (category I) and the scores of intralobular inflammation and necrosis (category II) were similarly higher in Fas antigen-positive cases than in Fas antigen-negative cases (p < 0.01), and there was a positive correlation between these scores and the degree of Fas antigen expression. In normal cases, Fas antigen was not detected. In patients with HBV infection, Fas antigen expression was closely correlated with the activity of the viral hepatitis. HBsAg was expressed by the majority of hepatocytes. However, Fas antigen was expressed by fewer hepatocytes than the number of HBsAg-positive cells. CONCLUSIONS: These findings suggest that the expression of Fas antigen may not be triggered only by HBV infection, and immunological interaction may be needed for the expression and for apoptosis to occur.

Adolescent↗
PubMed1996

Evidences for involvement of cyclooxygenase-2 in proliferation of two gastrointestinal cancer cell lines.

Cyclooxygenase (COX) consists of two isozymes, COX-1 and COX-2. The roles of these isozymes in the gastrointestinal tract are unknown. We investigated messenger RNA expression of the COX-1 and COX-2 genes in the gastrointestinal cancer cell lines MKN28, MKN45, KATO III CACO-2, DLD-1 and LoVo. These cell lines expressed comparable levels of COX-1 mRNA, although their expression of COX-2 varied. Therefore, we studied the effects of NS-398 and indomethacin, specific and non-specific inhibitors for COX-2, on proliferation of the cell lines. Both of the inhibitors suppressed proliferation of the two cell lines that highly expressed COX-2 (MKN45 and CACO-2). However, these inhibitors exerted minimal effects on proliferation of the other cell lines, which expressed significantly lower levels of COX-2. Therefore, it was proposed that COX-2 participates in proliferation of cancer cells because of over expression of the COX-2 gene.

Cell Division↗
PubMed1996

Quantitative analysis of antibody to hepatitis C virus envelope 2 glycoprotein in patients with chronic hepatitis C virus infection.

The significance of circulating antibody to hepatitis C virus (HCV) envelope glycoprotein 2 (E2)/nonstructural protein 1 (NS1) glycoprotein was studied in 83 patients with chronic HCV infection diagnosed by polymerase chain reaction (PCR). E2/NS1 antibody was quantitatively examined by a passive hemagglutination test using recombinant E2/NS1 glycoprotein encompassing amino acids 388 to 664 of the HCV-H strain. The results were correlated with clinical and virological features such as genotypes and viremic levels assessed by a competitive reverse-transcription PCR assay. E2/NS1 antibody was found in 73 patients (88%), and its occurrence was related to viremic levels. E2/NS1 antibody titers were low in asymptomatic HCV carriers with low levels of viral replication; 9 of 17 such patients tested positive for E2/NS1 antibody (53%), compared with 64 of 66 chronic hepatitis C patients (97%) (P < .01). A significant direct relationship was observed between viremic levels and E2/NS1 antibody titers (r = .52, P < .01). Of the 13 patients with low viremic levels of < 10(6) copies/mL, only 5 tested positive for E2/NS1 antibody (38%), whereas 68 of the 70 patients with viremic levels of > or = 10(6) copies/mL had it (97%) (P < .01). As for the relation to HCV genotypes, no difference was seen in E2/NS1 antibody titers among genotypes examined (1b, 2a, and 2b). These findings suggest that the E2/NS1 antibody tested exhibits no neutralizing activity in chronic HCV infection but may serve as a serological indicator of active virus replication.

Adult↗
PubMed1996

Gastric mucosal energy metabolism and intracellular mucin content changes in patients with liver cirrhosis.

Biopsy samples from patients with liver cirrhosis were investigated for changes in gastric mucosal energy metabolism and intracellular mucin content using high performance liquid chromatography and an image analysing system. The test group consisted of eight non-cirrhotic patients with endoscopically normal mucosa (controls) and eight cirrhotic patients with oesophageal varices. The amount of ATP, energy charge level and intracellular mucin content were all significantly decreased in cirrhotic patients when compared with those of the controls. The decrease in energy charge also correlated well with the decrease in intracellular mucin content in the gastric mucosa. The results indicate that gastric mucosal energy metabolism is impaired in cirrhotic patients concomitantly with a decrease in the intracellular mucin content in the gastric mucosa. These changes may weaken defensive mechanisms against acid and NSAID, resulting in gastric mucosal injury in cirrhotic patients.

