Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The coding region for the hepatitis B virus surface antigens contains three in-phase ATG codons which direct the synthesis of three related polypeptides. The 24-kilodalton major surface (or S) glycoprotein is initiated at the most distal ATG and is a transmembrane protein whose translocation across the bilayer is mediated by at least two uncleaved signal sequences. The product of the next upstream ATG is the 31-kilodalton pre-S2 protein, which contains 55 additional amino acids attached to the N terminus of the S protein. This pre-S2-specific domain is translocated into the endoplasmic reticulum. Using a coupled in vitro translation-translocation system, we showed that (i) the pre-S2 domain itself lacks functional signal sequence activity, (ii) its translocation across the endoplasmic reticulum membrane is mediated by downstream signals within the S domain, and (iii) the N-terminal signal sequence of the S protein can translocate upstream protein domains in the absence of other signals. The hepatitis B virus pre-S2 protein is an example of a natural protein which displays upstream domain translocation, a phenomenon whose existence was originally inferred from the behavior of synthetic fusion proteins in vitro.
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PMID:The N-terminal (pre-S2) domain of a hepatitis B virus surface glycoprotein is translocated across membranes by downstream signal sequences. 230 50

By using a preparation of inactivated rabies virus, the blood mononuclear cells from five rabies vaccine recipients were stimulated in vitro in the presence of interleukin 2. T cell lines that displayed significant proliferative responses to whole rabies virus and to preparations of rabies glycoprotein and nucleocapsid were obtained from all the individuals. Other antigens, such as diphtheria and tetanus toxoids, influenza A virus, hepatitis B surface antigen, and serum albumin, failed to induce the proliferation of the T cell lines. One of these rabies-specific T cell lines was found to proliferate in response to rabies antigens only when the antigen-presenting cells expressed homologous HLA-DR antigens. The use of mouse monoclonal antibodies specific for human T cell surface markers revealed that most of the cells of these rabies-reactive lines were of the helper/inducer class of T lymphocytes. Stimulation of the T cell lines with the rabies antigens induced the production of interferon-gamma, a lymphokine with potent antiviral activity. Several T cell clones were isolated from two of these cell lines, and most of them appeared to be specific for the antigenic components of the viral nucleocapsid. Two T cell clones specific for the rabies glycoprotein were also isolated from one of these lymphocyte interleukin 2-dependent lines. Further in vitro studies with rabies-specific T cells could help us to understand in more depth the role of regulatory T cells in the human immune response to rabies virus.
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PMID:Isolation and characterization of human T cell lines and clones reactive to rabies virus: antigen specificity and production of interferon-gamma. 241 20

A hybrid cell line producing monoclonal antibodies recognizing an epitope encoded by the pre-(S)2 region of hepatitis B virus (HBV) genome was obtained by fusion of mouse myeloma cells with lymphocytes from mice immunized with HBV. The monoclonal antibody Mo-F124 secreted from the hybrid line reacted with the pre-S(2) epitope expressed on the surface of both viral and recombinant HBsAg particles--pre-S(2) and S gene product--localised on 34 kD glycoprotein of the viral envelope. The pre-S(2) epitope was sensitive to digestion with V8 protease from Staphylococcus aureus. The enzyme abolished reactivity with Mo-F124 and polymerized human serum albumin (pHSA) binding activity of recombinant particles. Mo-F124 antibody was used to develop highly sensitive radioimmunoassays for determination of pre-S(2) epitope and anti-pre-S(2) antibody in sera of hepatitis B patients. Detection of a pre-S(2) epitope by the monoclonal antibody-based assay in the early phase of acute HBV infection correlated well with the presence of markers of active viral replication (HBeAg, HBV DNA). The appearance of anti-pre-S(2) antibody, usually in the third month after onset of symptoms, was followed by elimination of circulating HBsAg and seroconversion to anti-HBs in all tested cases of uncomplicated acute hepatitis followed by recovery. Anti-pre-S(2) response was not observed in patients with chronic hepatitis B or acute HBV infection progressing to chronic disease. The observed correlation of anti-pre-S(2) response with recovery suggests that the pre-S(2) epitope may represent one of the epitopes inducing antibodies that neutralize the hepatitis B virus.
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PMID:Monoclonal antibody recognizing pre-S(2) epitope of hepatitis B virus: characterization of pre-S(2) epitope and anti-pre-S(2) antibody. 243 50

