Heterogeneity in the structural glycoprotein (VP7) of simian rotavirus SA11.
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Carbohydrate Sequence↗
Biomedical subjects
D Y Graham
Publications and source records attributed to D Y Graham.
Pancreatic enzyme replacement: the effect of antacids or cimetidine.
The effect of the addition of sodium bicarbonate, aluminum hydroxide, magnesium hydroxide, calcium carbonate, or cimetidine to supplemental pancreatic enzyme therapy was investigated in patients with severe exocrine pancreatic insufficiency. Steatorrhea was reduced with the administration of three enzyme tablets with meals (73 vs 29 g/24 hr). The coadministration of enzyme tablets with either sodium bicarbonate (16.6 g/24 hr, P = 0.08), or aluminum hydroxide (18.4 g/24 hr, P = 0.029) yielded a greater reduction in steatorrhea than enzymes alone (29 g/24 hr). Neither magnesium-aluminum hydroxide (36.3 g/24 hr, P = 0.22), nor calcium carbonate (39.0 g/24 hr, P = 0.029), improved efficacy of enzyme therapy and, in fact, tended to enhance steatorrhea. With the administration of cimetidine there was no significant effect on steatorrhea compared to enzymes alone (32.1 vs 29 g/24 hr, P greater than 0.3). Intraduodenal lipase activity following test meals was found to be a poor predictor of the effectiveness of antacid therapy in improving the efficacy of supplemental enzymes.
Adult↗
Vascular-enteric fistula: diagnosis by colonoscopy.
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Aged↗
Does mixing pancreatic enzyme microspheres (Pancrease) with food damage the enteric coating?
Supplemental pancreatic enzymes are required for the treatment of malabsorption associated with cystic fibrosis. It is a general practice for enzymes to be sprinkled on, or administered in, food given to infants or children who require pancreatic enzyme replacement. We tested the effect of in vitro incubation of enteric-coated pancreatic enzyme microspheres with infant foods on total recoverable enzyme activity and on the enteric coating. Incubation of enzyme beads with foods with pH greater than 5 (i.e., chicken pH 6.5, veal pH 6.3, and green beans pH 5.6) was without significant effect on either parameter. There was a statistically significant, albeit minor, reduction in maximum enzyme activity recovered following incubation with applesauce (pH 3.5). In addition, the thickness of the enteric coating was significantly reduced. Whether changes in the enzyme beads results in improved or diminished efficiency of therapy remains to be determined. Lipase, unprotected by enteric coating, was rapidly inactivated in applesauce, emphasizing the need to instruct parents about which foods to avoid when administering pancreatic enzymes without enteric coating.
Food↗
Localization of rotavirus antigens in infected cells by ultrastructural immunocytochemistry.
Virus structural antigens were localized within a line of monkey kidney (MA104) cells infected with the simian rotavirus SA11 using electron microscopic immunoperoxidase techniques. When hyperimmune guinea-pig anti-SA11 serum was used, virus particles, membranes of virus-associated endoplasmic reticulum, and viroplasmic inclusions were most heavily labelled. A general cytoplasmic reaction (ribosomes, intracytoplasmic membranes, etc.) with anti-SA11 serum was also observed, but nuclei were unstained. In addition, several other virus-induced structures were found to contain rotavirus proteins, including convoluted smooth membrane within the endoplasmic reticulum, aberrant virus-like particles, and 15 to 20 nm diam. cytoplasmic tubules. Monospecific antiserum to VP7 (outer capsid glycoprotein, mol. wt. 38000) reacted strongly with virus particles and the virus-associated endoplasmic reticulum, but reacted poorly with viroplasmic inclusions. The nucleus and general cytoplasm were unstained with anti-VP7. In contrast, monospecific antisera to VP2 and VP6 (inner capsid proteins, mol. wt. 94000 and 41000 respectively) reacted very strongly with viroplasmic inclusions. Virus particles, endoplasmic reticulum and cytoplasmic ribosomes were also labelled with these sera. These results indicate that rotavirus inner capsid proteins are synthesized throughout the cytoplasm and become concentrated in viroplasmic inclusions, while the outer capsid glycoprotein is synthesized primarily on ribosomes of the rough endoplasmic reticulum. Thus, the outer capsid layer appears to be acquired during virus budding into cisternae of the endoplasmic reticulum.