Adenosine Diphosphate↗
PubMed1996

Progression of type C chronic hepatitis to liver cirrhosis and hepatocellular carcinoma--its relationship to alcohol drinking and the age of transfusion.

Alcohol drinking has been reported to be an important factor that modulates the development and prognosis of chronic hepatitis B; however, little is known about an interrelationship between alcohol intake and the progression of chronic hepatitis C to liver cirrhosis (LC) and hepatocellular carcinoma (HCC). We attempted to clarify this interrelationship in patients with hepatitis C and history of blood transfusion. Thirty LC and 85 HCC patients were enrolled. In patients with LC, no significant correlation was observed between the amount of alcohol intake and the period from transfusion to diagnosis. The period from transfusion to diagnosis in HCC patients with alcohol intake > or = 46 g/day and < 46 g/day were 26 +/- 6 and 31 +/- 9 years, respectively, resulting in a significant difference (p < 0.05). The period from transfusion to diagnosis of LC and/or HCC showed significant negative correlation with the age of transfusion (r = 0.82, Y = -0.67X + 48.0, p < 0.01; r = 0.76, Y = -0.70X + 54.1, p < 0.001, respectively). This correlation was also observed in patients with HCC, regardless of the amount of alcohol intake. In conclusion, these data suggest that alcohol drinking might be an important factor that promotes an occurrence of HCC in patients with hepatitis C, and that hepatitis C virus infection in the elderly promotes development of liver disease via LC to HCC.

Adult↗
PubMed1996

Treatment with recombinant interferon-alpha 2a for patients with chronic hepatitis C: predictive factors for biochemical and virologic response. Osaka Liver Disease Study Group.

BACKGROUND: The heterogeneity of the hepatitis C virus (HCV) genome has been reported to be associated with the effectiveness of interferon therapy. We investigated the correlation of the viral and host factors, including the degree of sequence complexity of the HCV genome for responses to interferon-alpha in patients with chronic hepatitis C. METHODS: Ninety-seven patients received a 26-week course of recombinant interferon-alpha 2a therapy. The sequence complexity of the envelope 1-2 region was evaluated by polymerase chain reaction-mediated single-strand conformation polymorphism (PCR-SSCP) analysis. RESULTS: Of the 85 patients who completed the treatment, 31 (36%) achieved a sustained response, and 28 (33%) showed a sustained loss of HCV RNA. A low HCV RNA level, determined by the branched DNA probe assay, and serotype group 2 HCV correlated with a sustained response. In patients with serotype group 1 HCV of more than the threshold of the branched DNA probe assay, a band number on PCR-SSCP analysis of more than 2 could be associated with inefficacy of interferon therapy. Multivariate analysis in the 50 patients whose sera were available for all the virologic tests showed that only the HCV RNA level is independently predictive of a sustained response. CONCLUSIONS: Determination of the HCV RNA level is most important for predicting the response before interferon therapy. PCR-SSCP analysis may be useful as an additional test for patients with a high HCV RNA level of serotype group 1 HCV.

Adult↗
PubMed1995

Transfection of N-acetylglucosaminyltransferase III gene suppresses expression of hepatitis B virus in a human hepatoma cell line, HB611.

beta-D-mannoside beta-1,4-N-acetylglucosaminyltransferase III (GnT-III) catalyzes the addition of N-acetylglucosamine in beta 1-4 linkage to the beta-linked mannose of the trimannosyl core of N-linked oligosaccharides and forms a bisecting GlcNAc structure. Although the biological meaning of the bisecting GlcNAc structure remains unclear, it is known that the attachment of a bisecting GlcNAc inhibits further processing of oligosaccharides by other glycosyltransferases. To investigate whether or not structural changes of oligosaccharides affect secretion and gene expression of hepatitis B virus (HBV), we introduced the GnT-III gene into a human hepatoma cell line, HB611, which secreted HBV-related proteins into the medium. Positive transfectants were cloned by hygromycin resistant selection. Three clones have high activities of GnT-III and secreted lower levels of HBV-related proteins into the medium in comparison with other clones. These clones showed marked suppression of HBV-related mRNAs and an increased binding with E-PHA as judged by lectin blot. Expression of beta actin, alpha fetoprotein, albumin, and prealubmin was not correlated with GnT-III activity in all the seven clones. Treatment of these cells with tunicamycin or swainsonine resulted in enhanced expression of HBV-related mRNA. These results indicate that some glycoproteins whose oligosaccharide structures are changed by over-expression of GnT-III suppress HBV gene expression.

