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)

A sensitive radioimmunoassay for cholylglycine, chenodeoxycholylglycine, deoxycholylglycine, and sulfolithocholylglycine was established using antibodies obtained from rabbits injected with albumin conjugates of these bile acids. Glycine-conjugated bile acid levels were measured in sera from 25 control subjects and 110 patients who had hepatic disease (alcoholic cirrhosis, hepatitis, cholestasis, and hepatic malignancy). Sulfolithocholylglycine was elevated in the sera of all 110 patients with hepatic disease. Cholylglucine was within normal range in only three. Chenodeoxycholylglycine was elevated in most sera of patients who had hepatitis, cholestasis, or hepatic malignancy. It was normal in most sera of patients who had alcoholic cirrhosis, suggesting that chenodeoxycholic acid may be subject to further biotransformations in these patients. Deoxycholylglycine was elevated in a minority of patients, none of whom had cholestasis. The data suggest that serum bile acids, particularly sulfolithocholylglycine, are a highly sensitive index for hepatic dysfunction.
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PMID:Levels of immunoreactive glycine-conjugated bile acids in health and hepatobiliary disease. 98 91

A controlled clinical trial comparing 2-Mercapto-Priopionyl-Glycine (2-MPG) plus B12 vitamin with B12 vitamin alone in chronic liver disease has been conducted in seven hospitals in Italy. Patients were divided into two groups on the basis of liver histology; group I included 26 patients showing histological evidence for chronic persistent hepatitis (C.P.H.) (according to De Groote et al.) whereas group II consisted of 54 patients with chronic aggressive hepatitis (C.A.H.) or compensated liver cirrhosis. Patients of each group were randomly allocated to 2-MPG plus B12 vitamin, or to placebo plus B12 vitamin, in a double-blind way. The drug (or placebo) was diluted in 500 ml of 10% Levulose, and administered intravenously; 1000 gamma of B12 vitamin were added to each bottle. Patients in the 2-MPG group received 2.5 gms of the drug daily; the treatment lasted for 30 days. The following parameters were checked in all patients on admission, and repeated at the end of treatment: Serum bilirubin, serum Cholesterol, A.P., BSP retention, Prothrombin time, S-GOT, S-GPT, Gamma-GT, Total serum Protein, serum electrophoresis, Immunoglobulins. Patients given 2-MPG showed significant decreases of serum transaminases, and improvement of BSP retention.
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PMID:[Controlled clinical trial of 2-mercapto-propionyl-glycine in chronic hepatopathies]. 125 87

Non-sulfated bile acid levels including cholic acid (CA), chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), lithocholic acid (LCA), ursodeoxycholic acid (UDCA), five taurine conjugates, and five glycine conjugates in duodenal juice were measured in 50 Chinese infants with cholestasis to test their diagnostic value. All 17 with biliary atresia (BA) cases, 11 out of 26 neonatal hepatitis (NH) cases and one case with paucity of the interlobular bile duct were without detectable bile acids. In those NH patients with detectable bile acids, the major components were conjugated forms of CA and CDCA, which was similar to all 6 cases of the comparison group with other diseases. The minor bile acid components identified in them were glycine conjugated UDCA, free CDCA, free CA, and free and conjugated DCA. Only one patient with NH had taurine conjugated LCA. The mean total duodenal bile acid level in 15 patients with NH was significantly lower than that in the 6 patients of the comparison group. Most patients with NH had a CDCA/CA ratio of less than one, indicating that cholic acid is the predominant form in their bile. Glycine conjugated bile acids were the predominant bile acids present in 11 out of 15 patients with NH and 4 out of 6 of the comparison group patients. The results suggest that the detection of duodenal bile acids by a sensitive HPLC method is of limited value in making a differential diagnosis between BA and NH.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Analysis of duodenal bile acids by high performance liquid chromatography in infants with cholestasis. 168 Sep 88

