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)

To analyse the immunological mechanism of hepatocellular injury in hepatitis B virus (HBV) infection, the immunoreactivity of HBV-encoded antigens as a target for cytotoxic T lymphocyte (CTL) response was examined using recombinant vaccinia virus (RVV) expressing surface protein (S), precore/core protein (PC), and core protein (C) of HBV. C3H/He mice (H-2k) were inoculated with each RVV. Their spleen cells were then harvested and stimulated in vitro with the histocompatible transfectant, which stably expressed hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and hepatitis B core antigen (HBcAg), and used as effectors. As the targets, L cells (H-2k) infected with individual RVV were used. Cytotoxic test was performed with various combinations and ratios of effectors and targets. The reactivity of PC-primed effectors against PC-expressing targets was greatest with 71.4% specific lysis on average at an effector/target ratio of 12.5:1 among all the combinations. C-primed effectors against C-expressing target also revealed rather high cytotoxicity (specific lysis, 40.6% at an E/T ratio of 12.5:1). Furthermore, PC-primed and C-primed effectors showed a cross-reactivity to the targets expressing other nucleocapsid antigen, respectively. S-primed effectors showed less lytic activity against S-expressing targets (specific lysis, 18.4% at an E/T ratio of 12.5:1). The CTL responses were blocked by anti-CD8 and anti-major histocompatibility complex (MHC) class I antibodies, but not by anti-CD4 or anti-MHC class II. These findings suggest that endogenously synthesized nucleocapsid antigen, especially PC, is a dominant target for the MHC class I-restricted CTL in H-2k mice and that this system may work as an efficient model to study immunopathogenesis of HBV infection.
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PMID:Relative immunogenicity of hepatitis B virus-encoded antigens as targets for cytotoxic T-cell response. 826 60

Immunization with soluble proteins only rarely induces a specific response of CD8+ CTL. We describe experiments that demonstrate the efficient and specific in vivo priming of CTL in BALB/c mice immunized with soluble hepatitis B virus (HBV)-derived surface (S) protein. A single (s.c., i.p. or i.v.) injection of a low dose (30 ng to 3 micrograms per mouse) of recombinant S protein particles without adjuvants induced a CTL response. This specific cytotoxic response was read out against a panel of different S protein-expressing transfected mouse cell lines. Effector cells of this response were Ld-restricted, CD3+ CD4- CD8+ CTL. H-2d/Ld+ (BALB/c, C.B-17) mice were responders; H-2d/Ld- (dm2) mutant mice and H-2b (C57BL/6) mice were nonresponders. Injections of various dosages of a S protein-derived, immunogenic, synthetic peptide into BALB/c mice by various routes did not prime CTL. After incorporation of S protein particles into IFA or aluminum hydroxide, these protein Ag lost their ability to specifically stimulate CTL in vivo. After priming of mice with S protein emulsified in IFA or adsorbed to aluminum hydroxide boost injections with native S protein particles were inefficient in stimulating a specific CTL response. These findings are of relevance for the design of synthetic subunit vaccines for which specific stimulation of CD8+ T effector functions is desired.
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PMID:Immunization with soluble hepatitis B virus surface protein elicits murine H-2 class I-restricted CD8+ cytotoxic T lymphocyte responses in vivo. 830 Nov 20

In this pilot study of the effects of interferon alfa in 10 anti-HIV positive, chronic hepatitis B patients treated with zidovudine (AZT), tolerance to interferon was good and similar to that in anti-HIV negative patients. After treatment, the HIV stage and CD4 lymphocyte count were unchanged. In two patients hepatitis B virus (HBV)-DNA and hepatitis B e antigen (HBeAg) disappeared and the serum alanine aminotransferase (ALT) returned to normal; loss of hepatitis B surface antigen (HBsAg) with absence of histopathological activity was observed after treatment in one of these patients. These preliminary results need to be confirmed by a larger study.
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PMID:Recombinant alpha interferon for chronic hepatitis B in anti-HIV positive patients receiving zidovudine. 831 71

