Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.4 (trypsin)
 42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study demonstrates that a serine endopeptidase of pancreatic origin (elastase 2) circulates in human blood. A specific and highly sensitive radioimmunoassay has been developed for pancreatic elastase 2 in human serum. The inactivation of elastase 2 employed as radioiodinated tracer with an active site-specific reagent (phenylmethanesulfonyl fluoride) was necessary to prevent its binding by serum alpha1-antitrypsin and alpha2-macroglobulin while maintaining its immunoreactivity. The assay is based upon competition of standard human pancreatic elastase 2 with 125I-labeled phenylmethanesulfonyl elastase 2 for specific antibody binding sites, after which a second antibody precipitation step is used to separate bound from free 125I-labeled phenylmethanesulfonyl elastase 2. The minimum detectable concentration of elastase 2 was 0.9 ng/ml. The average normal fasting serum level determined was 71 ng/ml, approximately 80-fold greater than the minimum detectable amount. The form of radioimmunoassayable elastase 2 in normal human serum has been investigated by gel filtration of serum samples on Sephadex G-200 followed by radioimmunoassay of column fractions. The majority of the immunoreactive elastase 2 is eluted from G-200 in the void volume. While a minor amount of elastase 2 is eluted in a position consistent with alpha1-antitrypsin-elastase 2 complex, no free elastase or free proelastase is detectable. Addition of exogenous elastase 2 to normal serum prior to gel filtration on G-200 produced an increase only in the peak of radioimmunoassayable elastase bound to alpha1-antitrypsin. In vitro experiments have demonstrated that while elastase 2 bound to alpha1-antitrypsin is immunologically reactive, alpha2-macroglobulin-bound elastase 2 cross-reacts less than 2% in this radioimmunoassay. The assay has been shown to be specific for elastase 2. Human pancreatic elastase 1, anionic trypsin, chymotrypsin I, and chymotrypsin II do not cross-react in this assay system. The major advantages of this radioimmunoassay over enzymatic assays are its high sensitivity and ability to measure the enzyme in terms of its total protein concentration.
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PMID:Pancreatic elastase in human serum. Determination by radioimmunoassay. 83 29

Human pancreatic elastase 1 (E1) is a glycoprotein containing two potential N-glycosylation sites, one of which carries a carbohydrate moiety [Wendorf, Geyer, Sziegoleit & Linder (1989) FEBS Lett. 249, 275-278]. In order to study its glycosylation, glycoprotein isolated from post-mortem pancreas tissue of 75 donors was digested with trypsin. Oligosaccharides were liberated from resulting glycopeptides by treatment with peptide-N4-(N-acetyl-beta-glycosaminyl)-asparagine amidase F, radiolabelled by reduction with KB3H4 and separated by h.p.l.c. and gel filtration. Major oligosaccharide alditol fractions, representing 67.8 mol% of total glycans, were characterized by methylation analysis and sequential degradation with exoglycosidases. The results revealed that about two-fifths of the partially truncated, mainly biantennary, complex-type glycans found comprised blood group A, B, Lea (or X), difucosyl A or difucosyl B determinants, which could be assigned to lactosamine antennae linked to Man(alpha 1-3)- residues of the sugar chains.
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PMID:Carbohydrate structure of human pancreatic elastase 1. 189 43

Serum pancreatic enzymes (amylase, trypsin, pancreatic elastase 1, pancreatic phospholipase A2) and serum pancreatic secretory trypsin inhibitor (PSTI) were measured in 22 patients with moderate or severe acute pancreatitis. Serum levels of all pancreatic enzymes were elevated at the initial determination, but they fell rapidly to normal in both moderate and severe pancreatitis. In contrast, PSTI in severe pancreatitis increased after admission and reached the maximum on the second to the forth day after onset. There was a significant positive correlation between the level of PSTI and that of acute phase reactant (fibrinogen, alpha 1-antitrypsin), and serum PSTI in severe acute pancreatitis changed as if it was one of acute phase reactants. There was also a significant negative correlation between the level of serum PSTI and that of alpha 2-macroglobulin.
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PMID:[Changes in serum pancreatic enzymes and pancreatic secretory trypsin inhibitor in patients with severe acute pancreatitis]. 241 44

