[Acute gastric mucosal lesion].
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Acute Disease↗
Biomedical subjects
H Fusamoto
Publications and source records attributed to H Fusamoto.
Selective suppression of N-acetylglucosaminyltransferase III activity in a human hepatoblastoma cell line transfected with hepatitis B virus.
UDP-N-acetylglucosamine: beta-D-mannoside beta-1,4-N-acetylglucosaminyl-transferase III (GnT-III) is a key enzyme in the branching of asparagine-linked oligosaccharides, which are present in surface membrane proteins of various tissues and in secretory glycoproteins. The activity of GnT-III was assayed in 2 human hepatoblastoma cell lines, Huh6, which was the parental cell line, and HB611, which was established by transfection of 3 tandem copies of the hepatitis B virus genome into Huh6. A significant difference in GnT-III activity was found between Huh6 and HB611 (136 +/- 18.3 pmol/h/mg versus 6.7 +/- 2.4 pmol/h/mg; mean +/- SD, P < 0.001), whereas levels of the glycosyltransferases alpha-3-D-mannoside beta-1,4-N-acetylglucosaminyltransferase IV, alpha-6-D-mannoside beta-1,6-N-acetylglucosaminyltransferase-V, and beta-1,4-galactosyltransferase were almost the same in both cell lines. Northern blot analysis indicated that the decreased activity of GnT-III in HB611 was due to the decreased transcript. When HB611 was treated with interferon-alpha, expression of hepatitis B virus-related mRNA decreased, and the activity of GnT-III increased from 8.5 +/- 3.8 to 22.0 +/- 7.2 pmol/h/mg (mean +/- SD, P < 0.05). This increase was not found in Huh6. Binding capacity with erythrocyte phytohemagglutinin in these cells using fluorescence-activated cell sorter analysis was different, suggesting that the structure of sugar chain on the cell surface might be altered by suppression of GnT-III activity. This is the first report that hepatitis B virus selectively suppressed the GnT-III activity in hepatoblastoma cells.
Blotting, Northern↗
[Etiological mechanism of hepatitis C].
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Autoimmunity↗
Endothelin-1 is involved in the pathogenesis of ischemia/reperfusion liver injury by hepatic microcirculatory disturbances.
Hepatic microcirculatory perturbation is observed after ischemia/reperfusion. Endothelin-1, a potent vasoconstrictive peptide, is known to modulate local circulation. This study was designed to examine whether endothelin-1 participates in the mechanism of microcirculatory disturbance and damage of the liver after ischemia/reperfusion. Ischemia in the median and left lateral lobes of the liver was induced for 60 min; it was followed by reperfusion for 24 hr. In some rats, endothelin-1 antiserum or control serum without endothelin-1-blocking activity was administered intravenously just before reperfusion. Rats were divided into three groups: an ischemia/reperfusion group that was injected with control serum, an endothelin-1 antiserum-treated group and a sham-operated group. Endothelin-1 concentrations in blood collected from the suprahepatic vena cava were measured before and after ischemia/reperfusion by use of a sandwich enzyme immunoassay. Index of blood volume in regional hepatic tissue and index of blood oxygenation in regional hepatic tissue were assessed with an organ reflectance spectrophotometry system before and at 5 min and 1, 2, and 24 hr after reperfusion. The endothelin-1 concentration in the ischemia/reperfusion group started to rise immediately at onset of reperfusion from basal values around 1 pg/ml and reached a value of 5 to 6 pg/ml 5 min after reperfusion; it was maintained at significantly high levels during the reperfusion period compared with the sham-operated group. Hepatic microcirculatory disturbance indicated by lowered index of blood volume in regional hepatic tissue and index of blood oxygenation in regional hepatic tissue levels was observed in the early phase of reperfusion in the ischemia/reperfusion group.(ABSTRACT TRUNCATED AT 250 WORDS)
Alanine Transaminase↗
Characterization of signaling pathways to Na+/H+ exchanger activation with epidermal growth factor in hepatocytes.