Results are reported for a small study of 11 patients positive for HIV and with chronic active viral hepatitis. Low dose zidovudine/interferon alfa-2b combined treatment produced a general reduction in alanine aminotransferase activities and increased the CD4 lymphocyte count, hepatitis B e seroconversion, and the loss of HIV p24 antigen. The treatment was well tolerated and progression of HIV disease was not seen.
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PMID:Zidovudine plus interferon alfa-2b treatment in patients with HIV and chronic active viral hepatitis. 831 72

We previously developed a method for introducing foreign genes into liver tissue using liposomes with incorporated hemagglutinating virus of Japan (HVJ, Sendai virus), and found that liver cells transfected with the E. coli beta-galactosidase gene or the gene for hepatitis B virus (HBV) surface protein (HBsAg) expressed these proteins in vivo. Here, we analyzed cellular reactions leading to hepatitis in the liver by expressing the genes of HBV in vivo. Lymphocytes were eluted directly from liver transfected with the HBsAg genes and shown to be cytotoxic only to cells expressing HBsAg in vitro. These lymphocytes were identified as cytotoxic T lymphocytes with the CD4- CD8+ phenotype. Transfer of these lymphocytes to transgenic mice with the whole HBV genome led to elevation of the serum glutamic-pyruvic transaminase (SGPT) level, indicating the induction of hepatitis due to the cytotoxic T lymphocytes in vivo. Similarly, direct transfer of the gene for the HBV secretory core protein (HBeAg) induced expression of HBeAg in hepatocytes and the appearance of antibody against HBeAg in the serum. However, using this system, we found that the lymphocytes infiltrating the transfected liver showed no cytotoxicity specific for HBeAg. These results indicate that expression of HBsAg, one of the components of virions, in animal liver induced hepatitis efficiently through generation of specific cytotoxic T lymphocytes (CTL) without any expression of the other viral components. This in vivo experimental system should be useful for evaluating how expression of a given gene induces cellular reactions and intrinsic functions in the living body.
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PMID:Use of the hemagglutinating virus of Japan (HVJ)-liposome method for analysis of infiltrating lymphocytes induced by hepatitis B virus gene expression in liver tissue. 839 62

"Zhuling-duotang (a polysaccharide preparation of the Chinese traditional herb medicine polyporusum bellatus) and hepatitis B vaccine (HB vaccine)" and "Persantin and bacillus calmeteguerin (BCG)" have been used to treat chronic hepatitis B. To elucidate their therapeutic mechanism, we studied the effects of zhuling-duotang, HB vaccine and BCG on immunoactivities of nomal human peripheral blood mononuclear cells (PBMCs). Cytotoxicity of PBMCs incubated with such drugs against target cells K562, HepG2 or 2.2.15 was detected by using 3H-TdR release assay. IL-2 and IFN-gamma activities of the supernatant were assayed. Immunofluorescent analysis of molecular CD4, CD8, CD16, IL-2R on the surface of PBMCs were done. The results showed that: (1) Zhuling-duotang and BCG could significantly increase the cytotoxicity of PBMCs. They could induce PBMCs to produce IL-2 but not IFN-gamma. They also could stimulate PBMCs to express IL-2R. Zhuling-duotang and BCG did not affect the percentage of CD4+, CD8+, CD16+ cells among PBMCs. (2) HB vaccine did not significantly increase the cytotoxicity of PBMCs. (3) The cytotoxicity of PBMCs induced by Zhuling-duotang combined with HB vaccine was not significantly higher than that of PBMCs induced by Zhuling-duotang alone.
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PMID:[The effects of zhuling-duotang, hepatitis B vaccine and bacillus Calmette-Guerin on immunoactivities of peripheral blood mononuclear cells: an in vitro research]. 858 87

