Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is believed that activation of zymogen proteases occurs in the early development of acute pancreatitis. This hypothesis was proved on subcellular fractions of rat pancreas after induction of pancreatitis by infusion of high doses of cerulein for 2 h. Secretory enzyme activities were measured spectrophotometrically in subcellular fractions obtained by differential ultracentrifugation. Additionally, trypsin and chymotrypsin activities were detected by enzyme blots after isoelectric focusing. Finally immunoblotting (Western-blot analysis) for amylase, lipase, trypsin/ogen, and chymotrypsin/ogen was carried out on fractions separated by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). In cerulein pancreatitis, subcellular fractions of secretory granules and vacuoles showed significant amounts of free trypsin and chymotrypsin activities compared with controls. The presence of free activities of serine proteases was paralleled by the appearance of numerous low molecular weight peptides detected by 2-dimensional electrophoresis and SDS-PAGE, which in part represented proteolytically cleaved secretory proteins. It is concluded that the intracellular activation of serine proteases that occurs in cerulein pancreatitis could contribute to further acinar cell destruction.
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PMID:Evidence of intracellular activation of serine proteases in acute cerulein-induced pancreatitis in rats. 170 79

Dog polymorphonuclear leukocyte cathepsin G was isolated from a granule extract using a two-step procedure including affinity chromatography on a Trasylol-Sepharose gel and ion-exchange chromatography on a CM 52 column. 22 of the first 24 N-terminal amino acids were determined and showed 83% and 71% identity to those of human and rat cathepsin G, respectively. Total amino-acid composition demonstrated the basic nature of the protein. In an SDS/polyacrylamide-gel electrophoresis the protein showed an Mr of 29,400 compared to the Mr of 26,800 calculated from the total amino-acid composition. The enzyme was shown to form complexes with alpha 1 alpha 2-macroglobulin and alpha 1-proteinase inhibitor. A specific enzyme-linked immunosorbent assay was developed for the determination of cathepsin G/alpha 1-proteinase inhibitor complex in dog plasma and tissue fluids. The mean concentration of cathepsin G in normal dog plasma was determined to be 38 micrograms/l, measured as cathepsin G/alpha 1-proteinase inhibitor complex. When active dog cathepsin G was added to normal dog plasma in vitro, approximately 56% could be measured by the assay. Slow intravenous infusion of a lethal dose of endotoxin in dogs was followed by a marked drop in white blood cell count and thrombocytes and a simultaneous rapid increase in plasma cathepsin G concentration, reaching a maximum level of 150 micrograms/l. Bile-induced experimental pancreatitis in dogs was accompanied by successive increase in cathepsin G levels in plasma as well as in peritoneal exudates, reaching a maximum level of about 300 micrograms/l in plasma and 18 mg/l in the exudates during the late stages of disease.
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PMID:Release of dog polymorphonuclear leukocyte cathepsin G, normally and in endotoxin and pancreatitic shock. Isolation and partial characterization of dog polymorphonuclear leukocyte cathepsin G. 191 May 80

Caerulein-induced acute pancreatitis is characterized by the occurrence of two membrane-bound vacuolar systems in acinar cells. Beside digestive enzymes containing secretory vacuoles, lysosomal autophagic structures can be identified at the ultrastructural level. In the present study glycoconjugate patterns of the surrounding membranes were characterized by ultrastructural lectin-binding experiments using five colloidal-gold labeled lectins with distinct sugar specificities. Furthermore, the profile of membrane glycoproteins of isolated vacuolar fractions was studied by SDS-PAGE and lectin-blotting. In pancreatitis, membranes of secretory vacuoles showed a significant lower degree of lectin-binding compared to normal zymogen granules. In contrast, newly appearing autophagic vacuoles in pancreatitis revealed a strong membrane labelling for most lectins used. The pattern of membrane glycoproteins of secretory and autophagic vacuoles as determined by SDS-PAGE and lectin-blotting differed from those of normal zymogen granules resembling the protein profile of smooth microsomes. Since this pattern requires a previous passage through Golgi stacks, it is assumed that the two types of vacuoles derive from Golgi elements. For the pathogenesis of caerulein pancreatitis these vacuolar post-Golgi structures seem to play an important role.
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PMID:Caerulein-induced acute pancreatitis in rats: changes in glycoprotein-composition of subcellular membrane systems in acinar cells. 228 36

