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 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

In Brazil, clinicians followed 32 transfusion-dependent beta-thalassemia patients, 1-49 years old, at the Regional Blood Center and the Department of Hematology of University Hospital of the School of Medicine of Ribeirao Preto to determine the prevalence of hepatitis B virus (HBV), hepatitis C virus (HCV), HIV-1, and HTLV-1. They also measured serum levels of ferritin and alanine aspartate transaminase (ALAT) to examine liver iron content and liver damage, respectively. 46.8% tested positive for antibodies to HCV, which was much higher than that of voluntary blood donors of the Regional Blood Center (1.4%) or of other countries. Yet it was about the same as that of multitransfused patients in the UK (23.2%), Italy (92.9%), and Saudi Arabia (33.3%). 3 of these 15 patients also tested positive for HBV markers. 15.5% tested positive only for HBV markers. 37.5% had no hepatitis markers. Hepatitis-positive people were older than those who tested negative for hepatitis (15.2 years vs. 8.5 years; p .05). The number of units of blood transfused and the levels of ferritin and ALAT were not statistically different between the 2 groups (192.1-336 vs. 135.2 and 36.6-52.3 U/l vs. 36.7 U/l, respectively). 75% of the HCV positive patients received more than 100 units of packed red blood cells while only 42% did in the HCV negative group. 2 people tested positive for HIV-1 1 of whom also tested positive for anti-HBs-Ag and the other for HCV antibodies. The HIV-1 cases had become infected before the blood bank began screening for HIV-1 in 1987. None of the patients receiving blood from the center became infected with HIV-1, yet 60% of hemophiliacs treated at the hospital were HIV-1 infected. No one tested positive for HTLV-1, even though all 32 patients had received more than 6250 units of blood not screened for HTLV-1. This reflected the low incidence of HTLV-1 in the general population (0.05%). No one was positive for HBs-Ag or HBe-Ag.
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PMID:The frequency of blood-born viral infections in a population of multitransfused Brazilian patients. 827 57

Hepatitis C virus (HCV) is responsible for most cases of chronic non-A, non-B hepatitis in multi-transfused children, but has been also implicated in at least one third of cases without history of parenteral exposure. We have recently evaluated the natural history of chronic hepatitis C in 37 children without underlying systemic diseases. None of the patients had a history of acute hepatitis and only 22 were symptomatic at presentation. Liver histology was consistent with active liver disease of mild to moderate activity in 42% of cases (one child had cirrhosis) and with persistent or lobular hepatitis in the remaining cases. During a mean follow-up period of 3.4 +/- 3.2 years symptoms were rarely observed and none of the patients developed liver failure, but 97% maintained abnormal alanine-aminotransferase levels. These results suggest that chronic hepatitis C in children, at least in its early stage, is a mild disease infrequently associated with severe liver lesions; however the persistence of liver damage over the years raises questions about the long-term outcome of the illness and about the rationale of antiviral therapy.
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PMID:Hepatitis C in childhood: epidemiological and clinical aspects. 837 55

A cDNA copy of the murine coronavirus [otherwise known as murine hepatitis virus (MHV)] surface (S) glycoprotein gene was isolated and expressed in DBT cells by using a recombinant vaccinia virus system. The expressed S protein induced extensive syncytium formation at neutral pH. Oligonucleotide mutagenesis was used to engineer an S protein gene in which codons for the proteolytic cleavage site, Arg-Arg-Ala-Arg-Arg, were replaced with an equal number of codons for amino acids with aliphatic or aliphatic hydroxyl side-chains. The mutated S protein was stably expressed in DBT cells and, in contrast to the wild-type protein, was not proteolytically cleaved. Nevertheless, the non-cleaved protein induced extensive syncytium formation. 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 fusion activity.
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PMID:Proteolytic cleavage of the murine coronavirus surface glycoprotein is not required for fusion activity. 838 59

