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Biomedical subjects

H Fusamoto

Publications and source records attributed to H Fusamoto.

At least 109 records · Page 6Linked to original sources
PubMed1993

Quantitative analysis of hepatitis C virus RNA: relationship between the replicative level and the various stages of the carrier states or the response to interferon therapy.

The authors quantified hepatitis C virus (HCV) RNA in serum by the competitive RT-PCR assay to correlate the replicative level of HCV with [1] various stages of the carrier states or [2] a sustained response to interferon therapy. The competitive RT-PCR assay employed is based on co-amplification of the target RNA with known amounts of synthetic mutated RNA having a novel restriction endonuclease (EcoRI) site. The titer of circulating HCV RNA defined as log10 (copy numbers/ml serum) were lower in asymptomatic blood donors (5.4 +/- 2.0) and in patients with chronic persistent hepatitis (7.3 +/- 1.1) compared with those having chronic active hepatitis (7.9 +/- 0.8), liver cirrhosis (7.8 +/- 0.7) and hepatocellular carcinoma (7.9 +/- 0.7). The initial titer of circulating HCV RNA of long-term responders before interferon therapy (7.1 +/- 1.2) was significantly lower than that of short-term responders (8.3 +/- 0.5) and non-responders (8.1 +/- 0.4). Multivariate multiple logistic regression showed that the titer of HCV RNA before therapy was the strongest independent predictor of a sustained response to interferon therapy. These results showed that the replicative level of hepatitis C virus is higher in advanced liver disease and that the replicative state of HCV is the most important factor influencing sustained response to interferon treatment.

Adult↗
PubMed1993

Antibodies to hepatitis C virus and hepatitis C virus infection.

The authors studied the interrelationship of antibody to hepatitis C virus core protein (anti-HCV core), antibody to C100-3 antigen (anti-C100-3) and serum hepatitis C virus RNA positivity in chronic liver disease patients. Anti-HCVcore was detected with high titers in 95% (69/73) of chronic non-A, non-B hepatitis patients, while anti-C100-3 was found in 60% (44/73). A close relationship was observed between detection of anti-HCVcore and viremia. Anti-HCVcore was also detected with low titers in 24% (10/41) of hepatitis B virus carriers negative for anti-C100-3. Hepatitis C virus RNA was found in 3 of the 10 anti-HCVcore-positive carriers. A significant correlation was observed between the occurrence of high titers of anti-HCVcore and serum hepatitis C virus RNA positivity. In chronic hepatitis C patients treated with interferon-alpha, a sustained reduction of anti-HCVcore was more closely associated with sustained virus clearance than that of anti-C100-3. These results indicate that anti-HCVcore may serve as a reliable marker of hepatitis C virus infection.

Antigens, Viral↗
PubMed1993

Cell kinetics of mucosal atrophy in rat stomach induced by long-term administration of ammonia.

BACKGROUND: Helicobacter pylori produces ammonia in the stomach from urea. The present study was undertaken to clarify whether ammonia has an etiological role in H. pylori-associated gastric mucosal atrophy. METHODS: Ammonia at 0.01% was administered as drinking water for 8 weeks and mucosal cell migration rate and cell proliferation were investigated in rat stomach. RESULTS: Long-term administration of 0.01% ammonia for 4-8 weeks decreased mucosal thickness in the antrum but not in the body. Acceleration of cell migration preceded the occurrence of mucosal atrophy. Labeling indices in both antral and body mucosa significantly increased in all ammonia-treated groups, compared with those of the control group. In the antrum, the proliferative zone was significantly enlarged as mucosal atrophy developed, whereas, in body mucosa, enlargement of the proliferative zone occurred despite the absence of mucosal atrophy. CONCLUSION: Ammonia at 0.01% accelerates epithelial migration, especially in the antrum, leading to mucosal atrophy. Acceleration of epithelial proliferation occurs during the development of mucosal atrophy.

Ammonia↗
PubMed1993

Quantitative analysis of hepatitis C virus RNA in serum during interferon alfa therapy.

BACKGROUND: Interferon alfa is effective for controlling disease activity in chronic hepatitis C. However, many responders suffer relapse after cessation of therapy. In the present study, the serum concentration of hepatitis C virus RNA was correlated with a sustained response to interferon therapy. METHODS: Fifty-three patients with chronic hepatitis C received a 26-week course of interferon alfa. Hepatitis C virus RNA was quantitated in serum at the beginning and end of treatment using a competitive assay that combined reverse transcription and polymerase chain reaction. RESULTS: In long-term responders, whose alanine aminotransferase levels remained within the normal range during the 24 weeks after therapy, the titer of viral RNA (logarithmic transformed copy numbers per milliliter of serum) before therapy (7.1 +/- 1.2) was significantly lower (P < 0.001) than that of short-term responders (8.3 +/- 0.5) who had a relapse within the 24 weeks after therapy and nonresponders (8.1 +/- 0.4). Multivariate multiple logistic regression showed that the titer of viral RNA before therapy was the strongest independent predictor of a sustained response to interferon-alfa therapy (P = 0.002). CONCLUSIONS: The titer of hepatitis C virus RNA is the most important factor influencing the sustained response to interferon treatment.

