PubMed Health⌕ Search

Biomedical subjects

J G Spenney

Publications and source records attributed to J G Spenney.

At least 19 recordsLinked to original sources
PubMed1994

Omeprazole versus H2-receptor antagonists in treating patients with peptic stricture and esophagitis.

BACKGROUND/AIMS: Although dysphagia in patients with peptic stricture is attributed to a decreased luminal diameter, coexistent esophagitis may be an equally important cause. The goals of this study were to determine whether medical healing of esophagitis in patients with stricture improves dysphagia and decreases dilatation need and to compare the efficacy and cost-effectiveness of omeprazole versus H2-receptor antagonists (H2RA). METHODS: Thirty-four dysphagic patients with peptic stricture and erosive esophagitis were dilated and randomized to omeprazole 20 mg every day versus H2RA (ranitidine 150 mg twice daily or famotidine 20 mg twice daily). Patients received further dilatations only if dysphagia frequency was greater than or equal to once per week. At 3 and 6 months, patients were assessed for esophagitis healing, dysphagia relief, and bougienage requirements. Cost-effectiveness of omeprazole and H2RA was determined. RESULTS: Patients with healed esophagitis at 3 and 6 months were more likely to dysphagia-free and to require fewer dilatations than patients with persistent esophagitis. At 6 months, omeprazole produced a significantly (P < 0.01) higher rate of esophagitis healing, dysphagia relief, and fewer dilatations compared with H2RA. Omeprazole was also 40%-50% more cost-effective. CONCLUSIONS: Esophagitis healing improves dysphagia and decreases dilatation need in patients with peptic stricture. Omeprazole heals esophagitis and relieves dysphagia more efficaciously than H2RA while decreasing costs to patients.

Aged↗
PubMed1994

LSA--a new liver-specific antigen in the rat. II: Immunological and biological properties.

The immunological and biological properties of a liver-specific antigen (LSA) from rat liver are described. LSA gave interspecies cross-reactions with liver extracts from several mammalian species, but no reaction of complete identify was observed. Moreover, no cross-reaction was found with chicken or frog livers, thus indicating the rather late appearance of LSA in the process of evolution. Experiments with fetal and neonatal liver extracts have indicated that LSA appears late in fetal development and is always present at birth. The biological properties of LSA were explored by several independent approaches. LSAg-Ab immunoprecipitates were stained positively with carbon naphthoxycholine iodide, an indirect evidence of choline esterase activity. LSA was also found to bind bile acids, thus suggesting organic anion properties. Finally, LSA was detected in the circulation of rats with acute carbon tetrachloride- and galactosamine-induced hepatocellular injury. This LSA is immunologically distinct from hepatitis B antigen, alpha-fetoprotein, carcino-embryonic antigen and, from each of several serum and liver proteins tested.

Animals↗
PubMed1992

LSA: a new liver-specific antigen in the rat. I. Purification and characterization.

A liver-specific antigen (LSA) was purified to homogeneity from rat liver by conventional methods of protein chemistry. By consecutive 100,000 g centrifugation, ammonium sulfate precipitation, ion-exchange chromatography on DEAE-cellulose, gel filtration on Sephadex G-200, ion-exchange chromatography on CM-cellulose and affinity chromatography on concanavalin-Sepharose, it has been possible to isolate a preparation that migrated as a single band on SDS-PAGE. This preparation gave a complete identity pattern with the original crude rat liver extract when tested by double immunodiffusion. This antigen has a molecular weight of 72.5 kD with an electrophoretic mobility in the region of alpha 2-globulins. The LSA proved to be thermolabile since exposure to 55 degrees C completely destroyed the antigen. Exposure of the LSA to different pH ranging from 4 to 10 had no detrimental effect on its antigenic activity. The amino acid composition of the LSA revealed that the acidic amino acids out-number the basic amino acids, with glutamic acid being the most abundant of them. Failure of beta-mercaptoethanol to split the LSA molecule suggests the absence of sulfhydryl groups related to its antigenic activity. Subcellular fractionation of rat liver revealed most of the antigenic activity in the 100,000 g supernate, i.e. the soluble cytoplasmic fraction of the liver (cytosol). By contrast, the LSA was absent from isolated Kupffer cells from rat liver. The absence of any carbohydrate or lipid from the purified preparation of this antigen, in conjunction with the destructive effects of trypsin suggest that the LSA is a protein or a moiety closely associated with proteins.

