Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ascitic fluid samples from 14 subjects with liver cirrhosis and from 13 patients with malignancy were investigated. Activated FX was present in ascitic fluid in small quantities with a mean value of 8.7 10(-3) IU/ml. The mean thrombin activity was 70.8 10(-3) IU/ml and the mean plasmin activity was 449.6 10(-3) CU/ml. High levels of fibrin/fibrinogen degradation products (mean 75.4 micrograms/ml) and of antithrombin III (mean 43.4%) were found. No statistically significant differences between values in liver cirrhosis and in malignancy were found. In 15 of 17 experiments 10-fold concentrated ascitic fluid caused irreversible platelet aggregation and [14C] serotonin release of normal platelet-rich plasma similar to collagen. The aggregating effect disappeared after addition of collagenase. These results do not support the concept that the coagulopathy after peritoneovenous shunting is a result of direct and rapid intravenous infusion of procoagulant substances. They rather point to a central role of collagen present in ascitic fluid.
 ...
PMID:Coagulant, fibrinolytic, and aggregating activity in ascitic fluid. 370 62

Experiments on mice have demonstrated ultrastructural changes in collagen and hepatocytes during reverse development of liver cirrhosis. Progressive lysis of collagenous fibers has been noted. Changes in hepatocytes point to a rise in the synthetic and endocytosis activity in these cells. It is suggested that exocellular lysis of collagen in the process under consideration is initiated by collagenase whereas subsequently it takes place under the action of lysosomal enzymes secreted by hepatocytes to the exocellular space.
 ...
PMID:[Ultrastructural aspects of the reversible nature of sclerotic changes in the liver]. 398 79

The susceptibility of hepatic collagen to homologous collagenase in human and experimental CCl4 cirrhosis of the liver has been explored in vitro by exposure of cryostat liver sections to the corresponding enzymes for different time periods. The morphology and extent of collagen degradation was studied by the Picrosirius red/polarizing microscopy technique. The results of various experiments indicate that collagen present in cryostat sections of both human and rat normal and cirrhotic livers is resistant to trypsin digestion for periods of exposure of up to 48 hours but that heating the sections to 60 C for 1 hour renders the collagen susceptible to degradation by trypsin. Incubation of cryostat liver sections with bacterial collagenase revealed progressive degradation of collagen with a uniform pattern of changes in the original color and diameter of the fibers. Exposure of liver sections to homologous collagenases gave rise to the same pattern of changes observed with bacterial collagenase, although less extensive when equal incubation periods were compared. Nevertheless, sufficiently prolonged incubation of liver sections with their homologous collagenases eventually showed degradation of all collagen present in all normal and cirrhotic liver sections. These observations suggest that in the presence of non rate-limiting concentrations of homologous collagenase, the susceptibility of hepatic collagen to the corresponding degrading enzyme is probably not responsible for the irreversibility of the disease.
 ...
PMID:The susceptibility of hepatic collagen to homologous collagenase in human and experimental cirrhosis of the liver. 615 26

The administration of progesterone increases the degree of liver cirrhosis in rats treated with CCl4 and ethanol. Pseudolobulation with large amount of interstitial fibrosis are obtained after only 6 weeks of treatment. The ability of progesterone to suppress collagenase activity is supposed to be responsible of the strong increase of cirrhosis.
 ...
PMID:[Rapid induction of liver cirrhosis in rats by treatment with ethanol, carbon tetrachloride and progesterone]. 625 75

A unifying concept that excessive proliferation of cells and turnover of cellular matrix contribute significantly to the pathogenesis of several diseases, including cancer, atherosclerosis, rheumatoid arthritis, psoriasis, idiopathic pulmonary fibrosis, scleroderma and cirrhosis of the liver, is presented. As corollaries to this concept, the following topics are considered: (1) the role of polypeptide hormones and hormone-like mediators in the initiation, promotion and maintenance of proliferative responses; (2) alterations in collagen metabolism and collagenase activity; (3) the role of proteinases; (4) the potential use of inhibitors of proteinases for prevention of disease; and (5) the potential use of inhibitors of proliferative polypeptide hormones for prevention of disease. As specific proteolytic and proliferative biochemical mechanisms which contribute to the pathogenesis of disease become identified, there is a unique opportunity to develop new pharmacologic methods of prevention.
 ...
PMID:Proliferative diseases. 626 92

