G protein-coupled cholecystokinin-B/gastrin receptors are responsible for physiological cell growth of the stomach mucosa in vivo.

Many peptide hormone and neurotransmitter receptors belonging to the seven membrane-spanning G protein-coupled receptor family have been shown to transmit ligand-dependent mitogenic signals in vitro. However, the physiological roles of the mitogenic activity through G protein-coupled receptors in vivo remain to be elucidated. Here we have generated G protein-coupled cholecystokinin (CCK)-B/gastrin receptor deficient-mice by gene targeting. The homozygous mice showed a remarkable atrophy of the gastric mucosa macroscopically, even in the presence of severe hypergastrinemia. The atrophy was due to a decrease in parietal cells and chromogranin A-positive enterochromaffin-like cells expressing the H+,K(+)-ATPase and histidine decarboxylase genes, respectively. Oral administration of a proton pump inhibitor, omeprazole, which induced hypertrophy of the gastric mucosa with hypergastrinemia in wild-type littermates, did not eliminate the gastric atrophy of the homozygotes. These results clearly demonstrated that the G protein-coupled CCK-B/gastrin receptor is essential for the physiological as well as pathological proliferation of gastric mucosal cells in vivo.

Interstitial cells of Cajal mediate inhibitory neurotransmission in the stomach.

The structural relationships between interstitial cells of Cajal (ICC), varicose nerve fibers, and smooth muscle cells in the gastrointestinal tract have led to the suggestion that ICC may be involved in or mediate enteric neurotransmission. We characterized the distribution of ICC in the murine stomach and found two distinct classes on the basis of morphology and immunoreactivity to antibodies against c-Kit receptors. ICC with multiple processes formed a network in the myenteric plexus region from corpus to pylorus. Spindle-shaped ICC were found within the circular and longitudinal muscle layers (IC-IM) throughout the stomach. The density of these cells was greatest in the proximal stomach. IC-IM ran along nerve fibers and were closely associated with nerve terminals and adjacent smooth muscle cells. IC-IM failed to develop in mice with mutations in c-kit. Therefore, we used W/W(V) mutants to test whether IC-IM mediate neural inputs in muscles of the gastric fundus. The distribution of inhibitory nerves in the stomachs of c-kit mutants was normal, but NO-dependent inhibitory neuro-regulation was greatly reduced. Smooth muscle tissues of W/W(V) mutants relaxed in response to exogenous sodium nitroprusside, but the membrane potential effects of sodium nitroprusside were attenuated. These data suggest that IC-IM play a critical serial role in NO-dependent neurotransmission: the cellular mechanism(s) responsible for transducing NO into electrical responses may be expressed in IC-IM. Loss of these cells causes loss of electrical responsiveness and greatly reduces responses to nitrergic nerve stimulation.

Human neoplasms elicit multiple specific immune responses in the autologous host.

Expression of cDNA libraries from human melanoma, renal cancer, astrocytoma, and Hodgkin disease in Escherichia coli and screening for clones reactive with high-titer IgG antibodies in autologous patient serum lead to the discovery of at least four antigens with a restricted expression pattern in each tumor. Besides antigens known to elicit T-cell responses, such as MAGE-1 and tyrosinase, numerous additional antigens that were overexpressed or specifically expressed in tumors of the same type were identified. Sequence analyses suggest that many of these molecules, besides being the target of a specific immune response, might be of relevance for tumor growth. Antibodies to a given antigen were usually confined to patients with the same tumor type. The unexpected frequency of human tumor antigens, which can be readily defined at the molecular level by the serological analysis of autologous tumor cDNA expression cloning, indicates that human neoplasms elicit multiple specific immune responses in the autologous host and provides diagnostic and therapeutic approaches to human cancer.

Identification of genetic determinants associated with susceptibility and therapeutic efficacy in Philadelphia-negative Myeloproliferative Neoplasms

Poster presented at the Scientific Toxomics Meeting, 28 September 2015, Lisbon, Portugal.

Biometry, stable isotopes and stomach contents of A. glacialis and B. saida from Northeast Greenland

Two gadoid fishes, Arctogadus glacialis and Boreogadus saida, often coexist (i.e. sympatric) in the fjords and shelf areas of the Arctic seas, where they likely share the same food resources. Diet composition from stomach contents, i.e. frequency of occurrence (FO) and Schoener's index (SI), and stable isotope signatures (d13C and d15N) in muscle of these sympatric gadoids were examined from two fjords in NE Greenland-Tyrolerfjord (TF, ~74°N, sill present) and Dove Bugt (DB, ~76°N, open). Twenty-three prey taxa and categories were identified and both gadoids ate mostly crustaceans. The SI values of 0.64-0.70 indicated possible resource competition, whereas FO differed significantly. A. glacialis fed mainly on the mysid Mysis oculata and other benthic-associated prey, whereas B. saida ate the copepod Metridia longa and other pelagic prey. Both diet and stable isotopes strongly suggest a spatial segregation in feeding habitat, with A. glacialis being associated with the benthic food web (mean d13C = -20.81 per mil, d15N = 14.92 per mil) and B. saida with the pelagic food web (mean d13C = -21.25 per mil, d15N = 13.64 per mil). The dietary differences and isotopic signals were highly significant in the secluded TF and less clear in the open DB, where prey and predators may be readily advected from adjacent areas with other trophic conditions. This is the first study on the trophic position of A. glacialis inferred from analyses of stable isotopes. The subtle interaction between the Arctic gadoids should be carefully monitored in the light of ocean warming and ongoing invasions of boreal fishes into the Arctic seas.

Water chemistry, and body temperature, swimming depth and stomach contents of Arctic char (Salvelinus alpinus) in inner Frobisher Bay, Canada

The influence of salinity, temperature and prey availability on the marine migration of anadromous fishes was determined by describing the movements, habitat use and feeding behaviours of Arctic char (Salvelinus alpinus). The objectives were to determine whether char are restricted to the upper water column of the inter-/subtidal zones due to warmer temperatures. Twenty-seven char were tracked with acoustic temperature/pressure (depth) transmitters from June to September, 2008/2009, in inner Frobisher Bay, Canada. Most detections were in surface waters (0-3 m). Inter-/subtidal movements and consecutive repetitive dives (maximum 52.8 m) resulted in extreme body temperature shifts (-0.2-18.1 °C). Approximately half of intertidal and subtidal detections were between 9-13 °C and 1-3 °C, respectively. Stomach contents and deep diving suggested feeding in both inter-/subtidal zones. We suggest that char tolerate cold water at depth to capture prey in the subtidal zone, then seek warmer water to enhance feeding/digestion physiology.

Diet in dyspepsia and other diseases of the stomach and bowels : an elementary treatise on their dietetic and hygienic management.

Mode of access: Internet.

The effects of alcohol upon digestion in the stomach,

Thesis statement on label affixed to inside front cover.

Syllabus of dermal pathology. Course no. 3, Nevi and neoplasms.

Mode of access: Internet.

A practical essay on diseases of the viscera : particulary those of the stomach and bowels, the liver, spleen and urinaty bladder, in which their nature, treatment and cure, are cleary pointed out and explained /

Mode of access: Internet.

A brief acconunt of the origin and progress of the patent syringe or stomach pump and lavement apparatus ... /

Mode of access: Internet.