UMLS:C0149521 - FACTA Search

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Query: UMLS:C0149521 (chronic pancreatitis)
7,199 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In 11 conscious normovolaemic patients with acute or chronic pancreatitis the effect of a continuous intravenous infusion of lysine-8-vasopressin, 5 IU/70 kg b.w./20 min on the portal and the hepatic venous blood flows was studied by using multiple portal catheters, oxygen saturation measurements and an indicator dilution technique with continuous infusion of 133Xe into the portal vein or its tributaries. During vasopressin infusion the total hepatic blood flow, estimated by the Bradley technique with indocyanine green dye, was reduced to 61% of the value at rest. Owing to the simultaneously occurring streamlining of the portal venous flow with incomplete mixing of indicator and blood, the portal and hepatic venous blood flows could be measured in only 3 of 9 patients. The reduction in the portal venous blood flow during vasopressin infusion was more marked than the decrease of the total hepatic flow, corresponding to a calculated increase of the hepatic arterial flow of 50%. Total splanchnic oxygen uptake and extrahepatic splanchnic oxygen uptake were unchanged during and after infusion of vasopressin. Thus, changes in splandhnic blood flow could be estimated from changes in arteriovenous oxygen differences. Also by this method a more pronounced reduction in the portal venous than of the hepatic venous blood flow was observed. The decrease during vasopressin infusion of the superior mesenteric venous flow was more marked than that of the splenic vein. The splanchnic circulatory changes may be different for other doses of vasopressin and in cirrhotic patients with higher hepatic arterial blood flow fractions.
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PMID:Effect of vasopressin on regional splanchnic blood flows in conscious man. 126 41

We report the first case to our knowledge of chronic pancreatitis associated with mitochondrial encephalopathy with the A8344G mitochondrial DNA (mtDNA) mutation. This 10-year-old-girl had suffered from recurrent abdominal pain with elevated serum amylase and lipase since the age of 6, and easy fatigability, tremor and astatic seizures since the age of 8. A biopsy of quadriceps muscle revealed ragged-red-fibers and cytochrome c oxidase deficiency. Analysis of mtDNA in peripheral blood identified an A8344G mutation in the mitochondrial tRNA(Lys) gene. Taken together with physical signs of myoclonic seizures and cerebellar dysfunction, we diagnosed her as myoclonic epilepsy with ragged-red fibers associated with chronic pancreatitis. Although no association between mitochondrial disease and pancreatitis has yet been established, this case suggests it is necessary to consider the participation of mitochondrial abnormality in the pathogenesis of recurrent pancreatitis.
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PMID:A case of MERRF associated with chronic pancreatitis. 1129 46

The activation peptide of mammalian trypsinogens contains a highly conserved tetra-aspartate sequence (D19-D20-D21-D22) preceding the K23-I24 scissile peptide bond, which is hydrolyzed as the first step in the activation process. Here, we examined the evolution and function of trypsinogen activation peptides through integrating functional characterization of disease-associated mutations with comparative genomic analysis. Activation properties of three chronic pancreatitis-associated activation peptide mutants (the novel D19A and the previously reported D22G and K23R) were simultaneously analyzed, for the first time, in the context of recombinant human cationic trypsinogen. A dramatic increase in autoactivation of cationic trypsinogen was observed in all three mutants, with D22G and K23R exhibiting the most marked increases. The physiological activator enteropeptidase activated the D19A mutant normally, activated the D22G mutant very poorly, and stimulated activation of the K23R mutant. The biochemical and structural data, taken together with a comprehensive sequence comparison, indicates that the tetra-aspartate sequence in mammalian trypsinogen activation peptides has evolved not only for optimal enteropeptidase recognition in the duodenum but also for efficient inhibition of trypsinogen autoactivation within the pancreas. Moreover, the use of lysine instead of arginine at the P1 position of activation peptides also has an advantageous effect against trypsinogen autoactivation. Finally, fixed substitutions in the key residues of the trypsinogen activation peptide may suggest the evolution of new functions unrelated to digestion, as found in the group III trypsinogens of cold-adapted fishes.
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PMID:Evolution of trypsinogen activation peptides. 1283 30

Enteropeptidase, a type II transmembrane serine protease, is localized to the brush border of the duodenal and jejunal mucosa. It is synthesized as a zymogen (proenteropeptidase) that requires activation by another protease, either trypsin or possibly duodenase. Active enteropeptidase then converts the pancreatic precursor, trypsinogen, to trypsin by cleavage of the specific trypsinogen activation peptide, Asp-Asp-Asp-Asp-Lys- Ile that is highly conserved in vertebrates. Trypsin, in turn, activates other digestive zymogens such as chymotrypsinogen, proelastase, procarboxypeptidase and prolipase in the lumen of the gut. The important biological function of enteropeptidase is highlighted by the manifestation of severe diarrhea, failure to thrive, hypoproteinemia and edema as a result of congenital deficiency of enteropeptidase activity in the gut. Conversely, duodenopancreatic reflux of proteolytically active enteropeptidase may cause acute and chronic pancreatitis.
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PMID:Enteropeptidase, a type II transmembrane serine protease. 1948 41

Chronic pancreatitis represents a risk factor for the development of pancreatic cancer. We find that heterozygous loss of histone H2A lysine 119 deubiquitinase BAP1 (BRCA1 Associated Protein-1) associates with a history of chronic pancreatitis and occurs in 25% of pancreatic ductal adenocarcinomas and 40% of acinar cell carcinomas. Deletion or heterozygous loss of Bap1 in murine pancreata causes genomic instability, tissue damage, and pancreatitis with full penetrance. Concomitant expression of Kras^G12D leads to predominantly intraductal papillary mucinous neoplasms and mucinous cystic neoplasms, while pancreatic intraepithelial neoplasias are rarely detected. These lesions progress to metastatic pancreatic cancer with high frequency. Lesions with histological features mimicking Acinar Cell Carcinomas are also observed in some tumors. Heterozygous mice also develop pancreatic cancer suggesting a haploinsufficient tumor suppressor role for BAP1. Mechanistically, BAP1 regulates genomic stability, in a catalytic independent manner, and its loss confers sensitivity to irradiation and platinum-based chemotherapy in pancreatic cancer.
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PMID:BAP1 is a haploinsufficient tumor suppressor linking chronic pancreatitis to pancreatic cancer in mice. 3254 68