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)

Six to 12 hr after IP injection of 400 mg/kg of D-galactosamine in rats a 5-fold increase in plasma insulin was observed. In addition, impaired glucose assimilation was present after an IV Load in spite of unchanged fasting glucose levels. In streptozotocin-diabetic rats (100 mg/kg IV) plasma insulin remained diminished 12 h after induction of D-galactosamine hepatitis. Under identical conditions of preparation and incubation, the liver plasma membranes of D-galactosamine-treated rats, in both normal and diabetic states, bound only 40--60% as much insulin per mg of membrane protein as those of the control rats. Scatchard analysis suggested that this was due to a decrease in the number of receptor sites in the membranes of the D-galactosamine-injected rats. No difference in the insulin degrading capacity and in insulin-receptor dissociation of the plasma membranes between control and D-galactosamine-treated groups was found. These data suggest that a reduction in the number of hepatic insulin receptors in galactosamine hepatitis can lead to insulin resistance and hyperinsulinaemia.
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PMID:Reduced insulin binding to hepatic plasma membranes in D-galactosamine-treated rats. 48 65

A specific and sensitive radioimmunoassay was used to measure the levels of antibody to a liver-specific membrane lipoprotein in patients with acute and chronic liver disease. Antibody was detected in 29 of 30 patients with chronic active hepatitis (all of 15 HBsAg-negative and 14 of 15 HBsAg-positive cases), and in 10 of 17 patients with chronic persistent hepatitis but at significantly lower titer. The titer of antibody to the lipoprotein showed a significant correlation with activity of disease as judged histologically and biochemically. Transiently elevated levels were found in 20 of 21 patients with acute viral hepatitis, but there was no correlation with the degree of liver damage. Antibody to liver-specific membrane protein may be part of the final common pathway of liver-cell damage in both HBsAg-positive and HBsAg-negative chronic activite hepatitis, whereas other immune mechanisms determine the liver-cell injury in acute viral hepatitis.
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PMID:Detection of antibodies directed against a liver-specific membrane lipoprotein in patients with acute and chronic active hepatitis. 66 44

Cell-mediated immunity to a liver specific membrane protein (LP1) has been studied in patients with different types of liver diseases, using the leucocyte migration inhibition test. A high frequency of cellular sensitization to LP1 was detected in untreated chronic active hepatitis, with no significant differences between HBsAg-positive and negative cases. Inhibition of migration is a long-lasting reaction in the spontaneous evolution of the disease, while immunosuppressive treatment normalizes the test only in cases with complete remission. In viral hepatitis B cell-mediated immunity to the liver specific membrane protein can be detected in the acute phase of the disease as a time-limited reaction, exhausted with the clearance of the virus from the liver. An inhibition of migration with LP1 was found also in some cases of HBsAg-positive post-hepatitis patients, in chronic persistant hepatitis, mainly HBsAg-positive, and in asymptomatic chronic carriers of the antigen B. Most of these cases showed a progression to chronic active hepatitis, in clinical and histopathological prospective studies. Our results suggest that cell-mediated immune response to liver specific antigens plays a major role in the pathogenesis of chronic active hepatitis. Moreover the evaluation of these reactions in chronic liver diseases may help in the diagnosis and in the control of the immunosuppressive therapy. Hepatitis B virus infection must be considered one of the possible cause responsible for the rising of autoimmunity to the liver.
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PMID:[Liver-specific proteins and autoimmunity in inflammatory liver diseases]. 101 92

