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)

In order to evaluate the influence of dilution, pH and ionic strength on the precipitation of t-PA and PAI-1 during euglobulin precipitation, we measured t-PA Ag, PAI-1 Ag and fibrinolytic activity in the euglobulin fraction made of pooled plasma from liver cirrhosis patients, under various conditions by changing pH, ionic strength and degree of dilution. The precipitation of t-PA Ag in the euglobulin fraction was enhanced by decreasing the ionic strength and greatest at pH 6.0. The fibrinolytic activity in the euglobulin fraction showed consistent changes with t-PA Ag under varying pH and ionic strength. The precipitation of t-PA Ag was not influenced by the dilution factor but the larger the dilution factor, the greater the PAI-1 and the smaller the fibrinolytic activity in the euglobulin fraction. PAI Ag in euglobulin fraction showed consistent changes with t-PA Ag in the euglobulin fraction regardless of the changes in ionic strength and pH. The amount of precipitation of t-PA and PAI-1 was increased by the presence of dextran sulfate, under varying pH, ionic strength and dilution conditions. Our results show that the currently used conditions for standard euglobulin precipitation are the most favorable for t-PA precipitation into the euglobulin fraction. The fibrinolytic activity exerted in the euglobulin fraction seems to depend on the amount of t-PA-PAI-1 complex rather than minimized protease inhibitor in the euglobulin fraction.
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PMID:The effect of dilution, pH and ionic strength of plasma on t-PA precipitation in euglobulin fraction. 130 75

Patients with liver disease have a variety of coagulation abnormalities. These derangements are of uncertain origin and do not always correlate with disease severity or activity. We have measured the levels and proportions of the total fibrin-related and fibrinogen-related antigens, the principal fibrin (D-dimer) and fibrinogen (D-monomer) degradation fragments and intermediates of fibrin formation (fibrin monomers) in patients with a variety of acute and chronic liver diseases in whom all known other precipitating causes of disseminated intravascular coagulation had been excluded. Fibrin-related and fibrinogen-related antigens were extracted from serum using antihuman fibrinogen-IgG covalently bound to activated amino-phenylthioether paper disks and were subjected to 4% to 11% sodium dodecyl sulfate-polyacrylamide gel electrophoresis under nonreducing conditions. Fibrin-related and fibrinogen-related antigen proportions were determined by densitometry, and their levels were measured by radioimmunoassay. Levels of total fibrin-related and fibrinogen-related antigens (and D-dimer) were significantly elevated (p less than 0.01) in patients with cirrhosis (121 to 641 ng/ml) and hepatocellular carcinoma (416 to 8,786 ng/ml) when compared with patients with acute viral hepatitis (84 to 322 ng/ml) and control subjects (38 to 186 ng/ml). In addition, D-monomer levels were elevated. These findings strongly suggest that disseminated intravascular coagulation is a component of the coagulopathy of certain liver diseases. Because fibrin-related and fibrinogen-related antigens have anticoagulant, vasoactive and immunosuppressive properties, their elevated presence may be biologically significant in these patients.
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PMID:Elevated fibrin-related and fibrinogen-related antigens in patients with liver disease. 132 11

Hepatic encephalopathy due to cirrhosis is frequently precipitated by exogenous factors, and the effectiveness of a specific treatment with neomycin sulfate has so far not been submitted to clinical trials. Over a period of five years, 102 cirrhotic patients developed hepatic encephalopathy at admission or during hospitalization, and 39 were randomized for treatment with either neomycin sulfate or placebo. Exclusion criteria were: 1. current usage of specific treatment for hepatic encephalopathy, 2. chronic hepatic encephalopathy and 3. multiple organ failure syndrome associated with hepatic encephalopathy. The group of excluded patients (n = 63) was compared with the randomized group (n = 39), and no statistical differences were found regarding sex and age distributions, Child-Pugh classification, etiology of cirrhosis, percipitating factors and grade of hepatic encephalopathy. These same parameters were also comparable among the 20 patients who received active neomycin and the 19 who were treated with placebo. The therapy for hepatic encephalopathy consisted in the control of precipitating factors associated with 6 g of neomycin sulfate "per os" or placebo. Therapeutic failure and death by the fifth day of treatment, occurred in four patients (10.2%), two in each of the randomized groups. The time elapsed between the initiation of the therapeutic procedure and regression to grade zero of hepatic encephalopathy was 39.11 +/- 23.04 hours for the group of active neomycin, and 49.47 +/- 21.92 hours for the placebo group, but this difference did not achieve statistical significance.
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PMID:Double-blind randomized clinical trial comparing neomycin and placebo in the treatment of exogenous hepatic encephalopathy. 148 68

