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)

Activities of alkaline phosphatase (ALP), gamma-glutamyl transferase (GMT), lactate dehydrogenase (LD), beta-glucuronidase (GLU) and cathepsin B-like (CB-like) were determined in blind-coded sera from 50 patients with primary liver carcinoma, liver cirrhosis and acute hepatitis, and from 40 control subjects of comparable age range. CB-like activity averaged 700% (p less than 0.01), 1590% (p less than 0.01) and 1600% (p less than 0.01) of control subjects in liver cirrhosis (n = 30), acute hepatitis (n = 5) and primary liver carcinoma (n = 15), respectively. In acute hepatitis group we have found significant correlation between CB-like and GLU activities (r greater than 0.95). This correlation, however, was not observed in primary liver carcinoma suggesting that alteration in CB-like activity is not due to generalized increases in lysosomal membrane instability. The primary liver carcinoma group exhibited also the modest increments in serum ALP, GMT and LD activities (p less than 0.01). This increment, however, was not detected in any of acute hepatitis or liver cirrhosis patients. For the first time the alkaline-stable form of CB-like in human serum is described. This form representing 40% of overall CB-like activity was present in all primary liver carcinoma patients. This form, however, was not present in sera of any of control subjects or in sera of patients with acute hepatitis and liver cirrhosis with the exception of two men, in whom we have probably dealing with an early stage of primary liver carcinoma. Although the nature of the increment in CB-like activity in cancer remains to be determined, such analyses may help to the early detection of malignant hepatoma (primary liver carcinoma).
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PMID:Serum alkaline-stable acid thiol proteinase--a possible marker for primary liver carcinoma. 614 23

Human hepatic collagenolytic cathepsin consisted of a major component having a molecular weight of 25 000 and a minor one of 35 000; the former is indistinguishable for cathepsin B in its enzymatic properties. Hepatic collagenolytic cathepsin increased in chronic active liver disease in proportion to hepatic hydroxyproline content. The ratio of collagenolytic cathepsin to hepatic hydroxyproline content remained within the normal range in chronic hepatitis, but decreased significantly in cirrhosis. These results suggest that collagenolytic cathepsin participates, at least partly, in the progress of hepatic fibrosis.
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PMID:Hepatic collagenolytic cathepsin in patients with chronic liver disease. 744 33

This study was carried out in an attempt to differentiate between the contribution of liver impairment and direct actions of alcohol in myopathy of alcoholic liver disease. Using an animal model of cirrhosis we have previously shown that protein synthetic potential in muscle was not significantly altered. We therefore investigated the possibility that muscle degradation is increased. Cirrhosis was induced by carbon tetrachloride gavage in male rats receiving phenobarbitone in their drinking water. Controls were given phenobarbitone alone. After 135 days the free, latent and total activities of the lysosomal enzymes cathepsin B and cathepsin D in gastrocnemius muscle were unaffected by the induction of experimental cirrhosis when expressed relative to tissue wet weight, protein or DNA. The non-lysosomal enzyme neutral protease was also measured in gastrocnemius muscle from control and cirrhotic rats. There was no difference between the two groups in the free, latent or total activities. Addition of ethanol and acetaldehyde to the assay mixtures in some cases significantly altered the relative activities of the proteases in latent and free compartments of the cirrhotic tissues. In control tissues a different pattern of response emerged. It is concluded that in cirrhosis, at least in the carbon tetrachloride-induced rat model, there is no change of the activity of cathepsin B and D and the neutral protease activity in gastrocnemius. Small but significant effects of ethanol and its metabolite acetaldehyde on latent and free muscle protease activity were demonstrated.
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PMID:Skeletal muscle protease activities are unaltered in cirrhotic rats but altered in response to ethanol and acetaldehyde in vitro. 766 39

