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)

Cirrhotic patients (23 with alcoholic cirrhosis, 5 with posthepatitic cirrhosis and 2 with cryptogenic cirrhosis) with ascites and portal hypertension were studied and divided into two groups corresponding to high or low risk to develop spontaneous bacterial peritonitis (SBP) related to the concentration of total protein in the ascitic fluid (A-TP): group I (high risk): A-TP < or = 1.5 g/dl and group II (low risk): A-TP > 1.5 g/dl. Fibronectin (FN), C3 and C4 concentrations were measured by radial immunodiffusion while total protein was measured by the biuret method. The mean values (group I vs group II) of C3 (12.59 +/- 4.72 vs 24.53 +/- 15.58 mg/dl), C4 (4.26 +/- 3.87 vs 7.26 +/- 4.14 mg/dl) and FN (50.47 +/- 12.49 vs 75.89 +/- 24.70 mg/dl) in the ascitic fluid were significantly lower (P < 0.05) in the group considered to be at high risk for SBP. No significant difference was observed in the plasma/ascites fibronectin ratio (3.91 +/- 1.21 vs 3.80 +/- 1.26) or gradient (131.46 +/- 64.01 vs 196.96 +/- 57.38) between groups. Fibronectin in ascites was significantly correlated to C3 (r = 0.76), C4 (r = 0.58), total protein (r = 0.73) and plasma FN (r = 0.58) (P < 0.05). The data suggest that the FN concentration in ascites is related to the opsonic capacity of this fluid, and that its concentration in the ascitic fluid may be a biochemical risk factor indicator for the development of spontaneous bacterial peritonitis.
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PMID:Fibronectin in the ascitic fluid of cirrhotic patients: correlation with biochemical risk factors for the development of spontaneous bacterial peritonitis. 936 7

The aim of this study was to follow semiquantitatively by immunohistochemical means the alterations of the expression of the hepatic glycoproteins tenascin, fibronectin, and laminin in two different models of chronic liver injury, i.e. thioacetamide-induced liver cirrhosis and fibrosis after bile duct ligation. The tenascin distribution pattern observed during cholostasis-induced liver fibrosis showed some similarities, but also some differences in comparison with the results obtained after TAA intoxication. Most importantly, the data show that tenascin staining was detectable in almost all areas of the chronically injured livers up to 3 and 6 months in bile duct-ligated and chemically-injured livers, respectively. Thus, tenascin does not seem to play only a transient role in the fibrogenetic process as previously suggested. Laminin was strongly stained in proliferating ductules, whereas only a weak continuous distribution was observed along the sinusoidal wall. Furthermore, our findings confirm the role of fibronectin as a pacemaker of fibrosis. Regional differences in the kinetics of the expression of the glycoproteins may reflect local differences in their production by parenchymal or non parenchymal cells or regional patterns of proteolytic activity.
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PMID:Expression of tenascin, fibronectin, and laminin in rat liver fibrogenesis--a comparative immunohistochemical study with two models of liver injury. 978 3

1. Fibronectins (FN) are believed to have a role in haemorheological perturbation associated with tissue damage. Fibronectins exist in two antigenically related forms, plasma (p) and cellular fibronectin, which has the extra domain sequences A (EDA) or B (EDB). The present study was designed to determine changes in plasma p-FN and EDA + FN under different types of surgical stress. 2. Sixty-two patients were divided into three groups: (i) group A, 33 patients undergoing hepato-pancreato-biliary surgery; (ii) group B, 19 patients undergoing laparoscopic cholecystectomy; and (iii) group C, 10 patients with postoperative complications. Plasma FN and EDA + FN levels were measured in these patients undergoing different types of surgical operation and either with or without liver cirrhosis using an enzyme-linked immunosorbent assay. 3. After surgery, a significant decrease in p-FN levels and a significant increase in EDA + FN levels was observed in all patient group compared with pre-operative levels. The duration of increased EDA + FN levels, but not p-FN levels, in group A patients was significantly longer than in group B patients. Although changes in p-FN levels between patients with and without liver cirrhosis were significantly different, there were no significant differences in the EDA + FN levels between these two patient groups. 4. In conclusions, EDA + FN and p-FN levels were found to exhibit opposite responses to surgical stress. Furthermore, with greater surgical stress, greater increases in EDA + FN levels were seen. The presence of liver cirrhosis had no significant effect on EDA + FN levels during the perioperative period; however, p-FN levels were significantly affected. 5. Thus, it is suggested that plasma EDA + FN levels reflect the magnitude of surgical stress more closely than do p-FN levels.
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PMID:Different responses to surgical stress between extra domain A+ and plasma fibronectins. 1008 18

