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 animals, the effects of vasoactive intestinal polypeptide (VIP) include peripheral vasodilation, hyperdynamic circulation, hyperglycemia, and hyperventilation. Because these phenomena are noted in patients with cirrhosis, it has been postulated that VIP might be escaping hepatic inactivation and entering the systemic circulatory system and contributing to these abnormalities. The major purpose of this study is to establish whether or not VIP levels are elevated in patients with cirrhosis. Additional goals are to determine if VIP levels are elevated in acute liver disease and in chronic illnesses with secondary liver involvement. The data demonstrate that patients with cirrhosis and those with acute liver disease or chronic illnesses with secondary hepatic involvement have a wide range of VIP levels with mean values significantly above that of normal individuals and patients with chronic illness and no liver involvement.
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PMID:Circulating levels of vasoactive intestinal polypeptide in liver disease. 47 38

Ascitic fluids from patients with cancer, cirrhosis, and congestive heart failure and from a patient with noninfectious tuberculosis contain measurable levels of tissue polypeptide antigen (TPA). Only the cancer patients had levels higher than 2.0 microgram TPA per ml. The average TPA levels of 29 cancer patients was 6.4 microgram/ml compared to 0.9 microgram/ml for the controls. Seventeen of 22 cancer ascitic fluids and 7 of 9 fluids from patients with liver disease were immunosuppressive as measured by the inhibition of [3H]thymidine incorporation into phytohemagglutinin-stimulated lymphocytes. Fluids from a patient with congestive heart failure and a patient with noninfectious tuberculosis were not suppressive. We were unable to obtain a significant correlation coefficient between immunosuppression and TPA levels in these fluids. In addition, TPA levels remained constant over a period of 18 months of testing, whereas the in vitro immunosuppressive activity was lost in 9 to 10 months. Sephadex G-200 fractionation of the ascitic fluid resulted in the TPA and immunosuppressive activity eluting in the first large molecular weight peak from the column. Although the 2 activities eluted together in this fractionation, the data suggest that TPA is not responsible for the immunosuppression.
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PMID:Immunosuppressive activity and tissue polypeptide antigen content of human ascitic fluids. 68 26

In liver biopsy specimens (between 8.5 and 22 mg wet weight) obtained from normal and thioacetamide-induced cirrhotic rat liver the polypeptide-chain-elongationpromoting activity (elongation factors 1 and 2) was determined. In liver cirrhosis the activity is reduced by about 50%.
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PMID:Determination of protein synthesis elongation factor activity in liver biopsy specimens from normal and cirrhotic rats. 86 37

Since transcobalamin II is the plasma binder of vitamin B12(cobalamin) that mediates delivery of cobalamin to tissues, we measured circulating levels of transcobalamin II after intravenous injection unlabeled cyanocobalamin in 12 control subjects and, because the liver is a major source of transcobalamin II, in eight patients with decompensated cirrhosis. Thirty minutes after injection of cyanocobalamin (200 ng per kilogram of body weight), total transcobalamin II (unsaturated plus cobalamin bound) declined in all 20 subjects to levels that averaged (+/- S.E.) 53.5 +/- 4.6 per cent of initial values. Subsequently, unsaturated transcobalamin II rapidly increased so that by eight hours, total transcobalamin II approached preinjection levels. Rates of regeneration of transcobalamin II were similar in control subjects and patients with liver disease. Unlike total transcobalamin II, total transcobalamin I was unaltered by injection of cyanocobalamin. Moreover, addition of cyanocobalamin to plasma in vitro did not alter measurements of total transcobalamin II. The rapid response of circulating transcobalamin II to cyanocobalamin injection strongly supports a dynamic role for this polypeptide during transport of a relatively large load of cobalamin.
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PMID:Changes in circulating transcobalamin II after injection of cyanocobalamin. 86 12