Animals↗
Identification, synthesis, and modifications of simian rotavirus SA11 polypeptides in infected cells.
The synthesis and processing of simian rotavirus SA11 polypeptides was investigated after infection of MA104 cells. [35S]methionine- or 3H-amino acid-labeled cell extracts were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Viral protein synthesis was maximal 3 to 5 h postinfection, and 12 major viral polypeptides were detected. Immunoprecipitation and peptide mapping experiments, demonstrated five viral structural proteins (125,000 daltons [125K], 94K, 88K, 41K, and 38K). Three proteins (53K, 35K, and 34K) were identified as nonstructural by comparison of their partial proteolysis maps with those from polypeptides of similar molecular weight synthesized in vitro from viral RNA transcripts. Assignment as to structural or nonstructural status of two other primary gene products (26K and 20K) remains tentative. Pulse-chase experiments and tunicamycin blockage of glycosylation revealed cotranslational or post-translational modifications (or both) and precursor-product relationships of several of the polypeptides. Tunicamycin inhibition of glycosylation identified a 35.5K polypeptide which was proven to be the precursor to the 38K structural glycoprotein by immunoprecipitation and peptide mapping analyses. Tunicamycin treatment of infected cells also resulted in the disappearance of other glycoprotein species (23K to 29K) and in the concomitant build-up of an unglycosylated 20K polypeptide, suggesting a precursor-product relationship between those polypeptides. Labeling with [3H]glucosamine or [3H]mannose suggested that the rotavirus glycoproteins contained high mannose oligosaccharides. The effects of amino acid analogs on rotavirus polypeptide synthesis and processing were also investigated.
Amino Acids↗
The effect of bran on bowel function in constipation.
Bran is widely used to treat a variety of gastrointestinal disorders. With few exceptions, investigative work has focused on the effect of bran in normal subjects. Despite its widespread use, there have been no systematic studies of bran in constipation. Wheat bran is the "gold standard" because no other natural fiber has yet been shown to be as effective in increasing fecal bulk. We evaluated the effect of two brans, wheat and corn (20 g/day), on fecal weight, fecal moisture content, bowel movement frequency, intestinal transit time, and symptoms in 10 constipated (less than or equal to 3 movements/wk) but otherwise healthy women. The administration of bran was associated with a significant increase in fecal weight (157%), bowel movement frequency (55%), and decrease in intestinal transmit time (50%). Percentage fecal moisture increased only with wheat bran (67.4-72.1%), whereas corn bran was significantly better than wheat bran in relieving symptoms of constipation.
Adult↗
Gastric radiotherapy as treatment of hereditary hemorrhagic telangiectasia.
A patient with hereditary hemorrhagic telangiectasia and von Willebrand's disease is described. He suffered recurrent episodes of gastrointestinal bleeding endoscopically localized to the cardia and body of the stomach. A cobalt 60 source was used to deliver 1600 rad to the patient's stomach. The effect of the radiation was remarkable in that he remained free of bleeding for more than 11 months. Radiotherapy should be considered for control of gastric bleeding in hereditary hemorrhagic telangiectasia.
Gastrointestinal Hemorrhage↗
Variceal hemorrhage: a critical evaluation of survival analysis.
