Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plasma levels of different amino acids were observed in 10 patients with severe hepatitis, 9 viral in origin and 1 toxic, over the course of the disease. There would appear to be a close relationship between the onset of encephalopathy and the appearance of a particular pattern in plasma amino acid equilibrium, characterised by a significant fall in the molar ratio existing between ramified amino acids (valine, leucine, isoleucine) and aromatic amino acids (phenylalanine and tyrosine). The role of these disturbances in the physiopathology of the encephalopathy and their effects on the synthesis of normal neurotransmitters and the intracerebral accumulation of false neurotransmitters is discussed.
 ...
PMID:[Variation of plasma amino acids in severe hepatitis with encephalopathy 10 cases]. 1 44

A mixture with essential and nonessential amino acids high in branched chain amino acids and low in aromatic amino acids (Fischer solution), and another synthetic mixture of branched chain amino acids containing 3 amino acids associated with the urea cycle (Hep-OU) were infused to control subjects and patients with severe hepatic disease. Alterations in serum aminograms, blood ammonia levels and electroencephalograms following the infusion were studied and compared with those obtained by a commercially available amino acid mixture. Short-term or continuous infusion of a commercially available amino acid solution to cirrhotic patients caused an increase in methionine, phenylalanine and tyrosine and a decrease in branched chain amino acids. These post-infusion results were similar to the patterns seen in hepatic encephalopathy. In cirrhotic patients, infusion of Fischer solution which contains small quantities of methionine and phenylalanine produced an increase in the concentrations of these 2 amino acids, probably because of impaired utilization by the injured liver. No marked alterations in serum aminograms, however, were observed in cirrhotic patients either immediately after, or 3 h after, the end of the Hep-OU infusion. Reduction of methionine, tyrosine and phenylalanine levels and elevation of the molar ratio of (valine + leucine + isoleucine)/(phenylalanine + tyrosine) were significant. The infusion of Hep-OU to patients with liver cirrhosis or subacute hepatitis resulted in clinical and neurological improvements and the restoration of the molar ratio of branched chain amino acids/aromatic amino acids.
 ...
PMID:An approach to nutritional therapy of hepatic encephalopathy by normalization of deranged amino acid patterns in serum. 15 28

Encephalopathic patients with cirrhosis of the liver consistently showed elevated levels of the aromatic amino acids, phenylalanine, tyrosine and free tryptophan as well as methionine in serum, whereas levels of the branched chain amino acids, valine, leucine and isoleucine, were depressed. Comatose patients with fulminant hepatitis had markedly elevated levels of all amino acids, the results being greatly different from those of cirrhotic patients. Molar ratios of (valine + leucine + isoleucine)/(phenylalanine + tyrosine) decreased both in cirrhotics with and without encephalopathy and in cases with fulminant hepatitis. Infusion of a commercially available L-amino acid solution in a cirrhotic patient induced a strikingly abnormal aminogram documented in hepatic encephalopathy. Therefore, effects of branched chain amino acid infusion on the deranged amino acid pattern were primarily studied for the purpose of improvement in hepatic encephalopathy by normalization of serum amino acid patterns. Elevated levels of the aromatic amino acids and methionine could be apparently depressed in a cirrhotic patient by this type of infusion but not in a case of fulminant hepatitis probably because of the poor utilization of these amino acids in severely impaired liver.
 ...
PMID:Serum amino acids in hepatic encephalopathy--effects of branched chain amino acid infusion on serum aminogram. 52 13

