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)

Eight patients with cirrhosis were infused with lysine vasopressin (10 microgram LVP) and triglyclylysine vasopressin (750 microgram and 2000 microgram Glypressin, GVP) on separate occasions. LVP infusion resulted in an increase in factor VIII, factor VIII-related antigen and plasminogen activator (PA). The factor VIII antigen: activity ratio decreased following infusion, but factor VIII electrophoretic mobility and in vitro decay rate were unchanged. GVP infusion produced no change in factor VIII or PA. Assay of vasopressin-like antigen and antidiuretic activity showed that GVP is cleaved to LVP in vivo. The low levels of LVP formed by this reaction might explain the prolonged vasometer effects of GVP, as well as its inability to cause release of factor VIII or PA. Compared to LVP, GVP has a longer pressor effect in vivo, has no effect on fibronolysis and exhibits no cardiotoxic effects and may therefore be the treatment of choice in bleeding oesophageal varices.
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PMID:Haemostatic effects of lysine vasopressin and triglycyl lysine vasopressin infusion in patients with cirrhosis. 676 67

A plasminogen activator, or class of activators, that absorbs to lysine-agarose is present in human plasma. We have developed a quantitative assay for this plasminogen activator. The assay involves removal of the activator from plasma with lysine-agarose affinity columns and subsequent measurement of the activity by the conversion of plasminogen to plasmin on standardized fibrin agar plates. Using this assay, we investigated three physiologic conditions that have in the past been associated with increased fibrinolytic activity to determine whether elevation of the LAPA was involved. Normal individuals undergoing strenuous physical exercise and others subjected to venous occlusion as well as patients with cirrhosis of the liver were examined. Treadmill exercise to maximal exertion produced up to 15-fold increases in the level of LAPA; venous occlusion produced similar elevation. Certain individuals did not show increase fibrinolytic activity in response to exercise or venous occlusion, as indicated by unchanged euglobulin lysis times. These fibrinolytic hyporesponders did not show an elevation of their LAPA levels. In the third group examined, patients with cirrhosis, 24 of 62 had elevated levels of LAPA. Supplementation of plasma from normal individuals with this plasminogen activator from exercised individuals and cirrhotics resulted in increased rates of clot lysis.
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PMID:A lysine-absorbable plasminogen activator is elevated in conditions associated with increased fibrinolytic activity. 678 11

In four control subjects and four patients with cirrhosis of the liver a multiple amino acid mixture was infused for 12 h at a constant rate of 68 and 56 mumol alpha-amino N/s, respectively. Before infusion the plasma amino N concentration was 2.4 +/- 0.2 (mean +/- SD) mmol/l in control subjects and 3.5 +/- 0.7 mmol/in patients (P less than 0.025). The concentration of alanine, proline, arginine, tyrosine, and citrulline was significantly increased in the cirrhosis group. 12 h after the infusion began approximately constant amino N concentrations of 11.4 +/- 1.8 mmol/l in controls and 13.7 +/- 3.9 mmol/l in patients were attained, and the urea N synthesis rate was 63 +/- 17 and 44 +/- 8 mumol/s, respectively (P less than 0.05). After correction for loss of amino acids in urine this means that on the average 94 per cent of the N load was recovered as urea. The plasma clearance of infused amino acids, calculated as the ratio between infusion rate and steady state concentration, was 6.0 +/- 1.2 and 4.1 +/- 0.9 ml/s for amino N in the control and cirrhosis group, respectively (P less than 0.025). The clearance of individual amino acids ranged between 2.5 and 28 ml/s. The clearance of most amino acids was decreased in the cirrhosis groups, and of glycine, proline, lysine, threonine, and arginine significantly so (P less than 0.05), reflecting accumulation of amino acids in patients. This indicates that a primary defect in the conversion of amino N in cirrhosis is the reduced urea synthesis.
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PMID:Elimination of infused amino acids from plasma of control subjects and of patients with cirrhosis of the liver. 680 68