The serum Ab response and the class I-restricted CTL response of C57BL/6 (H-2b) mice to hepatitis B (pre)core Ag (HBcAg, HBeAg) was studied. Injection of HBcAg particles without adjuvants into mice efficiently primed serum Ab responses but not CTL response. We constructed the expression plasmids pCMV-1/c and pCMV-1/e in which expression of HBcAg or HBeAg was driven by cytomegalovirus immediate early region promoter sequences. Stable murine RBL5/C transfectant lines expressing HBcAg were established. Intramuscular DNA immunization with plasmid pCMV-1/c (encoding intracellularly expressed core Ag) or pCMV-1/e (encoding secreted precore Ag) efficiently primed specific serum Ab responses and CTL responses. The CTL response elicited in this system was mediated by CD4-CD8+ effector cells primed in vivo. The CTL recognized the HBcAg93-100 8-mer peptide MGLKFRQL in the context of Kb. Hence, DNA immunization with HBcAg/HBeAg-expressing plasmids, but not immunization with exogenous HBcAg particles, elicits a class I-restricted CTL response of defined epitope/restriction specificity in H-2b mice.
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PMID:DNA immunization induces antibody and cytotoxic T cell responses to hepatitis B core antigen in H-2b mice. 862 3

Immune responses provoked by human immunodeficiency virus (HIV) infection ultimately are insufficient to control the disease and do not include strong lymphocyte-proliferative responses to HIV antigens or antibodies to many viral epitopes. A randomized double-blind, placebo-controlled trial evaluated the immunogenicity of recombinant HIV envelope vaccine (rgp160) in HIV-infected subjects with > or = 400/mm3 CD4 T cells. Controls received hepatitis B vaccine. Of subjects receiving rgp160, 98% developed lymphocyte-proliferative responses to the immunogen, 33% to a different envelope protein, and 56% and 60% to p24 and p66, respectively. All doses of vaccine (20, 80, 320, 1280 microgram) induced new responses. New antibodies to epitopes on rgp160 developed only in recipients of higher doses of rgp160. CD4 T cell percentages declined less rapidly in recipients of rgp160 than in controls. Vaccination of HIV-infected subjects with rgp160 results in cellular and humoral immune responses to HIV that infection itself had not stimulated.
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PMID:A randomized, placebo-controlled study of the immunogenicity of human immunodeficiency virus (HIV) rgp160 vaccine in HIV-infected subjects with > or = 400/mm3 CD4 T lymphocytes (AIDS Clinical Trials Group Protocol 137). 864 5

Nucleocapsid assembly in hepadnavirus replication requires selective encapsidation of the pregenomic RNA template and the viral polymerase by the core proteins. It has been shown that an encapsidation signal located at the 5' end of the pregenomic RNA is responsible for its interaction with the polymerase. In the present study, we have shown that a region located at the 3' periphery of the core open reading frame may interact with the viral polymerase in duck hepatitis B virus. By using an in vitro rabbit reticulocyte lysate translation system, we found that interaction of the polymerase with this region resulted in selective suppression of core mRNA translation. Insertion of this putative inhibitory sequence into the CD4 gene also led to a selective inhibition of CD4 mRNA translation in the presence of polymerase. Specific inhibition of core protein synthesis was observed in a chicken hepatoma cell line (LMH) cotransfected with core and polymerase plasmid DNA.
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PMID:Duck hepatitis B virus polymerase acts as a suppressor of core protein translation. 876 10

Twenty-four patients with moderately controlled insulin dependent diabetes with a duration of diabetes ranging from 2 to 10 years as well as 17 control subjects were vaccinated against hepatitis B virus using Gen Hevac B vaccine. The vaccine was injected 0.5 mL intramuscularly into the deltoid region on three separate occasions at intervals of 1 month. If subjects were still negative for anti-hepatitis B surface antigen (HBs) or had inadequate antibody after the third injection, a fourth administration of vaccine was given 3 months later. The mean anti-HBs titer was 243.3 +/- 97.2 mi.u./mL in control subjects and 39.8 +/- 53.2 in diabetic patients (P < 0.001). In the control group optimal protection was obtained in 100% of subjects, whereas 11 diabetic patients (45.8%) had low anti-HBs titer (< 10 mi.u./mL). All of 11 diabetic patients showed adequate (> 10 mi.u./mL) anti-HBs titer after the fourth dose of vaccine. In diabetic patients the most striking feature was the reduced CD4/CD8 ratio which was significantly lower (P < 0.001) than that of the control group. We conclude that diabetic children have an impaired immune response to hepatitis B vaccine. It is suggested that diabetic children should be vaccinated against hepatitis B virus with four injections instead of three.
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PMID:Reduced immune response to hepatitis B vaccine in children with insulin dependent diabetes. 877 51


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