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)

Histological study of biopsy specimens taken from the liver of 96 patients during operation for formation of a "small stomach" revealed fatty dystrophy of the liver in 93 patients (96.9%) which was attended by marked inflammatory and fibrous changes in 68 (70.8%) of them and by disturbed lobar structure of the liver (cirrhosis) in 2 patients (2.1%). Biochemical blood tests failed to show the pattern of the pathological changes before the operation. Study of the hepatobiliary system with methionine-75Se was the only method by which protein and pigment metabolism in the liver could be appraised. Examination of patients during 3 postoperative years showed a positive dynamics of changes in biochemical blood tests and improved protein metabolism in the hepatocytes according to the results of scanning of the liver with methionine-75Se. Thirteen repeated studies of the hepatic tissue collected from patients in different periods after operation for the formation of a "small stomach" showed a significant diminution of fatty dystrophy and inflammation of the parenchyma. The level of portal tract inflammation and portal fibrosis did not change. The findings suggest that there is an improved functional and morphological condition of the liver in weight loss caused by operation for the formation of a "small stomach", which allows this type of surgical intervention to be recommended for the treatment of patients with alimentary-constitutional obesity and initially diminished compensatory capacities of the liver.
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PMID:[State of the liver in patients with obesity at distant periods after formation of a "small stomach"]. 177 62

The amino acid composition of proteins from liver mitochondrial membranes has been studied in patients with normal liver, with biliary diseases and fatty liver, with obstructive jaundice or liver cirrhosis. A characteristic pattern of the amino acid composition in patients with normal liver has been found. In the mitochondrial membranes of patients with fatty liver tryptophan and lysine were decreased while [aspartic acid plus asparagine] and [glutamic acid plus glutamine] were increased compared to their counterpart in the normal liver. In patients with obstructive jaundice of short duration (less than two months) only a slight decrease in methionine content was found, while in the case of liver cirrhosis amino acid composition was markedly changed.
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PMID:Amino acid composition of human liver mitochondrial membranes in normal and pathological conditions. 186 76

Whether the plasma concentration of beta endorphin was increased in hepatic cirrhosis like that of smaller opioid peptides methionine enkephalin and leucine enkephalin was determined. Its concentration in chronic renal failure was also measured. Plasma beta endorphin was not significantly raised in cirrhotic patients with or without ascites (medians 5.2 pmol/l and 4.7 pmol/l respectively) compared with disease control subjects (4.9 pmol/l) and healthy control subjects (4.9 pmol/l). In contrast, the peptide was increased 2.5 fold (p less than 0.001) in chronic renal failure (12.4 pmol/l) and was found in many of these patients' urine. The data are compatible with the hypothesis that the liver may play an important role in the elimination of opioid peptides of octapeptide size or less but not the larger peptides such as beta endorphin.
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PMID:Plasma beta endorphin in cirrhosis and renal failure. 201 26

The energy-dependent conversion of methionine to S-adenosyl-L-methionine (SAMe) is catalysed by S-adenosyl-L-methionine synthetase (SAMe-synthetase) in the liver. In the hepatocyte, an equilibrium exists between the high and low molecular weight forms of SAMe-synthetase, which consist of a tetramer and a dimer, respectively, of a 48.5 kilodalton subunit. The 2 enzymic forms differ in their affinity for methionine and sensitivity to inhibition by pyrophosphate; 2 of the sulfhydryl groups of SAMe-synthetase have been identified as essential for the normal functioning of the enzyme. In patients with liver cirrhosis, a marked reduction in the utilisation of the high molecular weight SAMe-synthetase and displacement of the equilibrium occur, the molecular mechanism of which has yet to be established. This loss of activity is associated with a delay in methionine clearance and impairment of the trans-sulphuration pathway, which normally eliminates excess methionine by oxidising homocysteine to sulphate anion. It is hypothesised that in normal liver function the essential sulfhydryl groups of SAMe-synthetase are protected from oxidation by glutathione, a by-product of the trans-sulphuration pathway. However, glutathione levels are reduced in liver cirrhosis, and this may result in increased oxidation of the essential sulfhydryl groups, and consequent inactivation of the enzyme. Thus, the trans-sulphuration pathway may play an important role in the maintenance of normal SAMe-synthetase activity.
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PMID:Mechanisms and consequences of the impaired trans-sulphuration pathway in liver disease: Part I. Biochemical implications. 208 81

