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

The concentrations of total free amino acids, single free amino acids, urea, and ammonia were determined in plasma of mice during experimental infection with the MHV-3 strain of mouse hepatitis virus. Analysis of free amino acids was done by ion-exchange resin chromatography under conditions that allowed the use of a single chromatographic column, separation of glutamine and asparagine, and an accelerated rate of chromatography. The results showed that as early as 6 hr after infection there was a decrease in the concentration of several free amino acids as well as in the total concentration of free amino acids in plasma. For most of the amino acids the decrease persisted until 48 hr. Only at 72 hr, during severe cytolysis, did the concentration of amino acids increase significantly. It is suggested that the decrease during the initial phases of the infection may be due to a thermolabile factor that is produced by circulating leukocytes and that effects a flow of free amino acids from the plasma toward the liver. The final increase in concentration of several free amino acids reflects the cytolytic damage to the liver caused by the virus.
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PMID:Free amino acids in plasma during experimental infection of mice with the MHV-3 strain of mouse hepatitis virus. 19 86

Antibodies present in the sera of a group of children with autoimmune hepatitis react with human cytochrome P450 IID6. cDNA constructions of various fragments of human P450 IID6 were made and expressed and the resulting peptides were tested in immunoblot with patients' sera. These allowed identification of at least two antigenic sites on the P450 molecule. The main one, recognized by all sera tested, is located between amino acids 239 and 271. Synthesis of three peptides covering this area of the molecule allowed identification of a sequence of three amino acids (tyrosine-tryptophane-asparagine) located at position 261-263 that constitutes the essential part of the epitope. A protein sequence data-base search revealed homologies between this region of human P450 and proteins from Salmonella typhimurium, from human T lymphotropic virus types 1 and 2 and Herpes simplex virus type 1.
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PMID:Identification of the main epitope on human cytochrome P450 IID6 recognized by anti-liver kidney microsome antibody. 172 73

In order to clone hepatitis C (blood-borne non-A, non-B hepatitis) virus, lambda gt11-cDNA library was constructed from RNA extracted from 100 liters serum collected from 1,047 donors with elevated ALT levels and negative for hepatitis B virus-DNA. The library was immunoscreened on Y1090 cells with pooled serum obtained from patients with acute hepatitis C or chronic hepatitis C. By screening 29 clones specific for Japanese hepatitis C infection were isolated. The specificity of these clones for hepatitis C infection was determined by panels constructed in 3 laboratories. Of these, 12 clones were specific for American hepatitis C infection as well. The nucleotide sequence (201 bp) of one of them was determined to be unique compared to known human viruses including hepatitis A virus, hepatitis B virus and hepatitis D virus. Southern blot analysis showed the absence of the sequence of the human genome in the clone. The predicted amino acid sequence is rich in residues of lysine, arginine, glutamic acid and asparagine, while lacking leucine, cysteine and methionine.
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PMID:Cloning of a cDNA associated with acute and chronic hepatitis C infection generated from patients serum RNA. 250 78

Infection with hepadnaviruses and exposure to dietary aflatoxin are considered major risk factors in the development of hepatocellular carcinoma (HCC) both in humans and in animals. Recently, a broad range of mutations in the p53 tumor suppressor gene has been reported in human HCCs, predominantly from hepatitis B virus carriers in areas with either high or low levels of exposure to dietary aflatoxin. To determine whether p53 mutations are common to HCCs of hosts infected with related hepadnaviruses with and without treatment with aflatoxin, we studied the occurrence of mutations in the p53 gene in HCCs of ground squirrels and woodchucks with history of infection with ground squirrel hepatitis virus (GSHV) and woodchuck hepatitis virus, respectively. Sequencing of wild type p53 genes from ground squirrels and woodchucks revealed remarkable homology between the two species with only a few amino acid differences in exons 4, 8, and 9. Using direct polymerase chain reaction sequencing, we analyzed the state of the p53 gene (exons 4-9) in 20 HCCs from ground squirrels (2 uninfected, 7 with past, and 11 with ongoing infection with GSHV) and in 11 HCCs from woodchucks persistently infected with woodchuck hepatitis virus. Five GSHV carrier and two uninfected ground squirrels received i.p. administration of aflatoxin B1. We detected only one mutation in the p53 gene of the tested animals. This mutation was located in codon 176 of exon 5 in the HCC of a GSHV-positive ground squirrel treated with aflatoxin. Mutation was caused by a G to T transversion in the second position of the codon, resulting in the replacement of cysteine with phenylalanine, and was accompanied by a tumor-specific loss of heterozygosity. p53 allelic amino acid variation with sequences coding for aspartic acid or asparagine was present in codon 61 in the variable region of exon 4 in both HCCs and nonneoplastic tissues of ground squirrels. In view of the considerably lower apparent rate of mutations in comparison to human HCCs, we suggest a less important role for aflatoxin in the induction of p53 mutations in HCCs of ground squirrels. Alternatively, etiological factors other than p53 mutations may be of greater significance in the development of HCC in ground squirrels and woodchucks.
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PMID:State of the p53 gene in hepatocellular carcinomas of ground squirrels and woodchucks with past and ongoing infection with hepadnaviruses. 792 76

