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Biomedical subjects

J R Warren

Publications and source records attributed to J R Warren.

At least 55 records · Page 3Linked to original sources
PubMed1987

Rapid urease test in the management of Campylobacter pyloridis-associated gastritis.

Campylobacter pyloridis colonization of the stomach may be an etiological factor in gastritis and peptic ulceration. Campylobacter pyloridis produces large amounts of urease, and the presence of this enzyme in gastric mucosa usually indicates infection with the organism. In this paper we describe the use of a rapid urease test (CLOtest) to detect C. pyloridis infection in gastric mucosal biopsies. In 141 consecutive endoscopy cases, antral biopsies were taken for culture and histology, and an extra biopsy was inserted into the CLOtest gel. There were 79 patients infected with C. pyloridis, 78 of whom were detected by CLOtest: 75% were positive at 20 min, 92% at 3 h, and 98% at 24 h. There were no false positive results. Eighteen infected patients were rebiopsied after a course of amoxycillin and bismuth subcitrate. Active chronic gastritis resolved in eight of nine who were cleared of the organism, but histological gastritis was unchanged in nine patients who were still infected. CLOtest is a simple, sensitive, and highly specific test that enables the endoscopist to diagnose C. pyloridis infection in the endoscopy room. A negative test after antibiotic therapy correlates with clearance of the bacteria and healing of active gastritis.

Amoxicillin↗
PubMed1986

Muscarinic receptor coupling to intracellular calcium release in rat pancreatic acinar carcinoma.

Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of cholinergic receptor protein affinity labeled with the muscarinic antagonist [3H]propylbenzilylcholine mustard revealed a major polypeptide with molecular weight of 80,000-83,000 in both acinar carcinoma and normal acinar cells of rat pancreas. Muscarinic receptor protein is therefore conserved in pancreatic acinar carcinoma. A small but significant difference was detected in the affinity of carcinoma cell receptors (Kd approximately 0.6 nM) and normal cell receptors (Kd approximately 0.3 nM) for reversible binding of the muscarinic antagonist drug, N-methylscopolamine. In addition, carcinoma cell muscarinic receptors displayed homogeneous binding of the agonist drugs carbamylcholine (Kd approximately 31 microM) and oxotremorine (Kd approximately 4 microM), whereas normal cell receptors demonstrated heterogeneous binding, with a minor receptor population showing high affinity binding for carbamylcholine (Kd approximately 3 microM) and oxotremorine (Kd approximately 160 nM), and a major population showing low affinity binding for carbamylcholine (Kd approximately 110 microM) and oxotremorine (Kd approximately 18 microM). Both carcinoma and normal cells exhibited concentration-dependent carbamylcholine-stimulated increases in cytosolic free Ca2+, as measured by 45Ca2+ outflux assay and intracellular quin 2 fluorescence. However, carcinoma cells were observed to be more sensitive to Ca2+ mobilizing actions of submaximal carbamylcholine concentrations, demonstrating 50% maximal stimulation of intracellular Ca2+ release at a carbamylcholine concentration (approximately 0.4 microM) approximately one order of magnitude below that seen for normal cells. These results indicate altered muscarinic receptor coupling to intracellular Ca2+ release in acinar carcinoma cells, which manifests as a single activated receptor state for agonist binding, and increased sensitivity of Ca2+ release in response to muscarinic receptor stimulation.

Animals↗
PubMed1985

Evaluation of cultural techniques for isolating Campylobacter pyloridis from endoscopic biopsies of gastric mucosa.

One hundred and three gastroscopic biopsies from 80 patients were cultured for Campylobacter pyloridis and studied histologically. Active chronic gastritis, as shown by the presence of polymorphonuclear leucocytes, was diagnosed in 51 biopsies and C pyloridis was found in 47. Sixteen gastric biopsies showed normal histology (no inflammation); C pyloridis was detected in only one of these, and a second biopsy taken from this patient at the same time showed active gastritis. Biopsies could be kept at 4 degrees C for five hours without loss of viability of C pyloridis. An inoculum made by grinding the biopsy in a ground glass grinder consistently gave a much heavier growth of C pyloridis than one made by mincing the specimen. The campylobacter supplement ferrous sulphate, sodium metabisulphite, sodium pyruvate (FBP) (Oxoid) was inhibitory for some isolates; the inhibitory component was found to be sodium metabisulphite. Contaminants, but not C pyloridis, were inhibited by the incorporation of vancomycin 6 mg/l, nalidixic acid 20 mg/l, and amphotericin 2 mg/l, but higher concentrations inhibited C pyloridis. Undried plates kept in a plastic container at room temperature for up to two weeks were as satisfactory as freshly poured plates for the isolation of C pyloridis.

Adult↗
PubMed1985

Differentiation of muscarinic cholinergic receptors in acinar carcinoma of rat pancreas.