Sulfur amino acid metabolism was studied in patients with mild to severe forms of liver dysfunction and compared with that of healthy controls. Patients with mild liver dysfunction (for example, Gilbert's syndrome) had a normal sulfur amino acid metabolism. With increased inflammatory activity and cirrhosis (for example, chronic active hepatitis, alcohol-induced cirrhosis, and hepatic coma) a decreased ability to metabolize methionine (to cysteine, with cystathionine accumulation) and cysteine (to inorganic sulfate, with thiosulfate and N-acetylcysteine accumulation) was found. In contrast, transaminative metabolism of sulfur amino acids was preserved in patients with advanced forms of liver dysfunction, suggesting that transamination of sulfur amino acids is performed not only in the liver but also in extrahepatic tissues. Some implications of these findings are discussed.
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PMID:Sulfur amino acid metabolism in hepatobiliary disorders. 152 76

We have investigated the effects of nontoxic doses of vitamin A on the hepatic contents of collagen and sulfated glycosaminoglycans (SGAGs) in rats chronically treated with CCl4. When the animals were treated with this retinoid before the intoxication with CCl4, liver collagen level was significantly reduced as compared with that in rats that received only CCl4 (3.31 +/- 0.40 vs 5.00 +/- 0.61 mg/gm wet liver, mean +/- SD, respectively), although no significant differences were found for the relative proportion of type III collagen related to type I collagen. The absolute increment in the total amount of liver SGAG in the vitamin A--pretreated group was followed by a more important increase in the concentration of dermatan sulfate as compared with the CCl4 group (dermatan sulfate-to-heparan sulfate ratio: 1.15 for the CCl4 group vs 1.70 for the vitamin A--pretreated group). A significant proportion of the dermatan sulfate from this last group was of higher molecular weight when compared with the dermatan sulfate found in the liver of rats that received only CCl4. Our results indicate that the pretreatment with vitamin A modifies hepatic collagen and SGAG deposition and can inhibit or delay the development of liver cirrhosis in rats chronically treated with CCl4. We speculate that this effect could be due to the changes in the fat-storing (Ito) cells phenotype induced by vitamin A.
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PMID:Effects of vitamin A administration on collagen and sulfated glycosaminoglycans contents in the livers of rats treated with carbon tetrachloride. 159 6

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

In this study the risk of thrombosis in the portal venous system was assessed in patients with chronic variceal bleeding undergoing sclerotherapy. Twenty-two patients with cirrhosis were prospectively studied with angiography before initiation of sclerotherapy and at mean (+/- SD) 26 +/- 17-month (range, 8-63 months) follow-up. Sclerotherapy consisted of flexible endoscopy, intravariceal and paravariceal, using sodium morrhuate (1.5%-2%) and sodium tetradecyl sulfate (0.5%-1.5%), to obliteration. The mean number of sessions was 6.5 +/- 2.2 (range, 3-11), with a mean total amount of sclerosant of 62 +/- 25 mL (range, 25-112 mL). No patient developed splenic or portal vein thrombosis as shown by arteriography. The flow patterns of portal perfusion, vessel size, and coronary vein visualization showed no significant change. Only one patient had spontaneous reversal of portal flow. Splenic vein histology, examined in five patients in whom sclerotherapy failed and who required shunt surgery, was not significantly different from that in eight patients who had no prior sclerotherapy. It is concluded that under the conditions of the current study, chronic sclerotherapy did not increase the risk of thrombosis in the portal venous system and did not significantly alter the histology of the portal hypertensive splenic vein.
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PMID:Endoscopic variceal sclerosis does not increase the risk of portal venous thrombosis. 172 55

