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)

One hundred and four healthy, hepatitis B virus (HBV) seronegative males were enrolled in a single blind, randomized pilot study to compare antibody and clinical responses to a yeast recombinant pre-S2 + S vaccine and a yeast recombinant S antigen vaccine (Recombivax HBR). Participants received either a 12, 24 or 48 micrograms dose of pre-S2 + S vaccine (with a 1:5 ratio by weight of pre-S2 and S antigens) or a 10 micrograms dose of Recombivax HBR by intramuscular injection at 0, 1 and 6 months; their serological and biochemical responses were measured at 0, 1, 2, 3, 6 and 7 months, while their clinical responses were monitored for 5 days after each injection. The proportion of vaccines with minor local or systemic complaints (mainly sore arm, malaise, myalgia, fatigue) and the proportion developing antibody to surface antigen (anti-HBs) were similar for all vaccine groups. Transient elevations in alanine aminotransferase occurred infrequently. By 7 months almost all vaccinees developed anti-HBs, but titres were generally higher among recipients of pre-S2 + S vaccine. Antibody to pre-S2 antigen developed in 70-75% by 2 months and in 91-96% by 7 months. These data imply that the recombinant yeast pre-S2 + S vaccine is as well tolerated and as immunogenic as Recombivax HBR. Further studies are being conducted to assess antibody responses in larger numbers of healthy adults as well as in special populations with sub-optimal responses to currently licensed hepatitis B vaccines.
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PMID:Comparative safety and immunogenicity of yeast recombinant hepatitis B vaccines containing S and pre-S2 + S antigens. 187 19

A comparison was made of the results obtained in separate Phase I studies conducted in Japan on a recombinant hepatitis B vaccine (HBX-R) and a plasma-derived hepatitis B vaccine (H-B-VAX). Recombinant hepatitis B vaccine was administered intramuscularly (IM) to 40 subjects in a dose of 10 micrograms, while H-B-VAX was administered IM to 35 subjects in a dose of 20 micrograms. Each subject received three doses of the vaccine at times zero, 1 month and 6 months. In both trials, at the end of 7 months from the first vaccination all vaccinees had become seropositive for anti-HBs antibody. During the 1-6 month period after the first dose, the seroconversion rate was always higher in the H-B-VAX subjects than in the HBX-R subjects. The anti-HBs antibody titre was also always higher in the H-B-VAX group during that same 6-month period, but there was no longer any difference at the 7th month (H-B-VAX: HBX-R = 1064: 1164 IU/L). In an additional study on the effect of the administration route on the efficacy of HBX-R, 124 subjects were randomly allotted to an IM group and a subcutaneous (sc) group. In each group, HBX-R was administered in 3 doses of 10 micrograms, again at time zero, 1 month and 6 months. At the end of the 7th month, the anti-HBs seroconversion rates were 98% (55/56) in the IM group and 97% (57/59) in the sc group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of results for phase I studies with recombinant and plasma-derived hepatitis B vaccines, and controlled study comparing intramuscular and subcutaneous injections of recombinant hepatitis B vaccine. 294 16

Integration of the human and woodchuck hepatitis B viruses (HBV and WHV) in host chromosomes has been implicated in the development of hepatocellular carcinoma by different cis- and trans-acting mechanisms. The structure and coding capacity of abundant HBV and WHV transcripts of abnormal sizes produced from integrated viral sequences in one human and two woodchuck liver tumors were examined. Analysis of cDNA clones revealed in all cases hybrid virus-cell transcripts containing sequences of the viral surface gene, the viral enhancer, and different truncated versions of the viral X transactivator. Cotranscribed cellular sequences showing no significant coding function provided the signals for transcription termination. In two transcripts, the HBX and WHX genes truncated at carboxy terminal positions conserved transcriptional trans-acting capacity in transient transfection assays. These results lend support to the hypothesis that the integrated hepadnavirus X transactivator might participate in the development of woodchuck as well as human liver tumors by a common trans-acting mechanism.
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PMID:Hepadna virus integration generates virus-cell cotranscripts carrying 3' truncated X genes in human and woodchuck liver tumors. 771 96

