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

Monospecific antibodies against collagen types I, IV, fibronectin, and laminin were used to characterize the hepatic extracellular matrix in CCl4-induced cirrhosis. Of the four antigens studied, fibronectin was the first (2 weeks) to be deposited in Disse's space. Synthesis of fibronectin by hepatocytes was demonstrable by 3 weeks. This increased synthesis and deposition of fibronectin continued throughout the cirrhotic process. Type I collagen was deposited in the same areas as fibronectin, but there was a delay of 2 weeks between fibronectin deposition and the subsequent type I collagen deposition. Like fibronectin, type I collagen was localized in the rough endoplasmic reticulum of hepatocytes, but unlike fibronectin type I collagen synthesis was restricted to hepatocytes near zones of necrosis. Type I collagen and fibronectin synthesis were demonstrable only in hepatocytes. Type IV collagen deposition was noticeable after 3 to 4 weeks of CCl4 administration and continued throughout the cirrhotic process. Laminin deposition was delayed, with regard to type IV collagen, by 1 to 2 weeks. Except for this time lag, both basement membrane components codistributed in the space of Disse and were synthesized by the same cells: endothelial, smooth muscle, and Ito cells. The deposition of these two basement membrane components culminated with the formation of continuous endothelial basement membranes. The four extracellular matrix components studied were synthesized and secreted by resident cells of the normal liver. It is proposed that fibronectin deposition in the space of Disse, modulating collagen deposition, may be the crucial event in the cirrhotic process. The interposition of basement membranes between plasma and hepatocytes may have profound effects on hepatic systemic functions.
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PMID:The hepatic extracellular matrix. II. Electron immunohistochemical studies in rats with CCl4-induced cirrhosis. 389 94

When compared to age-matched normal weight normolipidemic control subjects, plasma factor XIII, plasma fibronectin and serum cholinesterase levels were found to be markedly decreased in patients with decompensated cirrhosis of the liver, not significantly changed in hyperlipoproteinemia type IIa (heterozygous subjects) and increased in hypertriglyceridemic subjects (type IIb and IV) as well as in hyperlipidemic nephrotic patients. A possible accelerated hepatic synthesis of certain plasma proteins including factor XIII and fibronectin in patients with the nephrotic syndrome as well as in endogenous hypertriglyceridemia is envisaged. It is also considered that mural thrombi, richer in factor XIII and fibronectin, would be more resistant to fibrinolysis and more readily attached to subendothelial structures.
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PMID:Clinical studies on plasma fibronectin and factor XIII; with special reference to hyperlipoproteinemia. 392 52

The liver is involved in the turnover of fibronectin in two different ways: hepatic synthesis contributes substantially to the plasma fibronectin pool, while Kupffer-cells, performing an important role of the reticuloendothelial system, remove fibronectin opsonized material from the circulation. In 45 patients with histologically confirmed liver cirrhosis and six patients with acute liver failure due to intoxication we determined fibronectin concentration in plasma by electroimmunoassay and additionally measured factor VIII-related antigen, which is a large glycoprotein not synthesized in the liver. Fibronectin levels in plasma were decreased in liver cirrhosis. This decrease was correlated with the extent of porto-caval collateral circulation. Very low levels were found in patients with acute liver failure. Factor VIII-related antigen levels were greatly increased as a function of the hepatic insufficiency. Between both parameters there was a significant inverse correlation. It is concluded that the simultaneous determination of both proteins provides reliable information about the remaining liver function.
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PMID:Fibronectin and factor VIII-related antigen in liver cirrhosis and acute liver failure. 642 89