To investigate the signaling pathways to Na+/H+ exchanger activation with epidermal growth factor in hepatocytes, we measured changes in cytosolic free calcium and intracellular pH levels at the single-cell level using digital imaging fluorescence microscopy of fura-2- or BCECF-loaded hepatocytes in primary culture. Epidermal growth factor induced cytosolic free calcium oscillations consisting of periodic trains of spikes with a latency period of up to several minutes. These calcium responses were inhibited by tyrosine kinase inhibitor genistein (100 mumol/L) and abolished by emptying of intracellular Ca2+ pools with 3 mumol/L thapsigargin, an inhibitor of Ca(2+)-ATPase on the endoplasmic reticulum. Epidermal growth factor (1 nmol/L) induced an intracellular pH increase of 0.12 +/- 0.07 units from the basal level of 7.25 +/- 0.09 units after several minutes of latency. This effect was completely abolished by 1 mmol/L amiloride, an inhibitor of the Na+/H+ exchanger. The epidermal growth factor-induced intracellular pH increase was inhibited by pretreatment of hepatocytes with genistein (100 mumol/L), thapsigargin (3 mumol/L) or calmodulin inhibitor W-7 (25 mumol/L), but not with protein kinase C inhibitor H-7 (50 mumol/L) or with cyclic AMP-dependent kinase inhibitor H-8 (60 mumol/L). Phorbol ester PMA (phorbol 12-myristate 13-acetate), a potent activator of protein kinase C, induced a slight intracellular pH increase significantly smaller than that with epidermal growth factor, whereas this effect was completely blocked by pretreatment with H-7, indicating that PMA-induced intracellular pH increase is mediated by protein kinase C pathways, unlike epidermal growth factor.(ABSTRACT TRUNCATED AT 250 WORDS)
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
Predicting interferon therapy efficacy from hepatitis C virus genotype and RNA titer.
We classified 53 Japanese patients with chronic hepatitis C who were treated with natural interferon-alpha into genotypes and also tested the amounts of hepatitis C virus (HCV) RNA. The rate of the long-term complete response group, whose alanine aminotransferase levels remained within the normal range during the six months after therapy, was significantly higher (P < 0.01) in the type-III patients (4/5, 80.0%) than in type-II patients (4/43, 9.3%). For these long-term complete responders, the amounts of HCV RNA was less than 10(7) copies/ml serum in type-II patients, whereas two type-III patients with relatively high amounts of HCV RNA responded completely. These results confirm that the genotype of HCV is an important factor for predicting the response to interferon therapy. The amounts of HCV RNA can also predict its efficacy in type-II patients.
Adult↗
Impaired gastric mucosal energy metabolism in congestive gastropathy in cirrhotic patients.
To clarify the characteristics of congestive gastropathy, we investigated gastric mucosal hemodynamics and energy metabolism in cirrhotic patients, using a reflectance spectrophotometry system and high performance liquid chromatography. The index of the gastric mucosal blood volume of cirrhotic patients with esophageal varices was significantly higher, and the index of gastric mucosal blood oxygenation significantly lower, than those in controls, thus indicating congestion and hypoxia in the gastric mucosa. Energy charge levels in the gastric mucosa of cirrhotic patients with esophageal varices were also significantly decreased. The energy charge level showed a strong linear correlation with the index of mucosal blood oxygenation in the antral (r = 0.996, P < 0.01) and body (r = 0.994, P < 0.01) mucosa of the stomach. These findings suggest that congestive gastropathy in a portal hypertensive state causes hypoxia in the gastric mucosa, leading to a mucosal energy deficit that may increase mucosal susceptibility to aggressive factors.
Chromatography, High Pressure Liquid↗
Serial quantitative analysis of serum hepatitis C virus RNA level in patients with acute and chronic hepatitis C.
To examine changes in the serum level of hepatitis C virus RNA in acute and chronic phases of hepatitis C virus infection, we tested serial serum samples of six patients with acute hepatitis C (posttransfusion: three; sporadic: three) and 11 patients with chronic hepatitis C using a competitive reverse transcription and polymerase chain reaction assay. The internal standard consisted of known amounts of synthetic mutated RNA. No patient with acute hepatitis showed resolution during the follow-up period (24-57 weeks). In posttransfusion cases, titers of hepatitis C virus RNA (log10[hepatitis C virus RNA copies/ml serum]) rose to a high level (7.5-9.5) in the early phase of infection (4-12 weeks after the transfusions) in association with the first serum alanine aminotransferase peaks. Titers of hepatitis C virus RNA then decreased, while serum alanine aminotransferase levels fluctuated with multiple peaks. In sporadic cases, titers of hepatitis C virus RNA had already reached a high level (7.0-7.5) at the first alanine aminotransferase peaks 2-3 weeks after the clinical onset. In chronic hepatitis C virus infection, titers of hepatitis C virus RNA remained high for follow-up periods of 6-12 years in patients with chronic active hepatitis. These results indicate that the replication of hepatitis C virus rose to a high level in the early phase of infection and that a high replicative level of hepatitis C virus might be related with progression of liver disease in the chronic phase of infection.
