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)

Plasma prekallikrein (PPK) is a single-chain glycoprotein synthesized in the liver. The aim of our study was to evaluate a plasma prekallikrein as the marker reflecting liver protein synthesis in patients with chronic liver diseases. PPK levels have been measured by own modification of amidolytic micro-assay in 43 patients with chronic liver diseases and 37 healthy volunteers as control group. As compared to control group, PPK level was significantly decreased in patients with chronic active hepatitis and with decompensated liver cirrhosis and significantly increased in patients with liver cirrhosis complicated by hepatocellular carcinoma. There was no difference in plasma prekallikrein between patients with compensated liver cirrhosis and controls. The results suggest that PPK might be a useful index for the assessment of residual functional liver mass in patients with chronic liver diseases.
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PMID:[Plasma prekallikrein in chronic liver diseases]. 883 36

Thermolabile beta-2 macroglycoprotein is a novel serum protein that was detected by an autoantibody in sera of a Japanese woman with systemic lupus erythematosus. We developed an enzyme-linked immunosorbent assay for this glycoprotein and measured its serum levels in patients with chronic liver disease. There were significant correlations between serum levels of this glycoprotein and those of albumin and cholinesterase. The serum levels of TL beta 2MG decreased with increasing severity of cirrhosis. Immunohistochemical staining using monoclonal anti-thermolabile beta-2 macroglycoprotein antibody revealed positive staining in the cytoplasm of the hepatocytes. These data strongly suggested that hepatocyte may be one of the production sites of this glycoprotein. Measurement of serum levels of this glycoprotein was useful for evaluation of hepatic function in chronic liver disease.
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PMID:Thermolabile beta-2 macroglycoprotein (Hakata antigen) in liver disease: biochemical and immunohistochemical study. 893 53

Sera from 14 normal control subjects, 30 patients with alcoholic liver diseases (fatty liver, n = 8; hepatitis, n = 13; liver cirrhosis, n = 9), 7 controls with chronic hepatitis B, and 8 controls with chronic hepatitis C were masured for their concentrations of antibodies against HepG2 membrane protein by a binding assay utilizing 125I-labeled protein A. When the cut-off level was set as the mean value plus 2 SD of normal control subjects, the incidence of positivity was 75%, 69.2%, and 77.8% in patients with alcoholic fatty liver, alcoholic hepatitis, and alcoholic cirrhosis, respectively. Both the mean serum antibody values and the positive incidence were significantly higher in patients with alcoholic liver diseases than in either the normal controls or in the control patients with chronic hepatitis. Sodium dodecylsulfate polyacrylamide gel electrophoresis of 125I-labeled HepG2 membrane protein precipitated with IgG from patients with alcoholic liver diseases revealed an immunoreactive band at a molecular weight of 78,000 daltons (gp78). The antibody activity remained after immunoabsorption by human liver-specific lipoprotein (LSP) but decreased when HepG2 cells were pre-treated with trypsin or neuraminidase. Consequently, gp78 appears to be a glycoprotein distinct from LSP, and is specifically recognized by IgG from patients with alcoholic liver diseases. This assay may provide a new system to measure autoantibody to hepatocytes in alcoholic liver diseases.
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PMID:Autoantibody against a 78 kDa membrane protein of HepG2 cell in the sera of patients with alcoholic liver diseases. 896 93

In cirrhosis, intrahepatic shunts and capillarization of sinusoids can result in impaired extraction of substrates by the liver irrespective of the metabolic capacity of the liver (intact hepatocyte theory). To evaluate the role of anomalies of uptake in impaired drug disposition, we studied the steady-state hepatic clearance and single-pass hepatic uptake of propranolol in isolated perfused livers obtained from patients with cirrhosis at the time of transplantation and from organ donors with normal liver architecture. The kinetics of propranolol transport in the liver were characterized by means of the multiple-indicator dilution technique, and the outflow pattern of propranolol in the hepatic veins was resolved into throughput material, which had swept past the hepatocytes along with albumin, and returning material, which had entered the cells but returned in the outflow after escaping cellular sequestration and metabolism. The steady-state clearance of propranolol was decreased in cirrhotics compared with organ donors, and the outflow profile differed between the two groups. In cirrhotic livers, half of the propranolol in the outflow consisted of throughput material and the other half of returning material; in organ donors, all of the propranolol in the outflow was returning material. In the presence of albumin and alpha 1-acid glycoprotein in the perfusate, about 80-85% of propranolol was protein bound; removal of albumin and alpha 1-acid glycoprotein from the perfusate it cirrhotic livers resulted in an increase in the free fraction of propranolol, an increase in steady-state extraction, and a decrease in the throughput component of propranolol in the outflow. We conclude that impaired uptake of protein-bound propranolol, as a result of capillarization and intrahepatic shunts, contributes to its impaired elimination in cirrhosis.
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PMID:Clearance by the liver in cirrhosis. III. Propranolol uptake by the isolated perfused human liver. 904 43

