Although cAMP is well known to regulate exocytosis in many secretory cells, its direct target in the exocytotic machinery is not known. Here we show that cAMP-GEFII, a cAMP sensor, binds to Rim (Rab3-interacting molecule, Rab3 being a small G protein) and to a new isoform, Rim2, both of which are putative regulators of fusion of vesicles to the plasma membrane. We also show that cAMP-GEFII, through its interaction with Rim2, mediates cAMP-induced, Ca2+-dependent secretion that is not blocked by an inhibitor of cAMP-dependent protein kinase (PKA). Accordingly, cAMP-GEFII is a direct target of cAMP in regulated exocytosis and is responsible for cAMP-dependent, PKA-independent exocytosis.

The instrumentation in Hall A at the Thomas Jefferson National Accelerator Facility was designed to study electro-and photo-induced reactions at very high luminosity and good momentum and angular resolution for at least one of the reaction products. The central components of Hall A are two identical high resolution spectrometers, which allow the vertical drift chambers in the focal plane to provide a momentum resolution of better than 2 x 10(-4). A variety of Cherenkov counters, scintillators and lead-glass calorimeters provide excellent particle identification. The facility has been operated successfully at a luminosity well in excess of 10(38) CM-2 s(-1). The research program is aimed at a variety of subjects, including nucleon structure functions, nucleon form factors and properties of the nuclear medium. (C) 2003 Elsevier B.V. All rights reserved

Ghrelin is primarily secreted from the stomach and has been implicated in the coordination of eating behavior and weight regulation. The effects of Helicobacter pylori infection on plasma ghrelin concentration and gastric ghrelin production still have not been well known. We determined plasma ghrelin concentration in a total of 160 consecutive individuals with normal body mass index including 110 H. pylori-infected and 50 H. pylori-negative subjects. The expression levels of ghrelin mRNA and ghrelin-producing cells in the gastric mucosa were quantified with real-time quantitative RT-PCR and immunohistochemistry, respectively. The severity of gastric atrophy was evaluated by serum pepsinogen concentrations. Plasma ghrelin concentration, gastric ghrelin mRNA, and ghrelin-positive cell numbers in gastric mucosa were significantly lower in H. pylori-infected subjects. The decrease in plasma ghrelin concentration in H. pylori-positive subjects was accompanied by an attenuation of ghrelin mRNA expression and a reduction of ghrelin-positive cell numbers in the gastric mucosa. Moreover, lower serum pepsinogen I concentrations and I/II ratio were significantly associated with lower plasma ghrelin concentrations in H. pylori-positive subjects. These findings suggest that impaired gastric ghrelin production in association with atrophic gastritis induced by H. pylori infection accounts for the decrease in plasma ghrelin concentration.

H. pylori infection has a negative impact on gastric and plasma ghrelin dynamics. Chronic inflammatory and atrophic changes associated with the infection may affect gastric ghrelin biosynthesis and contribute to the low circulating levels.

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