Serum levels of alpha 1-antitrypsin (alpha 1-AT) and alpha 2-macroglobulin (alpha 2-M) and, as controls, alpha 1-acid glycoprotein (alpha 1-AG) and haptoglobin were evaluated by means of laser nephelometry in 17 patients with acute viral hepatitis (AVH) type A, 16 with AVH-B, 12 with AVH-NANB and 8 with fulminant hepatitis B. On admission, alpha 1-AT levels were elevated in one third of AVH-A and AVH-B cases, but subsequently declined; alpha 2-M levels were elevated in about 40% of AVH-B patients during the 2nd, 3rd and 4th week after admission. No significant correlation was found between elevated levels of protease inhibitors and aminotransferase values or drug addiction and delta coinfection. alpha 1-acid glycoprotein and haptoglobin levels were always normal or low. Protease inhibitors did not show any elevation in fulminant hepatitis, while changes were found only in a few patients with AVH-NANB. Thus, no clearcut pattern of changes in protease inhibitors has been found in association with each type of hepatitis, although alpha 1-AT and alpha 2-M elevations are mainly found in AVH-B.
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PMID:Serum protease inhibitors in acute viral hepatitis. 243 42

Highly purified woodchuck hepatocyte plasma membranes demonstrated tight specific binding to glutaraldehyde-polymerized serum albumin immobilized on Sepharose macrobeads. This phenomenon was characterized in detail and used for recognition of the plasma membrane constituents involved in binding of the albumin polymer. The hepatocyte membrane-polyalbumin interaction was found to be ligand-specific, saturable, and time-dependent. Other characteristics of a specific receptor-ligand interaction were also noted, including a dependence on the temperature, pH, and ionic strength of the binding medium. Kinetic studies revealed the presence of two classes of binding sites for glutaraldehyde-polymerized albumin on purified membranes. The sites mediating the saturable high-affinity binding of polymer to hepatocyte membranes could not be solubilized by Triton X-100. Binding activity of Triton-insoluble membrane residues was inhibited by heat treatment and proteolysis, and was significantly suppressed by neuroaminidase digestion. These findings suggest a glycoprotein nature for the high-affinity binding sites and indicate that the corresponding receptors apparently are tightly associated with the plasma membrane matrix. In contrast, low-affinity binding of polymeric albumin was inhibited by both Triton X-100 and pronase, was resistant to neuraminidase, and was activated by lipase, suggesting that membrane lipids are important for the binding conduct. In conclusion, these results provide clear evidence that hepatocyte plasma membranes are endowed with at least two classes of chemically distinct binding components, which are able to specifically recognize serum albumin artificially modified by glutaraldehyde treatment. Therefore, they suggest that in vivo hepatocytes may perform a specific receptor-dependent uptake of ligands expressing glutaraldehyde-polymerized albumin specificity. This phenomenon may play an important role in the proposed participation of naturally modified human serum albumin as a bridge in the attachment and penetration into host hepatocyte of hepatitis B virus, which is known to possess a receptor that is specific for glutaraldehyde-cross-linked human serum albumin.
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PMID:Characterization of the binding sites for glutaraldehyde-polymerized albumin on purified woodchuck hepatocyte plasma membranes. 249 21

Serum pregnancy-associated alpha 2-glycoprotein (alpha 2-PAG) levels were evaluated in a follow-up study of patients with hepatitis B virus (HBV) infection and compared with biochemical and virological parameters. In a study of 25 patients with acute hepatitis, an association was found between high alpha 2-PAG values, ALT levels, and HBsAg in 20 patients (80%) (P less than 0.05), 18 recovered completely, and 2 had a protracted course. In five patients serum alpha 2-PAG levels were similar to those in the control group. On the other hand, eight (100%) chronic persistent HBV patients showed high levels of alpha 2-PAG (P less than 0.05) during the study period, and these levels correlated well with inflammatory activity and failure of HBsAg elimination. There were no significant differences in alpha 2-PAG values between asymptomatic HBsAg carriers and controls. Serial analysis of alpha 2-PAG, in correlation with viral markers, biochemical parameters, and histological data, would contribute to the ability to predict the final outcome of HBV infection.
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PMID:Serum pregnancy-associated alpha 2-glycoprotein levels in the evolution of hepatitis B virus infection. 252 83