The M protein of mouse hepatitis virus strain A59 is a triple-spanning membrane protein which assembles with an uncleaved internal signal sequence, adopting an NexoCcyt orientation. To study the insertion mechanism of this protein, domains potentially involved in topogenesis were deleted and the effects analyzed in topogenesis were deleted and the effects analyzed in several ways. Mutant proteins were synthesized in a cell-free translation system in the presence of microsomal membranes, and their integration and topology were determined by alkaline extraction and by protease-protection experiments. By expression in COS-1 and Madin-Darby canine kidney-II cells, the topology of the mutant proteins was also analyzed in vivo. Glycosylation was used as a biochemical marker to assess the disposition of the NH2 terminus. An indirect immunofluorescence assay on semi-intact Madin-Darby canine kidney-II cells using domain-specific antibodies served to identify the cytoplasmically exposed domains. The results show that each membrane-spanning domain acts independently as an insertion and anchor signal and adopts an intrinsic preferred orientation in the lipid bilayer which corresponds to the disposition of the transmembrane domain in the wild-type assembled protein. These observations provide further insight into the mechanism of membrane integration of multispanning proteins. A model for the insertion of the coronavirus M protein is proposed.
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PMID:Membrane assembly of the triple-spanning coronavirus M protein. Individual transmembrane domains show preferred orientation. 140 May 1

The 3' end of the turkey coronavirus (TCV) genome and the gene encoding the nucleocapsid protein (N) were cloned and sequenced. The gene encoding the membrane protein (M) was obtained by cloning a polymerase chain reaction (PCR)-amplified fragment obtained using bovine coronavirus (BCV)-specific primers. Furthermore, five TCV DNA fragments, obtained by PCR on RNA from clinical specimens and corresponding to either the N terminus of the M protein or the complete M protein were also cloned and sequenced. The sequence revealed a 3' non-coding region of 291 bases, an open reading frame (ORF) encoding the N protein with a predicted size of 448 amino acids, or an Mr of 49K, and an ORF encoding the M protein with a predicted size of 230 amino acids and an Mr of 26K. A third ORF, encoding a hypothetical protein of 207 amino acids with an Mr of 23K was found within the N gene sequence. The amino acid sequences of both the N and M proteins were more than 99% similar to those published for BCV. Extensive similarity was also observed between the amino acid sequences of the TCV N protein and those of murine hepatitis virus (MHV) (70%) and human respiratory coronavirus strain OC43 (HCV-OC43) (98%) and between the amino acid sequences of the predicted M proteins of TCV and MHV (86%). Such striking identity suggests that BCV, TCV and HCV-OC43 must have diverged from each other only recently. A potential N-glycosylation site was found at the N terminus of the TCV M protein and is situated at the same location in BCV, MHV and transmissible gastroenteritis virus.
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PMID:Sequence analysis of the turkey enteric coronavirus nucleocapsid and membrane protein genes: a close genomic relationship with bovine coronavirus. 185 95

The nucleotide sequence between the spike and membrane protein genes in the bovine coronavirus (BCV) genome was determined by sequencing cDNA clones of the genome, and open reading frames potentially encoding proteins of 4.9, 4.8, 12.7, and 9.5 kDa, in that order, were identified. The 4.9- and 4.8-kDa proteins appear to be vestiges of an 11-kDa protein for which a single nucleotide deletion event in the central part of the gene gave rise to a stop codon. The consensus CYAAAC sequence precedes the 4.9-, 12.7-, and 9.5-kDa ORFs and predicts that transcription will start from each of these sites. Northern analyses using sequence-specific probes and oligo(dT)-selected RNA demonstrated that the predicted transcripts are made, and that these correspond to mRNAs 4, 5, and 5-1. BCV mRNA 4 appears to be a counterpart to mouse hepatitis virus (MHV) mRNA 4 which, in the MHV JHM strain, encodes the putative 15.2-kDa nonstructural protein. BCV mRNAs 5 and 5-1 appear to be used for the synthesis of the 12.7- and 9.5-kDa proteins, respectively, which demonstrates a pattern of expression strikingly different from that utilized by MHV. MHV makes its homologs of the 12.7- and 9.5-kDa proteins from the single mRNA 5. In vitro translation analyses demonstrated that the BCV 9.5-kDa protein, unlike its MHV counterpart, is poorly made from downstream initiation of translation. Thus, from a comparison between BCV and MHV we find evolutionary evidence for the importance of the CYAAAC sequence in regulating coronavirus transcription.
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PMID:Sequence and expression analysis of potential nonstructural proteins of 4.9, 4.8, 12.7, and 9.5 kDa encoded between the spike and membrane protein genes of the bovine coronavirus. 214 56