Treatment of variceal hemorrhage is one of the most controversial subjects in medicine. The resurgence of old therapies (endoscopic sclerotherapy) and the introduction of new modalities (obliterative angiotherapy) has exacerbated the controversy. No widely accepted controlled therapeutic trial is available. The problem related to survival analysis has been studied in the light of the available information concerning the natural history of variceal bleeding. It is believed that controlled trials can be designed which will prove the efficacy, or lack of it, for any proposed treatment; however, valid conclusions based on previous studies are limited, largely because of the many confounding variables. Time, as a variable factor both for randomization and therapeutic intervention, has been largely ignored, yet, we believe it is the major variable in this setting. For the population of variceal bleeders, risk of rebleeding or death rapidly diminishes over the first few days after a bleed, and early survival may be the best marker for later survival. Neither presentation nor treatment seems to alter this fundamental behavior. Variceal hemorrhage may serve as a prototype for problems of survival analysis of diseases with early high mortality.
Actuarial Analysis↗
Alcohol hepatitis therapy.
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Hepatitis, Alcoholic↗
Prospective evaluation of biopsy number in the diagnosis of esophageal and gastric carcinoma.
A prospective trial was performed in which biopsy and cytology specimens were obtained on 202 consecutive patients including 47 with esophageal or gastric carcinomas. The first biopsy specimen yielded a correct diagnosis in the majority of instances: 70% of gastric carcinomas and 93% of esophageal carcinomas. Three additional biopsy specimens increased the yield to greater than 95%, a total of seven biopsy specimens yielded greater than 98%. Seven biopsy and cytology specimens yielded the correct diagnosis in all patients. Seventeen percent of all lesions subsequently proven to be malignant were thought to be benign, endoscopically. This reinforces the belief that all lesions seen at endoscopy should have biopsies performed and at least seven specimens should be obtained.
Biopsy↗
Mechanism of increase in steatorrhea with calcium and magnesium in exocrine pancreatic insufficiency: an animal model.
We used a rat model to investigate the phenomenon of increased steatorrhea associated with administration of calcium or magnesium containing antacids in humans with pancreatic insufficiency. Adult male rats with bile and pancreatic duct ligation were fed test meals containing 56 mumol [14C]triolein (0.5 ml), synthetic human bile (1.0 ml, 100 mumol bile salts, 75% glycine and 25% taurine conjugates, and 14.5 mumol lecithin), pancreatic enzymes (0.5 ml), and antacids (1.0 ml). The percent lipid malabsorbed when antacids were fed in addition to the test meal was: control 19.3 +/- 1%, NaHCO3 15.3 +/- 1% (P less than 0.05 vs. control), Al(OH)3 18.3 +/- 2%, Mg(OH)2 38.2 +/- 2% (p less than 0.001 vs. control), and CaCO3 42.4 +/- 1% (p less than 0.001 vs control). With NaCl, Al(OH)3, and NaHCO3 the malabsorbed fat was primarily triolein, whereas with Ca++ or Mg++ the majority of the lipid recovered was oleic acid. Calcium or magnesium administration was associated with precipitation of glycine-, but not taurine-, conjugated bile salts in the small intestine. When calcium was administered to animals in which the bile consisted entirely of glycine-conjugated bile salts, the lipid recovered (64.0 +/- 3% malabsorption) was almost entirely triolein suggesting reduced lipolysis. These studies suggest that these divalent cations exert their deleterious effect on replacement enzyme therapy by formation of poorly soluble calcium or magnesium soaps and precipitation of glycine conjugated bile salts.
Animals↗
Electrocoagulation of Mallory-Weiss tears.
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Electrocoagulation↗
Proteolytic enhancement of rotavirus infectivity: molecular mechanisms.