Clinical applications of radionuclide methods for the study of liver hemodynamics and hepatocyte function are examined. In particular, as for hemodynamic studies, perfusion assessment with radiocolloids, 99mTc-IDA scintigraphy or 99mTc-labeled red blood cells, is underlined; they allow characterization of the different cellular component of space-occupying liver processes. The use of hepatic perfusion index (HPI) is reconsidered both as prognostic parameter in cirrhotic patients and as predictor of liver metastasis from colorectal cancer. The diagnostic role of recent procedures, as those based on endorectal radiopharmaceuticals in the evaluation of portosystemic shunts in cirrhosis, is analyzed. Studies of hepatocyte function of practical concern are essentially devoted to the "excretory function" and "asialoglycoprotein metabolism". In the first case, a major role is played by IDA halogenated derivatives and functional parameters drawn from them by mathematico-statistical evaluations of radiohepatogram (simple or applied to compartmental models). For metabolic studies, at present an artificial glycoprotein, 99mTc-galactosylneoglycoalbumin (99mTc-NGA) that binds with hepatocellular receptors is used. Information on the rate of blood plasma clearance and liver uptake, receptor density (altered in some pathologic conditions) and plasmic hepatic flow, is supplied.
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PMID:Is there still a role for functional radionuclide study of the liver? 935 30

Plasma alpha 1 antitrypsin (alpha 1 AT) is the major serine protease inhibitor (Pi) in plasma. It is a glycoprotein, which presents many molecular variants. Allelic phenotypes are classified alphabetically according to their electrophoretic mobility in the Pi (Proteases inhibitor) system. More than 75 distinct protease inhibitor subtypes have been identified using isoelectric focusing (IEF). The major interest for detecting its microheterogeneity is the rare possibility of deficient alleles, which are responsible of low amounts in the alpha IAT production. The clinical use of the alpha 1AT phenotyping is the diagnosis of hereditary alpha 1AT deficiencies. The most common normal phenotype is MM; the major deficient phenotypes are MS, MZ, SS, SZ and ZZ. Hereditary deficiencies of the Pi, the most common inborn error in European people, lead to pulmonary emphysema in young adults or liver cirrhosis in children. IEF on polyacrylamide gels is the reference method for alpha 1AT phenotyping, but is very difficult to standardize. In the present study, we have developed IEF on agarose gels for Pi subtyping within a number of technical improvements. A 0.5 mm thin agarose gel (1.6%) is cast on polyester film; focusing is performed using carrier ampholines (pH = 4.2-4.9), using a very high voltage. Staining is done with a simplified silver nitrate method. The patterns of the different Pi phenotypes obtained with our technique are very attractive. The common subtypes corresponding to the alleles M1, M2, M3, S, Z are univocally demonstrated. Agarose gel allows the advantage of using a non toxic substance. Further the gels are easy to produce and the method is accessible to all clinical laboratories.
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PMID:[Determination of alpha 1 antitrypsin phenotypes in plasma using isoelectric focusing on this agarose gel]. 976 31

This study aimed to determine whether haptocorrin (HC), a vitamin B12 binder, is stored in hepatic cells and whether this storage is modified by hepatic carcinogenesis. It was carried out using immunohistochemistry on different liver tissues (normal liver and steatosis, N = 22; cirrhosis, N = 13; and hepatocellular carcinoma, N = 31). No significant immunostaining of HC was detected in noncancerous biopsies with the exception of in one case of cirrhosis. Hepatocellular carcinoma (HCC) sections showed a weak to moderate cytoplasmic staining of cancerous cells (93% of cases) and of noncancerous hepatocytes surrounding the tumor (95%) of cases. Sections with pseudoglandular structures showed a moderate to strong staining of their secretion products. These results and previous studies would seem to confirm the hypothesis that the raised HC serum level observed in HCC is due both to the increased hepatic synthesis of HC and to a decreased uptake by the liver of the particular isoform of this glycoprotein present in the serum of HCC patients.
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PMID:Human haptocorrin in hepatocellular carcinoma. 1010 89