This study investigates the effect of ethanol on enzyme synthesis and secretion in rat pancreatic lobules. Ethanol caused a dose-dependent inhibition of 3H-leucine incorporation into total protein. Examination of the time dependence showed that ethanol inhibited protein synthesis at each time point. Removal of ethanol partially reversed this inhibition. An autoradiograph of the newly synthesized proteins separated on SDS-PAGE showed that ethanol inhibited synthesis of all proteins. 14C-cycloleucine uptake was not altered by ethanol, excluding inhibition of amino acid uptake as the mechanism for the decreased protein synthesis induced by ethanol. Electron microscopy revealed no ultrastructural damage. Ethanol had no effect on the stimulated release of (i) amylase from zymogen granules nor (ii) newly synthesized pulse labelled enzymes. Acetaldehyde had no inhibitory effect on enzyme synthesis or secretion indicating that ethanol per se and not its metabolite is inhibitory. The decreased synthesis after acute exposure to ethanol with preservation of exocytosis would limit the autodigestive potential of pancreatic tissue. This may explain why isolated toxic doses of ethanol are rarely if ever associated with pancreatitis.
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PMID:The effect of ethanol on enzyme synthesis and secretion in isolated rat pancreatic lobules. 244 46

The mechanism leading to exocrine pancreatic disease in children differs from those encountered in adult patients: I. In acute pancreatitis autodigestion of the gland by proteolytic enzymes may occur and two mechanisms may play a role. 1. Reflux of biliary secretions (e.g. in malformations of the duct system) facilitates activation of trypsinogen by enteropeptidase and leads to the presence of active proteolytic enzymes in the gland (exogenous activation). 2. Lysosomal enzymes may play a role in the intracellular activation of zymogens if inflammation leads to a fusion of lysosomes with zymogen granules (endogenous activation). II. In chronic relapsing and hereditary pancreatitis malformations of the pancreatico-biliary duct system must be sought because surgery may be indicated (common channel syndrome and choledochal cysts). III. Among the hereditary diseases leading to pancreatic insufficiency cystic fibrosis (CF) plays the main role. Haplotype analysis has shown that two genetically different types of CF exists (PS and PI). The pancreas shows manifest insufficiency only in the PI-types which occur in more than 70% of cases but the distribution of haplotypes is different in different ethnic groups. In spite of the recent discovery of the cystic fibrosis gene the exact mechanism leading to exocrine pancreatic dysfunction in CF is not clear, but diminished chloride and bicarbonate secretion, may be the result of a disturbance in the regulation of chloride channels, on acinar or ductular level. In the Shwachman-Diamond syndrome a very severe type of exocrine insufficiency with unknown etiology is encountered at birth.
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PMID:[Physiopathology of the exocrine pancreas in children]. 269 2

Impaired secretion of lithostathine, a pancreatic glycoprotein capable of inhibiting the growth of CaCO3 crystals, has been reported in chronic calcifying pancreatitis. Controversial results were obtained, however, using immunoassays with different antibodies. The aim of this study was to purify and to measure juice lithostathine by a non-immunological method. Fast protein liquid chromatography (FPLC) on a cation exchange column eluted by a sodium chloride gradient, was used. The conditions appropriate to separate secretory (S) from hydrolysed (H) isoforms of immunopurified lithostathine were also used for juice analysis. Pancreatic juice was collected by endoscopic cannulation of the major pancreatic duct, after secretin stimulation, from eight patients with chronic pancreatitis (CP) and from eight controls. In all samples, S-isoforms of lithostathine (ranging from 16 to 19 Mr at SDS-PAGE) were the only constituent of two of the 15 peaks in which FPLC resolved the pancreatic proteins. The nature of these two peaks was confirmed by their coelution with immunopurified S-lithostathine and by immunoblot analysis with polyclonal anti-lithostathine antibodies. The ratio between the area of S-lithostathine peaks and the total area of proteic eluates, was always lower in CP patients (5.3 micrograms/mg of protein, median value; 0.2-15.4, range) than in controls (35.2 micrograms/mg; 16.6-55.9). It is concluded that lithostathine can be purified and measured in pancreatic juice by FPLC. Our results with a nonimmunological assay confirm a reduced secretion of lithostathine in patients with CP.
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PMID:Purification and assay of secretory lithostathine in human pancreatic juice by fast protein liquid chromatography. 773 74