Interaction between woodchuck hepatitis virus surface antigen and proteins of hepatocyte plasma membranes were examined in the course of woodchuck hepatitis virus infection. Membranes purified from animals with histologically confirmed acute hepatitis, active or persistent chronic hepatitis and the virus-related hepatocellular carcinoma were evaluated for the virus surface antigen contents, treated with agents eluting plasma membrane-bound antigen to test the extent of the antigen-membrane associations and incubated with purified, particulate woodchuck hepatitis virus surface antigen to determine membrane potential for the antigen adsorption. Hepatocyte plasma membranes originating from woodchucks chronically infected with the virus showed the highest quantities of the incorporated virus surface antigen among membranes studied, the behavior of bound antigen as an integral and a peripheral membrane protein and the resistance to bind an exogenous antigen. Similar properties were expressed by plasma membranes prepared from hepatocytes of nontumor parenchyma displaying chronic active hepatitis of a woodchuck hepatitis virus carrier with hepatoma. Furthermore, plasma membranes originating from animals with active or persistent chronic hepatitis demonstrated identical properties, implicating that histologic activity of the chronic liver inflammatory process is not dependent on the quantity of the virus surface antigen insertion into the membrane. In contrast, hepatocyte plasma membranes from animals with acute hepatitis showed significantly lower antigen quantities, presence of the antigen specificity exclusively behaving as an integral membrane protein and noticeable ability to bind an exogenous surface antigen of the virus. Comparable, but not identical, features were observed for hepatocyte membranes purified from nodules of hepatocellular carcinoma, suggesting that neoplastic transformation of infected hepatocytes is associated with loss of the membrane-bound antigen and with simultaneous, partial recovery of the membrane potential for the antigen binding. Comparative analysis of the properties on the woodchuck hepatitis virus surface antigen incorporation into hepatocyte plasma membranes in studied cases indicated that sustained infection with woodchuck hepatitis virus leads to an increase in the quantity of the membrane-incorporated antigen and to the appearance of the virus surface antigen specificity behaving as a peripheral membrane protein. In conclusion, this study demonstrated that the extent and the character of the antigen interaction with hepatocyte plasma membranes undergoes significant variations in the natural course of hepadna viral infect
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PMID:Characterization of the incorporation of woodchuck hepatitis virus surface antigen into hepatocyte plasma membrane in woodchuck hepatitis and in the virus-induced hepatocellular carcinoma. 253 20

There is sufficient knowledge of the biochemistry of Epstein-Barr virus (EBV) persistence and gene expression in latent growth-transforming infection and of the persistence and expression of other oncogenic viruses to permit interesting and possibly useful comparisons. Most smaller oncogenic viral genomes usually persist solely as integrated DNAs despite their ability to circularize. Papilloma and hepatitis viruses may persist as episomes, and parts of their genomes may integrate. Usually, only the oncogenic fragment of adenovirus DNA is integrated into cell DNA. In contrast, the entire EBV genome persists in cells as an episome or as integrated DNA. Thus, EBV may have novel mechanisms to maintain its complete genome as an episome or as a complete integrated virus DNA. Three viral genes are expressed in latently EBV-infected growth-transformed cells, each of which encodes one RNA and one protein. Two of the proteins are probably nuclear DNA-binding proteins; the third is probably a membrane protein. Thus, the repertoire of genes expressed is similar in complexity and intracellular distribution to that expressed by papova and adenoviruses in cellular transformation. The papova and adenovirus-transforming genes are partially analogous to retrovirus oncogenes. This similarity cannot as yet be extended to EBV. There is no homology at the DNA-sequence or protein-sequence level between EBV and other viral or cell oncogenes. Thus, it remains important to pursue analysis of the EBV-transforming genes. Identification of these genes is a first step in discerning their function in latent growth-transforming cell infection. Parts of each of these genes are being made in bacteria. The bacterial products enable us to make antisera that are specific for each of the viral proteins. These antisera can also be used to identify the viral proteins within latently infected growth-transformed cells or within cells stably expressing transfected virus genes. The antisera can also be used to study the association of Epstein-Barr nuclear antigen (EBNA) 1 and 2 with DNA and of the lymphocyte-determined membrane antigen (LYDMA) with the cell membrane. The three genes must be introduced into nontransformed cells to determine whether, alone or in combination, they are sufficient to accomplish cell growth transformation.
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PMID:Biochemistry of latent Epstein-Barr virus infection and associated cell growth transformation. 299 95

