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)

Vitronectin (VN), fibronectin (FN) and laminin (LM), which are known to be important glycoproteins in cell attachment, are produced by such liver cells as hepatocytes, Kupffer cells endothelial cells and Ito cells. In this study, the levels of plasma VN, FN and serum LM P1 in patients with chronic hepatitis, liver cirrhosis and hepatocellular carcinoma accompanied with cirrhosis were examined and compared with those in normal subjects. Plasma VN levels in patients with chronic hepatitis, compensated cirrhosis and decompensated cirrhosis were less than that in normal subjects. As hepatic dysfunction deteriorated, plasma VN level decreased in chronic liver diseases. Plasma FN levels in patients with compensated and decompensated cirrhosis were also less than that of patients with chronic hepatitis, which was not significantly different from that of normal subjects. Plasma VN and FN levels in patients with hepatocellular carcinoma were similar to those in patients with compensated cirrhosis. Plasma VN and FN levels in patients with chronic liver diseases including hepatocellular carcinoma showed positive correlations with serum albumin content, cholinesterase activity, and normalized normo test value. On the other hand, serum LM P1 levels in patients with chronic hepatitis, compensated cirrhosis and decompensated cirrhosis were higher than that of normal subjects. As hepatic dysfunction deteriorated, serum LM P1 level increased in chronic liver diseases. Level of serum type IV collagen 7S, which is related to hepatic fibrosis, was similar to that of serum LM P1; serum LM P1 concentration in patients with chronic liver diseases showed a significant positive correlation with that of serum type IV collagen 7S. Immunolocalization of VN in liver tissue from patients with chronic hepatitis and cirrhosis was examined by the method of avidin-biotin-complex staining, and positive reaction was observed in enlarged portal tracts, central veins and fibrous septa. These results suggest that decreased levels of plasma VN and FN and increased level of serum LM P1 in patients with chronic liver diseases are related to hepatic dysfunction, and that changes in the levels of these glycoproteins involved in cell attachment are important in the development of hepatic fibrosis in patients with chronic liver diseases.
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PMID:[Changes in plasma vitronectin, fibronectin, and serum laminin P1 levels and immunohistochemical study of vitronectin in the liver of patients with chronic liver diseases]. 170 42

Fat-storing (Ito) cells are perisinusoidal liver cells thought to play a central role in vitamin A metabolism and fibrongenesis. Glucocorticoids have been shown to be beneficial in the treatment of certain types of liver diseases by delaying the development of cirrhosis. To study the regulatory effects of dexamethasone on Ito cell gene expression, Ito cells were isolated from normal rat liver and primary cultures were established. The effect of dexamethasone on the synthesis of alpha 2-macroglobulin, apolipoprotein E, fibronectin and actin was examined. Protein synthesis was studied both at the protein level and at the RNA level by means of biosynthetic labeling, immunoprecipitation followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and by Northern blot analysis of total RNA. After exposure to dexamethasone for 20 hr, alpha 2-macroglobulin protein synthesis was increased threefold, whereas apolipoprotein E expression was decreased 80%. Biosynthesis of fibronectin remained unaffected by hormone treatment. The dexamethasone effect became detectable 5 hr after beginning the exposure. Deinduction kinetic experiments showed that the glucocorticoid effect was detectable more than 12 hr after the replacement of the dexamethasone-containing culture medium by medium without the hormone. Corresponding to the data obtained at the protein level, dexamethasone increased the steady-state levels of alpha 2-macroglobulin-specific messenger RNA and reduced apolipoprotein E-specific transcripts, whereas fibronectin and actin messenger mRNA remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dexamethasone modulates alpha 2-macroglobulin and apolipoprotein E gene expression in cultured rat liver fat-storing (Ito) cells. 171 36

We produced monoclonal antibodies (mABs) against human integrins. Competitive enzyme-linked immunosorbent assay (ELISA) revealed that each mAB bound to different antigenic determinants. We then developed sandwich-type enzyme immunoassays (EIAs) to measure the concentration of fibronectin receptor (FNR) and vitronectin receptor (VNR). Serum immunoreactive integrin levels were measured using these EIAs in various liver and malignant diseases. In almost all cases of liver cirrhosis (LC) and hepatocellular carcinoma (HCC), serum integrin levels were significantly elevated, but were in the normal range in gastric, colon, lung cancer, and acute hepatitis (AH). The correlation between serum FNR and VNR levels was statistically significant in all cases of liver disease, and no correlation was observed between these integrin levels and conventional biochemical markers such as AST, ALT, and GGT. The serum integrin levels were demonstrated to be a potential diagnostic marker for hepatic fibrogenesis and carcinogenesis, and these sandwich EIAs could be useful for determination of these integrins in clinical laboratory tests.
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PMID:Sandwich enzyme immunoassay for serum integrins using monoclonal antibodies. 172 78