2',5'-Oligoadenylate Synthetase↗
PubMed1993

Detection of hepatitis C virus RNA in liver tissues by an in situ hybridization technique.

Hepatitis C virus (HCV) infection of cells in liver tissues was determined by detecting HCV RNA by an in situ hybridization technique using synthetic oligonucleotide probes derived from the 5'-non-coding and core regions of HCV genome. Aggregated silver grains indicating hybridization with HCV RNA were observed over the nuclei as well as the cytoplasm of hepatocytes with none on non-parenchymal cells. The specificity of the hybridization was confirmed by absence of autoradiographic signals after ribonuclease predigestion, addition of an excess of non-labeled probes, or application of an M 13 probe. The hepatocytes with HCV RNA-positive signals were scattered in the periportal and mediolobular zones of liver lobules rather than in the pericentral zones. Fifteen out of 33 biopsy specimens from patients with chronic HCV infection studied had the HCV RNA-positive hepatocytes. These cells were more frequently detected in specimens with advanced periportal, bridging and intralobular necrosis but showed no correlation with the extent of inflammatory cell infiltration. These findings suggest a close correlation between the detection of HCV RNA in hepatocytes and advanced necrosis of the specimens.

Adult↗
PubMed1993

Serodiagnosis of chronic hepatitis C in Japan by second-generation recombinant immunoblot assay.

The seroprevalence of antibodies to hepatitis C virus (HCV) by a second-generation recombinant immunoblot assay (RIBA-2) was tested using 4 recombinant antigens. The results were correlated with those of C100-3 enzyme-linked immunosorbent assay (ELISA) and with the detection of HCV-RNA sequences by the polymerase chain reaction. Sera were obtained from 27 C100-3 ELISA-positive Japanese patients with chronic non-A, non-B liver disease and from 29 C100-3 ELISA-negative patients. All C100-3 ELISA-positive patients and 19 (66%) out of 29 C100-3 ELISA-negative patients reacted to two or more RIBA-2 antigens (reactive by RIBA-2). Of the remaining 10 C100-3 ELISA-negative patients, one patient reacted to just one antigen (indeterminate by RIBA-2), while 9 reacted to none of the 4 antigens (non-reactive by RIBA-2). Forty-three (93%) of the 46 RIBA-2-reactive patients and the single RIBA-2-indeterminate patient tested positive for HCV-RNA sequences, whereas only one (11%) of the 9 RIBA-2-non-reactive patients tested positive. These findings indicate that HCV infection is more prevalent than expected from the results of C100-3 ELISA, and that RIBA-2 is a more sensitive assay for estimating the presence of HCV infection in chronic liver disease.

Aged↗
PubMed1993

Expression of DNA methyltransferase in LEC rats during hepatocarcinogenesis.

The Long-Evans with a cinnamon-like color (LEC) rat is a mutant of the Long-Evans strain that develops hereditary hepatitis and hepatoma with ageing. Age-related changes in the mRNA expression of DNA methyltransferase (DNA MTase) were examined in livers of LEC rats using Long Evans with an agouti color (LEA) rats as controls. A dramatic increase in the expression of this mRNA was observed in LEC rats at 20 weeks when acute hepatitis appeared. Their high mRNA levels were maintained until 52 weeks of age. The mRNA expression as well as DNA MTase activities were found to be higher in cancer lesions than in adjacent normal tissue. These increases may be related to liver regeneration and to early events in cellular transformation of LEC rats.

Aging↗
PubMed1993

Measurement of redox states of mitochondrial cytochrome aa3 in regions of liver lobule by reflectance microspectroscopy.

To evaluate the sublobular distribution of oxygen tension, the redox states of mitochondrial cytochrome aa3 were assessed in local regions of the liver lobule by reflectance microspectroscopy. The reflected light from two focused microspots (20 microns in diam) on the surface of the perfused liver, placed on the stage of microscope, was conducted to the spectrophotometer with two separate light guides, giving the reflectance spectra. The redox state of cytochrome aa3 was calculated from the difference in reflectance between 603 and 630 nm. The degree of cytochrome reduction increased with the stepwise decline of the influent or effluent oxygen concentrations. The local oxygen concentration in periportal region for the half-maximal reduction of cytochrome aa3 was higher than that in pericentral region. In addition, the degree of cytochrome aa3 reduction increased with the distance from the periportal region, reflecting a physiological gradient of oxygen tension along the sinusoidal flow, although with an intersinusoidal heterogeneity within liver lobule.