To determine if alterations in collagen degradation may contribute to the pathogenesis of fibrosis and cirrhosis, we studied the hepatic collagenase activity of 20 baboons given alcohol containing diets or control diets under carefully controlled experimental conditions. We also studied 28 patients whose livers were biopsied for diagnostic purposes. Hepatic collagenase activity was significantly increased in baboons with fatty liver compared to levels in normal, control fed animals [(1.98 +/- 0.19 vs 1.20 +/- 0.08 units (microgram collagen digested/hour/mg liver protein) +/- S.E.M., p less than 0.001)]. The increase in hepatic collagenase activity persisted at the stage of fibrosis when compared to the activity in control baboons (2.16 +/- 0.07 vs 1.20 +/- 0.08 units +/- S.E.M., p less than 0.001). A single cirrhotic baboon available for study had an hepatic collagenase activity of 1.58 units. Patients with hepatic fibrosis had significantly higher hepatic collagenase activity than those with fatty livers [(9.12 +/- 0.94 (n =14) vs 4.52 +/- 0.54 (n = 7) units +/- S.E.M., p less than 0.001)]. However, in the group with cirrhosis, hepatic collagenase was lower [(3.92 +/- 0.61 (n = 7) units +/- S.E.M., p less than 0.001)] than in the group with fibrosis. Our findings suggest that the development of cirrhosis is coincident with, or favored by a failure of hepatic collagen degradative enzymes to keep pace with hepatic collagen synthesis.
 ...
PMID:Mammalian collagenase increases in early alcoholic liver disease and decreases with cirrhosis. 628 91

Correlation between content of hydroxyproline in urine, protein-bound hydroxyproline, alpha 2-macroglobulin as well as of collagen peptidase activity in blood serum and the intensity of collagen accumulation in liver tissue were studied in experimental liver tissue cirrhosis, which developed after chronic intoxication of rats with CCl4. Distinct relationship was shown between the level of hydroxyprolinuria and amount of collagen in liver tissue. Content of protein-bound hydroxyproline, alpha 2-macroglobulin and the collagen peptidase activity were quite unaltered in blood serum during the cirrhosis development. Protein-bound hydroxyproline and alpha 2-macroglobulin were markedly decreased in blood serum at the step of decompensated cirrhosis. Among the biochemical patterns studied in biological fluids only estimation of hydroxyproline in urine might distinctly reflect the intensity of liver tissue fibrosis.
 ...
PMID:[Significance of biochemical indices of liver fibrosis]. 628 30

Studies were conducted on collagenase activity on peripheral granulocytes of patients with various liver diseases. Total collagenase activity increased significantly in chronic active hepatitis (CAH) and in liver cirrhosis (LC), and, in these disorders, it correlated with the extent to which hepatic fibrosis has progressed. Active collagenase activity increased in CAH, but no differences from normal controls were found in other liver diseases. These results suggest that total collagenase may reflect the degree of hepatic fibrosis, and that active collagenase may be related to chronic active hepatitis lesions.
 ...
PMID:Collagenase activity in the granulocytes of patients with various liver diseases. 631 33

The mechanisms responsible for the increased hepatic collagen deposition in alcoholic cirrhosis remain unknown. The question of whether ethanol or acetaldehyde has a direct effect on collagen and noncollagen protein production was investigated in human fibroblasts with no detectable activity of alcohol dehydrogenase to distinguish the effects of these metabolites. To eliminate environmental factors, protein production by confluent human skin, fetal and hepatic fibroblasts was studied after three passages. Cells were labeled with [5-3H]proline for 4 hr in the presence of 0.2 mM ascorbate alone or with addition of either ethanol (50 mM) or acetaldehyde (0 to 300 microM). Rates of protein production were calculated from the radioactivities of collagenase-sensitive and collagenase-resistant proteins. Skin fibroblasts from alcoholic individual either with cirrhosis or without liver disease have comparable rates of collagen and noncollagen protein production. Acetaldehyde, in a concentration found in the liver during ethanol abuse, significantly increased collagen production by human skin fibroblasts (up to 140%), fetal fibroblasts (up to 240%) and hepatic fibroblasts (up to 70%) but the addition of ethanol had no significant effect on basal collagen production. The effect of acetaldehyde was dose-related and affected noncollagen protein production in a similar manner. Acetaldehyde did not cause changes in either proline transport or the specific activity of the proline precursor pool. This newly recognized stimulation of collagen production by acetaldehyde may be a possible mechanism of fibrogenesis in alcoholic individuals.
 ...
PMID:Acetaldehyde stimulates collagen and noncollagen protein production by human fibroblasts. 647 53

Antisera specifically directed against the amino-terminal precursor sequence of bovine p-N-collagen type III (Col 1-3 III) have been raised in rabbit. When tested in a radioimmunoassay, parallel displacement curves and complete cross-reactivity were observed between bovine and human purified Col 1-3 III. However, these displacement curves were not parallel to that obtained with serially diluted human sera which presented a smoother slope. Cleavage of the Col 1-3 III peptide by collagenase at high temperature yielded an immunoreactive preparation containing two smaller peptides (Col 1 plus Col 2) III. The displacement curves obtained with human or bovine (Col 1 plus Col 2) preparations were parallel to those obtained with serially diluted human sera or other human body fluids (amniotic and ascitic fluids). Quantitative measurements of the circulating antigen in normal and pathological conditions are possible only when the (Col 1 plus Col 2) is used as standard antigen. This radioimmunoassay represents an original and simple technique offering good accuracy. The amount of (Col 1 plus Col 2) III in human adults is 69.1 +/- 27.7 ng/ml, with a distribution of frequency close to the normal. It is increased in liver cirrhosis and other conditions characterized by an active neoformation of connective tissue.
 ...
PMID:Radioimmunoassay for the amino-terminal sequences of type III procollagen in human body fluids measuring fragmented precursor sequences. 649 23


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>