Liver fat-storing cells (FSC) play an important role in collagen deposition. During the induction of liver cirrhosis, FSC lose their fat droplets, acquire an actin-rich cytoskeleton and transform into myofibroblasts. Myofibroblasts have been associated with increased collagen production in cirrhotic livers. Cultured FSC resemble myofibroblasts. However, it is not known whether regulation of collagen gene expression is similar in FSC obtained from normal or cirrhotic livers. In this communication, we describe the characterization of two fat-storing cell lines, one from normal (NFSC) and one from CCl4-cirrhotic liver (CFSC), obtained after spontaneous immortalization in culture. We studied the effect of serum and various growth factors on cell proliferation. We determined the production of collagen and fibronectin and we analyzed the presence of mRNA transcripts of collagens type I, III, and IV, fibronectin laminin, transforming growth factor-beta and interleukin-6. We found that CFSC have a greater serum-dependency than NFSC. NFSC grow with a mixture of insulin and epidermal growth factor, whereas CFSC proliferate only with platelet-derived growth factor. Although we did not find significant differences in the expression of mRNAs for collagen type I, fibronectin and transforming growth factor-beta, collagen and fibronectin synthesis was increased 2- and 1.5-fold respectively. NFSC contained 1.6- and 2.0-fold more type III collagen and laminin mRNAs, respectively, than CFSC. Neither cell line expressed type IV collagen mRNA. NFSC but not CFSC produced interleukin-6. These results suggest that, except for the lack of transcripts of collagen type IV, both cell lines resemble primary cultures of FSC. However, significant differences in cell proliferation and interleukin-6 production between the two cell lines were found. We suggest that these cell lines could be useful tools to study possible differences in regulation of matrix production by FSC.
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PMID:Characterization of fat-storing cell lines derived from normal and CCl4-cirrhotic livers. Differences in the production of interleukin-6. 175 10

Pooled sera collected from cirrhotic patients was fractionated by affinity chromatography with a fibronectin receptor monoclonal antibody against the beta-subunit of fibronectin receptor. Eluates were assayed using Western immunoblotting. The relative mobility of the protein reactive with fibronectin receptor antibody was nearly identical to that of the beta-subunit of fibronectin receptor, confirming that fibronectin receptor is present in human serum. Serum levels of the beta-subunit of fibronectin receptor were analyzed by sandwich enzyme-linked immunosorbent assay in patients with various liver diseases. The serum level of fibronectin receptor (micrograms/ml) was significantly higher in patients with chronic hepatitis (inactive, 2.59 +/- 0.04; active, 3.45 +/- 0.13), cirrhosis (4.77 +/- 0.30), alcoholic liver disease (2.96 +/- 0.16) and hepatocellular carcinoma (4.71 +/- 0.49) than in normal subjects (2.11 +/- 0.08). Strong positive correlation was observed between serum levels of fibronectin receptor and histological findings, particularly in the degree of hepatic fibrosis. Immunohistochemical studies with fibronectin receptor antibody revealed that the beta-subunit of fibronectin receptor was present on the plasma membrane of hepatocytes and sinusoidal lining cells in the normal liver and was increased in fibrotic areas and on the plasma membrane of hepatocytes and sinusoidal lining cells of fibrotic liver. The serum level of fibronectin receptor in patients with chronic liver diseases may therefore be a useful marker of hepatic fibrosis.
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PMID:Detection of fibronectin receptor in sera: its clinical significance as a parameter of hepatic fibrosis. 183 May 62

To analyze relating factors to early repairment of the surgical margin of the remnant liver we measured plasma fibronectin (FN), coagulation factor XIII (XIII), polymorphonuclear leukocyte elastase (PMNE), platelet counts (Plt), prothrombin time (PT%) before and at the first, third, 7th and 14th days after liver resection in 25 patients. Changes in these factors (1) were compared with their clinical status, such as liver cirrhosis, high fever, abscess formation, duration of drainage and use of microwave tissue coagulator (MTC) (2). The multivariate analysis about the factors influencing the duration of hospital stay (3) were carried out. (1) In the all cases FN, XIII (14th), PT%, Plt decreased and PMNE increased significantly versus pre-operative data. There were significant correlations between FN and XIII, FN and PMNE. (2) In the cirrhotic group FN, XIII, PT% and Plt were significantly lower than those of non cirrhotic group. In the abscess formation group PT% was significantly lower than the no abscess formation group. In the MTC group XIII, PT% and Plt were significantly lower than those of the no-MTC group. In conclusion, FN, XIII, Plt and PT% in the cirrhotic, high fever, abscess formation or longer drainage group were in lower levels compared with the each control group. (3) By the multivariate analyses, abscess formation, high fever and liver cirrhosis were the most influencing factors for the duration of hospital stay.
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PMID:[Analysis of factors relating to early repairment of the surgical margin following liver resection--factors relating to duration of hospital stay]. 187 92