Analysis of muscarinic cholinergic receptors in pancreatic acinar carcinoma of rat by measurement of N-[methyl-3H]scopolamine binding has revealed a single homogenous population of muscarinic receptors in the tumor. The plasmalemma density (approximately 25 receptors/micron 2 of cell membrane surface) and dissociation constant (approximately 0.4 nM) of muscarinic receptors in acinar carcinoma cells are identical to the density and affinity of muscarinic receptors in normal acinar cells of rat pancreas. Muscarinic receptors in the carcinoma are functionally linked to cholinergic stimulation of cellular Ca2+ release. An equivalent number of functional muscarinic receptors is present in poorly differentiated carcinoma cells which are deficient in zymogen granules and protein secretion, as compared to well-differentiated carcinoma cells which contain granules and secrete protein in response to cholinergic stimulation. These observations indicate that muscarinic cholinergic receptors are displayed in normal fashion on tumor membranes and are fully expressed in carcinoma cells regardless of their degree of secretory development. Expression of muscarinic cholinergic receptors is thus a stable phenotypic property of pancreatic acinar carcinoma cells. This suggests that muscarinic receptor maturation is an early event in the differentiation of pancreatic exocrine cells, preceding acquisition of secretory responsiveness to cholinergic stimulation.

Amylases↗
PubMed1984

Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration.

Biopsy specimens were taken from intact areas of antral mucosa in 100 consecutive consenting patients presenting for gastroscopy. Spiral or curved bacilli were demonstrated in specimens from 58 patients. Bacilli cultured from 11 of these biopsies were gram-negative, flagellate, and microaerophilic and appeared to be a new species related to the genus Campylobacter. The bacteria were present in almost all patients with active chronic gastritis, duodenal ulcer, or gastric ulcer and thus may be an important factor in the aetiology of these diseases.

Adult↗
PubMed1983

Transformation of human erythrocyte shape by endotoxic lipopolysaccharide.

Human erythrocytes were observed to undergo a discocyte to echinocyte to spheroechinocyte shape transformation during brief incubation with endotoxic lipopolysaccharide. It was concluded that lipopolysaccharide-membrane interactions alter the curvature of erythrocyte membranes.

Dose-Response Relationship, Drug↗
PubMed1982

Concanavalin A binding and cytodifferentiation in pancreatic acinar carcinoma of rat.

The binding of concanavalin A to the plasmalemma of acinar carcinoma cells was characterized by electron microscopy utilizing horseradish peroxidase. Heavy labeling due to specific concanavalin A binding was detected on the plasmalemma of undifferentiated carcinoma cells lacking zymogen maturation, neoplastic cells of intermediate differentiation with only occasional zymogen granules, and highly differentiated acinar carcinoma cells containing numerous cytoplasmic zymogen granules. The plasmalemma of acinar carcinoma cells was also compared to the normal pancreatic acinar cell plasmalemma by measurement of specific 125I-labeled concanavalin A binding. Although only about one-third of pancreatic acinar carcinoma cells demonstrate mature zymogen differentiation, the acinar carcinoma had a full complement of normal plasmalemma receptors for 125I-labeled concanavalin A. It is concluded that, unlike normal pancreas, the presence of concanavalin A receptors on the plasmalemma of acinar carcinoma cells is not a specific membrane marker for differentiated cells containing zymogen granules.

Animals↗
PubMed1982

Polymyxin B suppresses the endotoxin inhibition of concanavalin a-mediated erythrocyte agglutination.

The lectin agglutinability of human erythrocytes has been utilized to examine interactions of gram-negative endotoxin with mammalian cell plasma membranes. Erythrocytes treated in buffer with Escherichia coli 0127:B8 lipopolysaccharide (LPS) or Salmonella minnesota Re595 glycolipid for 1 h became resistant to agglutination by the lectin concanavalin A (ConA) in buffer free of LPS or glycolipid. Polymyxin B, a cationic cyclic lipopeptide which specifically binds to the lipid A toxophore, was tested for possible effects on the LPS and glycolipid inhibition of Con A erythrocyte agglutination. The presence of polymyxin B during the initial 1-h treatment with LPS or glycolipid blocked the ability of the endotoxins to render erythrocytes refractory to agglutination by ConA. Inhibition by polymyxin B was stoichiometric, and in repeated experiments, LPS was completely suppressed in the hemagglutination assay at a polymyxin B:LPS weight ratio of 1:4.1 (increasing polymyxin concentration, constant LPS concentration) and 1:5.1 (constant polymyxin concentration, increasing LPS concentration). These stoichiometry values are similar to values obtained for inhibition by polymyxin B of LPS lymphoid cell activation. It was concluded, therefore, that endotoxin inhibition of ConA erythrocyte agglutination reflects interactions of erythrocyte membranes with the lipid A region of endotoxin. In addition, the stoichiometry of polymyxin B inhibition suggests a similar extent of lipid A-dependent LPS interaction with erythrocytes and lymphoid cells.

Concanavalin A↗
PubMed1982

Phthalate esters as peroxisome proliferator carcinogens.

