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)

LZ-8, a new and recently discovered immunomodulator from Ganoderma lucidum, has been shown to have immunosuppressive activity in vivo and to be a member of the immunoglobulin superfamily. In this paper we examined the in vivo effect of LZ-8 on antibody production using the hepatitis B surface antigen (HBs Ag) in mice. LZ-8 had mitogenic activity in vitro towards spleen cells of C57BL/10 (B10) and C57BL/10BR (B10BR) as previously shown towards those of DBA/2 mice. B10 and B10BR mice produced anti-HBs Ag antibody by the twice sensitization of the antigen while intraperitoneal administration of LZ-8 twice weekly into the mice (8 and 12 mg/kg) greatly prevented the production of antibody to HBs Ag (83.3-96.8% inhibition). We further examined the effect of LZ-8 administration on mitogen responsibility of spleen cells and on the T-cell subset population in both the spleen and lymph node but no significant differences were observed between the LZ-8 treated and untreated mice. These results suggest that the immunosuppressive activities of LZ-8, previously shown, such as the prevention of systemic anaphylaxis and the Arthus reactions, were caused by the blocking of antigen-specific antibody production.
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PMID:Immunomodulator, LZ-8, prevents antibody production in mice. 181 48

Proteins of the HBV envelope (env) are coded for by two adjacent regions of the HBV env gene: the pre-S and S regions. Antigenic determinants corresponding to amino acid sequences of both regions are recognized by human antibodies and are important in virus-neutralizing responses. Protective immune responses to HBV appear to be linked to the major HLA histocompatibility complex. Inbred and congenic strains of mice represent a model system relevant for studies on the genetic control of immune responsiveness of humans to HBV envelope proteins. Such mouse strains were ranked according to their antibody response to the S protein and divided into high [d,q], intermediate [a,k,b], and low [s] responders (letters in brackets indicate H-2 haplotype.) Selected pre-S antigenic determinants can be mimicked with high fidelity by synthetic peptide analogues that are immunogenic without any carriers. Thus it is possible to study directly the genetic control of immune responsiveness to pre-S epitopes mimicked by these peptides without having to consider the influence of carriers or of S protein. The results presented here show that inbred mouse strains can be ranked according to their antibody responses to the synthetic peptide pre-S(120-145) as follows: A/J[a] approximately equal to SWR/J[q] greater than C57BL/6J[b] approximately equal to AKR/J[k] approximately equal to SJL/J[s] much greater than DBA/2J[d] greater than BALB/cJ[d]. Only SJL/J[s] mice responded well to another synthetic peptide pre-S (12-32). Thus, H-2-linked genes regulating the immune response to S protein and to epitopes on pre-S-coded sequences are distinct. Anti-pre-S(120-145) responses in S protein-nonresponders circumvent this nonresponsiveness. This should be considered in the design of hepatitis B vaccines.
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PMID:Genetic restriction of immune responsiveness to synthetic peptides corresponding to sequences in the pre-S region of the hepatitis B virus (HBV) envelope gene. 405 55

Thymectomised and irradiated DBA/2 mice were injected intraperitoneally with human serum containing high titer of HBsAg, and were positive for HBsAg. Through the entire experiment neither degenerative and inflammatory lesions nor hepatitis B virus antigens could be detected in the liver of these animals by histomorphology and immunofluorescence, respectively. The sera of all these mice were negative for HBsAg by radioimmunoassay. By electron microscopy, however, increasing amounts of filaments and round particles measuring 20-22 nm in diameter could be observed in the endoplasmic reticulum of the mouse hepatocytes from the 8th day following injection. From the 90th day after inoculation the number of the filaments increased in an extreme degree. After fixation with KMnO4 and EDTA preferential staining, the filaments proved to be highly electrondense. According to the authors the filaments observed in mouse livers are lipoproteins produced by the hepatocytes in response to HBV inoculation. The appearance of the filaments is HBsAg-like, though their immunological characteristics become modified.
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PMID:HBsAg-like structures in immunosuppressed mice inoculated with human hepatitis B virus. 612 39