The liver is actively involved in the metabolism of the sulphur-containing essential amino acid, methionine. Methionine is transformed into S-adenosyl-L-methionine (SAMe) and then into sulphur-containing metabolites (cysteine, taurine and glutathione) via the trans-sulphuration pathway. Liver disease may affect the trans-sulphuration pathway and decrease the clearance of methionine, which leads to increased fasting methionine concentrations in blood and reduced formation of cysteine and glutathione. There is evidence that this defect, located at the level of SAMe-synthetase, may cause nutritional defects and contribute to negative nitrogen balance whenever non-essential sulphur-containing amino acids are not supplied in adequate amounts. In addition, cirrhotic patients may be at increased risk of hepatotoxicity after treatment with substances which are detoxified via glutathione. The SAMe-synthetase block may be overcome by administration of oral or intravenous SAMe, which improves the fasting amino acid profile and increases the hepatic glutathione concentration. Controlled studies on long term SAMe treatment in patients with cirrhosis are needed to confirm this possible beneficial effect.
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PMID:Mechanisms and consequences of the impaired trans-sulphuration pathway in liver disease: Part II. Clinical consequences and potential for pharmacological intervention in cirrhosis. 208 82

The major biological functions of S-adenosyl-L-methionine (SAMe) include methylation of various molecules (transmethylation) and synthesis of cysteine (trans-sulphuration). A stable double salt of SAMe has been found to be effective in intrahepatic cholestasis. The mechanism of its therapeutic effect is not fully understood but presumably involves methylation of phospholipids. Methylation of plasma membrane lipids may affect membrane fluidity and viscosity, which modulate the activities of a number of membrane-associated enzymes, for example, the activity of enzymes involved in Na+/Ca++ exchange (e.g. sarcolemmal vesicles), Na+/K+ adenosine triphosphatase (ATPase) [e.g. hepatocyte plasma membranes], and Na+/H+ exchange (e.g. plasma membranes of colonic cells). Recently, patients with cirrhosis were shown to have an acquired metabolic block in the hepatic conversion of methionine to SAMe. These patients, when administered conventional elemental diets, develop abnormally low plasma concentrations of cysteine and choline, 2 nonessential nutrients present in low concentrations in most elemental diets. These low concentrations probably reflect systemic deficiencies attributable to reduced endogenous syntheses of cysteine and choline caused by limited availability of hepatic SAMe. Such cirrhotic patients are often in negative nitrogen balance and have abnormal hepatic functions, which are corrected by cysteine and choline supplements. Noncirrhotic patients on parenteral elemental diets also become deficient in cysteine and choline. Consequently, these patients may require SAMe as an essential nutrient to normalise their overall hepatic transmethylation and trans-sulphuration activities.
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PMID:Biochemistry and pharmacology of S-adenosyl-L-methionine and rationale for its use in liver disease. 208 85

The B6 vitamers (pyridoxine, pyridoxamine, and pyridoxal) are primarily metabolized in liver to pyridoxal 5'-phosphate (PLP) and the deadend catabolite 4-pyridoxic acid. We have built on the elegant early work of Snell and others to describe the activities of the human liver enzymes responsible for vitamin B6 metabolism and to develop a model of the relative rates of these interconversions in vivo. This model is consistent with changes in plasma B6 after a load, the clearance of different vitamers (e.g., pyridoxine versus pyridoxal), and with the low plasma PLP in patients with cirrhosis. Because cirrhotics were found to be capable of PLP synthesis, we have used oral supplementation with pyridoxine to restore plasma PLP to the normal range, and have evaluated the effects of this intervention on amino acid metabolism. No significant differences were observed in plasma or urinary clearance of methionine (or cystathionine) after an oral load, nor in amino acid clearance from circulation after a protein load for cirrhotic patients before and after restoration of normal plasma PLP. Hence, the abnormal metabolism of vitamin B6 does not appear to be an important factor in the deranged amino acid metabolism in this disease. Nonetheless, this approach may be generally useful in assessing the importance of PLP in other abnormalities.
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PMID:Vitamin B6 metabolism by human liver. 219 6