Histidine-rich glycoprotein is a 3.8s alpha 2-glycoprotein of human plasma originally isolated in 1972 [1,2]. The biologic function of histidine-rich glycoprotein, however, is unknown. A recent report suggests that histidine-rich glycoprotein binds to the high-affinity lysine-binding sites of plasminogen and that histidine-rich glycoprotein may retard fibrinolysis by interfering with the binding of plasminogen to fibrin [3]. We have measured the plasma titers of histidine-rich glycoprotein in normal subjects and patients with advanced hepatic cirrhosis by single radial immunodiffusion with a monospecific antiserum. The levels in 22 patients were 7.0 +/- 2.5 mg/dl (mean +/- SD), whereas those in 20 control subjects were 11.8 +/- 2.7 (p less than 0.001). Upon two-dimensional crossed immunoelectrophoresis, the pattern of histidine-rich glycoprotein in liver cirrhosis was similar to that of normal histidine-rich glycoprotein. Since histidine-rich glycoprotein seems to function as an antifibrinolytic agent, the decreased titers in cirrhosis may be one factor contributing to the enhanced fibrinolysis commonly seen in this disorder.
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PMID:Reduced histidine-rich glycoprotein levels in plasma of patients with advanced liver cirrhosis. Possible implications for enhanced fibrinolysis. 711 73

The location of acetaldehyde binding sites in the axial unit cell of tendon collagen was investigated by neutron diffraction. Acetaldehyde forms spontaneous cross-links with specific residues in collagen. The use of deuterated acetaldehyde increased the neutron scattering length of these groups. The introduction of deuterated acetaldehyde at specific locations allowed the acetaldehyde-reacted collagen to be treated as multiple isomorphous derivatives for neutron fibre diffraction. The low resolution axially projected structure was determined using amplitudes of the first eight meridional reflections (d = 67 nm). Results indicate that the process of acetaldehyde labelling takes place at different rates at different sites within the collagen fibril. The position of acetaldehyde attachment correlates well with the position of lysine and hydroxylysine residues especially in the regions of the molecular termini. This information is relevant to the process of cirrhosis and fibrosis of the liver since adduction of collagen by acetaldehyde may interfere with normal Schiff base cross-link formation at the C- and N-termini. This may result in subsequent alterations in the intra- and inter-molecular cross-linking pattern of collagen molecules.
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PMID:The in vitro binding of acetaldehyde to collagen studied by neutron diffraction. 798 77

alpha 1-Antitrypsin is a circulating serine proteinase inhibitor that protects the lungs against proteolysis by the enzyme neutrophil elastase. Most northern Europeans have only the normal M form, but some 4% are heterozygotes for the Z deficiency mutant. This mutant is characterized by the substitution of a positively charged lysine residue for a negatively charged glutamic acid at position 342 and results in normal gene translation but reduced protein secretion into the plasma. The plasma levels of antitrypsin in homozygotes are only 15% of normal, the other 85% being retained in the endoplasmic reticulum of the hepatocyte. This review describes the effect of the Z mutation on the structure and function of antitrypsin and illustrates the importance of understanding protein structure in solving the mechanism of Z antitrypsin retention within the liver. We demonstrate that antitrypsin accumulation in the liver results from a unique interaction between antitrypsin molecules. The Z mutation perturbs the gap between the third and fifth strands of the A sheet, allowing the reactive center loop of one molecule to insert into the A sheet of a second. This loop-sheet polymerization results in the formation of chains of protein which form insoluble inclusions in the endoplasmic reticulum, resulting in hepatocellular damage and cirrhosis. In addition, the Z mutation results in a distortion of the circular dichroic spectrum, a rearrangement of the reactive center loop with respect to the A sheet, and a reduction in association rate constant with the cognate proteinase neutrophil elastase.
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PMID:A protein structural approach to the solution of biological problems: alpha 1-antitrypsin as a recent example. 821 81

To date, no attempt has been made to study alterations occurring in the amino acid profile in chronic models of thioacetamide-induced liver cirrhosis. In this work, changes in serum amino acids and proteins in rats with thioacetamide-induced liver cirrhosis are reported, together with changes in enzyme activities in the liver and serum. Seventeen female Wistar rats were used. Eight rats were given 300 mg thioacetamide/l in drinking water for 4 months and nine rats were given water ad libitum during the same time-period. Significant increases in glycine, alanine, serine, methionine, glutamate, ornithine, phenylalanine, tyrosine, histidine and proline were observed in rats with the resulting experimental liver cirrhosis. Threonine, taurine, glutamine, lysine and citrulline tended to increase while isoleucine, leucine, aspartate, arginine and tryptophan tended to decrease. Total and nonessential amino acids increased significantly in cirrhotic animals. Total essential and aromatic amino acids tended to increase in the thioacetamide-treated group, whereas branched chain amino acids tended to decrease in the same group. Regarding serum proteins, a decrease in albumin concentration in the thioacetamide-treated animals was the only change detected. The liver enzyme activities under observation (aspartate and alanine aminotransferases, glutamate dehydrogenase and threonine deaminase) were lower in the thioacetamide group. Decreases were significant for both transaminases and threonine deaminase. Results for serum activities showed that transaminases did not change in thioacetamide-treated rats in comparison with controls. In contrast, alkaline phosphatase rose dramatically in cirrhotic rats. We conclude that the serum amino acid pattern in this chronic model of liver cirrhosis resembles in part that of the corresponding human disease.
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PMID:Serum amino acid changes in rats with thioacetamide-induced liver cirrhosis. 857 92