Phospholipase A2 (PLA2, E.C. 3.1.1.4) was purified from rat pancreatic tissue by heat treatment of the homogenate and use of cation-exchange chromatography on a CM-Sepharose column. The enzyme was apparently homogenous on SDS polyacrylamide gel electrophoresis, and its mol wt was estimated to be 14,400. An antiserum raised against rat pancreatic PLA2 in a rabbit was used in a solid-phase enzyme immunoassay employing inorganic pyrophosphatase (E.C. 3.6.1.1) as the enzyme label. As measured by this assay, the concentration of pancreatic PLA2 in plasma was found to be above normal in rats with hemorrhagic pancreatitis induced by an intraductal injection of sodium taurocholate. PLA2 was localized in pancreatic acinar cells and in the chief cells in the mucosa of the glandular stomach by immunohistochemistry. By immunoelectron microscopy, the immunogold conjugates were mainly located on profiles of zymogen granules in acinar cells.
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PMID:Rat pancreatic phospholipase A2. Purification, localization, and development of an enzyme immunoassay. 850 52

In children with pancreatic disease, computed tomography (CT) has a primary role in the evaluation of pancreatitis, trauma, and malignancy. At CT, pancreatic abnormalities may manifest as pancreatic enlargement (tumor, acute pancreatitis), pancreatic atrophy (cystic fibrosis, chronic pancreatitis), cystic lesions (pseudocysts, congenital simple cysts, autosomal dominant polycystic kidney disease, von Hippel-Lindau disease, cystic fibrosis, cystic neoplasms), or fatty replacement (cystic fibrosis, Shwachman-Diamond syndrome, history of steroid therapy, Cushing syndrome, Johanson-Blizzard syndrome, obesity). CT is the best modality for evaluation of pancreatitis, allowing detection of pancreatic abnormalities as well as abnormal extrapancreatic fluid collections. In children who have undergone blunt abdominal trauma, CT has been shown to be the best initial imaging study, being more sensitive than ultrasound for detection of pancreatic injury. In neoplastic conditions, CT demonstrates the extent of disease, enables characterization of the tissue components of the tumor, and allows accurate posttreatment follow-up. Although the various diseases of the pancreas may have overlapping appearances at CT, the correct diagnosis can often be made on the basis of the CT findings in combination with the clinical history, laboratory data, and the patient's age.
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PMID:Pancreatic disease in children and young adults: evaluation with CT. 974 14

Inflammation of the pancreas (pancreatitis) has many presentations in children and adolescents, ranging from intrauterine congenital onset with sequelae of early exocrine pancreatic insufficiency as in the diseases of cystic fibrosis and Shwachman-Diamond syndrome to postnatal onset as a consequence of embryologic anomalies affecting pancreatic drainage postulated to exist in pancreas divisum, or of traumatic, obstructive, hemodynamic, metabolic or biochemical insults. The etiology is often elusive with up to 30% of cases being idiopathic. Modern imaging modalities of endoscopic ultrasonography and magnetic resonance cholangiopancreatography extend the diagnostic power of conventional abdominal ultrasonography and computed tomography. In addition, there is increasing pediatric experience with endoscopic retrograde cholangiopancreatography. Medical management remains supportive, with optimal timing and indications for surgery in cases of pancreatic necrosis and pseudocyst assessed. Three temporal patterns of pancreatitis appear in children: acute pancreatitis, recurrent acute pancreatitis, and chronic pancreatitis. Acute pancreatitis is of abrupt onset, often attributable to a specific cause, and of variable severity and duration but self-limited with eventual resolution. Acute attacks of pancreatitis recurring after periods of remission characterize acute recurrent pancreatitis and indicate an intrinsic problem or susceptibility. Chronic pancreatitis is present in most of these cases in which pancreatic inflammation and destruction never completely remits.
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PMID:Pancreatitis: etiology, diagnosis, and management. 1180 91

Enzymes with gelatinolytic activity were detected in Tityus bahiensis and Tityus serrulatus venom. Their activity was optimal at pH 8.0 in SDS-PAGE-gelatin. They were inhibited by PMSF but not by iodoacetamide, pepstatin or phenantrolin in the assay conditions used. This suggests that these enzymes are serine proteases. The presence of metal ions did not affect the proteolytic activity of these enzymes. Several possible functions may be envisaged for these enzymes: in tissue permeabilization, pancreatitis and toxin processing.
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PMID:Enzymes with gelatinolytic activity can be found in Tityus bahiensis and Tityus serrulatus venoms. 1207 59


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