The effect of carbon tetrachloride on rat-liver lysosomes.
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Biomedical subjects
Publications and source records attributed to D H Alpers.
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Alkaline phosphatase activity in the liver and intestine increases after bile duct ligation, reportedly by increased enzyme synthesis. To ascertain the mechanism of this increased synthesis in the absence of a cDNA clone encoding the enzyme, we have estimated the concentration of liver and intestinal alkaline phosphatase mRNA by translational analysis. Monospecific antiserum to rat placental alkaline phosphatase was raised. The resulting antiserum precipitated two peptides of 53 and 56 kd after translation of liver poly(A) + RNA. The precipitation of both peptides was blocked by the single 64 kd placental alkaline phosphatase. Processing of the cell-free products by microsomal membranes produced peptides of 62 and 64 kd. Antiserum to rat intestinal alkaline phosphatase also identified two peptides as products of intestinal RNA translation. After bile duct ligation, we confirmed a transient 2-fold increase in alkaline phosphatase activity in the intestine and a more constant 7-fold increase in the liver. However, the alkaline phosphatase mRNA concentration remained unchanged in both organs. We conclude that increased alkaline phosphatase synthesis after bile duct ligation results from an enhanced rate of translation of mRNA.
Until recently, structural information regarding large brush border proteins was obtained largely by protein purification and protein chemistry. Molecular biology has added the techniques of cell-free translation and cDNA cloning to provide additional information. In addition, the regulation of protein synthesis was largely deduced by the use of inhibitors of protein or nucleic acid synthesis. The ability to assess mRNA content by cell-free translation or by hybridization with isolated cDNA has expanded these studies. Moreover, polysomal isolation and organ explants can now be used to determine synthetic and secretion rates directly. Future research in these areas will depend upon the isolation of cDNA clones encoding specific enterocyte proteins to simplify structural analysis, as well as the use of intestinal cell lines to simplify measurement of synthetic rates and protein processing.
The prevalence of irritable bowel syndrome (IBS) in psychiatric practice was studied in 41 consecutive psychiatric outpatients. Different criteria for IBS were applied to the data set to determine the effects on the rates of IBS obtained. Depending on an option in the Rome criteria, IBS rates varied from 13% using the "and" requirement for combining abdominal pain and altered bowel function symptoms, to 41% using the "and/or" option described in the formal definition statement in 1990. The resultant prevalence rates of IBS varied greatly according to which published criteria were applied, with a maximum of 71%. This wide variation in rates depending on the criteria underscores the critical importance of standardizing diagnostic research criteria for IBS. An exemplary model of empirically based validation has been developed for psychiatric disorder criteria which, like IBS, are symptom-based and lack physiological determinants. Validated diagnostic criteria for IBS await similar study.
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BACKGROUND: The 1997 A.S.P.E.N. Research Workshop was held at the annual meeting in San Francisco, on January 26, 1997. The workshop focused on advances in clinical and basic research involving the interface between nutrient and luminal gastroenterology. METHODS: Presentations on the genetic regulation of gastrointestinal development, the molecular biology of small intestinal adaptation, the effect of nutrition support on intestinal mucosal mass, the relationship between nutrition and gastrointestinal motility, nutrient absorption, and gastrointestinal tract substrate metabolism were made by the preeminent leaders in the field. RESULTS: The investigators presented an insightful analysis of each topic by reviewing data from their own laboratories and the published literature. CONCLUSIONS: This workshop underscored the important interactions between nutrition and luminal gastroenterology at the basic science, metabolic/physiologic, and clinical levels. The integration of presentations from the different disciplines provided a unique interaction of information and ideas to advance our understanding of nutrition and gastrointestinal tract.