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)

The amino acid composition of proteins from liver microsomes has been studied in rats and in human subjects with normal liver, with obstructive jaundice or liver cirrhosis. The pattern of the amino acid composition of microsomes appeared to be species-specific. Phenylalanine, threonine, serine, proline, histidine and [aspartic acid plus asparagine] were increased, while alanine, tyrosine, glycine and arginine were decreased in the human compared to the rat microsomes. In patients with obstructive jaundice of short duration (less than two months) only a slight decrease in leucine and phenylalanine could be noticed, while in the case of liver cirrhosis amino acid composition was markedly changed.
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PMID:Amino acid composition of rat and human liver microsomes in normal and pathological conditions. 757 35

1. The Z deficiency variant of alpha 1-antitrypsin predisposes the homozygote to early-onset panlobular emphysema and results in the accumulation of antitrypsin within the hepatocyte, which leads to hepatocellular damage and cirrhosis. The mechanism of this accumulation has been shown to be due to the Z mutation (Glu-342-->Lys) perturbing the structure of the protein, allowing a unique interaction between the reactive-centre loop of one molecule and the A sheet of a second. This loop-sheet polymerization occurs spontaneously at 37 degrees C in purified plasma Z but not M antitrypsin. The rate of polymerization is greatly accelerated at 41 degrees C and is blocked by the insertion of a specific peptide into the A sheet of the antitrypsin molecule. Electron microscopy and circular dichroic spectral analysis confirm that the Z antitrypsin polymers formed in vitro have structural identity with those isolated from the liver of a Z homozygote. 2. That loop-sheet polymerization is a more general phenomenon was shown by the examination of a second deficiency variant, antitrypsin Siiyama (Ser-53-->Phe), which is also associated with liver inclusions. Electron microscopy confirmed that isolated antitrypsin Siiyama from the plasma of a homozygote was present as long chains of polymers identical with those of Z antitrypsin.
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PMID:Loop-sheet polymerization: the structural basis of Z alpha 1-antitrypsin accumulation in the liver. 803 2

To evaluate whether neutrophil bactericidal function, the ability to produce oxygen-derived free radicals, is altered in patients with chronic liver disease, we measured chemiluminescence amplified by a luciferin analog (Cypridina luciferin analog-dependent chemiluminescence) and luminol (luminol-dependent chemiluminescence) in response to N-formyl-Met-Lue-Phe by neutrophils from patients with chronic liver diseases due to C and/or B type hepatitis: chronic active hepatitis, cirrhosis and hepatocellular carcinoma. Both Cypridina luciferin analog-dependent chemiluminescence and luminol-dependent chemiluminescence were significantly decreased in neutrophils from patients with chronic liver disease (hepatocellular carcinoma < cirrhosis < chronic active hepatitis) when they were compared with normal healthy subjects. The reduction of Cypridina luciferin analog-dependent chemiluminescence in chronic active hepatitis and cirrhosis was more sensitive than Cypridina luciferin analog-dependent chemiluminescence; however, in hepatocellular carcinoma, luminol-dependent chemiluminescence was more reduced than luminol-dependent chemiluminescence. Although there were not significant correlations between glutamic pyruvic transaminase and Cypridina luciferin analog-dependent chemiluminescence/luminol-dependent chemiluminescence, there were significant negative correlations between total bilirubin and Cypridina luciferin analog-dependent chemiluminescence/luminol-dependent chemiluminescence. Furthermore, there were significant positive correlations between albumin/prothrombin time and Cypridina luciferin analog-dependent chemiluminescence/luminol-dependent chemiluminescence. These data suggest that an impaired ability to produce oxygen-derived free radicals may contribute to the susceptibility to infection in patients with chronic liver disease.
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PMID:Impaired ability of neutrophils to produce oxygen-derived free radicals in patients with chronic liver disease and hepatocellular carcinoma. 804 92