Chronic infection with hepatitis B virus (HBV) is associated with the development of human hepatocellular carcinoma (HCC). One of the HBV genes, HBx, may have transforming potential, but this issue is still the subject of controversy. One of the major difficulties in addressing this question is the lack of a suitable in vitro model. We used a nontransformed, differentiated murine hepatocyte cell line (AML12) to transfect the HBx gene and examine its transforming capabilities. Because mutations of the p53 gene, in particular at codon 249, have been implicated in HCC development in geographical areas with high incidence of the tumor, we also studied the putative cooperative role in transformation between HBx and mutated p53 by cotransfecting HBx with a murine p53 mutant equivalent to human ser249 (ser246p53). Transfection with HBx plasmids containing the HBx gene under the control of two different promoters resulted in fewer colonies than in control plasmids. The toxic effect of HBx on colony formation was abolished by cotransfection with 246p53, suggesting that the inhibitory effect requires functionally intact p53. Clonal cell lines that stably expressed HBx messenger RNA (mRNA) (HBX lines) were tested for their growth characteristics and their ability to grow in soft agar and form tumors in nude mice. At passages 19-27 after transfection, one of four HBx-expressing lines showed the capacity for anchorage-independent growth in soft agar and produced poorly differentiated hepatocellular carcinomas in 8 of 13 sites of injection in nude mice. HBX lines as well as clonal cell lines of cells transfected with 246p53 (246 cell lines), cotransfected with HBx and 246p53 (246x lines) or transfected with control plasmids, were analyzed by flow cytometry to determine the fraction of cells in S phase (SPF). 246 and 246X lines had similar SPFs that were approximately twofold greater than control or HBX lines. 246x lines showed morphological changes in culture such as marked cellular heterogeneity, cell crowding, and the presence of multinucleated giant cells, but their tumorigenicity was not increased compared with the HBX lines. These data show that HBx has a weak tumorigenicity in murine hepatocytes and that the addition of mutation of p53 at codon 249 to HBx expression does not increase tumorigenicity in AML12 cells.
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PMID:Analysis of the tumorigenicity of the X gene of hepatitis B virus in a nontransformed hepatocyte cell line and the effects of cotransfection with a murine p53 mutant equivalent to human codon 249. 890 70

The hepatitis B virus protein HBx is a promiscuous transactivator implicated in both cell growth and death and in the development of hepatocellular carcinoma. We recently reported that HBx can potentiate c-myc-induced liver oncogenesis in a transgenic model where low level expression of HBx induces no pathology. To assess if HBx could affect the hepatocyte turnover, we investigated the HBx-elicited apoptotic responses in transgenic livers and in primary hepatocyte cultures. Here we show that transgenic expression of HBx is associated with a twofold increase of spontaneous cell death in the mouse liver. The finding that apoptosis was enhanced to similar extents in HBx mice carrying homozygous p53 null mutations implied that functionally intact p53 was not required to transduce the death signal. A direct, dose-dependent apoptotic function of HBx was demonstrated in transient transfections of liver-derived cell lines. We further show that stable expression of HBx at low, presumably physiological levels in primary hepatocytes, induced cellular susceptibility to diverse apoptotic insults, including growth factor deprivation, treatment with anti-Fas antibodies or doxorubicine and oxidative stress. HBx expression, but not p53 status profoundly affected the commitment of cells to die upon apoptotic stimuli. These data strengthen the notion that HBX may contribute to HBV pathogenesis by enhancing apoptotic death in the chronically infected liver.
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PMID:p53-independent apoptotic effects of the hepatitis B virus HBx protein in vivo and in vitro. 979 83

These analyses of the UNOS Scientific Renal Transplant Registry data from 1994-1997 showed: 1. There was no significant difference in graft survival between en-bloc and solitary transplants from donors aged 3-4. 2. Double renal allografts should be considered as an alternative to discarding both kidneys when donors are regarded as unsuitable for single kidney transplantation. 3. Prolonged donor HTN had a statistically significant deleterious effect in the multivariate analysis (RR 1.2, p = 0.05 for duration > 10 yrs). 4. A donor history of diabetes, cigarette smoking, or cancer failed to show any significant deleterious effects on graft survival in the multivariate analysis. 5. Matching donors and recipients for HCV genotype may minimize the risk of superinfection when using kidneys from HCV-positive donors (RR 1.4, p = 0.02 for the D+/R- mismatch). 6. Hepatitis B core antibody-positive donors did not pose a significant risk in the multivariate analysis. 7. A high proportion of donors were CMV positive and transplanting kidneys from CMV-positive donors resulted in a significantly but not substantially poorer graft outcome. The highest risk (RR 1.2, p = 0.003) was observed in transplants to CMV-negative recipients. 8. Kidneys from NHBDs who died of trauma survived as well as those from conventional brain-dead donors. NHBDs promise to be an important source for expanding the cadaver donor pool.
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PMID:Expanded criteria donors. 1050 20

