UDP-galactosyltransferase (UDP-Gal-T) is a key enzyme in the synthesis of mucus glycoproteins, which play an important role in gastric mucosal defensive mechanisms. Helicobacter pylori (HP) induces gastritis and peptic ulcers, but mechanisms of HP-induced mucosal injury are not fully understood. To elucidate the mechanism whereby (HP) infection induces gastric mucosal injury, we investigated the effects of HP on the gastric mucosal defensive mechanism by measuring UDP-Gal-T activities in HGC-27, a mucin-producing gastric cancer cell line, treated with various HP-related materials (sonicated HP, HP culture supernatants, live HP). HP-related materials induced no significant changes in UDP-Gal-T activity, but the enzyme increased when we generated a low concentration of ammonia by adding sonicated HP and urea simultaneously. In contrast, UDP-Gal-T activity did not increase when we added live HP instead of sonicated HP. Next, we investigated the effects of HP on ethanol-induced injury in HGC-27 cells. Pretreatment with ammonia of a low concentration significantly protected cells from ethanol-induced injury. In contrast, pretreatment with live HP and urea generated ammonia of the similar concentration but did not protect cells from the injury. Our findings suggest that HP has an inhibitory effect against adaptive cytoprotection induced by ammonia by inhibiting the induction of UDP-Gal-T.
Gastric mucus glycoprotein is important for the protection of gastric mucosa from acid. UDP-galactosyltransferase (UDP-Gal-T) is a key enzyme for the synthesis of gastric mucus glycoprotein. In this study, we investigated the effects of five acid-secretion blockers, cimetidine, ranitidine, famotidine, roxatidine and omeprazole on the UDP-Gal-T activity in rat gastric mucosa to clarify the interaction of the acid-secretion blocker and the gastric mucosal barrier. Intraperitoneal administration of these drugs to rat increased pH of the gastric mucosal surface and significantly decreased the gastric UDP-Gal-T activities. When we administered citrate phosphate buffer (pH 2) to the rat stomach to inhibit the change of gastric pH induced by the acid-secretion blockers, the effects of famotidine, roxatidine and omeprazole on UDP-Gal-T activities were abolished, but cimetidine and ranitidine significantly decreased the enzyme activity. When we incubated the acid-secretion blockers with the homogenates of rat gastric mucosa, cimetidine and ranitidine significantly decreased UDP-Gal-T activities, whereas the other drugs showed no apparent influence on the enzyme activity. These findings suggest that the acid-secretion blockers decrease gastric mucin synthesis via the increase of the intragastric pH. In addition, among the acid-secretion blockers studied here, cimetidine and ranitidine also have direct inhibitory effects on the gastric UDP-Gal-T activity.
The aim of the present study is to analyze fatty acid composition in plasma phospholipids in patients with hepatocellular carcinoma (HCC) and liver cirrhosis (LC) and to elucidate the significance of polyunsaturated fatty acid on hepatocarcinogenesis. Arachidonic acid/Linoleic acid (AA/LA) molar ratios in plasma phosphatidylinositol in LC (1.42±0.29, p<0.01) and in HCC (1.24±0.12, p<0.001) were significantly lower than that in control subjects (2.78±0.16). The AA/LA molar ratio in plasma phosphatidylethanolamine in HCC (1.07±0.13) was significantly lower than that in control subjects (1.94±0.21, p<0.01). The plasma lysophosphatidylcholine (LysoPC) concentration in HCC (71.6±8.4nmol/ml, p<0.001) and in LC (80.9±12.0 nmol/ml, p<0.001) were significantly lower than that in control subjects (146.7±5.7nmol/ml). Plasma arachidonoyl-LysoPC was significantly higher in HCC (3.2±0.5mol%) compared with that in LC (1.5±0.3mol%, p<0.01) and in control subjects (1.9±0.lmol%, p<0.01). Plasma arachidonoyl-LysoPC may play an important role in the pathophysiology of HCC patients.
Antigen specific T-cell responses are important for the eradication of Hepatitis B virus (HBV) in acute infection. Flow cytometric analysis of intracellular cytokines is a simple method for studying the T-cell response at the single-cell level in a short period of time. In the present study, we invesfisated the hepatitis B virus (HBV)-specific T-cell response using flow cytometry. Eight patients with acute hepatitis B and 2 patients with fulminant hepatitis B were studied. Heparinized peripheral blood was incubated with recombinant HB core antigen (HBcAg), and intracytoplasmic cytokines were analyzed by flow cytometry. HBcAg-specific interferon-gamma positive CD4 T-cells were positive in 4 of 10 patients while HBcAg-specific interferon-gamma positive CD8 T-cells and interleukin-4 positive T-cells were negative in all patients. No intracytoplasmic cytokines were demonstrated in healthy subjects or with recombinant hepatitis C virus (HCV) antigens. HBcAg-specific CD4 T-cells could be detected by a sensitive flow cytometric analysis of the peripheral blood and the cytokine profile of these cells was Thl. These results suggest that HBcAg-specific Th1-type CD4 T-cells may play an important role in controlling viral clearance during acute HBV infection.
In the development of autoimmune chronic active hepatitis (AIH), the pathogenic relevance of autoimmune responses against asialoglycoprotein receptor (ASGPR) has been implicated. We have previously developed a capture enzyme-linked immunosorbent assay (ELISA) for detection of anti-ASGPR antibodies and found a high prevalence of anti-ASGPR antibodies in AIH and primary biliary cirrhosis (PBC). In this study, to clarify the clinical significance of the measurement of anti-ASGPR antibodies in autoimmune liver diseases we studied correlations between the titer of anti-ASGPR antibody and various laboratory data, activity and stage of the disease. We also determined the isotype of the anti-ASGPR antibody. In AIH, the anti-ASGPR antibody titer was positively correlated with serum γ-globulin and IgM values, but not with serum transaminase. The anti-ASGPR antibody titer in histologicallyactive disease with piecemeal necrosis was significantly higher than that in quiescent disease. The most common Isotype of anti-ASGPR antibodies detected in active AIH was IgM. We encountered a case of AIH where the titer of IgM anti-ASGPR antibody decreased by induction of remission with steroid therapy. These results suggest that the measurement of IgM isotype anti-ASGPR antibody might be useful for the evaluation of disease activity and effects of therapy in AIH patients.
Background/aims: Alterations of gastric mucin have been postulated as important pathogenic properties of Helicobacter pylori. In this study, we investigated gastric mucin synthesis in H. pylori-infected gastric mucosa by measuring UDP-galactosyltransferase (UDP-Gal-T) activity, a key enzyme for the synthesis of mucin, and the amount of intracellular mucin in the gastric mucosa. Methods: Gastric biopsy specimens were obtained from thirty-seven patients (20 H. pylori-positive and 17 H. pylori-negative). UDP-Gal-T activity of the biopsy specimens was measured by an assay system we had developed, using a peanut agglutinin lectin. The amount of intracellular mucin in the gastric epithelial cells was analyzed by measuring the cells' periodic acid-Schiff-alcian blue staining-positive substances. Results: UDP-Gal-T activities in the antral mucosa of H. pylori-positive patients were significantly lower than that of H. pylori-negative patients (p<0.05). The amount of intracellular mucin in the antral epithelial cells of H. pylori-positive patients was significantly lower than that of H. pylori-negative patients (p<0.01). Conclusions: H. pylori infection decreases gastric mucin synthesis by the inhibition of UDP-Gal-T activity. This effect may impair the gastric mucosal barrier and contribute to the mucosal injury induced by H. pylori infection.