Monocyte chemoattractant protein 1 (MCP-1) released from Helicobacter pylori stimulated gastric epithelial cells induces cyclooxygenase 2 expression and activation in T cells.

BACKGROUND: and aims: To clarify the interaction between gastric epithelial and mucosal T cells, we examined the role of cytokines released from epithelial cells in response to Helicobacter pylori water extract protein (HPWEP) in regulating T cell cyclooxygenase 2 (COX-2) expression and activation. METHODS: Media from MKN-28 cells incubated with HPWEP for 48 hours were added to Jurkat T cells and human peripheral T cells. C-C and CXC chemokine concentrations in MKN-28 cell media, and COX-2 expression, interferon gamma (IFN-gamma), and interleukin (IL)-4 secretions in T cells were determined by western blot analysis and ELISA methods. Distributions of COX-2 positive T cells and monocyte chemoattractant protein 1 (MCP-1) in tissue specimens with H pylori associated gastritis were determined as single or double labelling by immunohistochemistry. RESULTS: MCP-1, IL-7, IL-8, and RANTES were detected in media from MKN-28 cells incubated with HPWEP. Media as a whole, and MCP-1 alone, stimulated COX-2 expression and peripheral T cell proliferation. Anti-MCP-1 antibody inhibited media stimulated COX-2 mRNA expression in Jurkat T cells. Media stimulated IFN-gamma but not IL-4 secretion from peripheral T cells, while MCP-1 stimulated IL-4 but not IFN-gamma secretion. Both stimulated cytokine release, and peripheral T cell proliferation was partially inhibited by NS-398, a specific COX-2 inhibitor. In mucosa with gastritis, COX-2 was expressed in T cells and MCP-1 was localised mainly in epithelial and mononuclear cells. MCP-1 levels and the intensity of COX-2 expression in tissue samples were closely related. CONCLUSIONS: Cytokines such as MCP-1, released from gastric epithelial cells in response to HPWEP, seem to modulate T cell immune responses, at least in part via COX-2 expression.

Effect of acid suppression therapy on development of gastric erosions after cure of Helicobacter pylori infection.

BACKGROUND: Helicobacter pylori eradication markedly improves histological inflammation and decreases peptic ulcer recurrence, but little is known about the subsequent development of gastric mucosal injury. AIM: To investigate whether acid suppression treatment after eradication influences the development of gastric erosions. METHODS: Eighty-one patients (gastritis or peptic ulcer) after successful H. pylori eradication were divided into two groups: 40 received an H2-blocker for 6 months (H2-blocker-positive) and 41 received no treatment (H2-blocker-negative). Endoscopy was performed before, and at 3 and 6 months after completion of eradication. RESULTS: Cumulative prevalence of gastric erosions in the H2-blocker-positive group was significantly lower than in the H2-blocker-negative group, 25% vs. 42%, respectively. In the H2-blocker-negative group but not the H2-blocker-positive group, the cumulative prevalence of gastric erosions after eradication was higher in patients with less severe corpus atrophy or more severe corpus gastritis. CONCLUSIONS: Development of gastric erosions after H. pylori eradication may be controlled by acid suppression treatment. Less severe atrophy or more severe gastritis in oxyntic glands before eradication may be involved in the development of gastric erosions. These results support the idea that recovery of acid secretion may be one of factors for development of gastric mucosal erosions after successful eradication.

Aged Budd-Chiari syndrome attributed to chronic deep venous thrombosis with alcoholic liver cirrhosis.

Budd-Chiari syndrome is a rare disease, but there are many known causes. Recent studies showed that it can be an acquired lesion resulting from thrombosis in some elderly patients. We report a 74-year-old man with Budd-Chiari syndrome attributed to chronic deep venous thrombosis and alcoholic liver cirrhosis. When he was aged 45 years, stasis ulcers of the lower extremities appeared. Cerebral infarction and left hemiparesis occurred at age 71. Ultrasonography, venacavography, and three-dimensional-magnetic resonance imaging on admission demonstrated total obstruction of the inferior vena cava with several massive thrombi and developed collateral vessels. Although the etiology of the thrombosis remained obscure, we made some speculative assumptions that chronic disseminated intravascular coagulation (which is frequently observed in cirrhosis) or hereditary coagulopathy could be involved, from his familial history of thrombotic phenomena and a severe deficiency of clotting inhibitors. Despite the high mortality of untreated Budd-Chiari syndrome reported in previous studies, this patient had been alive for about 30 years from the suspected onset.

Highly efficient recovery of functional single-chain Fv fragments from inclusion bodies overexpressed in Escherichia coli by controlled introduction of oxidizing reagent--application to a human single-chain Fv fragment.

An improved and efficient refolding system for a single-chain antibody fragment (scFv) from inclusion bodies expressed in Escherichia coli was developed. Stepwise removal of denaturing reagent and controlled addition of oxidizing reagent were found to be the most effective conditions to achieve for almost complete recovery of functional monomeric scFv from inclusion bodies. Adding L-arginine to the refolding solution also increased the yield of refolded functional scFv. The single-chain Fv fragments of both a mouse anti-lysozyme monoclonal antibody, HyHEL10, and a human monoclonal antibody against the D antigen of the Rh blood group, D10, in solubilized inclusion bodies could be refolded under these conditions with yields of up to 95%. The refolding procedures developed in this study will contribute to providing a stable supply of large amounts of human single-chain Fv fragments.