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)

We measured the plasma concentration of a centrally derived noradrenaline (NA) metabolite, 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG), in 20 cirrhotic patients (eight with (group A) and 12 without (group B) hepatic encephalopathy (HE] and in 14 age matched healthy subjects to study if the central NA metabolism would be altered in liver cirrhosis patients, particularly in those with HE. The mean (SEM) plasma MHPG concentrations in the patient groups, group A (74.9 (8.6) pmol/l) and B (54.8 (7.2) pmol/l), were significantly (p less than 0.01) greater than in the control group (22.3 (2.0) pmol/l), and that in group A was significantly (p less than 0.05) greater than in group B. The plasma concentration of MHPG observed in these study subjects (n = 34) correlated (rs = 0.77, p less than 0.01) more strongly with the ratio of plasma catecholamine precursor amino acids (tyrosine and phenylalanine) to other neutral amino acids (tryptophan, leucine, isoleucine, and valine) known to compete with catecholamine precursor amino acids for uptake into the brain than with plasma concentration of tyrosine plus phenylalanine alone (rs = 0.63, p less than 0.01). In addition, the mean plasma MHPG concentrations measured in another group of eight cirrhotic patients (group C) during HE (79.3 (10.6) pmol/l) was significantly (p less than 0.01) greater than that measured after the recovery from HE (47.2 (5.2) pmol/l). The results suggest that the central NA metabolism may be altered in patients with liver cirrhosis, particularly in those with HE, and that the derangement in the central NA metabolism may be associated not only with an increase in plasma catecholamine precursor amino acids but also with a decrease in branched chain amino acids.
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PMID:Raised plasma concentrations of 3-methoxy-4-hydroxyphenylethyleneglycol in cirrhotic patients with or without hepatic encephalopathy. 273 59

To clarify the clinical significance of specific plasma amino acid abnormalities occurring in liver disorders with portal-systemic shunting, plasma amino acids and insulin levels were measured in idiopathic portal hypertension (IPH), extrahepatic portal occulusion (EHPO), and liver cirrhosis (LC). Three branched chain amino acids (BCAA: valine + leucine + isoleucine) were decreased in all three diseases in comparison with controls. Since plasma insulin measured during oral glucose tolerance tests did not specifically rise in LC, reduction of BCAA is not merely ascribed to hyperinsulinemia. Either portal-systemic shunting or some extent of liver damage may contribute to a fall in BCAA. Two aromatic amino acids (AAA: phenylalanine + tyrosine), which were within the normal range in EHPO and IPH, showed a marked increase in LC. Thus, changes of AAA probably mainly reflect the severity of the liver disease. The molar ratio of BCAA/AAA (MR) significantly correlated with ICG k, ICG R15, PT and the sum of blood ammonia in an oral ammonia tolerance test which may reflect the degree of hepatic disorder. MR diminished in the following decreasing order: controls, EHPO, IPH and LC.
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PMID:Plasma amino acid abnormalities in liver disease: comparative analysis of idiopathic portal hypertension, extrahepatic portal occlusion and liver cirrhosis. 277 20

Natural killer (NK) and activated killer (AK) cells appear to be important in immunoregulation, elimination of virus-infected cells and resistance to tumours. NK activity against K 562 and AK activity against FL target cells of peripheral blood mononuclear cells (PBMC) from patients with chronic persistent hepatitis (CPH), chronic active hepatitis (CAH), liver cirrhosis (LC) and hepatocellular carcinoma (HCC) were investigated using 51Cr release assay. Spontaneous NK activity of patients with LC (P less than 0.05) and HCC (P less than 0.001) was decreased when compared to that of controls. The sera and PBMC from patients with low NK activity had no inhibitory effect on the NK activity of normal subjects. Indomethacin treatment significantly enhanced the NK activity of controls (P less than 0.05), whereas the drug did not affect that of patients with low NK activity. The percentages of PBMC that reacted with monoclonal antibodies anti-Leu-7 and anti-Leu-11a were similar in controls and patients. However, a Leu-11a+/Leu-7+ ratio, and NK activity of Leu-11+ and Leu-7+ cell-rich populations were significantly decreased in cirrhotic and HCC patients when compared to controls. Interleukin 2 boosted both NK and AK activities of patients, but to a lesser degree in comparison with those of controls when similarly stimulated. gamma-Interferon also significantly augmented NK and AK activities of patients, but the levels of cytotoxicity were lower in HCC patients (P less than 0.05) than those of controls. These findings suggest that the decreased NK and AK activities in chronic liver disease and HCC are due to an altered subpopulation ratio of NK cells and a functional defect of effector cells.
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PMID:Natural killer and activated killer activities in chronic liver disease and hepatocellular carcinoma: evidence for a decreased lymphokine-induced activity of effector cells. 282 Jun 34