Ascitic fluid from patients with ovarian cancer and from patients with alcohol induced liver cirrhosis were compared in respect to hematological and related parameters (content of fibrinogen and fibrin (ogen) degradation products, fibrinopeptide A, F-CB3 related antigen, ratio of crosslinked fibrin to non crosslinked fibrin (ogen), fibronectin and total protein). In tumor ascites all parameters except FPA were significantly elevated compared with cirrhosis ascites. Tumor ascites contains a six-fold higher level of fibrin (ogen) degradation products. A considerable portion of it constitute crosslinked (factor XIII induced) high molecular weight fibrin derivatives. Their content is approx. 10 times higher in tumor ascites than in cirrhosis ascites. Characterization of the crosslinked fibrin derivatives revealed the presence of fragments DD, DY, and some other fragments compatible with XY, DXD, DXY, YXY and DXX. The fibronectin content is also significantly higher in tumor ascites compared with cirrhosis ascites. The value ranges showed no overlap. The findings suggest a turnover of fibrinogen in both ascitic fluids via coagulation and fibrinolysis. In tumor ascites however, fibrinogen seems to be catabolized to a higher degree via the degradation of crosslinked fibrin.
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PMID:Crosslinked fibrin derivatives and fibronectin in ascitic fluid from patients with ovarian cancer compared to ascitic fluid in liver cirrhosis. 647 9

Specific antibodies to collagen type IV, laminin, and fibronectin were used to localise these proteins by indirect immunofluorescence in frozen sections of normal and fibrotic liver. In normal livers distinct staining was found in basement membranes of blood and lymph vessels, of bile ducts and ductules and around nerve axons. Positive reactions for type IV collagen and fibronectin were also observed in the perisinusoidal space, while hepatocytes and most of the interstitial matrix of portal fields remained unstained. Liver specimens obtained from patients with alcoholic liver disease (fatty liver, hepatitis or cirrhosis) and chronic active hepatitis showed a more intense reaction with the antibodies in the perisnusoidal space including now distinct staining for laminin. These patterns were particularly prominent at borders between fibrotic septa and remnants of parenchyma or pseudolobules. Strong reactions were also found for type IV collagen and fibronectin in the periportal interstitium and in large fibrotic areas. The findings support previous electron-microscopical and chemical evidence for increased basement membrane production in human liver fibrosis and demonstrate that this may involve different proteins and occur at different anatomical sites.
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PMID:Distribution of basement membrane proteins in normal and fibrotic human liver: collagen type IV, laminin, and fibronectin. 698 3

We measured the concentration in plasma of fibronectin, a recently characterized high molecular weight glycoprotein, in patients with various liver diseases. We found that it was significantly increased in acute hepatitis, fatty liver, all types of chronic hepatitis and liver cirrhosis without clinical evidence of ascites. Only in patients at the decompensated stage of liver cirrhosis, i.e. patients with clinical evidence of the presence of ascites, was it significantly reduced. Based on the immunohistochemical study on biopsy specimens of the liver using anti-human fibronectin antiserum, we suggest a possible correlation of the elevated plasma fibronectin to the wide distribution of specific fluorescence associated with the fibrillar structures in necrotic areas, expanded portal areas or thick fibrous septa in the liver diseases. Accelerated catabolism of plasma fibronectin mediated by increased fibrinolytic activity may contribute to the decrease in the level of plasma fibronectin in severe liver cirrhosis.
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PMID:Distribution of fibronectin in plasma and liver in liver diseases. 703 11

We investigated the adherence of gelatinized lipid emulsion (GLE) to tissues and cells, the reaction system of this phenomenon and the clinical significance of the adherence-promoting factor (APF) in human serum. In the presence of fresh human serum, GLE adhered to all tested tissues and blood cells. APF was shown to be macromolecular alpha 2-globulin; it formed flocculent precipitate with gelatin, and adsorbed to gelatin-Sepharose. Therefore, we termed APF gelatin-reactive protein (GRP) although it may be identical or closely related to plasma fibronectin. We also noted a significant decrease in GRP activity in patients with systemic disorders including cancer, liver cirrhosis, and systemic lupus erythematosus when their sera were assayed by the GLE-rat liver system.
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PMID:Gelatin-reactive protein in human serum--bioassay, characterization and clinical significance. 712 Jun 76