Animals↗
PubMed1993

Roles of endothelin-1 and nitric oxide in the mechanism for ethanol-induced vasoconstriction in rat liver.

This study was designed to investigate the mechanism for ethanol-induced hepatic vasoconstriction in isolated perfused rat liver. Upon initiation of ethanol infusion into the portal vein at concentrations ranging from 25 to 100 mM, portal pressure began to increase in a concentration-dependent manner and reached maximal levels in 2-5 min (initial phase), followed by a gradual decrease over the period of ethanol infusion (escape phenomenon). Endothelin-1 antiserum significantly inhibited this ethanol-induced hepatic vasoconstriction by 45-80%. Cessation of infusion of endothelin-1 antiserum was followed by a subsequent increase in portal pressure. On the other hand, when a nitric oxide synthesis inhibitor, NG-monomethyl-L-arginine (L-NMMA), was infused into the portal vein simultaneously with ethanol, the initial phase of the response of portal pressure to ethanol was not altered and the peak values of portal pressure remained unchanged. However, after the peak increase in portal pressure, the rate of decrease was less than in the absence of L-NMMA. Thus, L-NMMA diminished the escape phenomenon and sustained the vasoconstriction. This study supports the hypothesis that two endothelium-derived vasoactive factors, endothelin-1 and nitric oxide, regulate hepatic vascular tone in the presence of ethanol.

Animals↗
PubMed1993

[Serodiagnosis of hepatitis C by a recombinant hepatitis C virus protein].

Anti-HCV prevalence was high in chronic non-A, non-B liver disease. Anti-C100-3 was detected frequently in each category of chronic non-A, non-B liver disease. Antibody to HCV core protein was detected more frequently in 95% with high titers. A significant correlation was observed between the occurrence of high titers of antibody to HCV core and serum HCV RNA positivity. In patients negative by the anti-C100-3 assay, 69% were anti-HCV-positive by the second-generation enzyme-linked immunosorbent assay and also positive by the reverse transcription-polymerase chain reaction. Thus, HCV is a major causative agent of chronic non-A, non-B hepatitis in Japan.

Antigens, Viral↗
PubMed1993

Changes in antibodies to specific hepatitis C virus antigens with interferon-alpha therapy: analysis by recombinant immunoblot assay.

Antibodies to hepatitis C virus NS3 (C33C), NS4 (5-1-1 and C100-3), and core (C22-3) proteins were tested for by a second-generation recombinant immunoblot assay of serum samples from 42 chronic hepatitis C patients treated with interferon-alpha. Antibodies to 5-1-1 and C100-3 were found in 83% (35/42) before therapy, and those to C22-3 and C33C in all patients. At 6 months after therapy withdrawal in patients with sustained virus clearance, only antibodies to 5-1-1 and C100-3 showed significant decreases (p < 0.05) (5/5 and 7/7, respectively). Antibodies to C22-3 and C33C decreased less frequently in only 11% (1/9) (p < 0.01) and 44% (4/9) (p < 0.05), respectively. Thus, antibodies to 5-1-1 and C100-3 are prone to decrease following a decline in viremia. The antibody to the C22-3 (core) protein was least likely to decrease and may serve as a reliable marker of exposure to the virus.

Adult↗
PubMed1993

Quantitative analysis of antibodies to hepatitis C virus during interferon-alpha therapy.

We quantified IgG antibodies to structural (core) and nonstructural (C100-3) hepatitis C virus proteins in 42 patients with chronic hepatitis C treated with a 6-mo course of interferon-alpha. Sera were drawn before and at the end of therapy and also 6 mo after therapy withdrawal; they were stored for later analysis of antibodies and serum hepatitis C virus RNA. Sustained virus clearance was observed at the end of therapy and 6 mo after therapy withdrawal in nine cases; it was accompanied with sustained reductions of antibody to hepatitis C virus core protein and antibody to C100-3 protein. A sustained reduction of antibody to hepatitis C virus core protein was specific to sustained virus clearance, although that of antibody to C100-3 protein was not. None of the patients who did not show reductions of levels of both antibodies at the end of therapy displayed sustained virus clearance. Five patients showed hepatitis C virus RNA negativity and normal aminotransferase levels at the end of therapy without reduction of antibody to hepatitis C virus core protein levels. Of these five patients, relapse of hepatitis occurred in four, and viremia was present 6 mo after therapy withdrawal in all cases. These results demonstrate that testing for antibody titers may add information for evaluating virus clearance after interferon therapy.

Adult↗
PubMed1993

Evaluation of effective portal venous flow in chronic liver diseases using echo-Doppler flowmetry combined with per jejunal portal scintigraphy.