Previous work from this laboratory has suggested that the plasma amino acid pattern, known to be deranged in hepatic encephalopathy, may be related causally. In order to test this hypothesis, 23% dextrose and a special amino acid solution whose components were calculated to normalize the plasma amino acid pattern were infused in 11 patients, eight with chronic cirrhosis and acute exacerbation (Group 1) and three patients with fulminant hepatitis (Group 2), in amounts of up to 120 Gm. of protein equivalent per 24 hours. Plasma amino acids were abnormal but different in both groups. In Group 1 (cirrhosis) changes in plasma amino acid pattern including elevated phenylalanine, tyrosine, glutamate, aspartate, and methionine and decreased valine, leucine, and isoleucine. In Group 2 all amino acids were elevated, with the exception of the branched chains which were normal. Hepatic encephalopathy improved in all patients in Group 1 and in one of three patients in Group 2 following the infusion. The ratio (see article) showed an excellent correlation with a grade of encephalopathy. When this ratio, previously 1.0 in the presence of encephalopathy, returned to the normal value near 3.0 to 3.5, encephalopathy improved. An excellent correlation was obtained between the ratio and the grade of encephalopathy and was dose related as well. The results suggest that different amino acid patterns in hepatic encephalopathy of differing etiologies require treatment modalities which may differ for the two types of encephalopathy. Whereas amino acid infusion appears to be a valuable, efficacious way of providing nutrition in treating hepatic encephalopathy in patients with cirrhosis and acute deterioration and coma, other means of therapy such as plasms "laundering" appear to be necessary in patients with fulminant hepatitis.
 ...
PMID:The effect of normalization of plasma amino acids on hepatic encephalopathy in man. 81 29

Plasma amino acids were measured in 18 patients with hepatic encephalopathy on a protein-restricted diet of 20 g or less daily. Plasma aminograms tended to group into two distinct patterns depending on the etiology of the patients' hepatic pathology. Patients with chronic liver disease with superimposed acute insults, i.e., gastrointestinal bleeding, infection, alcoholic hepatitis, had elevated levels of the aromatic amino acids, phenylalanine, tyrosine, and tryptophan, as well as methionine, glutamate, and aspartate, whereas levels of the branched chain amino acids, valine, leucine, and isoleucine, were consistently depressed. Those patients with previously normal livers and acute hepatic necrosis, i.e., "fulminant hepatitis," had grossly elevated levels of all amino acids except the branched chain amino acids, which were normal. Elevations of amino acid levels in this patient group tended to correlate with extent of hepatic necrosis and hence had prognostic significance. Additionally, the different patterns seen in these two groups tend to suggest the indicated therapy as well as predict its efficacy.
 ...
PMID:Plasma amino acid patterns in hepatic encephalopathy of differing etiology. 83 96

A 10 year old boy, in grade IV hepatic coma, was treated by combination of XAD-4 resin hemoperfusion (HP), activated charcoal HP (Adsorba 300C, Gambro), exchange transfusion by up to 12.0 liters of fresh whole blood, and regular dialysis. Serum free amino acids' values were consecutively assessed during 4 days of treatment. The liver was 490 gr in weight at autopsy and histologic examination revealed cellular necrosis compatible with fulminant hepatitis. Pre-treatment values of alanine, lysine, proline, phenylalanine, arginine, threonine, tyrosine and methionine were increased by 2 to 38 times of normal control, while those of cystine, glutamic acid, serine and glycine were minimally increased up to 1.7 times. Histidine, isoleucine, leucine and valine, on the other hand, were decreased by 20 to 30% and aspartic acid was the lowest at 14% of normal control. The effect of XAD-4 resin HP and exchange transfusion was rather non-specific by decreasing the total amount of amino acids. The molar ratios of branched chain amino acids vs. aromatic amino acids or essential amino were elevated by activated charcoal HP, but, did not reach to normal range.
 ...
PMID:[Variation of serum free amino acids in fulminant hepatitis treated with hepatic assists (author's transl)]. 740 29