The polypeptide compositions of single-shelled and double-shelled simian rotavirus particles were modified by exposure to proteolytic enzymes. Specifically, a major outer capsid polypeptide (VP3) having a molecular weight of 88,000 in double-shelled particles was cleaved by trypsin to yield two polypeptides, VP5* and VP8* (molecular weights, 60,000 and 28,000, respectively). The cleavage of VP3 by enzymes that enhanced infectivity (trypsin, elastase, and pancreatin) yielded different products compared to those detected when VP3 was cleaved by chymotrypsin, which did not enhance infectivity. The appearance of VP5* was correlated with an enhancement of infectivity. Cleavages of the major internal capsid polypeptide VP2 were also observed. The VP2 cleavage products had molecular weights similar to those of known structural and nonstructural rotavirus polypeptides. We confirmed the precursor-product relationships by comparing the peptide maps of the polypeptides generated by digestions with V-8 protease and chymotrypsin. The remaining rotavirus structural polypeptides, including the outer capsid glycoproteins (VP7 and 7a), were not altered by exposure to pancreatic enzymes. Cleavage of VP3 was not required for virus assembly, and specific cleavage of the polypeptides occurred only on assembled particles. We also discuss the role of cleavage activation in other virus-specific biological functions (e.g., hemagglutination and virulence).
Animals↗
Identification of rotavirus particle types.
Negative-contrast electron microscopy of purified rotavirus particles reveals two particle types: single-shelled and double-shelled particles. The relationship of these particle types, seen by negative staining, to the enveloped and various types of nonenveloped particles seen in thin sections of virus-infected cells was determined. Thin-section and negative-contrast electron microscopic analyses were performed on cell lysates from simian rotavirus. SA11-infected cells and on highly purified double- and single-shelled particles. In thin sections, double-shelled particles appeared as smooth-edged ovals containing dense nucleoids, whereas single-shelled particles had ragged edges and threads of material extending from their centers. The majority of nonenveloped particles seen in thin sections of infected cells were identified as double-shelled particles. Enveloped particles showed typical membrane structure and were observed rarely in crude rotavirus stocks, although they constitute about 10% of the particles within infected cells. It is hypothesized that the enveloped form is a transient one and the envelope is lost in the endoplasmic reticulum of the host cells. Finally, the 50-55 nm type IV particles seen within lysosome-like bodies in infected cells were identified as subviral particles formed from input virions.
Animals↗
The course of patients after variceal hemorrhage.
We analyzed the clinical course of 85 consecutive, endoscopically verified variceal bleeders. Most patients were alcoholics with advanced stages of hepatic dysfunction. Bleeding was major in all, and medical mortality was 42% at 6 wk. Factors affecting mortality and factors not affecting survival, such as age and comorbid conditions, were identified. Sixty percent of early deaths and 40% of late deaths were attributable to bleeding. Approximately one-third of patients experienced rebleeding within 6 wk, and one-third of survivors experienced subsequent bleeds. In these patients significant improvement with observation was often anticipated, but could not be verified. The majority of deaths associated with variceal bleeding occur soon after the bleeding episode. Those who survive the hospitalization for bleeding may not fare worse than others of similar hepatic functional reserve but who have not experienced bleeding. We demonstrated that statistically significantly different survival curves could be obtained from the same population by changing the zero time for calculating survival. For example, a 1-yr survival rate of 34% for all medically treated patients could be raised to 52% by eliminating from consideration those who failed to survive 2 wk. The long-term survival course of those surviving greater than 2 wk was not statistically significantly different from published series of unselected cirrhotics without bleeding. Variceal bleeding is a common accompaniment of advanced liver disease. We propose that any substantial improvement in long-term survival must improve survival for the early period. If controlled trials are to be done, patients should be matched for hepatic functional reserve and identical zero time for calculating survival must be used.
Ascites↗
Double-blind multicenter comparison of 1,200 mg. and 1,000 mg. cimetidine in hospitalized and ambulatory duodenal ulcer patients.
A multicenter double-blind study was made to compare whether 1,000 mg dosage of cimetidine, the dose commonly employed in the United Kingdom, was as effective as the 1,200 mg. dose recommended in the United States for the treatment of duodenal ulcer. Our second goal was to test whether hospitalization would enhance the efficacy of cimetidine in the healing of duodenal ulcer. There was no difference in healing rate after either one (40%) or four (86%) weeks of therapy. In addition, hospitalization (one week) did not enhance the efficacy of cimetidine therapy.
Adult↗