We conducted a prospective, descriptive cohort study of all 217 cases of acute viral hepatitis (AVH) seen in adults during 1992 at the sole hospitals with infectious disease departments in the second and third largest cities in the Kingdom of Saudi Arabia. In addition, we undertook a nested case-control study. Our goals were (1) to determine the causes, demographics, risk factors, and clinical characteristics of AVH in the Kingdom; (2) to evaluate the reliability of diagnostic tests for acute hepatitis C and E; and (3) to assess the relative importance, characteristics, and risk factors of a sixth hepatitis agent, non-A-E. All cases and controls completed a questionnaire. Cases provided blood samples for studies of serum bilirubin, alanine and aspartate aminotransferases, and antibody to hepatitis viruses as well as genome detection studies. The results of serological and molecular tests were used to categorize each case as hepatitis A, B, C, D, E, or non-A-E. Historical, clinical, and laboratory determinants were statistically analyzed by comparisons between groups with different types of AVH and controls. Analysis of risk factors suggested that hepatitis C and D were parenterally transmitted, while hepatitis A, E, and non-A-E were not; the route of transmission of hepatitis B was unclear. Hepatitis E was strongly associated with living or traveling on the Indian subcontinent. The clinical disease caused by all six agents was indistinguishable. The putative sixth agent caused 13% of cases. The second-generation tests for antibody to HCV and HEV were relatively reliable for the diagnosis of AVH.
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PMID:Acute viral hepatitis in Saudi Arabia: seroepidemiological analysis, risk factors, clinical manifestations, and evidence for a sixth hepatitis agent. 852 54

We examined 95 ground squirrels to compare the histological appearance of liver sections from animals that were chronically infected with ground squirrel hepatitis virus (GSHV) (n = 29), uninfected (n = 42), or had recovered from infection (n = 24). We studied the effects of long-term infection because these animals had been infected with GSHV for up to 10 years. Chronic infection generally produced a mild, persistent hepatitis characterized by light lymphocytic and plasmacytic portal infiltrates with occasional individual necrotic hepatocytes and small aggregates of Kupffer cells or mononuclear inflammatory cells in the parenchyma. In a few of the portal tracts from each of the more inflamed livers (grade 2), the inflammatory infiltrate penetrated the limiting plate and extended into the adjacent parenchyma. Hepatitis (grades 1 or 2) was detected more often in chronically infected animals (17 of 29) than in recovered (4 of 24) or uninfected ground squirrels (7 of 42). Fibrosis was generally not increased, but fine strands of collagen extended from the portal tracts and central veins into the parenchyma of about one quarter of the infected and recovered animals. Cytoplasmic pigment accumulation and variation in the size of hepatocyte nuclei appeared to be related to aging, not infection. Serum levels of aspartate and alanine transaminases (AST and ALT) were mildly elevated in samples from seven infected animals compared with seven control animals. Despite many years of chronic infection, liver injury was similar to that reported in previous studies on animals infected for shorter intervals, indicating that liver injury is not progressive in GSHV-infected ground squirrels.
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PMID:Non-neoplastic liver disease associated with chronic ground squirrel hepatitis virus infection. 867 46

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.
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PMID:A hydrophobic heptad repeat of the core protein of woodchuck hepatitis virus is required for capsid assembly. 879 54