Acute Disease↗
Hepatitis C virus genotype and RNA titer in the progression of type C chronic liver disease.
Hepatitis C virus genotype and the amounts of circulating HCV RNA are the most important factors in determining the efficacy of interferon therapy for chronic hepatitis C. To clarify the correlation of these two factors to the progression of liver disease, we classified 148 Japanese patients with type C chronic liver disease into genotypes and also measured their HCV RNA titers (logarithmic transformed copy number/ml serum) by competitive reverse transcription-polymerase chain reaction. We found type II in 23 (76.7%) of 30 patients with chronic persistent hepatitis, 34 (79.1%) of 43 with chronic active hepatitis, 29 (72.5%) of 40 with cirrhosis and 30 (85.7%) of 35 with hepatocellular carcinoma. Thus, there was no significant difference in the prevalence of type II among the various stages of chronic liver disease. We also found the RNA titer to be significantly higher in patients with chronic active hepatitis (8.0 +/- 0.8) than in those with chronic persistent hepatitis (7.0 +/- 1.0, p < 0.001), and also those with cirrhosis (7.6 +/- 0.8, p < 0.05) or hepatocellular carcinoma (7.7 +/- 0.8, p < 0.05). When the titers were compared among genotypes, there was no significant difference between type II and III at any stage (type II vs. type III: chronic persistent hepatitis, 7.2 +/- 1.0 vs. 6.7 +/- 0.8; chronic active hepatitis, 8.1 +/- 0.7 vs. 7.8 +/- 1.0; cirrhosis, 7.7 +/- 0.8 vs. 7.8 +/- 0.7; hepatocellular carcinoma, 7.7 +/- 0.8 vs. 7.8 +/- 0.5). In conclusion, although genotype affects interferon therapy efficacy, it seems to have little influence on serum RNA levels and the progression of type C chronic liver disease.
Adult↗
Hepatitis C virus replication and antibodies to structural and nonstructural viral proteins in chronic hepatitis C.
The correlation between hepatitis C virus replication and antibodies to both structural (core) and nonstructural (C100-3) hepatitis C virus proteins (anti-HCVcore and anti-C100-3, respectively) was assessed. The concentration of serum hepatitis C virus RNA was determined by a competitive reverse transcription-polymerase chain reaction assay, and antibody titers were determined by endpoint dilution. No correlation was found between viremic levels and antibody titers in 42 chronic hepatitis C patients. At the end of a 6-month course of interferon-alpha therapy, 18 patients became negative for hepatitis C virus RNA. In the other 24 patients, post-treatment viremic levels ranged from 10(-6.5)-10(0.5) of pretreatment levels. Both anti-C100-3 and anti-HCVcore frequently decreased in patients whose viremic levels dropped to the negative range or to < 10(-2) of pretreatment levels. Anti-C100-3 decreased in all such cases (25/25), while anti-HCVcore decreased in 18/25 (72%) (p < 0.01), indicating that anti-C100-3 is more likely to decrease following suppression of viral replication than anti-HCVcore. These data suggest that hepatitis C virus antibodies may serve as a marker of suppression of viremia following interferon therapy even in patients who do not clear the virus.
Adult↗
Hepatitis C virus antibody and hepatitis C virus replication in chronic hepatitis B patients.
We assessed hepatitis C virus infection in 156 chronic hepatitis B patients using second-generation hepatitis C virus antibody (anti-HCV). Active virus replication was further investigated in anti-HCV-positive cases by means of polymerase chain reaction assay for the detection of serum hepatitis C virus RNA. Anti-HCV prevalence was higher in patients negative for hepatitis B e antigen (HBeAg) (10/48, 21%) than in HBeAg-positive patients (10/108, 9%) (p < 0.05), and the reactivity (cut-off index) in anti-HCV enzyme-linked immunosorbent assay of the positive cases was significantly higher in HBeAg-negative patients (4.1 +/- 0.1) than in -positive ones (3.6 +/- 0.6) (p < 0.05). The prevalence of hepatitis C virus RNA in anti-HCV-positive cases was also higher in the HBeAg-negative group (9/10, 90%) than in the -positive group (3/10, 30%) (p < 0.01). Viremia was found in association with high reactivity in anti-HCV ELISA (cut-off index > 3.5) in both groups. Nine (90%) of 10 such cases were viremic in the HBeAg-negative group compared with three (43%) of seven in the HBeAg-positive group (p < 0.05). These results suggest that hepatitis C virus replication may be influenced by hepatitis B virus replicative states, indicating possible interference between hepatitis B and C viruses.
Adult↗
IgG and IgM core antibodies and viral replication in hepatitis C virus carriers.