Serum tissue polypeptide antigen (TPA) was determined in 86 cirrhotic patients who underwent a thorough clinical and laboratory evaluation. Increased serum TPA levels were found in 87.2% of the patients (81% of Child's A, 81.3% of Child's B and 97% of Child's C) with very high levels in some cases. There were significant correlations between TPA and several clinical and biochemical tests, especially AST (r = 0.678, p < 0.000001), and this enzyme was the best predictor of TPA levels. Patients with abnormal AST had also significantly higher serum levels of TPA than those with normal AST in each of the Child's class (p < 0.01 for each). TPA values were found to be more frequently abnormal than AST ones in cirrhotics (p = 0.009) and could be used as indirect markers of activity in these patients. The underlying mechanism involved in the increase in TPA in cirrhosis was probably related to the cytolytic/regenerative activity of the liver. TPA cannot be used as a tumor marker in these patients.
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PMID:A clinical and laboratory evaluation of the behavior of tissue polypeptide antigen in liver cirrhosis. 129 4

Patients with hepatocellular carcinoma (HCC), gastrointestinal, lung, and ovarian cancers were shown to have autoantibodies to nuclear and nucleolar antigens as detected by immunofluorescence on cell substrates. The frequency of antinuclear antibodies (ANAs) was significantly higher (P less than 0.001) in patients with HCC (57/184 = 31%) than in patients with chronic hepatitis or liver cirrhosis (25/187 = 13%). Although a range of fluorescence patterns was observed, a higher percentage of nucleolar fluorescence was detected in HCC, and three of these nucleolar antigens were identified. They were NOR-90, nucleolus organizer region doublet polypeptides of 93 and 89 kDa involved in RNA polymerase I transcription; fibrillarin, a 34 kDa protein of the nucleolar U3 ribonucleoprotein particle which is engaged in preribosomal RNA processing; and nucleophosmin/protein B23, a 37 kDa polypeptide which is associated with ribosome maturation and cellular proliferation. All these antigens are nucleolar components that are engaged in some aspect of ribosome biosynthesis. Since autoantibodies to these nucleolar antigens have also been found in systemic autoimmune diseases, they do not represent autoimmune reactions unique to cancer but might reflect reaction pathways related to immune responses that are antigen-driven. The ANA response in HCC appears to be dynamic reactions to this antigen-drive since some patients with chronic liver disease showed seroconversion to ANA positivity, marked increase in titer and/or change in antibody specificity preceding or coincident with clinical detection of HCC. These changes in ANA showed a close temporal relationship with transformation from long-established chronic liver disease to HCC.
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PMID:Nucleolar antigens and autoantibodies in hepatocellular carcinoma and other malignancies. 131 27

In 1974, Prince et al. reported the existence of posttransfusion hepatitis with a long incubation period which was not related to hepatitis B virus (HBV). These cases were named "non-A, non-B" (NANB) hepatitis. The genome of NANB hepatitis virus was discovered recently using a recombinant complementary DNA (cDNA) approach. It was termed the hepatitis C virus (HCV), and a specific diagnostic tool for the circulating HCV antibody (anti-HCV) was developed using a purified viral polypeptide derived from recombinant yeast expressing a small part of the HCV genome. HCV is believed to be the main cause of blood-borne non-A, non-B hepatitis worldwide, which frequently evolves to chronic hepatitis and cirrhosis, and which may also be involved in the development of hepatocellular carcinoma. HCV is classified as part of the flaviviridae family and contains a positive-stranded RNA molecule by approximately 10 kb nucleotides. The HCV genome encodes a large polyprotein precursor, which is processed in structural nucleocapsid and envelope proteins and in non-structural proteins (NS1-NS5). Nucleotide sequence comparisons of distinct HCV isolates have shown a significant genetic variability between the different HCV strains. At present the diagnosis of HCV infection depends on various anti-HCV tests including second generation HCV Ab. Antigenic markers for HCV are being developed but the concentrations of HCV antigens in serum are at the lower limit of detectability by existing immunoassay technology. A polymerase chain reaction has been used to detect HCV RNA in the serum and liver. Serum HCV RNA disappears from serum after effective IFN treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Fundamental studies of hepatitis C virus: a review]. 133 74