Portal circulation changes due to the progression of chronic liver disease and portal venous flow are also affected by pharmacotherapy. Thus, noninvasive measurement of effective portal venous flow (EPVF) is highly desirable. We evaluated EPVF under steady-state conditions using echo-Doppler flowmetry combined with per jejunal portal scintigraphy in 32 patients with chronic liver disease. After introduodenal administration of 37 MBq (1 mCi) of 123I-iodoamphetamine, scintigraphy of the pulmonary and hepatic regions was performed and a portosystemic shunt index (SI) calculated. EPVF was calculated as follows: EPVF = PVFx (1-SI/100). EPVF in chronic hepatitis, compensated cirrhosis and decompensated cirrhosis was 12.0 +/- 1.8 ml/min/kg, 10.3 +/- 1.6 ml/min/kg and 8.0 +/- 2.5 ml/min/kg, respectively. There were significant differences in EPVF between all groups, although PVF was similar in each group. EPVF correlated with liver function tests and was a better indicator of liver function than PVF. Measurement of EPVF may provide useful information in the management of patients with chronic liver disease.

Adult↗
PubMed1993

[Expression of the protein kinase C genes during liver regeneration].

Protein kinase C (PKC) plays an important role in intracellular signaling. PKC consists of a family of at least eight distinct enzymes. How PKC can be responded to liver regeneration and growth is largely unknown. In an in vivo experiment, regenerating liver after partial hepatectomy (Hx) and carbon tetrachloride (CCl4) administration, expression of the PKC alpha-type was increased, with a single peak, after Hx and CCl4 administration. On the other hand, the PKC epsilon-type gene was activated with biphasic peaks following Hx but was elevated with a single peak after the CCl4 administration. In an in vitro experiment using primary cultured hepatocytes, both of the PKC alpha-type and epsilon-type genes could be induced only by combination of insulin and serum. These results demonstrate that both isoforms of PKC are identically regulated by extra- and intracellular stimuli, thereby influencing growth control of hepatocytes.

Animals↗
PubMed1993

Evaluation of structural change in diffuse liver disease with frequency domain analysis of ultrasound.

To evaluate structural changes in diffuse liver disease, frequency domain analysis was applied to ultrasonic signals from the liver. We assumed that liver tissue is a collection of semiregularly arrayed small scatterers of ultrasound. We applied cepstral analysis to the ultrasonic waveforms and evaluated the periodicity of scalloping of the power spectrum caused by an interference effect among liver scatterers of a given spacing. Patients with liver conditions involving nonspecific change (n = 6), chronic hepatitis (n = 11), cirrhosis (n = 7) or fatty liver (n = 6) were examined. One hundred ultrasonic signals were obtained noninvasively with a 3.5-MHz transducer, and the space among scatterers was calculated for each signal using cepstrum analysis. Two statistical parameters, mode and kurtosis, were determined from the distribution of the space among scatterers for each patient; these parameters were compared with the histological findings in the liver. Space among scatterers kurtosis decreased with progress of liver fibrosis, and space among scatterers mode increased in cirrhosis. Neither space among scatterers kurtosis nor space among scatterers mode was affected by pathological fat in the liver. These results suggest that we can evaluate fibrotic changes in diffuse liver disease and that we can also noninvasively discriminate diffuse fibrotic liver disease from fatty liver.

Chronic Disease↗
PubMed1992

Enhancement of hepatitis-B surface-antigen expression by 5-azacytidine in a hepatitis-B-virus-transfected cell line.

The human hepatoblastoma-derived cell line HB611 secretes hepatitis-B surface antigen (HBsAg) and hepatitis-B e antigen (HBeAg) into the medium. Hepatitis-B-virus (HBV) DNA integrated into the cellular genome was found to be hypermethylated. When the cells were treated with 5-azacytidine for 3 days, the level of HBsAg in the medium increased, while the level of HBeAg remained constant. The level of alpha-fetoprotein (AFP) decreased with the 5-azacytidine treatment. Southern blot analysis of DNA digested with HpaII or MspI showed that 5-azacytidine treatment resulted in hypomethylation of the integrated HBV DNA, suggesting that 5-azacytidine increased HBsAg production in the cells through hypomethylation of the HBV genomic DNA.

Azacitidine↗
PubMed1992

Ammonia: a possible promotor in Helicobacter pylori-related gastric carcinogenesis.

Helicobacter pylori (HP) has been shown to possibly be a pathogen of gastric carcinoma. HP has urease activity and produces ammonia in the stomach. In this study, the role of ammonia on gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) were investigated in rats. After 24 weeks pretreatment with MNNG (83 mg/l), 0.01% ammonia or tap water as a drinking water was administered for 24 weeks. The ammonia-treated rats showed a significantly higher incidence of gastric cancer (percent of animals with tumors and number of tumors per rat). Ammonia would thus appear to have an important role in HP-related human gastric carcinogenesis.

Adenocarcinoma↗