Amino Acids↗
PubMed1988

Stress ulcer prophylaxis in medical patients: who, what, and how much?

Stress ulcers are a frequently encountered problem in critically ill medical patients. Gastric acid and decreased gastric mucosal blood flow appear to be important in the pathogenesis of these lesions. Occult bleeding from stress ulcers is common, although significant bleeding occurs in less than 20% of patients. The mortality of bleeding is dependent on the severity of the underlying diseases. A number of processes have been suggested as risk factors; however, prolonged mechanical ventilation, a coagulopathy, and the presence of more than one risk factor place the patient at greatest risk. Titration of the gastric pH to greater than four with either antacids or H2-receptor antagonists provides effective prophylaxis. The continuous infusion of the H2-receptor antagonists is also efficacious. Sucralfate appears to be another useful alternative with several potential advantages. Prophylactic therapy decreases the incidence of stress ulcer-related bleeding, although it does little to improve the survival of the critically ill patient.

Antacids↗
PubMed1984

Autonomous cholesterol biosynthesis in murine hepatoma. A receptor defect with normal coated pits.

These studies indicate that autonomous cholesterol biosynthesis by hepatocellular carcinoma may result from absent or defective receptors for chylomicron remnants on the surface of the malignant hepatocytes. In vivo, DAB2 hepatoma or liver were perfused with chylomicron remnants labeled with tritiated palmitic acid. Normal liver had chylomicron remnant uptake/gm tissue that was ten times that of hepatoma. In vitro studies using isolated hepatocytes and cultured DAB2 hepatoma cells showed similar results. Uptake of chylomicron remnants labeled with 3H-palmitic acid by normal hepatocytes during a 4-hour period was ten times that of hepatoma cells. Both in vivo and in vitro differences were statistically highly significant (P less than 0.005). Since many surface receptors are related to the coated pits, the cellular membranes of both neoplastic and normal liver cells were examined by electron microscopy. Coated pits were present in both the hepatoma and normal liver cells and occupied 2.61% and 2.65% of the cell surface, respectively. The defective uptake of chylomicron remnants by DAB2 hepatoma appears to be related to the chylomicron remnant receptor and not to the coated pit-internalization mechanism.

Animals↗
PubMed1983

Biochemical mechanisms of acid secretion by gastric parietal cells.

Knowledge of the biochemical basis of gastric acid secretion has progressed dramatically in the last 25-30 years. Today, only the overall physiological consequences can be described by the carbonic anhydrase reaction; the biochemical details are much more complicated and remain incompletely resolved. The controversy between a redox, directly substrate linked, mechanism and an ATPase mechanism seems largely resolved. The marked redox changes in gastric mitochondria have been ascribed to anoxia of in vitro mucosae since isolated cells and gastric glands do not demonstrate these transitions. These findings are also in accord with stable content of NAD/NADH and NADP/NADPH in resting and secreting in vivo canine gastric mucosa. The subsequent finding that acid secretion by permeabilized gastric glands is ATP dependent even when substrate and mitochondrial metabolism is blocked by cyanide is convincing support for a proton-ATPase mechanism. Techniques for isolation and purification of mucosal membranes have yielded considerable progress in defining the enzymatic mechanism of acid secretion. Electron microscopy has demonstrated the unique system of intra-cellular membranes of the parietal cell. Several investigators have isolated these membranes by centrifugation and free-flow electrophoresis of mucosal cell membranes. In the purest preparations the membranes appear to contain only a few peptides, most of which seem to be components of the gastric ATPase. SDS polyacrylamide electrophoresis of these purified membranes has demonstrated a 100K dalton peptide that is phosphorylated in the presence of ATP. Radiation target analysis suggests that the native ATPase exists as a trimer of the 100¿K dalton peptide.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphatases↗
PubMed1982

Evidence for heterogeneity of hepatic bile salt sulfotransferases in female hamsters and rats.