Blotting, Northern↗
PubMed1995

Transforming growth factor beta up-regulates expression of the N-acetylglucosaminyltransferase V gene in mouse melanoma cells.

beta-1,6-N-acetylglucosaminyltransferase V (GnT-V) (EC 2.4.1.155) that catalyzes beta-1,6 branching in asparagine-linked oligosaccharides is activated on viral or oncogenic transformation and is associated with tumor metastasis. To study the molecular mechanisms involved in regulation of expression of the GnT-V gene, we cloned cDNA and genomic DNA for the enzyme (Saito, H., Nishikawa, A., Gu, J., Ihara, Y., Soejima, Y., Sekiya, C., Niikawa, N., and Taniguchi, N. (1994) Biochem. Biophys. Res. Commun. 198, 318-327). We found that transforming growth factor beta (TGF beta) specifically induced GnT-V expression in mouse melanoma cells. The activity of GnT-V was increased 24 h after the addition of TGF beta and remained at high levels up to 72 h. Northern blot analysis showed that the mRNA levels of GnT-V were consistent with the increased activity. To further investigate the nature of the induction, mRNA stability and transcriptional activity were assayed. The enhancement of the GnT-V mRNA expression resulted from prolonged mRNA stability, not from increased transcription. Consequently, elevated mRNA levels were observed even 72 h after the addition of TGF beta. Lectin blot analysis involving leukoagglutinin showed newly synthesized beta-1,6 branching structures in the sugar chains of a protein of approximately 130 kDa at 48 h after TGF beta treatment. These results suggested that TGF beta caused changes in the sugar chains of proteins in melanoma cells by up-regulating GnT-V expression.

Animals↗
PubMed1995

Clinical characteristics and antibody profiles of chronic hepatitis C patients: relation to hepatitis C virus genotypes.

Genotyping of 179 consecutive Japanese chronic hepatitis C patients was carried out based on the variation in the hepatitis C virus (HCV) core gene. The results were correlated with clinical features and antibody responses toward specific HCV proteins deduced from the nucleotide sequence of genotype I/1a. Genotypes II/1b, III/2a, and IV/2b were identified in 138 (77%), 24 (13%), and 12 (7%) patients, respectively. Five patients had double infections. Genotype dependence was observed only for antibody response toward the NS4 (5-1-1) protein, which was infrequent in genotype III/2a patients (33%) compared with genotype II/1b (81%; P < 0.01) and genotype IV/2b (75%; P < 0.05). Following interferon-alpha therapy, sustained amniotransferase normalisation was achieved by 89% (eight of nine) patients without antibody to the 5-1-1 protein and 33% (17 of 51) with it (P < 0.01). These findings indicate that absence of antibody response to the 5-1-1 protein is frequent in genotype III/2a HCV carriers and may serve to predict responses to interferon therapy.

Adult↗
PubMed1995

Serial density analysis of hepatitis C virus particle populations in chronic hepatitis C patients treated with interferon-alpha.

In interferon treatment of chronic hepatitis C patients, the biochemical and virological responses mostly parallel each other. However, some patients who show persistent ALT normalization display continued viremia after cessation of therapy. High-density hepatitis C virus (HCV) particles, which are immune complex forms, are reported to be less infectious both in vitro and in vivo. To assess whether high-density HCV contributes to the response discrepancies and to clarify the association with patient outcome, sera were examined from chronic hepatitis C patients who were treated with interferon-alpha. This study included 10 sustained responders with viremia (SR + ve), 5 SR without viremia, 3 transient responders (TR), and 3 nonresponders (NR). The SR + ve patients were defined as those with continued ALT normalization and serum HCV-RNA positivity at 24 weeks after therapy completion. Serum samples obtained before and 24 weeks after therapy were ultracentrifuged on 35% sucrose. The ratio between high-density and low-density HCV was determined by quantification of HCV-RNA titers in the bottom and top fractions by competitive reverse transcription and by the polymerase chain reaction, and expressed as the bottom/top (B/T) ratio. The B/T ratios before therapy were 1:1 in all groups of patients, and 1:1 after therapy in TR and NR groups. Five out of 6 SR + ve patients who showed 1:1 ratio after therapy relapsed within 1 year. In contrast, all SR + ve patients whose ratios were 10-100:1 continued to show ALT normalization. These findings demonstrate that patients who have high-density HCV dominance after therapy show persistent ALT normalization despite viremia, which can be explained by predominance of the neutralized immune complex.