The function and phenotypes of peripheral blood natural killer (NK) cells from patients with chronic liver disease and hepatocellular carcinoma (HCC) were examined using a 4 hr 51Cr release NK assay and two-color flow cytometry utilizing anti-Leu-7 and anti-Leu-11 monoclonal antibodies. There was no significant difference between control and patient groups in the percent representation of a total of NK, Leu-7-11+ or Leu-7+11- cells except that the percent representation of Leu-7+11- cells was significantly increased in patients with liver cirrhosis (LC) in comparison with that of chronic active hepatitis (CAH). On the other hand, patients with LC and HCC had lower absolute numbers of a total of NK, Leu-7-11+ and Leu-7+11- cells than did controls or patients with CAH, reflecting the diminished peripheral blood lymphocyte count. Our data indicate that decreased in vitro NK activity in patients with LC and HCC observed in the present study may be due to a functional defect of NK cells.
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PMID:Phenotypic expression of natural killer cell associated membrane antigens in patients with chronic liver disease and hepatocellular carcinoma. 284 43

The neurological disorders seen in patients with chronic renal failure and liver cirrhosis are analogous. Previous in vivo studies have shown that the impaired blood-brain amino acid transport seen in rats with chronic renal failure is similar to that of rats with portocaval anastomosis. To elucidate whether a comparable underlying pathogenic mechanism plays a role in both pathological conditions, blood and brain amino acid levels together with amino acid transport by isolated brain microvessels have been studied in rats with chronic renal failure and in sham-operated rats. Brain microvessels isolated from rats with experimental chronic renal failure showed that the uptake of labeled large neutral amino acid, i.e., leucine or phenylalanine, but not of lysine or alpha-methylaminoisobutyric acid, was significantly increased with respect to sham-operated rats; conversely, the uptake of glutamic acid in rats with chronic renal failure was significantly lower compared with values in controls. Kinetic analysis indicated that this was mainly due to increased exchange transport activity (Vmax) of the L-system, rather than to changes in the affinity (Km) of the carrier system for the relative substrate. These data, together with the significant rise of brain glutamine levels and an increased brain-to-plasma ratio of the sum of large neutral amino acids, are analogous to what was previously observed in rats with portocaval anastomosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Uptake of amino acids by brain microvessels isolated from rats with experimental chronic renal failure. 290 21

As an initial step in testing the hypothesis that immunoregulatory abnormalities are important in the pathogenesis of primary sclerosing cholangitis, we determined the number and percentage of lymphocyte subsets in the peripheral blood of 33 patients with primary sclerosing cholangitis. In these patients, when compared with normal and diseased controls, there was a significant reduction in the total number of circulating T cells because of a disproportionate decrease in Leu-2a (suppressor/cytotoxic) cells. This decrease resulted in a significantly increased ratio of Leu-3a to Leu-2a cells. Patients with cirrhosis had significantly higher Leu-3a/Leu-2a (helper/suppressor) ratios than did noncirrhotic patients; both disease groups, however, had ratios that were significantly higher than controls. The number and percentage of B cells were significantly increased. Alterations in the percentage of B cells correlated significantly with histologic stage and concentrations of gamma globulin, serum IgG, and bilirubin. We conclude that these abnormalities are suggestive of a defect in immunoregulation in primary sclerosing cholangitis, which is not secondary to advanced liver disease alone and appears to be independent of chronic ulcerative colitis or obstructive jaundice.
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PMID:Lymphocyte subsets in primary sclerosing cholangitis. 295 97

