alpha-chymotrypsin and Liver-Diseases

Kallistatin, a human serine proteinase inhibitor, is a newly identified tissue kallikrein inhibitor. It binds strongly to tissue kallikrein but weakly to other serine proteinases such as chymotrypsin and elastase. The tissue distribution and changes in kallistatin levels in human diseases were characterized by using specific monoclonal and polyclonal antibodies against kallistatin. Kallistatin antigen levels in blood cells, fluids, and tissues measured with a specific enzyme-linked immunosorbent assay showed displacement curves that were parallel with those in purified kallistatin, indicating their immunologic identity. Expression of kallistatin mRNA in platelets, neutrophils, lymphocytes, monocytes, endothelial cells, hepatocytes, and colon and prostate carcinoma cells was identified by reverse transcription-polymerase chain reaction followed by Southern blot analysis. Plasma kallistatin concentration was 22.1 +/- 3.5 micrograms/ml in 30 normal subjects and 21.1 +/- 3.8 micrograms/ml in 5 patients with C1 inhibitor deficiency. A significantly reduced kallistatin level (7.2 +/- 2.5 micrograms/ml, p < 0.001) was seen in plasma samples from 9 patients with liver disease and 10 patients with sepsis (7.7 +/- 3.5 micrograms/ml, p < 0 .001). Further, kallistatin levels in 10 women taking oral contraceptives (19.8 +/- 3.8 micrograms/ml) and 21 pregnant women (14.9 +/- 3.3 microg/ml) were significantly lower than those seen in healthy individuals. These data suggest that kallistatin is found in plasma, is produced mostly in the liver, and can be consumed during sepsis. Its consumption in sepsis may indicate a protective role to prevent blood pressure lowering.

Topics: Antibodies, Monoclonal; Base Sequence; Blood Cells; Blotting, Western; Body Fluids; Carrier Proteins; Chymotrypsin; Enzyme-Linked Immunosorbent Assay; Female; Humans; Kallikreins; Liver Diseases; Male; Molecular Sequence Data; Pancreatic Elastase; Pregnancy; Sepsis; Serpins; Tissue Distribution

Antitrypsin Siiyama is a rare example of the deficiency variants of antitrypsin that accumulate in the endoplasmic reticulum of the hepatocyte. The common example is Z antitrypsin, which has a mutation (Glu342-->Lys) at the junction of the head of the fifth strand of the A sheet and the base of the reactive center loop. It was previously shown that Z antitrypsin spontaneously polymerizes due to the insertion of the reactive center loop of one molecule into the A sheet of a second. The mutation in antitrypsin Siiyama (Ser53-->Phe) affects a residue that provides a ridge for the sliding movement that opens the A sheet, and it had been predicted that this would result in the same type of loop-sheet polymerization observed with the Z variant. We confirm this here and show that virtually all the plasma antitrypsin in a homozygote for the Siiyama variant was polymerized due to non-covalent bonding with a loss of accessibility of the reactive center loop. The common basis of the polymerization of Z and Siiyama antitrypsin is supported by identical findings on electron microscopy. Taken together these results confirm that loop-sheet polymerization is a general mechanism and as such is likely to be responsible for the intracellular inclusions associated with liver pathology.

Topics: Adult; alpha 1-Antitrypsin; Animals; Cattle; Chymotrypsin; Homozygote; Humans; Liver Diseases; Male; Microscopy, Electron; Models, Molecular; Mutation; Phenylalanine; Polymers; Serine

We studied 229 patients with biopsy verified liver disease and compared the plasma levels of alpha 1-antichymotrypsin and alpha 1-antitrypsin. We found a significant overall correlation between alpha 1-antichymotrypsin and alpha 1-antitrypsin levels (r = 0.50, p less than 0.001). The strongest correlations were found in patients with chronic active hepatitis (r = 0.76, p less than 0.0001) and alcohol hepatitis (r = 0.60, p less than 0.001). Several clinical subgroups lacked correlation. Unexpectedly high alpha 1-antichymotrypsin values were found in patients with venous congestion. We also used the alpha 1-antichymotrypsin/alpha 1-antitrypsin ratio as a tool to identify PiZ carriers (intermediate alpha 1-antitrypsin-deficiency, PiZ). The sensitivity and predictive values were low and did not exceed that obtained by the simple use of an isolated alpha 1-antitrypsin determination. A small subgroup with low alpha 1-antichymotrypsin/alpha 1-antitrypsin ratio included patients with chronic active hepatitis of unknown etiology. Hypo-alpha 1-antichymotrypsinemia may be secondary to the liver disease per se or be an expression of an abnormal genetic trait.