Circulating concentrations of digestive enzymes, certain lysosomal hydrolases and protease inhibitors were measured in 19 heavy smokers and 13 non-smokers before (basal) and at 15, 30, and 60 minutes after a single intravenous injection of secretin (75 CU). In smokers, basal serum amylase and immunoreactive pancreatic elastase 2 (IRE2) concentrations were about 100% and 25% higher respectively, than in the non-smokers, whereas, no differences were observed in basal immunoreactive cationic trypsinogen (IRCT) concentrations and in acid phosphatase and beta-glucuronidase activities between the two groups. Furthermore, a single injection of secretin to cigarette smokers significantly increased serum amylase, IRCT and IRE2 by 155%, 200%, and 100%, respectively when compared with their corresponding basal levels. No such increment was observed in the non-smokers. In addition, there were no significant differences in serum trypsin or elastase inhibitory capacity or immunoreactive alpha 1-protease inhibitor and alpha 2-macroglobulin levels between smokers and non-smokers. The levels and inhibitory capacity of these protease inhibitors was also not affected by secretin injection. These data suggest that cigarette smoking enhances the responsiveness of the exocrine pancreas to a physiological stimulus such as secretin, with resultant substantial increase in the concentrations of pancreatic hydrolases in blood.
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PMID:Raised serum concentrations of pancreatic enzymes in cigarette smokers. 243 81

Previous studies on the pathogenesis of abdominal aortic aneurysms have shown both elastase-like activity in the aortic wall and a decreased elastin content. The present study, using specific radioimmunoassays for pancreatic elastase 2 (IRE2) and cationic trypsin(ogen) (IRCT), investigates the concentrations of these proteases which are known to circulate in blood, in abdominal aortic aneurysms. Aortic specimens were obtained from 32 patients with aneurysms and 21 patients with atherosclerotic occlusive disease. Aortic tissue, obtained at autopsy from young adults, served as controls. Elastase-like activity was 300% and 800% higher, respectively, in aortic homogenates from aneurysms in comparison to occlusive disease and control aortic tissue. This was associated with 1.4-fold higher level of IRE2 and 2.7-fold higher levels of IRCT as compared to occlusive disease. Although there was no significant difference in the aortic collagen concentration among all 3 groups, the elastin content of aneurysmal aorta was 85% and 74% lower, respectively, in comparison to control and occlusive aorta. The results of this investigation demonstrate the presence of pancreatic elastase 2 and cationic trypsin(ogen) in abdominal aortic aneurysmal tissue and suggest that circulating pancreatic proteases contribute to the pathophysiology of aneurysms of the infrarenal aorta.
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PMID:Assessment of the role of pancreatic proteases in human abdominal aortic aneurysms and occlusive disease. 318 Apr 83

To elucidate the injurious effects of alcohol on the human pancreas, serum pancreatic enzymes were followed for the first 2 months of abstinence in 31 asymptomatic alcoholics. Sequential declines of serum enzymes were observed in immunoreactive human pancreatic elastase 1 and trypsin (IRE and IRT) as well as gamma-glutamyl transpeptidase (gamma-GTP), creatine phosphokinase (CPK) and glutamate-oxaloacetate transaminase (GOT) during the abstinence. The incidence of abnormally high enzyme activities found initially changed by the end of 2 months of abstinence as follows: from 55 to 6% for IRE, from 25 to 0% for IRT, from 3 to 6% for amylase, from 76 to 22% for gamma-GTP, from 69 to 39% for CPK, from 55 to 12% for GOT, and from 38 to 12% for GPT, respectively. The decline suggests that excessive intake of alcohol enhances the escape of the enzymes from the pancreas into the serum, probably altering membrane permeability or cellular metabolism of the pancreas, a direct toxic effect of alcohol.
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PMID:Changes in serum pancreatic enzymes during 2 months' abstinence in asymptomatic chronic alcoholics. 618 Jun 32