The functions of delta antigens (HDAgs) in the replication of hepatitis delta virus (HDV) have been identified previously. The small HDAg acts as a transactivator, whereas the large HDAg has a negative effect on replication. To understand the molecular mechanisms involved in the control of HDV replication, we have established a replication system in Huh-7 cells by cotransfecting a monomeric cDNA genome of HDV and a plasmid encoding the small HDAg. We demonstrate that a leucine repeat in the middle domain of the small HDAg is involved in binding to the HDV genome and transactivation of HDV replication. When the leucine repeat was disrupted by a substitution of valine for leucine at position 115, both RNA-binding and transactivation activity of the small HDAg were abolished. In contrast, the binding and transactivation activities were not affected when Leu-37 and Leu-44 of the small HDAg were replaced by valines. In addition, small and large HDAgs can interact with each other to form protein complexes in vitro. The complex formation that may lead to the trans-dominant negative regulation of large HDAg in HDV replication is mediated by a cryptic signal located between amino acid residues 35 and 65 other than the putative N-terminal leucine zipper motif. Furthermore, an extra 21-amino-acid extension near the N terminus converts the small HDAg into a pseudo-large HDAg with negative regulation activity of HDV replication even though the extreme C-terminal residue is unchanged.
 ...
PMID:Functional motifs of delta antigen essential for RNA binding and replication of hepatitis delta virus. 847 58

In this study, a previously not documented variant of hepatitis B virus was described in Chinese patients with fulminant hepatitis. The entire precore/core region amplified from samples was cloned into a bacterial vector and sequenced by dideoxy chain termination reaction. Double amino acid substitutions were seen in the precore region in the isolates: one from glycine to aspartic acid at codon 29 previously reported; the other substitution of phenylalanine for valine at codon 17 in the cleavage site of hepatitis B virus. Loss of hepatitis B virus e antigen in these patients with fulminant hepatitis might therefore be due to the mutation in the cleavage site, rather than the emergence of a stop codon in the precore region of hepatitis B virus. Accumulation of hepatitis B e antigen precursor within the hepatocytes might account for the fulminant hepatitis exacerbation.
 ...
PMID:[Genetic variation in the cleavage site of the precore region of hepatitis B virus in Chinese patients with fulminant hepatitis]. 873 42

The capsid particle of hepadnaviruses is assembled from its dimer precursors. However, the mechanism of the protein-protein interaction is still poorly understood. A small region in the capsid protein of woodchuck hepatitis virus (WHV) contains four hydrophobic residues, including leucine 101, leucine 108, valine 115, and phenylalanine 122, that are conserved and spaced every seventh residue in the primary sequence to form a hydrophobic heptad repeat (hhr). A hydrophobic force often plays an important role in the interaction of proteins. Therefore, to investigate the role of this region in capsid assembly, we individually changed the codons specifying these four hydrophobic amino acids to codons specifying alanine or proline. In addition, we examined the in vivo infectivity of a WHV genome bearing a naturally occurring single amino acid change (histidine 104-->proline) in the hhr region. The phenotype of each altered genome was determined in both eukaryotic and prokaryotic systems by a capsid protein assay and electron microscopic examination. We show that replacement of any one of the four hydrophobic residues with alanine did not prevent capsid assembly. However, assembled capsid particles were not detected if combinations of any two of the four residues were substituted with alanines or if the spacing of these four hydrophobic residues was changed. An individual introduction of a proline (which dramatically changes the secondary structure of proteins) into different positions of this small region also abolished capsid assembly in vitro or viral replication in vivo. These results suggested that the hhr region of the core protein of WHV was critical for capsid assembly.
 ...
PMID:A hydrophobic heptad repeat of the core protein of woodchuck hepatitis virus is required for capsid assembly. 879 54

The polymerase gene of Mouse Hepatitis Virus strain JHM (MHV-JHM) encodes a polyprotein larger than 750 kilodaltons. This polyprotein is proposed to be processed by several viral proteinases into functional subunits. The amino-terminal subunit is p28, which is cleaved by the first viral papain-like proteinase domain. In this study, we identified the cleavage site of this papain-like cysteine proteinase by amino acid sequencing of radiolabeled polypeptide adjacent to p28. Proteolysis occurs between the glycine-247 and valine-248 dipeptide bond. To determine which amino acid residues are critical for proteolysis, we preformed site-directed mutagenesis on the coding sequences surrounding the cleavage site and assayed for the efficiency of cleavage of p28 in an in vitro transcription and translation system. We report that glycine-247 and arginine-246 are the most critical residues for efficient processing of p28.
 ...
PMID:Proteolytic processing of the MHV polymerase polyprotein. Identification of the P28 cleavage site and the adjacent protein, P65. 883 May 20


1 2 Next >>