Sequences encoding the surface projection glycoprotein of the coronavirus, murine hepatitis virus (MHV), strain JHM, have been cloned into pAT153 using cDNA produced by priming with specific oligonucleotides on infected cell RNA. The regions of three clones pJMS1010, pJS112 and pJS92, which together encompass the surface protein gene have been sequenced by the chain termination method. The sequence of the primary translation product, deduced from the DNA sequence, predicts a polypeptide of 1,235 amino acids with a molecular weight of 136,600. This polypeptide displays the features characteristic of a group 1 membrane protein; an amino-terminal signal sequence and carboxy-terminal membrane and cytoplasmic domains. There are 21 potential glycosylation sites in the polypeptide and a cysteine-rich region in the vicinity of the transmembrane domain. During maturation proteolytic processing of the polypeptide occurs and at positions 624 to 628 the sequence Arg-Arg-Ala-Arg-Arg is found, which is similar to a number of basic sequences involved in the cleavage of enveloped RNA virus glycoproteins. The fusogenic properties of the MHV surface protein do not appear to correlate with a strongly hydrophobic region at the putative amino terminus of the carboxy-terminal cleavage product.
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PMID:Nucleotide sequence of the gene encoding the surface projection glycoprotein of coronavirus MHV-JHM. 302 48

Adverse drug reactions may mimic almost any kind of liver disease. Acute hepatitis is often due to the formation of reactive metabolites in the liver. Despite several protective mechanisms (epoxide hydrolases, conjugation with glutathione), this formation may lead to predictable toxic hepatitis after hugh overdoses (e.g. paracetamol), or to idiosyncratic toxic hepatitis after therapeutic doses (e.g. isoniazid). Both genetic factors (e.g. constitutive levels of cytochrome P-450 isoenzymes, or defects in protective mechanisms) and acquired factors (e.g. malnutrition, or chronic intake of alcohol or other microsomal enzyme inducers) may explain the unique susceptibility of some patients. Formation of chemically reactive metabolites may also lead to allergic hepatitis, probably through immunization against plasma membrane protein epitopes modified by the covalent binding of the reactive metabolites. This may be the mechanism for acute hepatitis produced by many drugs (e.g. amineptine, erythromycin derivatives, halothane, imipramine, isaxonine, alpha-methyldopa, tienilic acid, etc.). Genetic defects in several protective mechanisms (e.g. epoxide hydrolase, acetylation) may explain the unique susceptibility of some patients, possibly by increasing exposure to allergenic, metabolite-altered plasma membrane protein epitopes. Like toxic idiosyncratic hepatitis, allergic hepatitis occurs in a few patients only. Unlike toxic hepatitis, allergic hepatitis is frequently associated with fever, rash or other hypersensitivity manifestations; it may be hepatocellular, mixed or cholestatic; it promptly recurs after inadvertent drug rechallenge. Lysosomal phospholipidosis occurs frequently with three antianginal drugs (diethylaminoethoxyhexestrol, amiodarone and perhexiline). These cationic, amphiphilic drugs may form phospholipid-drug complexes within lysosomes. Such complexes resist phospholipases and accumulate within enlarged lysosomes, forming myeloid figures. This phospholipidosis has little clinical importance. In a few patients, however, it is associated with alcoholic-like liver lesions leading to overt liver disease and, at times, cirrhosis. Subjects with a deficiency in a particular isoenzyme of cytochrome P-450 poorly metabolize perhexiline and are at higher risk of developing liver lesions. Prolonged, drug-induced liver-cell necrosis may also lead to subacute hepatitis, chronic hepatitis or even cirrhosis. This usually occurs when the drug administration is continued, either because the liver disease remains undetected or because its drug aetiology is overlooked. Several autoantibodies may be present.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Acute and chronic drug-induced hepatitis. 304 68


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