CD8+ CTL responses constitute a critical component for vaccines developed to eliminate intracellular pathogens. One approach to achieve broad CTL diversity is based on genetically linking immunogenic peptides from multiple proteins to form poly-epitope Ags. To address the influence of flanking residues on class I Ag presentation, H-2d-restricted HIV-1 and mouse hepatitis virus CTL epitopes were linked via various spacer residues. The resulting 20 to 31 amino acid peptides were expressed using recombinant vaccinia viruses to monitor both CTL recognition and induction. Our data indicate that recognition is profoundly influenced by the nature of intervening residues forming carboxyl-terminal flanks for one and amino-terminal flanks for the other epitope. Flanking amino acids with aromatic (tyrosine), basic (lysine), and small aliphatic side chains (alanine) supported efficient CTL recognition of both epitopes. By contrast, acidic and helix breaking residues (glycine, proline) specifically inhibited recognition of the adjacent amino-terminal epitope. Flanking residues inhibitory for recognition were also detrimental for CTL induction, suggesting similar processing mechanisms in vitro and in vivo. The ratios of peptide-specific CTL precursors primed by the tandem epitopes varied up to 50-fold depending on molecular context. These data demonstrate a substantial role of carboxyl-flanking residues in governing the efficiency of class I Ag presentation both in vitro and in vivo. The dramatic influence of flanking residues on the hierarchy of CTL responses indicates that CTL induction by poly-epitope Ags can be optimized by strategically linking epitopes via selection of appropriate spacer residues.
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PMID:Flanking residues alter antigenicity and immunogenicity of multi-unit CTL epitopes. 887 18

When administered with D-galactosamine, lipopolysaccharide endotoxins produce a good experimental animal model of hepatitis. This galactosamine plus endotoxin model has been used widely, but the acute effect of this fixed combination of two chemicals on hepatic and extrahepatic biotransformation has not been determined. Therefore, either 2 or 4 hr after a single intraperitoneal dose of 300 mg/kg galactosamine plus 30 micrograms/kg lipopolysaccharide was administered, serum, liver, kidney, intestine, and spleen were collected. Serum enzymes (alanine and aspartate aminotransferases, sorbitol dehydrogenase, and gamma-glutamyltranspeptidase) were elevated dramatically 2 and 4 hr after treatment. Cytochrome P450 monooxygenase activity toward benzo-[a]pyrene was increased in kidney 4 hr after treatment, whereas dealkylation of 7-methoxycoumarin or 7-ethoxyresorufin was unchanged in any tissue at either time point. An increase in UDP-glucuronosyltransferase activity toward 4-methylumbelliferone and 4-hydroxybiphenyl was noted in the intestine. Conjugation of 1-chloro-2,4-dinitrobenzene with glutathione was increased in intestine and spleen 2 hr after treatment. gamma-Glutamyltranspeptidase activity was unaltered in all tissues studied. Reduced glutathione concentrations were increased significantly by different amounts depending on which organs were studied 2 or 4 hr after treatment. These results indicate that galactosamine/lipopolysaccharide-induced liver injury is not accompanied by major effects on the examined biotransformation reactions.
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PMID:Minimal effect of acute experimental hepatitis induced by lipopolysaccharide/D-galactosamine on biotransformation in rats. 895 52

Ten muskrats (Ondatra zibethicus) each were infected with 17,000 eggs (long-term study) and eight muskrats each were infected with 8,000 eggs (short-term study) of Capillaria hepatica (Nematoda). Food intake, body weight, and selected clinicopathological parameters were measured every 2 days for 28 days in the short-term study and every 14 days for 184 days in the long-term study. Muskrats in the short-term study had moderate to severe necrotizing granulomatous hepatitis associated with mild anorexia and weight loss, varying degrees of leukocytosis with eosinophilia and elevation of serum alanine and aspartate aminotransferases. No significant changes in packed cell volume, hemoglobin, total plasma protein, albumin, blood urea nitrogen, bilirubin, lactate dehydrogenase or alkaline phosphatase were found among animals from the short-term study. Muskrats in the long-term study had severe necrotizing granulomatous hepatitis associated with marked anorexia, weight loss and 60% mortality over 39 days post-inoculation (PI); animals that survived for 184 days did not return to pre-inoculation body weights despite returning to normal food intake. Hepatic lesions at 184 days PI consisted of minimal to severe liver replacement by C. hepatica eggs. No statistically significant differences in values of clinical parameters between inoculated animals and a non-inoculated control group from the long term study were found.
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PMID:Clinicopathological features and histopathology of experimental hepatic capillariasis in muskrats (Ondatra zibethicus). 902 99


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