Multiple injections of D-galactosamine induce liver fibrosis and cirrhosis in rats. The purpose of this immunopathological study was to correlate inflammation and hepatic extracellular matrix remodeling after repeated administration of galactosamine. Rats were given 10, 20, 30, 40, 60, 80, 100 and 140 intraperitoneal injections of D-galactosamine (500 mg/kg body wt, three times weekly). Controls received injections of saline solution. Cryostat sections of liver tissue obtained on biopsy or autopsy were immunostained with a panel of monoclonal and polyclonal monospecific antibodies reactive with macrophages, T and B lymphocytes, desmin, the extracellular matrix components fibronectin; laminin; collagen types I, III and IV; and the fibronectin receptor alpha 5 beta 1. Total RNA was extracted and Northern-blot analysis was performed with a specific cDNA probe for rat collagen type III. Spotty liver cell necrosis and mild portal and parenchymal inflammation was seen after 10 injections of galactosamine. After 20 to 40 injections, expansion of protal tracts, prominent bile ductular proliferation and gradual formation of fibrous septa were encountered with the development of cirrhosis at later intervals. These progressive histological changes were paralleled by a gradual increase of desmin-positive cells in developing septa with deposition of fibronectin; collagen types I, III, and IV; and laminin. Northern-blot analysis showed that this accumulation of extracellular matrix was not accompanied by increase of mRNA for collagen type III. In conclusion, repetitive administration of galactosamine causes progressive liver disease with prominent bile ductule proliferation and development of fibrous septa. These pathological alterations bear some resemblance to the morphological changes in chronic biliary disease in human beings.
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PMID:Immunohistochemical study of hepatic fibrosis induced in rats by multiple galactosamine injections. 750 72

In order to clarify the significance of serum level of vitronectin receptor (VNR) in alcoholic liver disease (ALD), we have investigated the relationship with fibronectin receptor (FNR) and histological liver features in 21 ALD patients. Serum level of VNR and FNR was measured by enzyme immunoassay. Liver disease activity was scored based on levels of fibrosis and focal intralobular necrosis and degeneration. The serum level of VNR (micrograms/ml) was significantly higher in the patients with hepatic fibrosis (9.87 +/- 2.51) and liver cirrhosis (10.80 +/- 1.52) than in normal subjects (5.51 +/- 0.52, P < 0.01) and fatty liver subjects (6.58 +/- 0.58, P < 0.05). A positive correlation was found between serum levels of VNR and fibronectin receptor (FNR) (P < 0.05). A positive correlation was observed between the serum level of FNR and the degree of hepatic fibrosis or focal intralobular necrosis and degeneration, while no correlation was found between the serum level of VNR and the degree of histological features. A positive correlation was also noted between the serum level of FNR and N-terminal type III procollagen aminopeptide (PIIIP) (P < 0.001), while no correlation was observed between the serum level of VNR and PIIIP. We conclude that the serum level of VNR is increased in patients with advanced alcoholic liver disease. However, the mechanism by which serum levels of beta subunit of VNR and FNR are increased may be different.
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PMID:Serum vitronectin receptor in alcoholic liver disease: correlation with fibronectin receptor and morphological features. 751 80

The determination of fibronectin (FN) concentration in plasma has been performed in the group of 77 patients (60-with various chronic liver diseases, 6-with AIDS IVc, 11-healthy patients). The purpose of this study was: evaluation of the value of plasma FN determination in assessment the degree of liver fibrosis and the degree of liver damage. The obtained results were compared with routine biochemical tests and histopathological picture of liver sections. Among patients with liver diseases, we observed that plasma FN concentration was significantly lower only in the group with decompensated liver cirrhosis, in relation to control group. Non significant lower values of FN was observed in the group of patients with chronic hepatitis, as well as non significant higher ones in the group with cholestasis and fibrosis. It has been concluded that determination of plasma FN concentration has not any importance in evaluation of degree of liver fibrosis and its only one from many functional liver tests.
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PMID:[Plasma fibronectin in chronic liver disease--marker of fibrosis?]. 763 58


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