A radioimmunoassay for determination of human pancreatic elastase 1 was developed and the interaction of pancreatic elastase 1 with serum protease inhibitors (alpha 2-macroglobulin and alpha 1-antitrypsin) was investigated. Gel filtration studies showed that immunoreactive elastase 1 was present in serum and intact plasma as a complex with alpha 1-antitrypsin. Proelastase 1 in human pancreatic juice did not bind to protease inhibitors. But, after incubation with human serum or after activation with bovine trypsin, it was present as a complex with alpha 1-antitrypsin. The pancreatic elastase 1 content of the serum, measured by radioimmunoassay, was found to be influenced by the contents of both serum alpha 2-macroglobulin and alpha 1-antitrypsin. A significant inverse correlation was observed between the serum immunoreactive elastase 1 and alpha 2-macroglobulin contents in various hepatic diseases. The concentration of serum immunoreactive pancreatic elastase 1 was 1.79 +/- 0.62 ng/ml (mean +/- SD) in 28 normal controls. Its concentration was significantly increased in patients with acute pancreatitis, and although its concentration varied widely in patients with pancreatic cancer, its average concentration in these patients was significantly elevated.
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PMID:Radioimmunoassay of human pancreatic elastase 1. In vitro interaction of human pancreatic elastase 1 with serum protease inhibitors. 619 79

The total daily amount of extractable cationic trypsin, chymotrypsin, and pancreatic elastase 2 in feces and ileostomy fluids has been studied in normal individuals and healthy colectomized subjects. Quantitation was performed using immunological assays with polyethylene glycol as a fecal marker. The extractable amount of each of these enzymes in the feces of normal individuals was less than 1 mg/24 h. However, in fecal extracts from antibiotic-treated normal individuals a 100-fold increase in immunoreactive cationic trypsin was observed, while chymotrypsin and elastase 2 were only 2- to 3-fold higher. In extracts from ileostomy fluids cationic trypsin, elastase, and chymotrypsin all showed mean values in the order of 50-200 mg/24 h. The characterization of the immunoreactivity of pancreatic proteases showed no qualitative differences when measured in duodenal juice or fecal and ileostomy extracts.
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PMID:Determination of immunoreactive trypsin, pancreatic elastase and chymotrypsin in extracts of human feces and ileostomy drainage. 655 6

A peak of immunoreactive pancreatic elastase 2 with a molecular weight consistent with that of a complex of elastase 2 and alpha 1-protease inhibitor (also referred to as alpha 1-antitrypsin) can be detected by radioimmunoassay in normal human serum or plasma (Geokas et al., J. Biol. Chem. 252:61-67, 1977). This material has been purified by gel filtration on Sephadex G-200 and by ion-exchange chromatography on DEAE-cellulose. The alpha 1-protease inhibitor-bound immunoreactive elastase 2 has been dissociated by incubation with hydroxylamine, and the resulting immunoreactive product isolated by gel filtration on Sephadex G-100. The dissociated immunoreactive elastase 2 was shown by affinity chromatography on turkey egg white inhibitor-bound agarose, before and after activation by bovine trypsin, to consist only of proelastase 2. A second peak of immunoreactive material associated with the high molecular weight fraction of plasma has been shown to result from a specific interaction of the 125I-labeled phenylmethanesulfonyl-elastase 2 employed as tracer in the radioimmunoassay with alpha 2-macroglobulin, resulting in apparent immunoreactivity. These results demonstrate that all of the detectable immunoreactive pancreatic elastase 2 in normal human plasma is proelastase 2 bound to alpha 1-protease inhibitor.
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PMID:Demonstration of a pancreatic proelastase 2-alpha 1-protease inhibitor complex in normal human plasma. 696 39

The determination of faecal pancreatic elastase 1 is a reliable test for the diagnosis of chronic pancreatic diseases in man due to its high sensitivity and specificity (93%). A clinical study was performed to investigate the detectability of canine faecal pancreatic elastase with polyclonal anti human pancreatic elastase 1 antibodies in 52 dogs with chronic diarrhoea and weight loss. To assess the diagnostic value of this parameter for the diagnosis of exocrine pancreatic insufficiency (EPI) in dogs faecal chymotrypsin activity was determined and serum trypsin-like immunoreactivity (TLI) concentration was measured within the Ceruletid test in all patients. The study revealed that canine faecal pancreatic elastase cross reacts with polyclonal anti human pancreatic elastase 1 antibodies. In comparison with the results of the other pancreas tests it was proved that the concentration of canine faecal pancreatic elastase determined by rocket immunoelectrophoresis is highly sensitive for EPI in dogs (sensitivity 100%) but there are species differences in specificity between man and dog (specificity 56.5%).
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PMID:[Determination and clinical relevance of fecal pancreatic elastase in dogs]. 993 98


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