Plasma fibronectin was determined in 29 patients with decompensated cirrhosis (7 patients had bacterial infection) and 23 patients with malignant liver disease. The obtained values were compared with the fibronectin values in 20 healthy subjects belonging to the control group in order to determine the possible diagnostic value of this dimer glycoprotein of high molecular weight whose role in the organism has not been completely explained. Fibronectin was determined on nephelometer with the use of specific antiserum by Behringwerke. The results expressed as mean values and SD were compared with monofactorial variance analysis (method One-way ANOVA). Fibronectin values in patients with liver cirrhosis were statistically significantly lower than in the control group (p < 0.01), which is also the case with correlation with malignant liver disease (p < 0.01). The fibronectin values in patients with malignant diseases were almost the same as the control group values (p < 0.01). In 7 patients with liver cirrhosis and bacterial infection the fibronectin values were statistically significantly higher in relation to those in the remaining 22 patients with cirrhosis but without bacterial infection (p < 0.001). The investigation in this study indicated that the decrease of mean fibronectin values is related to hepatic failure which is of diagnostic value, while normal values in malignant diseases do not favor the opinion on fibronectin as a tumor marker. Higher fibronectin values in infection in patients with liver cirrhosis are not clear, which indicated the total complexity of the relation between fibronectin as a dimer glycoprotein and chronic liver diseases including malignant.
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PMID:[Diagnostic importance of fibronectin in chronic liver diseases]. 1035 2

Chronic liver disease evaluation is a very complicated process requiring complex assessment of numerous liver functions. In addition to standard methods of investigation we perform biotransformation liver tests for evaluation of microsome enzyme system. Markers of fibrogenesis represent modern noninvasive tests for fibrotic liver process detection in different diseases. The key role in the process of fibrogenesis have the adipose liver cells (ITO cells) producing collagen I, III, IV and lamilin. These cells may be transformed into myofibroblasts-like cells under specific conditions. Kupffer cells and monocytes produce substances stimulating the proliferation and transformation of liver ITO cells as also proteoglycans and hyaluronic acid synthesis. Mediators of this fibrogenetic activity are platelet derived growth factor (PDGF), transforming growth factors alpha and beta, lymphokines and monokines released by T-lymphocytes and macrophages, interleukin 1-alpha and interferon-tau. Acetaldehyde and its metabolites are important stimulators of collagen production by liver fibroblasts. The most often used markers of hepatic fibrogenesis are the following: procollagen III peptide, procollagen IV. type (one of its end carboxypeptide chains is determined-either with 7s collagen or NC1), hyaluronic acid, fibronectin, tenascine and unduline. As the most sensitive markers of fibrinogenesis are considered: hyaluronic acid, laminine, procollagen IV. type. Less often used are enzymes participating in collagen synthesis: prolyl-4-hydroxylase,lysyl-hydroxylase, galactosyl-hydroxylysyl-glucosyl-transferase, monoaminooxidase and N-acetyl-beta-D-glucoseaminidase. Breakdown of collagen is a multienzymatic process, catalysed by collagenases and other proteolytic enzymes. Decreased activity of collagenase is a supporting factor of cirrhosis development. Cirrhosis may be connected also with the levels of inhibitors such as e.g. serum/tissue? inhibitor of metalloproteinase. Biochemical markers of fibrogenesis are useful in regular monitoring of disease development and treatment effectivness and should be an inseparable part of progression assessment in all chronic hepatopathies. (Fig. 3, Ref. 49.)
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PMID:[Biochemical markers of fibrogenesis in liver diseases]. 1049 95