A viral T cell epitope was genetically inserted within the periplasmic MalE protein of Escherichia coli in two different permissive insertion sites and resulting hybrid proteins were used to study the in vitro and in vivo immunogenicity of the foreign T cell epitope. Purified hybrid MalE proteins containing the T cell epitope 120-132 (PreS:T) from PreS2 region of hepatitis B virus HBsAg inserted alone or with its adjacent B cell epitope (132-145) were able to induce strong peptide-specific T cell responses in mice. In vitro stimulation of primed lymph node cells or specific T cell hybridomas by the hybrid proteins required processing of the inserted T cell epitope and was inhibited by antigen-presenting cells fixation. The inserted T cell epitope was presented in vitro, in association with appropriate major histocompatibility complex molecules, as efficiently as free synthetic peptide. The in vitro immunogenicity of MalE hybrid proteins was increased by inserting four tandemly repeated copies of PreS:T, either at site 133 or 303. These results were confirmed in vivo by comparing the proliferative responses of lymph node cells from DBA/1 mice primed with MalE hybrid proteins containing one or four copies of PreS:T. Thus, the use of MalE hybrid proteins expressing multiple copies of a given foreign T cell epitope allows the induction of peptide-specific T cell response with a lower dose of priming antigen.
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PMID:Induction of T cell responses by chimeric bacterial proteins expressing several copies of a viral T cell epitope. 822 77

In the present study, we analyzed the capacity of seven strains of mice to produce Abs against the neutralization poliovirus C3 B cell epitope, chemically or genetically linked to two different carrier proteins (MalE and keyhole limpet hemocyanin) or to recombinant hepatitis B surface Ag particles. Following immunization with these different immunogens, all strains of mice developed high Ab titers against the carrier proteins. However, only four strains of mice developed a significant Ab response against the poliovirus C3 B cell epitope. Indeed, in contrast to BALB/c, DBA/1, DBA/2, and 129 sv mice, C57BL/6, C3H, and CBA/J mice failed to produce anti-C3 Abs after immunization with the various C3 immunogens. Using various H-2 congenic strains on BALB/c or C57BL/10 background, this study clearly showed that the response to the C3 B cell epitope is not controlled by MHC genes. In contrast, analysis of anti-C3 Ab responses in IgH congenic mouse lines on BALB/c or C57BL/6 background demonstrated that the capacity to respond to this B cell epitope is controlled by genes closely linked to V(H) genes. This study therefore represents the first demonstration that the V(H) polymorphism can limit the Ab response to a viral neutralization epitope, and therefore has important implications for vaccine development.
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PMID:Control by Ig genes of the responsiveness to a neutralization viral B cell epitope. 912 Feb 81

Competition for binding to MHC class II molecules between processed peptides derived from a single protein Ag is considered an important parameter leading to the presentation of a limited set of peptides by APCs. We tested the relevance of this competition process in a model Ag, the MalE protein, by deleting T cell epitopes or by introducing a competitor T cell peptide. We identified in DBA/1 (I-Aq) mice six immunodominant T cell determinants in the MalE sequence, 89-95, 116-123, 198-205, 211-219, 274-281, and 335-341. Synthetic peptides carrying these determinants were classified in three groups as weak, intermediate, or strong I-Aq binders in competition experiments with the PreS:T peptide of hepatitis B surface Ag. In vivo, synthetic MalE peptides with weak and intermediate MHC binding capacity were inhibited in their capacity to stimulate proliferative response in the presence of the PreS:T competitor peptide, whereas the strongest MHC binder was not. Strikingly, the insertion of the potent competitor PreS:T peptide into the MalE sequence, as a single copy or as four copies, did not inhibit the proliferative response to the six immunodominant peptides of the recipient protein. Moreover, deletion in the protein sequence disrupting either the weak (198-205) or strong (335-341) MHC binding determinant of MalE did not modify the proliferative response to the remaining T cell determinants as compared with wild-type MalE protein. Altogether, these results show that peptide competition for MHC binding may not represent the most important event in processes leading to immunodominance.
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PMID:Immunodominance does not result from peptide competition for MHC class II presentation. 946 34