We studied IgG and IgM antibodies to hepatitis C virus core protein (anti-HCVcore) in relation to serum virus RNA levels in 71 hepatitis C virus carriers. Viremic levels ranged from 10(4)-10(9) copies/ml and were high in 34 chronic active hepatitis patients compared with 17 asymptomatic carriers and 20 cases of chronic persistent hepatitis (p < 0.01). IgG anti-HCVcore was found in 67/71 (94%), but four asymptomatic carriers with low levels of viremia (10(4)-10(5.5) copies/ml) tested negative. IgM anti-HCVcore was found in patients with high levels of viremia (10(8)-10(9) copies/ml), and one (6%) asymptomatic carrier and nine (26%) chronic active hepatitis patients tested positive. In chronic hepatitis patients, viremic levels were significantly higher in cases positive for IgM anti-HCVcore than in negative ones (p < 0.01). However, no correlation was found between the occurrence of IgM anti-HCVcore and serum aminotransferase levels or the histologic activity index. These findings suggest that although IgG anti-HCVcore is sensitive, low viremic patients can escape this screening, and that the IgM anti-HCVcore is induced in association with high levels of virus replication.
Adult↗
Identification and diameter assessment of gastric submucosal vessels using infrared electronic endoscopy.
In this study, an electronic endoscope was applied for observation of gastric submucosal vessels, with infrared illumination, in anesthetized dogs. An in-vivo spectrophotometry showed that infrared light at 620-820 nm penetrates the abdominal and gastric wall. During the endoscopy performed in dogs, the infrared radiation penetrated the abdominal wall and gastric wall from the outside, and was detected by the endoscope's charge-coupled device. A television monitor displayed a network of gastric vasculature, which was identified as veins in the gastric wall by injecting saline or indocyanine green into the vein. Using this system, it was possible to measure venous diameters of more than 0.2 mm by comparison with a reference wire. The diameter obtained by the image analysis correlated lineally to that of a vascular template prepared from the same stomach. Thus, it may become possible to assess gastric submucosal hemodynamics using infrared endoscopy, a new application in electronic endoscopy.
Abdominal Muscles↗
Hepatitis C virus antibodies and virus replication in asymptomatic blood donors.
We assessed hepatitis C virus (HCV) infection in 99 asymptomatic blood donors positive using a first-generation HCV antibody assay. When tested with second-generation assays, 86 (87%) donors were reactive (group 1), 2 (2%) were indeterminate (group 2), and 11 (11%) were non-reactive (group 3). Viraemia was revealed by polymerase chain reaction in all group 1 cases. The 2 group 2 cases and 6 (55%) group 3 cases were also viraemic. Viraemia was confirmed by a branched DNA assay in the 2 group 2 cases and 4 (36%) group 3 cases. Serum HCV RNA levels were further studied using a competitive reverse transcription-polymerase chain reaction assay. All cases in groups 2 and 3 were low viraemic (range 10(4)-10(5.5) copies/ml) compared with the 9 group 1 cases examined (range 10(7)-10(9) copies/ml). No correlation was evident between viraemic levels and antibody cut-off index in the first-generation assay. These findings indicate the possibility that low levels of viraemia can occur in individuals non-reactive in second-generation HCV antibody assays.
Adult↗
Endothelin-1 is involved in hepatic sinusoidal vasoconstriction after ischemia and reperfusion.
Endothelin-1 (ET-1), a vasoactive peptide, causes a significant rise in portal vein pressure, which is most likely a result of severe vasoconstriction in the liver. In this study, the effect of ET-1 on sinusoidal vasoconstriction in the liver after ischemia and reperfusion was directly investigated using intravital microscopy. In anesthetized female Sprague Dawley rats (200-250 g) ischemia of the median and left liver lobes was induced for 90 min by temporary ligation of the left pedicle. After declamping and a 90-min reperfusion period, the livers were exposed for intravital microscopy. Using a Nikon MM-11 fluorescence microscope (545 nm, 330x), a CCD camera (Cohu FK 6990), and a SVHS video recording unit, the hepatic microcirculation was directly investigated. Besides sham groups, two ischemia groups were studied, receiving ET-1 antiserum (anti-ET-1; 0.5 ml; Peptide Inst., Osaka, Japan) or NaCl 0.9% (0.5 ml) 5 min prior to reperfusion of the liver (n = 6/group). Following a transient drop in the mean arterial blood pressure in the anti-ET-1-treated groups, comparable systemic hemodynamic conditions among the four groups were noted during intravital microscopic assessment at the end of the 90-min reperfusion period. Reduction in the sinusoidal diameters during postischemic reperfusion (7.7 +/- 0.5 microm) was prevented by anti-ET-1 treatment (9.6 +/- 0.25 microm; P < 0.01; mean + SEM) back to control values (9.6 +/- 0.32 microm), while most of other microcirculatory parameters did not show significant differences. The results supported further the role of ET-1 in dysregulation of the sinusoidal vascular tone in the liver, e.g., after ischemia and reperfusion.