Alterations in protein and amino acid metabolism have been postulated to explain the frequent observations of muscle wasting and decreased plasma branched-chain amino acid concentrations in cirrhosis. In order to investigate the changes in protein metabolism, we have measured the rates of leucine turnover and oxidation in six stable, biopsy-proven cirrhotics and six age and sex-matched healthy control subjects after an overnight fast, using [1-13C]leucine tracer. Following a primed constant-rate infusion of [1-13C]leucine, the 13C enrichments of plasma leucine and expired CO2 were used to estimate leucine turnover and oxidation, respectively. Fat-free body mass was estimated from the measurements of total body water as quantified by H2[18O] tracer dilution. The rates of CO2 production and oxygen consumption were measured hourly during the study period, using open-circuit respiratory calorimetry. Urinary urea, ammonia and total nitrogen excretion rates were quantified from timed urine samples. Even though the plasma leucine levels were lower in cirrhotics as compared with controls (100.5 +/- 17.1 vs. 138.3 +/- 20.4 mumoles per liter, mean +/- S.D., p less than 0.001), the rates of leucine turnover were not significantly different in the two groups (89.4 +/- 19.0 vs. 87.8 +/- 19.0 mumoles per kg X hr). In contrast, the rates of leucine oxidation were significantly reduced in cirrhosis (8.1 +/- 2.5 vs. 12.7 +/- 3.1 mumoles per kg X hr, p less than 0.01). When all subjects were considered, the leucine oxidation rate was correlated with plasma leucine concentration (r = 0.62, p less than 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Leucine metabolism in stable cirrhosis. 308 96

Patients with liver disease have increased plasma concentrations of the endogenous opioid peptides methionine enkephalin and leucine enkephalin. As an initial investigation to determine whether opioid peptides contribute to any of the clinical manifestations of hepatic disease nalmefene, a specific opioid antagonist devoid of agonist activity, was given to 11 patients with cirrhosis. They all experienced a severe opioid withdrawal reaction on starting the drug. In the nine patients with primary biliary cirrhosis pruritus was greatly alleviated, fatigue seemed to improve, and plasma bilirubin concentration, which had been rising, showed a modest fall in all except one patient. These results indicate that blocking opioid receptors has an effect on some of the metabolic abnormalities of liver disease.
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PMID:Opioid peptides and primary biliary cirrhosis. 314 46

The effects of the administration of tryptophan on toxic cirrhosis induced by intermittent carbon tetrachloride (CCl4) intoxication in the rat were investigated. Rats received CCl4 (0.45 ml/100 g body wt ip) twice weekly for 10-14 weeks. Tryptophan (30 mg/100 g body wt) by stomach tube was administered 1 hr before killing. Tryptophan improved hepatic polyribosomal aggregation and [14C]leucine incorporation into protein in vitro of control rats as well as long-term CCl4-treated rats that had developed toxic cirrhosis. However, the effects were more marked in control than in experimental rats. Tryptophan administration induced an increase in labeled nuclear RNA release in vitro and a decrease in labeled tryptophan binding to nuclear protein in vitro of livers of rats receiving long-term CCl4 and of control rats. The results indicate that the stimulatory effects of a single administration of tryptophan in toxic cirrhotic livers are similar to, but somewhat less than, those which occur in livers of normal, control rats.
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PMID:Effect of tryptophan on toxic cirrhosis induced by intermittent carbon tetrachloride intoxication in the rat. 339 62

Free amino acids were measured under postabsorptive conditions in plasma and intracellular water of skeletal muscle obtained by needle biopsy in nine healthy controls and 14 subjects suffering from clinically stable liver cirrhosis. The aromatic amino acids phenylalanine and tyrosine in cirrhotics were elevated to the same extent in plasma and in muscle water. Branched-chain amino acids were uniformly reduced in plasma, but in muscle water only valine was significantly lower (222 +/- 92 mumoles per kg intracellular water vs. 368 +/- 82, p less than 0.001), while isoleucine (142 +/- 63 vs. 103 +/- 30), leucine (223 +/- 88 vs. 226 +/- 36) and branched-chain amino acids as a whole (589 +/- 186 vs. 681 +/- 88) were normal or elevated with an increased muscle:plasma ratio (3.12 +/- 2.03 vs. 1.41 +/- 0.37, p less than 0.05 for isoleucine; 3.00 +/- 1.28 vs. 1.85 +/- 0.27, p less than 0.025 for leucine; 2.24 +/- 0.64 vs. 1.69 +/- 0.13, p less than 0.05 for total branched-chain amino acids. Our data show that, in cirrhosis, plasma concentrations of branched-chain amino acids do not reflect their levels in muscle cellular water; only the intracellular pool of valine is severely depleted. This suggests that higher amounts of valine supplementation may be useful in nutritional treatment of liver cirrhosis. The elevated muscle:plasma gradients for branched-chain amino acids may result from abnormalities in their transport through muscle-plasma membrane.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Free amino acids in plasma and skeletal muscle of patients with liver cirrhosis. 341 24


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