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We studied the effects of acidic pH on the currents through voltage-gated K+ channels, Kv1.2, Kv1.4, and their tandem construct (Kv1.4-Kv1.2). Kv1.4 currents were inhibited considerably under acidic pH in a voltage-independent manner, whereas Kv1.2 currents were less inhibited in an apparently voltage-dependent manner. The apparent voltage-dependent block of Kv1.2 currents was mostly ascribed to the shift of activation voltage, which is probably due to surface charge effects of H+ ions. Mutagenesis analysis identified the histidine residue at 508 (H508) in the S5-H5 linker as a molecular determinant of pH sensitivity of Kv1.4. Currents through the tandem channel showed intermediate characteristics between the two parent channels in both sensitivity and voltage dependence of pH effects. Our results suggest that 1) the H508 plays a critical role in determining pH sensitivity of Kv1.4; and 2) the two parent channels, Kv1.2 and Kv1.4, are involved in determining pH sensitivity and apparent voltage dependence of the tandem channel.

BACKGROUND: Development of gastric mucosa associated lymphoid tissue (MALT) lymphoma is thought to be closely associated with host immune reactions to Helicobacter pylori. AIM: To investigate humoral immune responses in patients with MALT lymphoma to antigens shared by H pylori and human gastric epithelial cells. METHODS: Sera were obtained from H pylori positive patients with MALT lymphoma (n = 11) or other gastroduodenal diseases (peptic ulcer, n = 40; non-ulcer dyspepsia, n = 20) and from H pylori negative healthy control subjects (n = 10). Antibodies to HGC-27 human gastric epithelial cells and human recombinant heat shock protein (Hsp) 60 were examined using an enzyme linked immunosorbent assay (ELISA) and immunoblotting. RESULTS: Antibody titres to HGC-27 cells were significantly elevated in H pylori positive patients with MALT lymphoma when compared with titres in patients with other gastroduodenal diseases and in healthy subjects. Immunoblotting of sera from patients with MALT lymphoma often detected a band with a molecular mass corresponding to Hsp60, and both ELISA and immunoblotting showed elevated antibody titres to the recombinant human Hsp60. Antigenic similarity between Hsp60 and H pylori HspB was documented by immunoblotting experiments. CONCLUSIONS: Autoantibodies reactive with host gastric epithelial cells are often increased in MALT lymphoma, and Hsp60 is a major target antigen. Immune responses induced by immunological cross reactivity between H pylori HspB and human Hsp60 in gastric epithelium may be involved in the development of MALT lymphoma.

Background/aims: Clip closure of mucosal defects after colorectal endoscopic submucosal dissection (C-ESD) may decrease the incidence of delayed adverse events. The size of the defect to be closed by conventional clip is limited, however, and we sometimes encounter incomplete closure when the defect is located at the flexure. As, theoretically, underwater clip closure (UCC) could achieve complete closure despite these difficult cases, we investigated its feasibility., Methods: We retrospectively analyzed 21 patients who underwent UCC after C-ESD. The main outcome was the UCC success rate, defined as complete closure of the defect. Other outcomes were procedure time, number of clips, and the delayed adverse event rate., Results: The median resected specimen size was 31 mm (range 18-47 mm). The UCC success rate was 100%. The median procedure time was only 11 min (range 6-21 min). The median number of clips was 9 (range 5-16). No delayed adverse event occurred., Conclusion: It is feasible to use UCC to close large mucosal defects, although further studies are warranted to assess its efficacy., (© 2018 S. Karger AG, Basel.)