Free amino acid (AA) concentrations in plasma and quadriceps femoris muscle were determined in 19 healthy volunteers and in 16 patients with hepatic cirrhosis and portal hypertension. Nutritional state was impaired as judged by overt muscle wasting (9/16), triceps skinfold thickness less than 70% of normal in 8/14 (57%), and creatinine-height index below 70% in 5/12 (42%). In the plasma of patients the typical amino acid pattern of cirrhosis was to be observed: Elevation of tyrosine and methionine (p less than 0.01), uniform reduction of branched chain amino acids (p less than 0.001) resulting in a decreased molar ratio of BCAA/AAA from 2.85 +/- 0.05 in normal individuals to 1.35 +/- 0.12 in cirrhotics (p less than 0.001). Levels of the gluconeogenic AA glutamine, glutamate, aspartate, alanine, glycine, threonine, serine and lysine were lowered (p less than 0.05). In muscle of cirrhotics, intracellular AA concentrations exhibited a similar pattern with two major exceptions: Tyrosine and phenylalanine were augmented (p less than 0.001). Surprisingly, BCAA levels were altered heterogeneously; those of gluconeogenic BCAA decreased: Valine from 0.34 +/- 0.03 to 0.20 +/- 0.03 mmol/l (p less than 0.001), isoleucine 0.09 +/- 0.01 to 0.05 +/- 0.02 mmol/l. However, the concentration of ketogenic leucine remained unaltered in muscle. Nevertheless, the molar ratio of BCAA/AAA was considerably reduced from 3.70 +/- 0.04 to 0.81 +/- 0.08 (p less than 0.001). Most of the gluconeogenic AA exhibited reduced intramuscular concentrations, but glutamine levels were normal. The pattern of plasma and muscle free AA in hepatic cirrhosis is thus characterized by accumulation of aromatic AA and by depletion of gluconeogenic AA, especially BCAA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characteristic pattern of free amino acids in plasma and skeletal muscle in stable hepatic cirrhosis. 231 39

We quantitated alpha 1-antitrypsin mRNA in normal, alpha 1-antitrypsin-deficient cirrhotic and biliary cirrhotic livers using two-dimensional electrophoretograms of [35S]methionine-labeled translational products of total hepatic RNA and RNA/DNA hybridization. alpha 1-Antitrypsin precursor product was identified by immunoprecipitation. The relative abundance of alpha 1-antitrypsin product from normal (0.989 +/- 0.197), cirrhotic (0.956 +/- 0.062) and alpha 1-antitrypsin deficient (0.818 +/- 0.12) livers was not significantly different. Although (RNA/DNA) was decreased in the PiZZ cirrhotic livers compared to normal (0.56 +/- 0.045 vs. 0.95 +/- 0.225), it equaled that found in the PiM cirrhotic livers (0.56 +/- 0.055). The concentration of alpha 1-antitrypsin mRNA [relative abundance X (RNA/DNA)], while decreased in PiZZ compared to normal liver, is thus no different in PiZZ cirrhotics than in PiM cirrhotics. We confirmed this observation by quantitation of the alpha 1-antitrypsin mRNA using an alpha 1-antitrypsin genomic probe. By RNA/DNA hybridization, alpha 1-antitrypsin mRNA was equal in PiM cirrhotic and PiZZ cirrhotic (38.48 +/- 4.5 vs. 31.93 +/- 2.1), but significantly decreased from noncirrhotic PiM liver (58.36 +/- 12.7). We conclude that alpha 1-antitrypsin mRNA is decreased in cirrhosis of any etiology, and this decrease appears to represent a general response of the liver to injury. Since the decreased alpha 1-antitrypsin mRNA in PiM cirrhotics is associated with normal serum alpha 1-antitrypsin levels, it is unlikely that the decreased alpha 1-antitrypsin mRNA in PiZZ cirrhotics accounts for their decreased serum levels.
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PMID:Hepatic alpha 1-antitrypsin mRNA content in cirrhosis with normal and abnormal protease inhibitor phenotypes. 243 90

To evaluate the level of serum thyroxine-binding globulin (TBG) in various liver diseases, TBG and T4, T3, FT4 were measured by radioimmunoassay in 29 HBsAg carriers (C), 27 patients with acute hepatitis (AH), 18 patients with inactive chronic hepatitis, 70 patients with chronic active hepatitis (CAH), 31 patients with active cirrhosis (AC), 20 patients with inactive cirrhosis (IC), 38 patients with hepatocellular carcinoma (HCC), 12 patients with metastatic Ca to the liver (Met.) and in 81 normal controls. All the patients were clinically euthyroid. The TBG as well as T4 in patients with AH, CAH, AC HCC and, Met. were significantly higher than those in controls. The T3 level was significantly elevated in CAH and AC patients. The TBG level did not correlate with serum albumin or bilirubin levels, but did correlate significantly with alanine transaminase (ALT) (r = 0.54, p less than 0.01). However, the correlation was positive in chronic active hepatitis (r = 0.40, p less than 0.01) but negative in hepatocellular carcinoma (r = -0.32, p less than 0.05). The data suggested: (1) Significant TBG and T4 elevation was found in all active liver diseases and HCC. (2) In the presence of high T4 in patients with liver disease, normal FT4 excluded the diagnosis of hyperthyroidism. (3) The elevation of TBG levels in chronic hepatitis appeared to parallel the severity of hepatocytolysis, and therefore might be the result of hepatocytolysis; while the elevation of TBG in HCC might be due to increased synthesis by the malignant cells.
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PMID:[Changes in thyroid hormone concentration in liver disease]. 250 36


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