A drug-induced allergic hepatic disorder model was established using a hapten and carrier. Penicillin G was bound to glycine for the preparation of N-hydroxy succinic imidylglycinyl benzylpenicillate (PG-Gly-OSu). Using this as the hapten and liver protein as the carrier, guinea pigs were sensitized with liver protein bound to PG-Gly-OSu. After 2 weeks, the sensitized guinea pigs were directly challenged with hepatocytes bound to PG-Gly-OSu through a mesenteric vein and hepatocellular disorder was induced. When the sensitized guinea pigs were challenged with PG-Gly-OSu alone or with liver protein alone, hepatocellular disorder could not be induced. These results suggest that the combination of PG-Gly-OSu as the hapten and liver protein as the carrier elicits a hepatocellular disorder similar to drug-induced allergic hepatitis.
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PMID:Preparation of a drug-induced allergic hepatic disorder model with penicillin as hapten. 179 65

Hepatitis C virus is a positive single-strand RNA virus distantly related to flaviviruses. Therefore RNA replicase, an RNA-dependent RNA polymerase, may be essential for the replication of hepatitis C virus, as well as other RNA viruses. In this study we synthesized the recombinant polypeptide (HCV-NS5 antigen) with a 576 bp cDNA encoding a part of the NS5 region of the HCV genome that has the Gly-Asp-Asp motif. The antibody against this polypeptide was obtained from rabbit serum. In Western-blot analysis with NS5 IgG HCV antibody, an 84-kD protein was clearly detected as a single band in the microsomal fraction but not in the nuclear and mitochondrial fractions or in the cytosol fraction. Immunohistochemically, HCV-NS5 antigen was clearly stained in the cytoplasm of hepatocytes but not in the nucleus or cell membrane. Moreover, as determined on immunoelectron microscopy, HCV-NS5 antigen was demonstrated with fine granular distribution along the endoplasmic reticulum but not in other organelles, including the nucleus and mitochondria. Immunoreaction in other cell types was negative. These results indicate that replication of HCV may occur only in hepatocytes and that HCV-NS5 may be produced in the endoplasmic reticulum of these cells. HCV-NS5 antigen was stained only in the livers of hepatitis C virus-positive patients but not in sections from patients with chronic type B hepatitis or alcoholic fibrosis. In chronic type C liver disease, the overall detection rate of HCV-NS5 antigen was 56% (33% in chronic persistent hepatitis, 52% in chronic active hepatitis and 86% in cirrhosis).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Detection of antigens related to hepatitis C virus RNA encoding the NS5 region in the livers of patients with chronic type C hepatitis. 750 61

Mouse hepatitis virus strain A59 encodes a papain-like cysteine proteinase (PLP-1) that, during translation of ORF1a, cleaves p28 from the amino terminus of the growing polypeptide chain. In order to determine the amino acid sequences surrounding the p28 cleavage site, the first 4.6 kb of murine hepatitis virus strain A59 ORF1a was expressed in a cell-free transcription-translation system. Amino-terminal radiosequencing of the resulting downstream cleavage product demonstrated that cleavage occurs between Gly-247 and Val-248. Site-directed mutagenesis of amino acids surrounding the p28 cleavage site revealed that substitutions of Arg-246 (P2) and Gly-247 (P1) nearly eliminated cleavage of p28. Single-amino-acid substitutions of other residues between P7 and P2' were generally permissive for cleavage, although a few changes did greatly reduce proteolysis. The relationship between the p28 cleavage site and other viral and cellular papain proteinase cleavage sites is discussed.
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PMID:Identification of the murine coronavirus p28 cleavage site. 781 47