Lysinuric protein intolerance (LPI) is a rare autosomal recessive inborn error of metabolism, characterised by defective transport of the cationic amino acids lysine, arginine and ornithine. To date there are few reported necropsy cases. This report describes the necropsy findings in a 21 year old female patient originally diagnosed as having LPI in 1973. Liver function tests deteriorated and immediately before death jaundice, hyperammonaemia, coma, metabolic acidosis, and a severe bleeding diathesis developed. At necropsy, there was micronodular cirrhosis of the liver with extensive fatty change in hepatocytes. The lungs showed pulmonary alveolar proteinosis. Immunofluorescence and electron microscopy revealed the presence of a glomerulonephritis with predominant IgA deposition. These necropsy findings reflect the spectrum of lesions reported in LPI, providing further evidence of an association between this condition and pulmonary alveolar proteinosis, cirrhosis and glomerulonephritis.
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PMID:Necropsy findings in lysinuric protein intolerance. 865 15

Previous research showed that risk factors associated with hepatocellular carcinoma (HCC) include infection with hepatitis B (HBV) and hepatitis C (HCV) viruses, exposure to aflatoxin B1 (AFB1), and liver cirrhosis, due primarily to alcohol consumption. To determine whether AFB1 may play a role in HCC in the United States, a search for AFB1 adducts and p53 alterations, potentially induced by AFB1, was conducted in the United States in 23 HCC patients with available tissue samples. The presence of AFB1 tumor-DNA and -serum lysine adducts and mutant p53 product was determined by immunoassays and codon 249 p53 mutation by restriction enzyme analysis. HBV and HCV serology and serum HBV-DNA were also determined. Thirteen patients were positive for HBV by HBs antigen or anti-HBc antigen or by polymerase chain reaction for HBV-DNA sequences. Nine patients were free of HBV and HCV markers; 5 of 22 sera tested were anti-HCV positive. p53 Protein expression, determined by immunohistochemical staining, was present in 5 of the 23 tumor tissues, whereas p53 codon 249 mutations were not observed in the 5 cases in which tissue was available for study. AFB1 tumor-DNA adducts were present in 3 of 19 tumor tissues, and in 1 of these 3 samples p53 protein was also detected. Sera from only 5 of the patients were tested for AFB1-lysine adducts, and all were positive. In these five patients, neither p53 protein nor a mutation on codon 249 was detected. The demonstration that AFB1-DNA and -lysine adducts are present in HCC patients in the United States is intriguing but requires further substantiation because of the small number of subjects in this pilot study. To elucidate the pathogenetic significance of these findings, further investigation, including studies in larger patient cohorts and properly selected controls, is warranted.
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PMID:Does aflatoxin B1 play a role in the etiology of hepatocellular carcinoma in the United States? 1062 3

gamma-Aminobutyric acid (GABA) is an inhibitory neurotransmitter, elevated in plasma of patients with liver cirrhosis. Pipecolic acid (PA), a metabolite of lysine, and known to be a GABA receptor agonist, is also seen high levels in the plasma. To clarify the relationship of GABA, PA and liver function, plasma GABA and PA in three groups of chronic liver diseases (compensated cirrhosis, decompensated cirrhosis and decompensated cirrhosis with hepatic encephalopathy, HE) were analyzed and their liver functions were compared. This analysis demonstrated that both plasma GABA and PA were higher in these patients than in normal subjects. Plasma PA, but not plasma GABA, was closely correlated with plasma ammonia concentration in each group. No correlation was noted between plasma GABA and PA in each group. Plasma pipecolic acid was significantly higher in patients with esophageal varices than in patients with no varices. These findings suggest that increased PA may reflect the degree of portal hypertension. Although both GABA and PA are increased in chronic liver disease, they may have a different origin and disappearance rate including metabolic mechanism.
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PMID:Comparative study on the correlation of plasma gamma-aminobutyric acid and pipecolic acid with liver function in patients with liver cirrhosis. 1093 64


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