Matrix metalloproteinase-2 (MMP-2) is involved in extracellular matrix remodeling. It is secreted as a proenzyme and activated by membrane type-MMPs (MT-MMP), such as MT1-MMP. In liver fibrosis, MMP-2 is highly expressed in myofibroblasts and may have a profibrogenic role. The mechanisms of its activation in the liver are still unclear. The aim of this work was to show that pro-MMP-2 is efficiently activated in human fibrotic liver and to investigate the role of cell-matrix interactions in this process. Liver specimens obtained from patients with active cirrhosis were compared to normal liver specimens. Human hepatic myofibroblasts were cultured either on plastic, fibronectin, laminin, or on collagen I gels. MMP-2 activity was visualized by gelatin zymography. MMP-2 active form (59 kd) was detected in active cirrhosis but not in normal liver. Myofibroblasts cultured on plastic, fibronectin, or laminin predominantly expressed inactive pro-MMP-2 (66 kd). In contrast, myofibroblasts cultured on collagen I markedly activated the enzyme. Similar results were obtained using membrane fractions from cells previously cultured on collagen or plastic. Activation was inhibited by the tissue inhibitor of metalloproteinases-2 but not by tissue inhibitor of metalloproteinases-1, implicating a MT-MMP-mediated process. Culture on collagen I up-regulated MT1-MMP protein detected by Western blotting, but decreased MT1-MMP mRNA. This study shows that MMP-2 is activated in fibrotic liver. It suggests that interactions between collagen I and myofibroblasts promote this process through a post-translational increase of MT1-MMP expression in these cells.
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PMID:Matrix metalloproteinase-2 activation in human hepatic fibrosis regulation by cell-matrix interactions. 1049 46

Enzyme immunoassay measured concentrations of basic extracellular matrix proteins, collagen type 3 (C-3) and fibronectin, in blood plasm of 119 patients with chronic hepatic diseases. 30, 16, 18, 6 and 49 of them had chronic hepatitis of minimal activity (MiACH), that of moderate activity (MACH), intermediate activity (CHIA), high activity (HACH) and hepatic cirrhosis (HC), respectively. The highest C-3 level occurred in C-stage HC, the lowest--in MiACH. Fibronectin was the highest in HACH, minimal--in C-stage HC. C-3 and fibronectin levels correlated with severity of mesenchymal-inflammatory syndrome in CH and HC; in CHIA, HACH and in B-stage HC--with cytolysis markers. A direct relationship was found between protein-synthetizing function of hepatocytes and fibronectin levels in CHIA, HACH and HC while it was inverse in relation to C-3 amount in HC. Thus, tests for plasm C-3 and finronectin expand potentialities of laboratory diagnosis of the process activity in CH and HC, allow prediction of probability of CH transformation into HC.
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PMID:[Diagnostic implications of extracellular matrix proteins in chronic hepatitis and hepatic cirrhosis]. 1105 39

Transforming growth factor (TGF-beta) is the protein playing a principal role in the intracellular signalling. The most important function is ability to stimulate synthesis of extracellular matrix proteins, what is responsible for wound formation and tissue reconstruction. The damage of hepatocytes is a signal for macrophages and platelets activation, resulting in release of TGF-beta and over-expression of genes responsible for morphologic and functional changes in Ito cells. They undergo transformation into myofibroblasts and become the source of extracellular matrix proteins, such as: collagens, fibronectin, laminin, entactin, tenascin, undulin. The consequence of their accumulation in the space of Disse and inside hepatic lobuli is fibrosis, which is the form of tissue healing in the place of necrosis. However continuous action of damaging agent leads to massive fibrosis and reconstruction of liver, what is clinically manifested as cirrhosis. The role of transforming growth factor beta in the pathogenesis of liver diseases and its possible use as an indicator of disease progression were discussed in this paper.
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PMID:[Transforming growth factor beta in pathogenesis of liver diseases]. 1114 21