Topics: Adolescent; Adult; Aged; alpha 1-Antichymotrypsin; alpha 1-Antitrypsin; alpha 1-Antitrypsin Deficiency; Chymotrypsin; Female; Genetic Carrier Screening; Hepatitis, Alcoholic; Hepatitis, Chronic; Humans; Liver Diseases; Liver Diseases, Alcoholic; Male; Middle Aged; Phenotype

Assessment of the clinical value of the pancreolauryl test (PLT) in the literature range from "useless" to a specifity of 95% and a sensitivity of 98%. In this work, our own data are presented in relation to various reference methods. The results are derived from the largest collective investigated to data, comprising 40 controls and 391 patients (108 with chronic pancreatitis and 283 with other gastrointestinal disorders). The specifity of the the PLT varies between 81% and 95% according to the "quality" of the control collective. The PLT is particularly frequently pathological in patients with diseases in the region of the gallbladder/bile duct and the gastrointestinal tract. The sensitivity of the PLT for chronic pancreatitis varies between 68% and 100%, depending on 9 different reference methods employed. Based on the prevalence of chronic pancreatitis with exocrine insufficiency in various patient collectives, the predictive value of the PLT for the presence of this disorder can be calculated using our data.

Topics: Cholangiopancreatography, Endoscopic Retrograde; Cholecystokinin; Cholelithiasis; Chronic Disease; Chymotrypsin; Diagnosis, Differential; Exocrine Pancreatic Insufficiency; Gastrointestinal Diseases; Humans; Liver Diseases; Pancreatic Diseases; Pancreatic Function Tests; Pancreatitis; Secretin; Tomography, X-Ray Computed

The serum levels of alpha-1-antichymotrypsin (ACT) were studied in 168 patients with various liver diseases and cancers in conjunction with other liver function tests, serum sialic acid, AFP and CEA. The ACT levels in acute viral hepatitis and chronic hepatitis were not significantly altered compared with the normal level (220 +/- 40 microgram/ml), although the level was slightly increased or decreased temporarily during the acute phase of the former. In liver cirrhosis, the mean level was significantly lower than the normal in spite of the absence of signs of hepatic decompensation (168 +/- 51 microgram/ml, p less than 0.001). In contrast to cirrhosis, the levels were increased to various extents in 65% of cases with hepatoma, in spite of the association of liver cirrhosis in the majority of them. Much higher levels were observed in all cases of metastatic liver cancers and cancers of the pancreas and the biliary tract. The elevations were observed even in cases without the increase of AFP or CEA. Both in cirrhosis and cancers, ACT levels were not correlated with any of serum bilirubin and serum enzyme activities, but were positively correlated with the levels of plasma fibrinogen and serum sialic acid. The measurement of serum ACT level can be taken advantage of for the diagnosis and monitoring of liver cirrhosis and liver cancers, particularly of hepatoma without AFP elevation.

Topics: alpha 1-Antichymotrypsin; alpha-Fetoproteins; Blood Sedimentation; Carcinoembryonic Antigen; Carcinoma, Hepatocellular; Chymotrypsin; Fibrinogen; Humans; Liver Cirrhosis; Liver Diseases; Liver Neoplasms; Sialic Acids

Topics: Body Weight; Celiac Disease; Child, Preschool; Chymotrypsin; Cystic Fibrosis; Duodenum; Feces; Humans; Infant; Intestinal Diseases; Liver Diseases; Pancreas; Pancreatic Diseases; Time Factors

Topics: Antifibrinolytic Agents; Blood Platelets; Cholestasis; Chymotrypsin; Fatty Liver; Fibrinolysin; Hepatitis; Humans; Hypersplenism; Liver Cirrhosis; Liver Cirrhosis, Biliary; Liver Diseases; Trypsin Inhibitors

Topics: Adult; Aged; Amylases; Biliary Tract Diseases; Bromelains; Chymotrypsin; Clioquinol; Dehydrocholic Acid; Diarrhea; Endopeptidases; Gastric Acidity Determination; Gastrointestinal Agents; Humans; Lipase; Liver Diseases; Middle Aged; Oxyphenonium; Pancreatic Diseases; Pancreatin; Phenanthrolines; Stomach Diseases; Trypsin

The material comprises 34 patients with anicteric biliary diseases, 20 with obstructive jaundice, 8 with hepatic cirrhosis, and 3 with haemochromatosis. The intestinal contents were aspirated in four subsequent periods of 20 minutes each after ingestion of a standard meal. The volume, pH, and the concentration of alpha-amylase, trypsin, chymotrypsin and lipase were determined in the collections. The concentration of lipase was more markedly reduced than concentrations of amylase and of trypsin in patients with anicteric biliary diseases and in patients with hepatic cirrhosis. Concentrations of enzymes below the lowest normal value throughout the period of digestion represented an uncommon finding. The exocrine pancreatic function is rarely found to be reduced in patients with biliary or with hepatic disorders.

Topics: alpha-Amylases; Biliary Tract Diseases; Chymotrypsin; Digestion; Duodenum; Female; Humans; Hydrogen-Ion Concentration; Intestinal Secretions; Lipase; Liver Diseases; Male; Pancreas; Trypsin

Topics: Adolescent; Child; Cholelithiasis; Chymotrypsin; Clinical Enzyme Tests; Cystic Fibrosis; Diagnosis; Exocrine Pancreatic Insufficiency; Feces; Gastrointestinal Diseases; Geriatrics; Humans; Infant; Intubation; Intubation, Gastrointestinal; Liver Diseases; Pancreatic Neoplasms; Pancreatitis; Trypsin