This paper is a study to identify the clinical significance of high-molecular-mass alkaline phosphatase (ALP:E:C..3.1.3.1.), ALP-lipoprotein-X complex (LP-X) and intestinal variant ALP. We used cellulose acetate and agarose gels and techniques including wheat germ lectin, cetavlon-diethyl ether, thermostatability, neuraminidase and L-phenylalanine to improve the electrophoretic separation of the alkaline phosphatase isoenzymes. Patients' serum samples were electrophoresed from a diverse group of individuals ill with cholestasis, neoplastic disease metastatic to the liver, hepatocellular carcinoma, cirrhosis, diabetes mellitus, and chronic renal disease. Agarose gels provided better separation of ALP isoenzymes than cellulose acetate gels. The results also indicated that high-molecular mass ALP is present in patient's serum in conditions associated with cholestasis especially caused by hepatic malignancy. High-molecular mass ALP was frequently found to co-exist with the liver isoenzyme and LP-XALP complex. The intestinal variant was identified in patients with malignancy, cirrhosis, chronic renal disease and diabetes mellitus. Intestinal ALP coexisted concomitantly with a variant intestinal ALP. Intestinal variant ALP is most likely composed of intestinal ALP attached to a cellular membrane-binding domain, or may be an artifact produced by neuraminidase incubation.
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PMID:Clinical significance of serum high-molecular-mass alkaline phosphatase, alkaline phosphatase-lipoprotein-X complex, and intestinal variant alkaline phosphatase. 804 46

To investigate body protein turnover and the pathogenesis of increased concentration of plasma phenylalanine in liver cirrhosis, we have studied phenylalanine and leucine kinetics in cirrhotic (diabetic and nondiabetic) patients, and in normal subjects, both in the postabsorptive state and during a mixed meal, using combined intravenous and oral isotope infusions. Postabsorptive phenylalanine concentration and whole body rate of appearance (Ra) were approximately 40% greater (P < 0.05) in patients than in controls. Leucine concentrations were comparable, but intracellular leucine Ra was also increased (P < 0.05), suggesting increased whole body protein breakdown. Postprandial phenylalanine Ra was also greater (P < 0.05) in the patients. This difference was due to a diminished fractional splanchnic uptake of the dietary phenylalanine (approximately 40% lower in the cirrhotics vs. controls, P < or = 0.05). Postprandial leucine Ra was also increased in the patients, but splanchnic uptake of dietary leucine was normal. Thus both increased body protein breakdown and decreased splanchnic extraction of dietary phenylalanine can account for the increased phenylalanine concentrations in liver cirrhosis.
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PMID:Fasting and postprandial phenylalanine and leucine kinetics in liver cirrhosis. 804 3

This paper documents dose-dependent effects of ornithine aspartate (OA) on postprandial hyperammonemia and plasma amino acids. Ten patients with cirrhosis were randomized to undergo 1 out of 4 infusion series. Each series consisted of four 8-h infusions (09:00 h-17:00 h), with placebo (NaCl), 5 g, 20 g or 40 g of OA being administered on separate days in varying sequences. This 4-fold crossover design was double-blind. On infusion days, patients received 2 oral protein loads (0.25 g/kg at 09:00 h and 0.5 g/kg at 13:00 h). Venous blood samples were drawn every 2 h and the 24-h urine was collected. In addition to measuring plasma ammonia and amino acids, the urea production rate, serum glucose and serum insulin were analyzed. A significant postprandial rise in the ammonia concentration was noted during the infusions of placebo and 5 g of OA but did not occur with the dosages of 20 g (after the second protein load) and 40 g (after both protein loads). Furthermore, the latter dose, compared with placebo, significantly reduced plasma ammonia after the minor protein load. Urea production rate increased when 20 g or 40 g of OA was administered. Of the amino acids involved in the metabolic pathways of ornithine and/or aspartate, glutamate showed a rise in its plasma level following infusion of 40 g of OA, whereas glutamine did not. Concentrations of methionine, phenylalanine, tyrosine, threonine, serine and glycine declined progressively with increasing doses of OA (5-40 g). The highest dose of the drug caused hyperglycemia and hyperinsulinemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of ornithine aspartate on plasma ammonia and plasma amino acids in patients with cirrhosis. A double-blind, randomized study using a four-fold crossover design. 815 Nov 4

The absolute and relative concentrations of 16 plasma amino acids in 48 mostly dystrophic infants and children (median of age 1 1/2 years) with extrahepatic biliary atresia and mainly stable preterminal cirrhosis were compared with those of controls. Patient plasma amino acid data were analysed statistically for diagnostic usefulness and correlated with standard biochemical quantities of liver function and of liver perfusion. In the patients the total amounts of non-essential and essential amino acids were reduced by 19% and with the same significance (p < 0.0005). Plasma tyrosine was increased (+40%), while taurine (-44%) and branched chain amino acids (+28.8% to -34.7%) were decreased. Methionine values varied widely. In the molar fractional plasma amino acid profile, only alanine, valine, and leucine were decreased, while threonine, methionine, tyrosine, phenylalanine, ornithine, and serine were increased. Discriminate function analysis showed that the plasma amino acid data discriminated 93.8% of the patients from controls. The concentrations of some amino acids in plasma seemed to have been influenced by protein-calorie deficiency in the patients. The valine/tyrosine ratio and the Fischer index (ratio branched chain/aromatic amino acids) were significantly reduced in the patients versus controls (1.54 +/- 0.55 vs 3.08 +/- 0.55 and 1.66 +/- 0.39 vs 3.00 +/- 0.48). A number of significant correlations (range of r: 0.37-0.59, p < 0.05, 30-48 data pairs) were calculated between plasma amino acid data and several standard biochemical quantities of liver function. The statistical analyses also showed that the Fischer index began to decrease gradually and linearly early in the progression of liver failure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The plasma amino acid profile and its relationships to standard quantities of liver function in infants and children with extrahepatic biliary atresia and preterminal liver cirrhosis. 831 65