Excessive accumulation of collagen in the extracellular matrix has a crucial role in fibrosis. Thus pharmacological inhibition of collagen deposition is likely to be beneficial for patients suffering from fibrotic disorders such as liver cirrhosis. Prolyl 4-hydroxylase catalyzes the formation of 4-hydroxyproline in collagens and other proteins with collagen-like amino acid sequences by the hydroxylation of proline residues in -X-Pro-Gly- sequences. The reaction products, 4-hydroxyproline residues, serve to stabilize the collagen triple helices under physiological conditions. Conversely, collagen chains that contain no 4-hydroxyproline cannot fold into triple helical molecules that are stable at body temperature. The prolyl 4-hydroxylase reaction therefore seems to be a particularly suitable target for the pharmological regulation of excessive collagen formation. The reaction catalyzed by prolyl 4-hydroxylase requires Fe2+, 2-oxoglutarate, O2 and ascorbate and involves an oxidative decarboxylation of 2-oxoglutarate. The active enzyme is an alpha 2 beta 2 tetramer that consists of two types of inactive monomer and has two catalytic sites. Some parts of the catalytic sites may be built up cooperatively of both the alpha and beta subunits, but the alpha subunit appears to contribute the major part. The beta subunit contains the carboxyl-terminal tetrapeptide sequence -Lys-Asp-Glu-Leu which is essential for the retention of a polypeptide within the lumen of the endoplasmic reticulum. Since the alpha subunit lacks the carboxyl-terminal retention signal, one function of the beta subunit in the prolyl 4-hydroxylase tetramer may be to retain the enzyme within the endoplasmic reticulum.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prolyl 4-hydroxylase and its role in collagen synthesis. 166 65

The discovery and subsequent clinical application of somatostatine, a polypeptide neurohormone of 14 amino acids, and of its analogs, opens a novel chapter of neuroendocrinology that is still in full evolution and to a large extent unknown. The isolation of an octapeptide, a selective somatostatine analog, permits to prolong its action, in fact it has a halflife of about 140 min in old subjects and about 100 min. in the young. Thanks to its excellent tolerability, the synthetic hormone can be usefully applied in the treatment of acromegaly, gigantism and hypersomatotropinemic conditions in general, and even in other clinical branches, such as treatment of esophageal hemorrhage due to the rupture of varices in liver cirrhosis or to erosion of gastric blood vessels in patients suffering from peptic ulcer disease.
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PMID:[New prospects in the therapeutic use of somatostatin and its derivatives]. 167 25

Formalin-fixed, paraffin-embedded specimens from 110 cases of chronic hepatitis and 108 cases of cirrhosis were stained for HBxAg by the avidin-biotin complex technique using specific antisera made against full-length HBxAg polypeptide or derived synthetic peptides. These tissues were also stained for the HBsAg and HBcAg by the peroxidase-anti-peroxidase method. Among patients with chronic hepatitis, 86% were HBsAg positive in liver cells, 60% were surface antigen positive and 32% were core antigen positive. Among patients with cirrhosis, 97% were HBsAg positive in liver cells, 72% were surface antigen positive and 17% were positive for core antigen. Staining specificity was demonstrated, in part, by using preimmune sera in the place of primary antibody, by blocking of the primary antibody with the appropriate antigen before assay and by testing uninfected liver controls. The persistence and high frequency of HBxAg in liver cells from patients with chronic liver disease suggest that it may play one or more important roles in the pathogenesis of chronic infection. It is possible that detection of HBxAg in the liver could be an additional new diagnostic marker for hepatitis B virus infection. However, the function(s) of HBxAg in the pathogenesis of the chronic liver disease, if any, remains to be explained.
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PMID:HBxAg in the liver from carrier patients with chronic hepatitis and cirrhosis. 171 39


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