In an attempt to evaluate the effect of quinidine in the treatment of patients with cirrhosis and muscle cramps, 31 cirrhotic patients with muscle cramps were randomly divided into two groups and given orally 400 mg of quinidine sulfate per day or placebo, respectively. Baseline clinical and laboratory data for these two groups were similar. Four weeks after oral administration of quinidine, the number of cramps significantly decreased from 14.4 +/- 1.7 (mean +/- S.E.) to 4.4 +/- 1.1 episodes (p less than 0.0001), but it remained unchanged in the placebo group (from 11.8 +/- 1.0 to 11.5 +/- 1.5 episodes, p greater than 0.05). In addition, 88% of the 16 patients on quinidine and 13% of the 15 patients on a placebo showed a greater than 50% reduction in the number of cramps during a 4-week treatment period (p less than 0.0001). The peak and trough serum levels of quinidine in patients having received quinidine for 2 weeks were 1.3 +/- 0.1 and 0.7 +/- 0.1 mg/l, respectively. There was a significant relationship between serum quinidine concentrations and attenuation of cramps. No significant adverse effect was observed during the study, except for five (31%) patients who developed mild diarrhea after quinidine therapy. Diarrhea subsided spontaneously or was controlled by medications without the interruption of quinidine therapy. It was concluded that quinidine is a safe and effective drug for the treatment of cirrhotic patients with muscle cramps.
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PMID:A randomized controlled trial of quinidine in the treatment of cirrhotic patients with muscle cramps. 205 Oct 2

Sera from patients with autoimmune chronic active hepatitis were found to contain IgG-class antibody to the acidic glycosphingolipid fraction from rabbit hepatocyte plasma membrane by solid-phase enzyme-linked immunosorbent assay. Using serum positive for the antibody as a probe, we isolated the target antigen by Iatrobeads column chromatography. Analysis by thin-layer chromatography and negative ion fast atom-bombardment mass spectrometry revealed that the antigen was sulfatide. The presence of antisulfatide antibody was also confirmed by immunoblotting. The reactivity of the serum with sulfatide was diminished by preincubation of the serum with galactosylceramide-6-sulfate and sulfatide, indicating that the antibody reacted with sulfated galactosylceramide regardless of the position of the sulfate residue. The antibody was found in 92.3%, 42.9%, 15.8%, 14.2%, 0% and 0%, respectively, of patients with autoimmune chronic active hepatitis, primary biliary cirrhosis, cirrhosis, systemic lupus erythematosus, chronic active hepatitis and chronic persistent hepatitis. Thus antisulfatide antibody was characteristic of autoimmune-type chronic liver diseases. Antisulfatide antibody was absorbed by rabbit hepatocyte plasma membrane. Preincubation of sera with sulfatide immobilized on Sepharose decreased their reactivities with not only sulfatide but also rabbit plasma membrane and rat hepatocytes. Therefore sulfatide may be a target antigen of the antibody to hepatocyte surface membrane.
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PMID:Hepatocyte plasma membrane glycosphingolipid reactive with sera from patients with autoimmune chronic active hepatitis: its identification as sulfatide. 221 Jun 70

This study was performed in order to elucidate the mechanisms of systemic endotoxemia in liver cirrhosis. For this purpose, the method of measuring biliary endotoxin was established. Endotoxin levels between in the bile and in the plasma in cirrhosis were compared using a modified method of chromogenic quantitative endotoxin assay in an attempt to clarify liver function of clearing portal endotoxin originated from the gut. And functional activities of the reticuloendothelial system were also examined by radioassay with 59Fe-labelled iron-chondroitin sulfate colloid and by enzymohistochemistry of acid phosphatase. Both the plasma and biliary endotoxin levels in liver cirrhosis were significantly higher, compared to those in control. The functional activities of the reticuloendothelial system, particularly of the Kupffer cells, were decreased in liver cirrhosis. These data provide evidence that in liver cirrhosis systemic endotoxemia is mainly due to a decrease of functional activities of Kupffer cells. On the other hand, the excretion of endotoxin into the bile is increased, compensating the decreased functional activities of Kupffer cells. This implies that the uptake of endotoxin and its excretion into the bile by hepatocytes might be one of the mechanisms of clearing excess endotoxin in the plasma in liver cirrhosis. This study also draws the importance of measurements of endotoxin levels in the bile in liver diseases.
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PMID:[Endotoxemia and its compensatory mechanisms in experimental liver cirrhosis]. 223 2


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