Animals↗
Effects of hepatitis B virus antigens on interferon-gamma production of peripheral blood mononuclear cells from hepatitis B virus carriers and healthy individuals.
BACKGROUND: Although the precise mechanisms of persistent infection by hepatitis B virus are not yet known, several lines of studies suggest that hepatitis B e antigen in sera might modulate the immune response of the host. The aim of this study was to clarify the effects of hepatitis B virus antigen on cytokine production of lymphocytes. METHODS: We studied the effects of recombinant hepatitis B core antigen and surface antigen on interferon-gamma production of phytohemagglutinin-stimulated peripheral blood mononuclear cells from hepatitis B virus carriers and healthy individuals. Hepatitis B core antigen used in this study shared the antigenic site responsible for hepatitis B core and e antigen. RESULTS: Although pre-incubation of peripheral blood mononuclear cells with hepatitis B core/e antigen followed by stimulation with phytohemagglutinin significantly reduced the production of interferon-gamma, pre-incubation with hepatitis B surface antigen did not affect them. CONCLUSIONS: These results indicate that hepatitis B core/e antigen has the ability to inhibit interferon-gamma production of lectin-stimulated peripheral blood mononuclear cells in vitro, suggesting that secretion of hepatitis B e antigen into sera might be how hepatitis B virus escapes the immuno-surveillance system of the host.
Adult↗
Immunohistochemical detection of Fas antigen in liver tissue of patients with chronic hepatitis C.
Apoptosis is a type of cell death that occurs in acute or chronic hepatitis. It has been suggested to be mediated through Fas antigen. To evaluate the role of apoptosis on liver injury of chronic hepatitis C, we studied the expressions of Fas antigen and hepatitis C virus antigen (core antigen) immunohistochemically. Forty liver biopsy samples from patients with type C chronic liver disease were immunostained for Fas antigen and hepatitis C virus antigen. Expression of Fas antigen was found mainly in the cytoplasm of hepatocytes, and these positive cells were found particularly among infiltrating lymphocytes at the advancing edges of "piecemeal necrosis." The histological activity index showed inflammation of both portal and periportal areas to be more severe in the Fas antigen-positive samples than in the Fas antigen-negative ones (p < 0.05 and p < 0.001, respectively). Furthermore, semiquantitative analysis revealed more expression of Fas antigen in the liver tissues with active inflammation than in those without it (p < 0.01). The prevalence of Fas antigen expression in the hepatitis C virus antigen-positive group was higher than that in the hepatitis C virus antigen-negative group (p < 0.05). Our findings suggest that Fas antigen expression (apoptosis) plays an important role in inflammation in the hepatitis C virus-infected liver, particularly in the active inflammation of chronic hepatitis C.
Adolescent↗
Hepatitis C virus replication and antibody responses toward specific hepatitis C virus proteins.
We assessed the correlation between hepatitis C virus replication and antibody responses toward hepatitis C virus core (C22-3), NS3 (C33C), NS4 (5-1-1 and C100-3) and NS5 proteins in 59 virus carriers. The concentration of serum hepatitis C virus RNA was determined by a competitive reverse transcription-polymerase chain reaction assay. All 50 patients with high viremic levels of > or = 10(6) copies/mL had antibodies to C22-3 and C33C. Antibodies to 5-1-1, C100-3 and NS5 proteins were detected less frequently (p < 0.01) in 72% (36 of 50), 78% (39 of 50) and 84% (32 of 38) of such patients, respectively. As for the nine patients with low viremic levels of < 10(6) copies/mL, antibodies to C22-3, C33C, 5-1-1 and NS5 proteins were detected in only one patient (11%), which was significantly less than the frequency for highly viremic patients (p < 0.01). Antibody to C100-3 was also found less frequently in only four patients (44%) (p < 0.05). Thus, only four (44%) of the nine low viremic patients tested positive for any antibody compared with all 50 highly viremic patients (p < 0.01). These results indicate that highly viremic carriers can be detected by the presence of hepatitis C virus antibodies, but a considerable proportion of low viremic carriers may not show any serological evidence of hepatitis C virus infection.
Adult↗