The preS1 surface glycoprotein of hepatitis B virus is targeted to the endoplasmic reticulum (ER) and is retained in this organelle when expressed in the absence of other viral gene products. The protein is also acylated at its N terminus with myristic acid. Sequences responsible for its ER retention have been identified through examination of mutants bearing lesions in the preS1 coding region. These studies reveal that such sequences map to the N terminus of the molecule, between residues 6 and 19. Molecules in which this region was present remained in the ER; those in which it had been deleted were secreted from the cell. Although all deletions which allowed efficient secretion also impaired acylation of the polypeptide, myristylation alone was not sufficient for ER retention: point mutations which eliminated myristylation did not lead to secretion. These data indicate that an essential element for ER retention resides in a 14-amino-acid sequence that is unrelated to previously described ER retention signals.
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PMID:Novel N-terminal amino acid sequence required for retention of a hepatitis B virus glycoprotein in the endoplasmic reticulum. 258 18

Eight liver biopsy specimens from five patients with PAS-negative intracisternal hyalin were investigated by immunofluorescence for: (1) immunoglobulins (Ig) G, A, M, D, E; (2) light chains (kappa and lambda); (3) complement components C1q, C4, C3c, C5, C9; (4) C1-inactivator; (5) C3-activator; (6) alpha 1-antitrypsin; (7) alpha 1-antichymotrypsin; (8) plasminogen; (9) fibrinogen; (10) fibrinogen breakdown products D and E; (11) fibronectin; (12) prealbumin; (13) albumin; (14) betalipoprotein; (15) apolipoprotein; (16) alpha 1- and alpha 2-glycoprotein; (17) cholinesterase; (18) ceruloplasmin; (19) haemopexin; (20) myoglobin; (21) placenta lactogen; (22) transferrin; (23) actin; (24) myosin; (25) cathepsin D; and (26) hepatitis B surface and core antigens (HBsAg and HBcAg). The globules reacted significantly with antisera against C3c (three patients), C4 (three patients), C3-activator (one patient) and fibrinogen (two patients). The cause of the protein accumulation is not clear. Serial studies indicate the possibility of a disturbance of protein secretion and an as yet unidentified immune complex disorder.
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PMID:Immunohistological investigations of PAS-negative globular intracisternal hyalin in human liver biopsy specimens. 285 88

Carcinogenic viruses have been discovered in numerous animal species over the last 80 years but their role in human cancer has only recently become an important issue. With EB virus involved with endemic Burkitt's lymphoma and undifferentiated nasopharyngeal carcinoma, hepatitis B virus with primary liver cancer, papilloma viruses with carcinoma of the cervix, and T-cell leukaemia virus with adult T leukaemia, 20-25% of all human cancer appears to have a virus component in its causation. By analogy with certain virus-induced animal cancers, vaccine prevention of infection should greatly reduce subsequent tumour development; vaccines against hepatitis B virus are already on trial for this purpose in populations at risk. Experiments are described in which an EB virus subunit vaccine consisting of the virus-determined membrane antigen glycoprotein molecule of molecular mass 340 kDa (MA gp340) has been prepared by two purification methods. Material from one of these has successfully protected cotton-top tamarins against a 100% lymphomagenic dose of challenge virus and investigations are under way to identify an immunogen, based on MA gp340, suitable for use in man. Genetically engineered bacterial, yeast, and mammalian cells expressing the gp340 gene are already available; this gene has also been inserted into vaccinia and varicella virus vectors. Powerful new adjuvants are also considered, together with future strategies for human vaccine studies.
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PMID:The Florey lecture, 1986. Vaccine prevention of virus-induced human cancers. 288 67

A glycoprotein was isolated and purified to homogeneity from the serum of a patient with chronic non-A, non-B hepatitis. NaDodSO4/PAGE of the glycoprotein revealed a single major band at Mr approximately 77,000. Antibodies to this glycoprotein were shown to possess the following immunoreactivity: (i) they reacted by radioimmunoassay with sera obtained at the time of diagnosis from 17 of 42 patients with non-A, non-B hepatitis and with only 2 of 58 sera from either matched controls or patients with hepatitis A or hepatitis B, (ii) they reacted with sucrose gradient fractions from a proven infectious non-A, non-B hepatitis serum at a peak density of 1.14 g/ml and in the soluble protein fractions on top of the gradient, and (iii) they reacted in ELISA with disrupted human T-cell lymphocytotropic virus type III (HTLV-III), and (iv) they reacted in immunoblots with a protein of Mr 74,000 derived from HTLV-III.
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PMID:A glycoprotein associated with the non-A, non-B hepatitis agent(s): isolation and immunoreactivity. 299


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