The serum levels of lysosomal cathepsin B and L and Stefin A, an intracellular inhibitor of these proteolytic enzymes, were determined in patients with hepatocellular carcinoma (HCC) and/or liver cirrhosis (LC) and correlated with some clinical and biochemical parameters of these diseases. Cathepsin B serum levels were increased in HCC and in LC patients as compared to normal subjects (p < 0.001). However no difference was observed between HCC and LC groups. Interestingly, a significant relationship was evidenced between cathepsin B serum content and the grade of severity of cirrhosis (r = 0.41; p < 0.001). Cathepsin L was significantly elevated only in sera of cancer patients as compared to normal subjects or LC patients (p < 0.001) and significantly correlated with the number of malignant lesions (r = 0.49; p = 0.001). Stefin A serum levels were increased in HCC and LC patients as compared to healthy subjects (p < 0.02). However, these levels were significantly higher in the LC group as compared to the HCC group (p < 0.05). In cancer patients, a significant relationship was observed between Stefin A serum content and tumor size (r = 0.35; p < 0.05), number of neoplastic lesions (r = 0.556; p < 0.001) and serum alpha-fetoprotein (r = 0.38; p < 0.01). These data suggest that cathepsin B and L and Stefin A may be potentially useful as additional biochemical parameters to monitor the therapeutic response of these diseases to clinical treatments and to identify patients with cirrhosis developing precancerous lesions.
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PMID:Lysosomal cathepsins B and L and Stefin A blood levels in patients with hepatocellular carcinoma and/or liver cirrhosis: potential clinical implications. 897 98

Hepatitis C virus (HCV) is a major cause of chronic liver diseases. A high risk of chronicity is the major concern of HCV infection, since chronic HCV infection often leads to liver cirrhosis and hepatocellular carcinoma. Infection with the HCV genotype 1 in particular is considered a clinical risk factor for the development of hepatocellular carcinoma, although the molecular mechanisms of the pathogenesis are largely unknown. Autophagy is involved in the degradation of cellular organelles and the elimination of invasive microorganisms. In addition, disruption of autophagy often leads to several protein deposition diseases. Although recent reports suggest that HCV exploits the autophagy pathway for viral propagation, the biological significance of the autophagy to the life cycle of HCV is still uncertain. Here, we show that replication of HCV RNA induces autophagy to inhibit cell death. Cells harboring an HCV replicon RNA of genotype 1b strain Con1 but not of genotype 2a strain JFH1 exhibited an incomplete acidification of the autolysosome due to a lysosomal defect, leading to the enhanced secretion of immature cathepsin B. The suppression of autophagy in the Con1 HCV replicon cells induced severe cytoplasmic vacuolation and cell death. These results suggest that HCV harnesses autophagy to circumvent the harmful vacuole formation and to maintain a persistent infection. These findings reveal a unique survival strategy of HCV and provide new insights into the genotype-specific pathogenicity of HCV.
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PMID:Dysfunction of autophagy participates in vacuole formation and cell death in cells replicating hepatitis C virus. 2199 53

Beta-hydroxy-beta-methylbutyrate (HMB) is a leucine metabolite with protein anabolic effects. We examined the effects of an HMB-enriched diet in healthy rats and rats with liver cirrhosis induced by multiple doses of carbon tetrachloride (CCl4). HMB increased branched-chain amino acids (BCAAs; valine, leucine and isoleucine) in blood and BCAA and ATP in muscles of healthy animals. The effect on muscle mass and protein content was insignificant. In CCl4-treated animals alterations characteristic of liver cirrhosis were found with decreased ratio of the BCAA to aromatic amino acids in blood and lower muscle mass and ATP content when compared with controls. In CCl4-treated animals consuming HMB, we observed higher mortality, lower body weight, higher BCAA levels in blood plasma, higher ATP content in muscles, and lower ATP content and higher cathepsin B and L activities in the liver when compared with CCl4-treated animals without HMB. We conclude that (1) HMB supplementation has a positive effect on muscle mitochondrial function and enhances BCAA concentrations in healthy animals and (2) the effects of HMB on the course of liver cirrhosis in CCl4-treated rats are detrimental. Further studies examining the effects of HMB in other models of hepatic injury are needed to determine pros and cons of HMB in the treatment of subjects with liver cirrhosis.
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PMID:Effects of beta-hydroxy-beta-methylbutyrate supplementation on skeletal muscle in healthy and cirrhotic rats. 3132 41