Gel filtration and anion-exchange chromatography have been used to investigate whether 3'-phosphoadenylylsulfate:bile salt sulfotransferase activity from female rat and hamster liver is heterogeneous. Using these techniques at least three different enzyme activities were demonstrated with two different bile salt substrates. In both animals, but particularly the rat, there was a marked difference in the substrate specificity between each of the peaks of enzyme activity. The reducing agent, 2-mercaptoethanol, enhanced the proportion of the highest molecular weight (130 000) form of the enzyme from rat liver detected with glycochenodeoxycholate as substrate. This effect was duplicated by alkylation of sulfhydryl groups with iodoacetamide and is interpreted as being due to intermolecular association caused by disruption of intramolecular disulfide bonds.

Alkylation↗
PubMed1982

A unique "mini" pepsinogen isolated from bullfrog esophageal glands.

The evolutionary homology of pepsinogens was further evaluated by isolating and characterizing the pepsinogen of the esophageal glands of Rana catesbeiana. Like other pepsinogens, this esophageal enzyme was activated by acid; the resulting pepsin was optimally active between pH 1.4 and 2.0, and was irreversibly denatured above pH 7.0. Chromatography on DEAE-cellulose at pH 7.0 separated four acid protease fractions corresponding to pepsinogens B, D, A, and C. Hydroxylapatite chromatography of the major peptic fraction, pepsinogen A, followed by rechromatography on DEAE-cellulose at pH 8.5 yielded pure pepsinogen A which was free of detectable contaminants. Estimation of molecular weight by gel filtration on Sephadex G-75, by polyacrylamide gel electrophoresis in 0.1% SDS and by sedimentation equilibrium gave values of 31,500, 33,500, and 33,700, respectively. These studies suggest that the difference between bullfrog and other pepsinogens is located in a 90 to 110 amino acid (Mr 9,000 to 11,000) region of the molecule which must be remote from the catalytic and immunogenic sites. This lower molecular weight pepsinogen should thus provide a simpler molecular model for study of the catalytic and immunogenic properties. The pepsinogen from bullfrog gastric mucosa was found to have similar properties which suggested that gastric and esophageal pepsinogens of bullfrog are derived from a common ancestral origin. This archetypic pepsinogen may have undergone deletions late in evolution to render modern bullfrog pepsinogen structurally dissimilar from other described pepsinogens. The modern bullfrog enzyme has retained peptic enzymatic activity despite these evolutionary changes.

Amino Acids↗
PubMed1982

Aminopyrine accumulation by mammalian gastric glands: an analysis of the technique.

Isolated gastric glands from rabbits and parietal cells from dogs have recently become useful in studying the control and enzymatic mechanisms of gastric H+ secretion. The present studies were performed to determine the experimental variables that account for widely differing aminopyrine accumulation reported in various publications. We found that two principle factors were responsible for wide differences in aminopyrine accumulation. First, we found that commercially available aminopyrine contained an unidentified impurity that increased with storage. A procedure for purification is included. The contaminant is not accumulated in secreting gastric glands and thereby reduces the aminopyrine ratio that can be achieved. Mixing of glands appeared to be the second important variable. It was found that incubation in 1.5-ml capped conical polypropylene centrifuge tubes in the horizontal position with shaking in the long axis of the tubes gave aminopyrine ratios that were more than double the results obtained by other mixing techniques. In addition a gland density of 1--2 mg dry wt/ml glands and a mixing rate of 110 cycles/min gave the best results. Calculations indicate that, at high gland densities, even modest amounts of impurity in the aminopyrine will significantly reduce aminopyrine ratios. With optimal conditions our greatest aminopyrine ratio was 1,050, which suggests an H+ concentration of approximately 67 mM in the canaliculi and tubulovesicular membrane system of the parietal cell. Such a level of function approaches that of the intact in vivo organ.

