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 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

Chronic liver disease is associated with raised basal and TRH-stimulated PRL and GH levels. In a recent study we found the kidney to be the main site of prolactin elimination in patients with liver disease. In order to determine whether this is specific for PRL or a more general mechanism for polypeptide removal, we studied the elimination of GH, which resembles PRL in molecular weight and primary amino acid sequence, in 5 patients with portal hypertension and hepatic cirrhosis and 5 patients with noncirrhotic portal hypertension. Plasma GH levels were measured before and after TRH in peripheral, hepatic and renal vein samples, taken during diagnostic hepatic vein catheterization. An excessive paradoxical increase of GH after THR stimulation was found in 4 out of 5 cirrhotic patients but in none of the noncirrhotic individuals (p less than 0.025). After TRH the mean hepatic venous levels were significantly lower than the peripheral venous levels in 4 out of 5 noncirrhotic patients but in only 1 of the 5 cirrhotic patients (p less than 0.05). The mean renal vein GH levels were significantly lower than the peripheral levels in 3 out of 5 noncirrhotic patients and in none of the cirrhotic patients. In 2 patients in whom renal and hepatic plasma flow was measured, renal extraction of GH was found to be 0 to 6.4 micrograms, while liver extraction amounted to 22.1 and 34.7 micrograms of GH during the same 60-min period. Despite the similarity in molecular weight and primary amino acid sequence between PRL and GH, GH appears to be mainly taken up by the liver while PRL is mainly eliminated by the kidney in this group of patients with portal hypertension. This suggests that the renal elimination of prolactin is not solely dependent on glomerular filtration. The selective hepatic removal of growth hormone is probably related to a specific action of growth hormone on liver metabolism.
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PMID:Peripheral elimination of growth hormone in chronic liver disease. 680 53

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

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

People with genetic variants of cholinesterase (ChE) have been reported to have prolonged apnea with the use of myorelaxant succinylcholine. For the silent type variant ChE, two cases of mutation have been reported. In one case, the exon 2 of ChE gene was disrupted by a 342 bp insertion of Alu element. In the other case, a frame shift mutation was identified at Gly-117 (GGT-->GGAG) to create a stop codon at nucleotide 384. Dibucaine resistant ChE was examined and found to have a point mutation at nucleotide 209 (A-->G) that converted Asp-70 to Gly, and consequently reduced the affinity of ChE for choline esters. In addition, another two types of a point mutation reducing ChE activity were reported on K variant (Ala-539-->Thr) and a case of (Gly-365-->Arg) in a patient with liver cirrhosis.
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PMID:[Gene analysis of human cholinesterase variants]. 846 62

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

Chronic hepatitis resulting from hepatitis C virus (HCV) infection develops into cirrhosis in at least half of infected patients and increases the risk of hepatocellular carcinoma. The pathogenic effects of a number of viruses result from the disturbance of intracellular signal cascades caused by viral antigens. Therefore, we investigated the interaction of nonstructural protein 3 (NS3) of HCV with the cyclic AMP-dependent signal pathway. We found a similarity between the HCV sequence Arg-Arg-Gly-Arg-Thr-Gly-Arg-Gly-Arg-Arg-Gly-Ile-Tyr-Arg localized in NS3 and the general consensus sequence of protein kinase A (PKA). Consequently, the catalytic (C) subunit of PKA bound to a bacterially expressed fragment of HCV polyprotein containing amino acid residues 1189 to 1525. When this fragment was introduced into cells, it inhibited the translocation of the C subunit into the nucleus after stimulation with forskolin. The result of this inhibition was significantly reduced histone phosphorylation. Therefore, the presence of NS3 in the cytoplasm of infected cells may affect a wide range of PKA functions and contribute to the pathogenesis of the diseases caused by HCV.
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PMID:Nonstructural protein 3 of hepatitis C virus blocks the distribution of the free catalytic subunit of cyclic AMP-dependent protein kinase. 906 Jun 39

To elucidate the relationship between the frequency of core mutations and precore mutation of hepatitis B virus (HBV) in Japanese HBV carriers, we investigated the nucleotide sequence of the precore/core region of HBV in 26 Japanese HBV carriers [15 who were HBe antigen-negative (HBeAg-) and 11 who were HBeAg-positive (HBeAg+)]. The number of amino acid changes (5.9 +/- 3.8) in the core region of HBV in HBeAg-carriers was significantly greater than that in the HBeAg+ carriers (1.5 +/- 1.0; P < 0.005). The precore stop codon mutation was found in 93.3% of HBeAg-negative HBV carriers, while no precore mutation was found in the HBeAg-positive HBV carriers, suggesting that the frequency of core mutations may be associated with the presence of the precore stop codon mutation. However, there was no significant difference in the frequency of amino acid changes among HBeAg-HBV carriers. The mean number of core amino acid changes of liver cirrhosis patients, chronic active hepatitis patients, chronic persistent hepatitis patients, and asymptomatic carriers were 2.7 +/- 1.5, 6.0 +/- 2.2, 4.7 +/- 1.2, and 8.4 +/- 5.3, respectively. We detected hot spots for core mutations, which showed characteristic localizations and specific substitutions: Gly-87, Leu-97, and Thr-130 were detected exclusively in patients with chronic liver disease with or without HBeAg. To address further the relationship between frequency of core mutations and the presence of the precore stop codon mutation, we investigated the precore/core nucleotide sequence serially along with seroconversion in three patients with chronic hepatitis B in whom the hepatitis either became inactive or remained active after the seroconversion. Emergence of the precore stop codon mutation and a significant increase in core amino-acid changes after seroconversion were noted in all three patients. Our results suggest a close association between the frequency of core amino acid changes and the presence of the precore stop codon mutation; some characteristic core mutations may be associated with the clinical course of chronic hepatitis B in Japanese patients.
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PMID:Association between frequency of amino acid changes in core region of hepatitis B virus (HBV) and the presence of precore mutation in Japanese HBV carriers. 934 86

Upon activation by liver injury, hepatic stellate cells produce excessive fibrous tissue leading to cirrhosis. The hepatotoxin CCl(4) induced activation of RSK, phosphorylation of C/EBPbeta on Thr(217), and proliferation of stellate cells in normal mice, but caused apoptosis of these cells in C/EBPbeta-/- or C/EBPbeta-Ala(217) (a dominant-negative nonphosphorylatable mutant) transgenic mice. Both C/EBPbeta-PThr(217) and the phosphorylation mimic C/EBPbeta-Glu(217), but not C/EBPbeta-Ala(217), were associated with procaspases 1 and 8 in vivo and in vitro and inhibited their activation. Our data suggest that C/EBPbeta phosphorylation on Thr(217) creates a functional XEXD caspase substrate/inhibitor box (K-Phospho-T(217)VD) that is mimicked by C/EBPbeta-Glu(217) (KE(217)VD). C/EBPbeta-/- and C/EBPbeta-Ala(217) stellate cells were rescued from apoptosis by the cell permeant KE(217)VD tetrapeptide or C/EBPbeta-Glu(217).
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PMID:C/EBPbeta phosphorylation by RSK creates a functional XEXD caspase inhibitory box critical for cell survival. 1168 16


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