In transgenic animals, genotype-specific modifiers exert a control over transgene methylation and expression that may or may not be position dependent. These factors belong to different classes, some of them possibly related to modifiers of position-effect variegation in Drosophila. The study of hepatitis B virus (HBV) gene expression in transgenic mice has revealed the existence of many factors influencing transcription, including hormones and tissue-specific transcription factors. We now report the effect of genotype-specific modifiers on HBV surface antigen (HBsAg) expression and transgene methylation. Compared with the C57BL/6 background, the DBA/2 and 129sv backgrounds cause enhancement of HBsAg expression, with little or not effect on transgene methylation or transcription. In contrast, a single cross with a BALB/c mouse is responsible for de novo methylation and silencing of the transgene in all offspring. Several modifiers appear to segregate in the progeny of a transgenic E36 male mouse crossed with (C57BL/6 x BALB/c) F1 females, with the emergence of a high-expressor group. Our observations suggest that different modifiers act cooperatively, at both the transcriptional and post-transcriptional levels, as part of a complex system regulating transgene expression. This transgenic model provides a system to genetically map new mouse strain-specific modifiers, some of them involved in epigenetic modification and transcription control.
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PMID:Control of expression and methylation of a hepatitis B virus transgene by strain-specific modifiers. 962 86

Background: Chronic infection with HBV (CHB) or HCV (CHC) is the most common chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma in humans, their infections have distinct pathogenic processes, however, little is known about the difference of glycoprotein glycopatterns in serum between hepatitis B virus (HBV)- and hepatitis C virus (HCV)-infected patients. Methods: A method combining the lectin microarrays, letin-mediated affinity capture glycoproteins, and MALDI-TOF/TOF-MS was employed to analyze serum protein glycopatterns and identify the glycan structures from patients with CHB (n = 54) or CHC(n = 47), and healthy volunteers (HV, n = 35). Lectin blotting was further utilized to validate and assess the expression levels of their serum glycopatterns. Finally, the differences of the glycoprotein glycopatterns were systematically compared between CHB and CHC patients. Conclusions: As a result, there were 11 lectins (e.g., HHL, GSL-II, and EEL) exhibited significantly increased expression levels, and three lectins (LCA, VVA, and ACA) exhibited significantly decreased expression levels of serum protein glycopatterns only in the CHB patients. However, DBA exhibited significantly decreased expression levels, and two lectins (WGA and SNA) exhibited significantly increased expression levels of serum glycopatterns only in the CHC patients. Furthermore, LEL and MAL-I showed a coincidentally increasing trend in both CHC and CHB patients compared with the HV. The individual analysis demonstrated that eight lectins (MPL, GSL-I, PTL-II, UEA-I, WGA, LEL, VVA, and MAL-I) exhibited a high degree of consistency with the pooled serum samples of HV, CHB, and CHC patients. Besides, a complex-type N-glycans binder PHA-E+L exhibited significantly decreased NFIs in the CHB compared with HV and CHC subjects (p < 0.01). The MALDI-TOF/TOF-MS results of N-linked glycans from the serum glycoproteins isolated by PHA-E+L-magnetic particle conjugates showed that there was an overlap of 23 N-glycan peaks (e.g., m/z 1419.743, 1663.734, and 1743.581) between CHB, and CHC patients, 5 glycan peaks (e.g., m/z 1850.878, 1866.661, and 2037.750) were presented in virus-infected hepatitis patients compared with HV, 3 glycan peaks (1460.659, 2069.740, and 2174.772) were observed only in CHC patients. Our data provide useful information to find new biomarkers for distinguishing CHB and CHC patients based on the precision alteration of their serum glycopatterns.
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PMID:Comparative Analysis for Glycopatterns and Complex-Type N-Glycans of Glycoprotein in Sera from Chronic Hepatitis B- and C-Infected Patients. 2887 Dec 30