Adult↗
PubMed1995

Tumor necrosis factor-alpha and interferon-gamma inhibit synergistically viral replication in hepatitis B virus-replicating cells.

The effects of tumor necrosis factor-alpha and/or interferon-gamma on the replication of hepatitis B virus were examined using HB611 cells. These cells were derived from human hepatoblastoma cells, Huh6, by integrating hepatitis B virus DNA, and produce hepatitis B virus continuously. Each of the cytokines inhibited hepatitis B virus replication in the cells assessed as the amount of episomal hepatitis B virus DNA, without a decrease in cell viability. When the two cytokines were administered together, the inhibitory effect became greater. Incubation of the cells with 1,000 U/ml tumor necrosis factor-alpha decreased HBV DNA replicative intermediates by 55%, and that with 1,000 U/ml interferon-gamma decreased these by 51%. Furthermore, incubation with 1,000 U/ml tumor necrosis factor-alpha and 1,000 U/ml interferon-gamma in combination decreased HBV DNA replicative intermediates by 71%. In contrast, the amount of hepatitis B virus RNA and secretion of hepatitis B e antigen were not apparently reduced by the cytokines, and 2',5'-oligoadenylate synthetase activity was not detected in the supernatant. These results suggest that tumor necrosis factor-alpha and interferon-gamma inhibit hepatitis B virus replication by blocking some step in reverse transcription and that the 2',5'-oligoadenylate synthetase is not involved in the mechanism underlying the inhibition by these two cytokines.

2',5'-Oligoadenylate Synthetase↗
PubMed1995

Roles of hepatocyte growth factor and its receptor in gastric mucosa. A cell biological and molecular biological study.

Hepatocyte growth factor (HGF) stimulates the growth of hepatocytes and other epithelial cells. A gene for the HGF receptor, c-met, is detected in the intestinal tract and the liver, as well as in gastric carcinoma cells. However, the role of HGF in the regeneration of the normal gastric mucosa is not known. The purpose of the present study was to elucidate the effects of HGF on the morphogenesis of cultured gastric mucosal cells and to evaluate the role of HGF and c-met in the healing process in rat gastric mucosa. The cultured gastric mucosal cells developed a branching morphology in a collagen matrix supplemented with HGF or fetal calf serum. They did not form this morphology on a plastic dish or in the collagen without HGF or the serum. In an in vivo study, total RNA was extracted from rat gastric mucosa 6, 24, 48, and 96 hr after the exposure to a solution of 0.6 M HCl. HGF messenger RNA was not detected, but c-met was expressed in the mucosa. The increased expression of c-met was followed by healing of the mucosal injury. These results indicate that HGF plays important roles in the morphogenesis of gastric mucosal cells and that the HGF receptor gene participates in the healing process of gastric mucosa.

Animals↗
PubMed1995

Colonic mucosal hemodynamics and tissue oxygenation in patients with ulcerative colitis: investigation by organ reflectance spectrophotometry.

Colonic mucosal hemodynamics were investigated at the rectosigmoidal region of the colon in 46 patients with ulcerative colitis and in 18 normal subjects by organ reflectance spectrophotometry under colonoscopy. The value for the index of mucosal hemoglobin concentration (IHb) was significantly higher, and value for the index of mucosal hemoglobin oxygen saturation (ISO2) was significantly lower in patients with active ulcerative colitis than values in the normal controls or in patients with inactive ulcerative colitis. The results indicate mucosal congestion and hypoxemia in patients with active ulcerative colitis. The changes in IHb and ISO2 correlated well with the severity of ulcerative colitis scored by endoscopic findings and with the number of infiltrating inflammatory cells in the mucosa analyzed histologically in biopsy samples. In conclusion, the colonic mucosal microcirculation in patients with active ulcerative colitis was disturbed and showed congestion and hypoxemia. The analysis of hemodynamic changes may be helpful for assessing the activity of ulcerative colitis.

Adult↗