Cirrhosis is one of the most common causes of mortality worldwide, because hepatic dysfunction constitutes a potentially lethal condition. Having demonstrated the hepatoprotective effect of adenosine against CCl(4)-induced cirrhosis, the present study was aimed at assessing adenosine's effect on an already-established micronodular cirrhosis. Chronic administration of CCl(4) (10 weeks) induced a cirrhotic state, characterized by increased liver fibronectin and collagen types I and III content, enhanced expression of alpha-1 (I) collagen mRNA, portal hypertension, and liver dysfunction. After CCl(4) discontinuation (5 weeks), increased persitance of alpha-1 (I) collagen mRNA expression and deposition, enhanced proline incorporation into collagen and prolyl hydroxylase activity evidenced active fibrogenesis. Several weeks after CCl(4) withdrawal, deposited collagen showed an enhanced type I/III ratio, which was associated with deficient collagenolytic activity in cirrhotic livers. Liver expression of some metalloproteinases (MMPs) and of tissue inhibitors of MMPs (TIMPs) also indicated decreased collagen breakdown in cirrhotic livers. Parameters indicative of oxidative stress (mainly protein oxidation) were persistently augmented. These events were coincident with diminished regenerative capacity of the cirrhotic liver. Intraperitoneal adenosine administration to CCl(4)-induced cirrhotic rats blocked active fibrogenesis and increased the collagen degradation (most probably by decreasing liver TIMPs levels), normalizing collagen-type ratios. In addition, the nucleoside promoted an effective hepatocyte's proliferation in the cirrhotic liver and accelerated normalization of parameters indicative of liver function and oxidative stress. Thus, adenosine readily reversed an experimental cirrhosis through stimulating liver collagenolytic and proliferative capacities, as well as by accelerating functional recovery.
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PMID:Adenosine reverses a preestablished CCl4-induced micronodular cirrhosis through enhancing collagenolytic activity and stimulating hepatocyte cell proliferation in rats. 1158 63

Cells termed myofibroblasts are prominent in the injury response of all epithelial tissues. They exhibit proliferation, migration, production of collagen and other extracellular matrix (ECM) molecules, and contraction, all for containing the injury and closing the wound. When the injury is limited in time, the final stage of the repair involves a dismantling of the cellular apparatus and restoration of normal tissue structure. With multiple cycles of repair, however, there is net accumulation of ECM, to the detriment of tissue structure and function. Repair-related ECM coalesces into fibrous bundles and, over time, undergoes changes that render it resistant to degradation. The result is a scar. In the skin, a scar may have cosmetic importance only. In the liver, however, extensive scarring is the setting for unregulated growth and neoplasia; also, fibrous bands disrupt normal blood flow, leading to portal hypertension and its complications. With regard to therapy for fibrosis, the first consideration is elimination of the injury factor. However, given that many liver diseases do not have effective therapies at present, strategies targeting fibrogenesis per se are under development. The main source of myofibroblast-like cells and ECM production in the liver is the perisinusoidal stellate cell, which responds to injury with a pleiotypic change termed activation. Activation is orchestrated by cytokines and the ECM itself. Among the cytokines involved in this process, transforming growth factor-beta (TGF-beta) is particularly prominent. The early changes in ECM include de novo production of a specific "fetal" isoform of fibronectin, which arises from sinusoidal endothelial cells. It is stimulated by TGF-beta and acts directly on stellate cells to promote their activation. Based on these and other advances in understanding the fundamentals of the injury response, several strategies now exist for altering fibrogenesis, ranging from agents that block TGF-beta to traditional Chinese herbal extracts. Arrest of fibrogenesis, even with underlying cirrhosis, is likely to extend life or prolong the time to transplant. Whether it reduces the risk of hepatocellular carcinoma remains to be proven. Although TGF-beta antagonists are effective anti-fibrogenic agents, they will require detailed safety testing because of the finding that several forms of epithelial neoplasia are associated with altered regulation of TGF-beta.
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PMID:Chronic liver injury, TGF-beta, and cancer. 1179 78


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