The efficacy and safety of lomefloxacin in the treatment of patients with hepatitis due to the use of routine antituberculosis agents were estimated. The trial group included 20 patients (10 with increased activity of enzymes such as alanine and asparagine transaminases, alkaline phosphatase and gamma-glutamate dehydrogenase) who were treated for various forms of tuberculosis with antitubeculosis drugs. The treatment course with lomefloxacin was 4 weeks (400 mg twice a day at 12-hour intervals). The criteria of the enrolment to the trial group were a more than 2-3 times higher activity of the enzymes and the absence of the markers of the virus hepatitis A, B and C. The therapy efficacy before and after the use of lomefloxacin was estimated clinically and by the findings of the laboratory and instrumental investigations. As a result of the treatment with lomefloxacin normalization of the enzyme activity and a favourable time course of the main disease were observed in the patients with drug hepatitis due to the use of antituberculosis agents requiring continuation of the antituberculosis therapy. An important result of the complex treatment with lomefloxacin and antituberculosis agents was discontinuation of the tubercle bacilli isolation in 70 per cent of the patients. Lomefloxacin proved to be a safe and efficient up-to-date agent for the treatment of tuberculosis in patients with hepatitis due to the use of antituberculosis drugs.
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PMID:[Lomefloxacin in phthisiatric practice]. 982 4

A clinical observation over 57 liquidators of the Chernobyl accident aftermath (ChAAL) with associated diseases of the digestive and hepato-biliary system revealed abnormalities in blood enzymic activity, presenting as elevation of, in particular, alanine aminotransferase as well as of asparagine aminotransferase, gamma-glutaminetranspeptidase, alkaline phosphatase, lactate dehydrogenase, and of blood mineral composition at the expense of an increase in certain minerals. Disturbances in underlying process of bodily metabolism promote the development and association of erosive and ulcerous lesions of the stomach and duodenum with chronic noncalculous cholecystitis, persistent hepatitis in ChAAL.
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PMID:[Metabolic disorders in digestive and hepatobiliary pathology in those who worked in the cleanup of the aftermath of the accident at the Chernobyl Atomic Electric Power Station]. 1005 Apr 54

The short-term aim of chronic hepatitis B treatment is the suppression of Hepatitis B Virus (HBV) replication, as shown by the loss of HBV DNA by DNA hybridization and the loss of Hepatitis B e Antigen (HBeAg). Loss of Hepatitis B s Antigen (HBsAg) and HBV DNA as assayed by Polymerase Chain Reaction (PCR) is very difficult to achieve. There are two important treatment approaches. The first is immunomodulation, comprising Interferon (IFN) and other cytokine treatment and therapeutic vaccination. The second is antiviral treatment, which mainly includes treatment with nucleoside analogs. There are many limitations to IFN treatment, because it has succeeded only in a small number of patients with a high level of transaminase and a low level of HBV DNA. The theoretical basis of therapeutic vaccination is the use of a vaccine that contains epitopes known to stimulate Human Leucocyte Antigen (HLA)-restricted cytotoxic T cell activity in order to lyse the HBV-infected hepatocytes. Several strategies of hepatitis vaccination are the incorporation of both pre-S and S antigen, the incorporation of a Cytotoxic T Lymphocyte (CTL)-specific antigen, the use of an HBV vaccine complexed to Hepatitis B Immune Globulin (HBIG), and DNA vaccination. One of the limitations of therapeutic vaccination is the short duration of immunity to the CTL antigen. Lamivudine is an oral nucleoside analog with potent antiviral action. It rapidly reduces the HBV DNA level, a level that soon returns to pretreatment level after drug administration is terminated. This drug does not affect the covalently bond closed circular (ccc)DNA of infected hepatocytes; it only inhibits the formation of new viruses. One-year of Lamivudine treatment significantly improved necroinflammation and reduced the progression of fibrosis and the histologic activity index. HBeAg seroconversion occurred after prolonged treatment. The emergence of a tyrosine-methionine asparagine aspargine YMDD mutant is one of the drawbacks of lamivudine treatment. Therefore a combination with other antiviral agents or immune modulators, such as therapeutic vaccination, is likely to be more effective.
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PMID:New options in the treatment of chronic hepatitis. 1291 91