Hepatitis delta virus (HDV) encodes two proteins, the small hepatitis delta antigen (SHDAg) and large hepatitis delta antigen (LHDAg). Both proteins are identical except for the presence of additional 19 amino acids at the C terminus of LHDAg. While SHDAg is required for HDV RNA replication, LHDAg inhibits replication and is required together with hepatitis B surface antigen for the assembly of HDV. The C-terminal last 4 amino acids of LHDAg (Cys-Arg-Pro-Gln) is an isoprenylation motif. It has previously been shown that the mutation of the Cys inhibited the assembly of HDV. In order to discern whether this effect is due to change of amino acid residue or abolition of isoprenylation, we constructed several LHDAg mutants of the terminal three amino acid residues and tested their abilities to be packaged with HBsAg by cotransfection experiments. We also made GST-fusion proteins of these mutants and tested their abilities to be isoprenylated in rabbit reticulocyte lysate system. We found that some, but not all, of the substitutions of the amino acid residues other than the Cys also inhibited isoprenylation and that the status of isoprenylation of these mutant proteins correlated well with their abilities to be packaged with HBsAg into virions. This result indicates that isoprenylation, rather than the primary amino acid sequence, is required for LHDAg packaging. Furthermore, we found that the attachment of an isoprenylation motif to SHDAg did not enable it to be packaged with HBsAg and that the deletions of any 5 amino acids in the last 15 amino acids (amino acids 196 to 210) unique to the LHDAg abolished the packaging ability. In contrast, the deletion of 33 amino acids (amino acids 163 to 195) upstream of the last C-terminal 19 amino acids of LHDAg did not interfere with its packaging ability. Therefore, we conclude that the 15 amino acids upstream of the isoprenylation site of LHDAg are also essential for HDV assembly, and a large portion of the alleged C-terminal Pro/Gly-rich region (amino acids 146 to 195) is not required for the assembly process.
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PMID:Isoprenylation of large hepatitis delta antigen is necessary but not sufficient for hepatitis delta virus assembly. 811 40

The surface glycoprotein (S) of the murine hepatitis coronavirus MHV normally undergoes proteolytic cleavage during transport to the cell surface. To determine whether the cleavage of the MHV-JHM S glycoprotein is required to activate its ability to fuse cellular membranes, the protease recognition sequence in a cDNA copy of the S gene was altered from Arg-Arg-Ala-Arg-Arg into Ser-Val-Ser-Gly-Gly by site directed mutagenesis. The mutated and wild type S genes were expressed by means of recombinant vaccinia viruses and it could be shown that the mutated S protein was not cleaved when it was expressed in mouse DBT cells, in contrast to the wild type S protein. Nevertheless, the non-cleaved S protein induced extensive syncytium formation in mouse DBT cells. These results clearly indicate that the non-cleaved form of the MHV S protein is able to mediate cell membrane fusion. Thus, proteolytic cleavage is not an absolute requirement for its fusion function.
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PMID:Proteolytic cleavage of the murine coronavirus surface glycoprotein is not required for its fusion activity. 820 24

Serum hepatitis B virus (HBV) DNA from 4 infants with fulminant hepatitis B, 3 infants with acute self-limited hepatitis B, and 15 infants with chronic HBV infection were amplified by polymerase chain reaction followed by direct sequencing of the region of HBV genome encoding the major antigenic epitopes of hepatitis B surface antigen (HBsAg). All infants were born to carrier mothers and administered immunoprophylaxis from birth. Serum HBV DNA from 13 carrier children born to carrier mothers who did not receive immunoprophylaxis and had comparable length of infection were studied as controls. An S mutant (residue 126, Thr to Ala) initially found in an infant with fulminant hepatitis was replaced by another S mutant (residue 145, Gly to Arg) 4 days later. In a girl with chronic hepatitis B, Ala-126 variant and Arg-145 variant were found at 17 and 25 months of age, respectively. The Arg-145 variant persisted for 8 years in an asymptomatic male carrier and for 1 year in an infant with chronic hepatitis B. The Ala-126 variant persisted for 11 years in one child who had an early loss of hepatitis B e antigen. In the majority of the infants' mothers, corresponding mutations in HBsAg were not detected in serum by direct sequencing. The S mutants detected in three carrier infants were not found in their mothers' serum after cloning and sequencing of 10 DNA clones from each maternal sample. None of the 13 control patients had detectable S mutants. These results suggest that S variants emerge or are selected under the immune pressure generated by the host or by administration of hepatitis B immune globulin and hepatitis B vaccination. An S mutant (residue 129, Gln to Arg) found in one mother-infant pair suggested a direct maternal-infant transmission, resulting in immunoprophylaxis failure. None of the family members of children infected with Arg-145 variant had the same variant infection, implying this variant's low transmissability.
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PMID:Surface gene mutants of hepatitis B virus in infants who develop acute or chronic infections despite immunoprophylaxis. 930 14

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


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