That Ito cells in rat liver express desmin was confirmed by immunohistochemical technique. Anyhow, changes of desmin-positive cells, lysozyme-positive cells and fibronectin were further studied in experimental cirrhosis of rat. It was found that desmin-positive cells, with the transitional features between Ito cells and myofibroblasts or fibroblasts under electron microscope, increased in number and expression of desmin in the necrotic areas as well as in the cellular fibrous septa, but decreased in number in the fibrous septa except those areas close to the edges of the septa. These results suggested that Ito cells, myofibroblasts and fibroblasts may belong to the same cellular system and play an important role in the pathogenesis of cirrhosis. Meanwhile, it was also noted that changes of both fibronectin and lysozyme-positive cells were correlated with those of desmin-positive cells. These provide evidence in vivo that fibronectin and Kupffer cells may exert certain effects on the migration and proliferation of Ito cells in cases of liver cirrhosis.
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PMID:[Dynamic changes of Ito cells in experimental cirrhosis of rat]. 191 24

To investigate the clinical significance of ascitic fluid in patients with a malignancy, an abdominal paracentesis to evaluate the ascitic fluid was performed in 10 patients with a hepatocellular carcinoma (HCC) and in 7 patients with liver cirrhosis (LC). The AFP levels in the ascitic fluid and in the serum of the HCC patients was found be significantly higher than that of the LC patients. In addition, the ratio of albumin/total protein in ascitic fluid was also higher in the HCC patients. However, no significant findings were uncovered with regard to the concentration of lipid in ascitic fluid, in either type of patient although 2 HCC patients were found to have a very high concentration of total cholesterol. The cytological findings provided no reliable marker because of significant number of false negatives in the HCC patients. Also, there was no significant difference between the fibronectin levels in the ascitic fluid of either type of patients. This finding differs from previous studies, and suggests that the fibronectin levels in the ascitic fluid may not be a useful marker in determining a malignancy.
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PMID:[Clinical analysis of ascitic fluid in patients with liver cirrhosis and hepatocellular carcinoma]. 197 86

Measurement of fibronectin in ascites has been proposed for the differentiation of ascites either due to malignant growth in the peritoneal cavity or liver cirrhosis with portal hypertension. The high ascitic fibronectin concentration in patients with peritoneal carcinomatosis was thought to be due to the synthesis of this protein by neoplastic cells. Therefore in ascites of malignant origin cellular fibronectin should be present as it is synthesized by neoplastic cells. On the other side the transsudative ascites due to liver cirrhosis with portal hypertension should mainly contain plasma-fibronectin, which is secreted by hepatocytes into the bloodstream. With the aid of two different monoclonal antibodies and immunoblotting of partially digested or intact ascitic fibronectin, cellular fibronectin could be demonstrated in ascitic fluid of 10 patients with peritoneal carcinomatosis, 13 patients with liver cirrhosis, one patient with right-sided heart failure and one patient with Budd-Chiari-Syndrome. As determined by a specific ELISA 8 out of 10 samples of malignant ascites contained more than 30 mg/l of cellular fibronectin, whereas 10 out of 13 samples of ascites due to liver cirrhosis contained less than 10 mg/l. Whereas in ascites of malignant origin cellular fibronectin represented about 20% of total fibronectin, in portal ascites fibronectin represented sometimes more than 50% of total fibronectin. Cellular fibronectin of non-malignant origin is probably produced by mesothelial cells or peritoneal macrophages. Therefore, fibronectin accumulating in peritoneal carcinomatosis is only to some extent locally produced, but mainly caused by an unhindered exsudation of plasma-fibronectin.
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PMID:[Genesis of fibronectin in ascites--detection of cellular and plasma fibronectin in portal and malignant ascites]. 205 24

Alcoholic hepatitis is a necrotizing, often inflammatory, process that is an important precursor to the development of cirrhosis. Acetaldehyde, which is derived from alcohol by the action of alcohol dehydrogenase, is apparently the most important factor leading to alcohol-induced liver injury. Other factors of importance in determining the appearance and rate of progression of liver diseases in patients who are chronic alcoholics include sex, nutritional status, and various immunologic reactions. In addition, there is an incompletely understood genetic predisposition to the development of alcoholic hepatitis. Several histologic features found in patients with alcoholic hepatitis have been evaluated in efforts to determine which are of prognostic value. The predominance of the alcohol-induced injury in zone III of the hepatic lobule; deposition of collagen, IgA, and fibronectin in the space of Disse; defenestration of endothelial cells; and transformation of lipocytes and myofibroblasts to fibroblasts have been investigated. Prolongation of the prothrombin time and marked elevation of serum bilirubin levels are indicators of a subgroup of patients with alcoholic hepatitis who have a poor prognosis, especially if there is also evidence of hepatic encephalopathy. Supportive care and abstinence from alcohol are the foundations of therapy. Corticosteroid therapy appears to decrease the number of early deaths in patients with severe alcoholic hepatitis. Other experimental approaches to therapy include the use of propylthiouracil, anabolic-androgenic steroids, and insulin and glucagon.
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PMID:Alcoholic hepatitis: pathogenesis and approaches to treatment. 223 74


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