Albumin-synthesis rates were measured in nine patients with stable cirrhosis and compared with those of eight healthy volunteers by means of a new technique using stable isotopes. Four grams of L-[1-13C]leucine was injected over 10 min, and blood samples were drawn at intervals. Serum free [13C]leucine enrichment, taken to be the precursor for albumin synthesis, and 13C enrichment of leucine in albumin, isolated with differential solubility in absolute ethanol from trichloracetic acid-precipitated serum proteins, were measured on mass spectrometry. Albumin synthesis, expressed as a fractional rate, was 7.9% +/- 0.3%/day in the controls and 7.9% +/- 1.1%/day in the cirrhotic patients. Albumin synthesis, expressed as an absolute rate, was lower in the cirrhotic group (cirrhotic, 119 +/- 17 mg/kg/day; controls, 146 +/- 8 mg/kg/day), but because of the relatively small number of patients the difference was not significant. However, the absolute rate of albumin synthesis significantly correlated with the Child-Turcotte score (p = 0.024) and its Pugh modification (p = 0.027). The rate of albumin synthesis also correlated with serum phenylalanine concentration but not with serum albumin concentration and intravascular albumin mass or with other clinical indexes of liver function or integrity when taken separately. However, the significant correlation between albumin synthesis and Child score suggests that albumin synthesis might be useful for the clinical judgment of patients with cirrhosis.
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PMID:Albumin synthesis rates in cirrhosis: correlation with Child-Turcotte classification. 834 57

Adult respiratory distress syndrome (ARDS) following infection is one of the postoperative complications of hepatectomy of cirrhosis. In this study we focused on the anti-microbial activity of neutrophils. We measured production of active oxygen species by neutrophils, and simultaneously examined their nutritional status, immunity and ICG (K-ICG) disappearance ratio. When compared to the controls, the patients with cirrhosis had significantly lower production of O2- upon stimulation by N-formyl-Met-Leu-Phe (fMLP) or opsonic zymosan (OZ). The presence of cancer did not affect results for the groups studied. Overall H2O2 production was lower in cirrhotic patients than in controls. There was a positive correlation between O2- production and K-ICG, which was used to estimate the severity of cirrhosis. Indicators of nutrition and immunity were also lower in cirrhotic patients, but neither of these indicators correlated with the production of active oxygen species. From these results, we concluded that the production of active oxygen species by neutrophils is lower in cirrhotic patients than in controls. Moreover, this decline correlates with the severity of cirrhosis.
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PMID:Decreased production of active oxygen species by neutrophils in patients with liver cirrhosis and hepatocellular carcinoma. 839 32

Glutathione and amino acid concentrations were measured in arterial and hepatic vein plasma in four healthy volunteers and two patients with cirrhosis. There was no significant splanchnic efflux of glutathione (95% confidence limits, -0.501 to 0.405 mumol/min). After infusion of N-acetylcysteine (NAC) in a high dose (150 mg/kg body weight primer plus 15 mg/(h x kg BW), corresponding to treatment of acetaminophen overdose, there was no change in the splanchnic glutathione efflux (95% confidence limits, -0.531 to 0.375 mumol/min). NAC increased hepatic plasma flow rate from 0.90 +/- 0.531 min-1 to 0.97 +/- 0.11 (mean +/- SEM; p < 0.05). The effects of NAC treatment on plasma amino acids corresponded to an increased load on hepatic metabolic N conversion and transamination among nonessential amino acids. Splanchnic uptake of serine, alanine, cystine, isoleucine, and phenylalanine increased after NAC compatible with stimulated hepatic glutathione synthesis. In contrast to the rat, plasma glutathione in man probably originates mainly from extrahepatic tissues.
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PMID:No net splanchnic release of glutathione in man during N-acetylcysteine infusion. 851 1


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