In chronic hepatitis C the rate of relapse after an end-of-treatment response to interferon may exceed 50%. The usefulness of retreatment of relapsers with interferon in obtaining a complete sustained response and the role of clinical, virological and immunological features in determining long-term efficacy of retreatment are unclear. We aimed to assess the efficacy of interferon retreatment in obtaining a complete sustained response, to evaluate whether increasing the dose may enhance responsiveness, and to identify possible predictors of sustained response. We enrolled 42 patients with biopsy-proven chronic hepatitis C without cirrhosis who had previously responded to a six-month course of Interferon-alpha2b (total dose: group A, 22 patients, 234 MU; group B, 20 patients, 468 MU) and then relapsed. All, except one, were HCV-RNA negative at the end of first cycle of interferon; most (31/42, 74%) were infected by HCV 1b. Subjects were randomly allocated to receive another cycle of interferon either at the original dose (group A1: 234 MU, 11 patients; group B1 468 MU, 10 patient) or twice the original dose (group A2: 468 MU, 11 patients; group B2: 936 MU, 10 patients). At the end of the second cycle of interferon, 24 subjects (57%) had normal ALT and were HCV-RNA negative, and 16 (39%) had normal ALT, but were HCV-RNA positive. A complete sustained response was obtained in eight patients (19%), at a similar rate in all treatment groups. Complete sustained responders were different from the other patients in terms of age (35.9 +/- 10.4 vs 44.1 +/- 8.8, P = 0.027), rate of infection with non-1b HCV (6/8 vs 5/34, P = 0.0005), serum HCV-RNA (74,016 vs 321,428 median copies/ml, P = 0.037) and serum levels of 90K/MAC-2 BP (5.76 +/- 3.01 vs 10.25 +/- 5.16 units/ml, P = 0.02), an N-glycoprotein implicated in cellular defense functions. Multivariate logistic analysis validated age and HCV genotype as independent predictors of CSR. Among noncirrhotic relapsers who received a total interferon dose > or = 234 MU in the first cycle, retreatment usually induced end-of-treatment response. A complete sustained response was obtained in only one of every five subjects. Increasing the dose of interferon above that of the first cycle did not enhance the rate of sustained response. In conclusion we might assert that young subjects infected by non-1b HCV and with low levels of HCV-RNA and of 90K/MAC-2 BP are the best candidates for retreatment.
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PMID:Viral and host factors in determining response of relapsers with chronic hepatitis C to retreatment with interferon. 1023 12

Secretion of the alpha-subunit of pituitary glycoprotein hormones usually follows the secretion of intact gonadotropins and is increased in gonadal failure and decreased in isolated gonadotropin deficiency. The aim of the present study was to determine the levels of the alpha-subunit in the serum of patients with cirrhosis of the liver and to compare the results obtained for eugonadal cirrhotic patients with those obtained for cirrhotic patients with hypogonadotropic hypogonadism. Forty-seven of 63 patients with cirrhosis (74.6%) presented hypogonadism (which was central in 45 cases and primary in 2), 7 were eugonadal, and 9 women were in normal menopause. The serum alpha-subunit was measured by the fluorimetric method using monoclonal antibodies. Cross-reactivity with LH, TSH, FSH and hCG was 6.5, 1.2, 4.3 and 1.1%, respectively, with an intra-assay coefficient of variation (CV) of less than 5% and an interassay CV of 5%, and sensitivity limit of 4 ng/l. The serum alpha-subunit concentration ranged from 36 to 6253 ng/l, with a median of 273 ng/l. The median was 251 ng/l for patients with central hypogonadism and 198 ng/l for eugonadal patients. The correlation between the alpha-subunit and basal LH levels was significant both in the total sample (r = 0.48, P < 0.01) and in the cirrhotic patients with central hypogonadism (r = 0.33, P = 0.02). Among men with central hypogonadism there was a negative correlation between alpha-subunit levels and total testosterone levels (r = -0.54, P < 0.01) as well as free testosterone levels (r = -0.53, P < 0.01). In conclusion, although the alpha-subunit levels are correlated with LH levels, at present they cannot be used as markers for hypogonadism in patients with cirrhosis of the liver.
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PMID:Pituitary glycoprotein hormone a-subunit secretion by cirrhotic patients. 1034 72

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


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