The phthalate ester di(2-ethylhexyl) phthalate is both a peroxisome proliferator and a hepatic carcinogen. Peroxisome proliferators as a class are hepatocarcinogenic in rodent species. However, none of the peroxisome proliferators tested to date including the phthalate esters and related alcohol and acid analogs have demonstrated mutagenic or DNA-damaging activity in the in vitro Salmonella typhimurium/microsomal or the lymphocyte 3H-thymidine assays. A working hypothesis is proposed that peroxisome proliferation itself initiates neoplastic transformation of hepatic parenchymal cells by increasing intracellular rates of DNA-damaging reactive oxygen production. Evidence which supports such a hypothesis includes increased fatty acid beta-oxidation, elevated H2O2 levels, accumulation of peroxidized lipofuscin, disproportionately small increase in catalase, and elevated peroxisomal uricase activity which accompany peroxisome proliferation in hepatocytes. Direct testing of this hypothesis will provide insight into mechanisms of phthalate ester carcinogenicity and cytotoxicity.

Animals↗
PubMed1982

Secretagogue response in rat pancreatic acinar carcinoma.

The secretion of protein, like cell proliferation, is an integrated response that reflects structural organization of the cell periphery. Stimulation of protein secretion was thus utilized for comparison of integrated responses of the cell periphery in pancreatic acinar carcinoma of the rat and integrated responses in normal rat pancreas. Results of this comparison include: a) The stimulation of protein secretion in acinar carcinoma fragments by carbamylcholine chloride and cholecystokinin octapeptide, pancreatic secretagogues that interact with specific plasma membrane receptors, was only a fraction (one-fifth to one-half) of that observed in normal pancreatic minilobules. b) The Ca2+ ionophore A23187 and the cyclic nucleotide N6,O2'-dibutyryl cyclic AMP, secretagogues that act independently of specific membrane receptors, did not stimulate secretion in the acinar carcinoma. The observed quantitative and qualitative differences in protein secretion indicate fundamental differences in cell periphery organization between the normal and transformed acinar cells of pancreas.

Animals↗
PubMed1981

Transplantable pancreatic acinar carcinoma.

Fragments of the nafenopin-induced pancreatic acinar cell carcinoma of rat have been examined in vitro for patterns of intracellular protein transport and carbamylcholine-induced protein discharge. Continuous incubation of the fragments with [3H]-leucine for 60 minutes resulted in labeling of rough endoplasmic reticulum, Golgi cisternae, and mature zymogen granules, revealed by electron microscope autoradiography. This result indicates transport of newly synthesized protein from the rough endoplasmic reticulum to mature zymogen granules in approximately 60 minutes. The secretagogue carbamylcholine induced the discharge of radioactive protein by carcinoma fragments pulse-chase labeled with [3H]-leucine. A maximal effective carbamylcholine concentration of 10(-5) M was determined. The acinar carcinoma resembles normal exocrine pancreas in the observed rate of intracellular protein transport and effective secretagogue concentration. However, the acinar carcinoma fragments demonstrated an apparent low rate of carbamylcholine-induced radioactive protein discharge as compared with normal pancreatic lobules or acinar cells. It is suggested that the apparent low rate of radioactive protein discharge reflects functional immaturity of the acinar carcinoma. Possible relationships of functional differentiation to the heterogeneous cytodifferentiation of the pancreatic acinar carcinoma are discussed.

Animals↗
PubMed1980

Activity of carcinogens, carcinogen analogs, and metabolic inhibitors in the lymphocyte tritiated thymidine assay.

Inhibition of tritiated thymidine ([3H]dThd) incorporation into replicating DNA of concanavalin A (Con A)-stimulated C57BL/6J splenic lymphocytes has been further evaluated as an end point for rapid in vitro discrimination between carcinogenic and noncarcinogenic chemicals. Results of this evaluation include: a) Inhibition of [3H]dThd incorporation into DNA of Con A-stimulated cells clearly discriminated between known DNA-damaging chemical carcinogens (N-methyl-N-nitrosourea, 4-nitroquinoline 1-oxide, 4-(hydroxyamino)quinoline 1-oxide, benzo[a]pyrene, 7,12-dimethylbenz[a]anthracene, and benz[a]anthracene) and non-DNA-damaging metabolic inhibitors of replication (dimethyl sulfoxide, ethanol, hydroxyurea, cycloheximide, potassium cyanide, and oligomycin). b) Inhibition of [3H]dThd incorporation also discriminated between carcinogens and noncarcinogens in the two pairs 4-nitroquinoline 1-oxide versus quinoline-N-oxide, and benzo[a]pyrene versus pyrene. c) Inhibition of [3H]dThd incorporation did not quantitatively discriminate between the structurally related strong carcinogen dimethylbenz[a]anthracene, the weak carcinogen benz[a]anthracene, and the equivocal carcinogens anthracene and phenanthrene. d) Inhibition of [3H]dThd incorporation was not a sensitive in vitro end point for the carcinogenic hypolipidemic drug 4-chloro-6-(2,3-xylidino)-2-pyrimidinylthioacetic acid (Wy-14,643).

Animals↗