Aminopyrine↗
PubMed1982

Properties of immunoglobulin A in serum of individuals with liver diseases and in hepatic bile.

In comparison with normal individuals, sera of patients with alcoholic cirrhosis and other liver diseases had two to four times higher levels of immunoglobulin A and three to ten time higher levels of polymeric immunoglobulin A. The possible participation of the liver in the selective removal of polymeric immunoglobulin A from serum into bile was investigated by analyzing immunoglobulin A in serum and bile specimens obtained from a group of patients with T-tube drainage of the common bile duct. Gel filtration revealed three principal fractions of biliary immunoglobulin A: secretory immunoglobulin A with J chain and secretory component; polymeric immunoglobulin A associated with J chain; and monomeric immunoglobulin A devoid of J chain and secretory component. Secretory component-complexed immunoglobulin A composed only 50% or less of the total biliary immunoglobulin A. In comparison with immunoglobulin G, polymeric forms of immunoglobulin A appeared to be selectively transported into bile whereas monomeric immunoglobulin A was not. These data suggested that the liver selectively transports polymeric immunoglobulin A from serum into bile by both secretory component-dependent and -independent mechanisms.

Aged↗
PubMed1981

15-Hydroxyprostaglandin dehydrogenase and delta 13 reductase content of gastrointestinal organs of rabbits and rats.

15-Hydroxyprostaglandin dehydrogenase was measured in various gastrointestinal and non-gastrointestinal tissues from rabbits and rats. In addition, delta 13 reductase activity was measured in fundic and antral mucosae and gastric muscle from rabbits. In rabbits, antral mucosa contained the greatest activity of 15-hydroxyprostaglandin dehydrogenase and was 6 times more active than rabbit lung and fundic mucosa. In rat, duodenal mucosa was more active than antral mucosa or pancreas, suggesting that interspecies variations may exist. delta 13 reductase in rabbit gastric tissues was also more active in antral mucosa than in fundic mucosa or gastric muscle. The high activities of these enzymes in antral mucosa in conjunction with the known large prostaglandin content, particularly PGE2 and PGI2, suggest a large biological turnover of prostaglandin in these tissues.

15-Oxoprostaglandin 13-Reductase↗
PubMed1980

Stoichiometry of the NADH-oxidoreductase reaction for dehydrogenase determinations.

The NADH oxidoreductase reaction with resazurin was most rapid at pH 6.5. FMN (10 mumol/l) markedly stimulated the reaction, and the optimal concentration of resazurin was 50 mumol/l. The oxidation of NADH by NADH oxidoreductase with resaruzin as electron acceptor gave a variable yield of fluorescent product, resorufin. The yield was pH dependent and was greatest at pH 6.5. Measurements of oxygen consumption in the reaction mixture demonstrated that dissolved O2 was an alternative electron acceptor. The increased yield of resorufin at pH 6.5 was due to more rapid reduction of resazurin rather than oxygen. In contrast, at pH 9.0 oxygen was the preferred electron acceptor. The sensitivity of assays utilizing this indicator reaction can be improved by these optimized conditions.

Dihydrolipoamide Dehydrogenase↗
PubMed1980

Determination of the pool size and synthesis rate of bile acids by measurements in blood of patients with liver disease.

1. A simplified technique for the measurement of bile-acid pool size and synthesis rate has been developed in patients with liver disease. Isotope dilution studies in blood and bile were performed after intravenous injection of [24-14C]cholic acid with radioimmunoassay for the measurement of the bile-acid concentration. The interpolated pool sizes and synthesis rates, determined from results from both blood and bile, were not significantly different. The concentration of bile acids in the blood of healthy controls was not sufficiently elevated to permit application of this technique. 2. Three out of six patients with cirrhosis had a markedly reduced pool size compared with that of controls, whereas those with cholestasis had an unchanged pool size. The daily synthesis rate was reduced in both groups. Liver disease caused a redistribution (0.5-16%) of the bile-acid pool to the blood, which was associated with enhanced urinary excretion of cholic acid and its metabolites.

Adult↗