We report studies of a Greek boy of gypsy origin that show that he has severe deficiency of glycine N -methyltransferase (GNMT) activity due to apparent homozygosity for a novel mutation in the gene encoding this enzyme that changes asparagine-140 to serine. At age 2 years he was found to have mildly elevated serum liver transaminases that have persisted to his present age of 5 years. At age 4 years, hypermethioninaemia was discovered. Plasma methionine concentrations have ranged from 508 to 1049 micro mol/L. Several known causes of hypermethioninaemia were ruled out by studies of plasma metabolites: tyrosinaemia type I by a normal plasma tyrosine and urine succinylacetone; cystathionine beta-synthase deficiency by total homocysteine of 9.4-12.1 micro mol/L; methionine adenosyltransferase I/III deficiency by S -adenosylmethionine (AdoMet) levels elevated to 1643-2222 nmol/L; and S -adenosylhomocysteine (AdoHcy) hydrolase deficiency by normal AdoHcy levels. A normal plasma N -methylglycine concentration in spite of elevated AdoMet strongly suggested GNMT deficiency. Molecular genetic studies identified a missense mutation in the coding region of the boy's GNMT gene, which, upon expression, retained only barely detectable catalytic activity. The mild hepatitis-like manifestations in this boy are similar to those in the only two previously reported children with GNMT deficiency, strengthening the likelihood of a causative association. Although his deficiency of GNMT activity may well be more extreme, his metabolic abnormalities are not strikingly greater. Also discussed is the metabolic role of GNMT; several additional metabolite abnormalities found in these patients; and remaining questions about human GNMT deficiency, such as the long-term prognosis, whether other individuals with this defect are currently going undetected, and means to search for such persons.
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PMID:Glycine N -methyltransferase deficiency: a new patient with a novel mutation. 1473 80

Bacterial L-asparaginases are enzymes that catalyze the hydrolysis of l-asparagine to aspartic acid. For the past 30 years, these enzymes have been used as therapeutic agents in the treatment of acute childhood lymphoblastic leukemia. Their intrinsic low-rate glutaminase activity, however, causes serious side-effects, including neurotoxicity, hepatitis, coagulopathy, and other dysfunctions. Erwinia carotovora asparaginase shows decreased glutaminase activity, so it is believed to have fewer side-effects in leukemia therapy. To gain detailed insights into the properties of E. carotovora asparaginase, combined crystallographic, thermal stability and cytotoxic experiments were performed. The crystal structure of E. carotovoral-asparaginase in the presence of L-Asp was determined at 2.5 A resolution and refined to an R cryst of 19.2 (R free = 26.6%) with good stereochemistry. Cytotoxicity measurements revealed that E. carotovora asparaginase is 30 times less toxic than the Escherichia coli enzyme against human leukemia cell lines. Moreover, denaturing experiments showed that E. carotovora asparaginase has decreased thermodynamic stability as compared to the E. coli enzyme and is rapidly inactivated in the presence of urea. On the basis of these results, we propose that E. carotovora asparaginase has limited potential as an antileukemic drug, despite its promising low glutaminase activity. Our analysis may be applicable to the therapeutic evaluation of other asparaginases as well.
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PMID:Structural and functional insights into Erwinia carotovora L-asparaginase. 1864 44

Platelets are reported to be causally involved in experimental hepatitis. Jo2, an agonistic anti-Fas antibody, induces hepatitis in mice. We examined the in vivo behaviors of platelets in mice injected with this antibody (analyzed by measuring 5-hydroxytryptamine, a constituent of platelets). We found that Jo2 induces platelet accumulation predominantly in the liver, and that this hepatic platelet accumulation (HPA) precedes the increases in hepatitis markers (alanine- and asparagine-aminotransferases [ALT and AST]). By electron microscopy, we detected entry of platelets into hepatocytes, and also evidence of apoptosis among hepatocytes. A caspases-3/6/7/8/10 inhibitor prevented the Jo2-induced HPA and hepatitis. In platelet-depleted mice, contrary to our expectations, the Jo2-induced hepatitis was not reduced, and actually the increase in AST was significantly augmented, although the survival time of mice given a lethal dose of Jo2 was significantly increased (nearly doubled). Interestingly, prior induction of HPA by a low dose of lipopolysaccharide markedly reduced Jo2-induced hepatitis. Jo2 also induced HPA and hepatitis in mice deficient in both IL-1 and TNFalpha, although Jo2 increased the blood level of TNFalpha in wild-type mice. These results suggest that in Jo2-induced hepatitis: (i) platelets accumulate predominantly in the liver as a result of hepatic lesions, and that this precedes the release of transaminases from hepatocytes, and (ii) IL-1 and TNFalpha are not essential for Jo2-hepatitis. We hypothesize that platelet accumulation in the liver may, contrary to our expectations, be protective when the hepatitis is local or not severe, but harmful when hepatitis is severe.
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PMID:Hepatic platelet accumulation in Fas-mediated hepatitis in mice. 1943 97


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