Hepatitis B virus (HBV) is a major etiological factor associated with hepatocarcinogenesis, but its role in the transformation process remains unclear. We previously documented the accumulation of genetic alterations in a HBV-transfected cell line. In the present study, we addressed the effect of HBV and its replication on the genome and phenotype of the host cell. Parental HBV-free Hep G2 cells and two HBV-transfected variant lines Hep G2215 and Hep G2T14. 1, which do and do not replicate HBV, respectively, were used to monitor genetic alterations in conjunction with HBV profile in vitro and in vivo. Comparison of in vitro growth rates showed that Hep G2T14.1 cells grew more rapidly, while Hep G2215 cells, replicating HBV, grew slower than parental Hep G2 cells. Molecular analysis confirmed an HBV integration site (s) in both variants, and reverse trancriptase-polymerase chain reaction (RT-PCR) amplification documented expression of transcript for the HBX protein, which has recently been implicated in the compromised efficiency of cellular DNA repair. Tumorigenisity testing indicate a comparable rate of tumor formation in nude mice of both HBV-transfected variants, giving rise to tumors in 3 weeks; parental Hep G2 cells did not form tumors in nude mice. Tumor tissue from nude mice injected with Hep G2T14.1 cells showed no change in HBV status. However, a new HBV integration site was detected in tumor tissue from Hep G2215-injected mice. Two cell lines derived from the respective tumor tissue grew in vitro at rates compatible to those observe before passage in nude mice. The Hep G2215 tumor-derived line continued to replicate HBV, while HBV status remained unchanged in the Hep G2T14.1 tumor-derived line. Unique genetic alterations were detected in both transfected cell lines, and Hep G2215 cells particularly showed cellular mosaicism and clonal selection when analyzed after the passage in nude mice. Further genetic alterations were detected in tumor-derived cell lines. Interestingly, the de novo genetic alterations in the Hep G2215 cells, which maintain the ability to replicate HBV, included a new HBV integration site, several chromosome rearrangements and loss of heterozygosity (LOH) of one p53 allele. Western analyses of p21/Waf1 protein indicate an upregulation of the protein in cells that replicate HBV. Based on the combined data, we hypothesize that the genetic alterations in the cellular genome could also be generated as a function in the presence of HBV and HBV replication. Possible mechanisms that could be implicated in cumulative mutagenetic events are discussed.
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PMID:Hepatitis B virus-transfected Hep G2 cells demonstrate genetic alterations and de novo viral integration in cells replicating HBV. 1102 76

The X protein (HBX) of the hepatitis B virus (HBV) has been shown to be important for the establishment of HBV infection in vivo. Our previous studies suggested that interaction of HBX with the proteasome complex may underlie the pleiotropic functions of HBX. In this study, we generated a series of woodchuck hepatitis virus (WHV) X mutants, including mutants of the domain interacting with the proteasome, and studied their infectivity in woodchucks. Many of the mutants were defective in transactivation but none of them were completely replication defective in vitro. In vivo, all the wild-type and some X mutant-transfected animals demonstrated evidence of infection with anti-WHc and/or anti-WHs seroconversion. Most of the wild-type- and X mutant-transfected animals had transient viremia. Some animals were later challenged with infectious WHV. Animals inoculated with X mutants, including those with no serologic evidence of infection, were protected from the challenge, suggesting previous infection with resulting protective immunity. Our study demonstrates that the previously described functional domains of HBX are biologically important and the X-defective mutants, possibly as attenuated viruses, are not completely replication defective in vivo.
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PMID:X-deficient woodchuck hepatitis virus mutants behave like attenuated viruses and induce protective immunity in vivo. 1171 44

The X-gene product of hepatitis B virus (HBX) modulates a variety of viral and cellular genes relevant to hepatocarcinogenesis, where alpha-fetoprotein (AFP) is produced by hepatoma cells. In the present study, the possible mechanism by which HBX regulates AFP expression was investigated using three human hepatoma cells, HepG2, HuH-7 and Hep3B, which are known to contain the wild-type, the mutant-type and the deletion of p53, respectively. Transfection with the HBX expression vector stimulated the co-transfected AFP reporter gene expression in HepG2 cells and HuH-7 cells, but not in Hep3B cells. Transfection with the p53 expression vector repressed the AFP reporter gene expression in all three hepatoma cells, while overexpression of HBX counteracted the p53-induced repression. In addition, a G-->A substitution at nucleotide -119 in the AFP promoter sequence abrogated the stimulatory effect of HBX on the AFP promoter in HepG2 cells. These results suggest that HBX interacts with p53 to up-regulate AFP gene transcription probably by restoration of the p53-mediated repression of the AFP promotor activity.
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PMID:Transactivation of human alpha-fetoprotein gene by X-gene product of hepatitis B virus in human hepatoma cells. 1189 35

Survivin is an anti-apoptotic protein that is overexpressed in most human cancers. We show that survivin forms complexes with a cellular protein, hepatitis B X-interacting protein (HBXIP), which was originally recognized for its association with the X protein of hepatitis B virus (HBX). Survivin-HBXIP complexes, but neither survivin nor HBXIP individually, bind pro-caspase-9, preventing its recruitment to Apaf1, and thereby selectively suppressing apoptosis initiated via the mitochondria/cytochrome c pathway. Viral HBX protein also interacts with the survivin- HBXIP complex and suppresses caspase activation in a survivin-dependent manner. Thus, HBXIP functions as a cofactor for survivin, and serves as a link between the cellular apoptosis machinery and a viral pathogen involved in hepatocellular carcinogenesis.
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PMID:HBXIP functions as a cofactor of survivin in apoptosis suppression. 1277 88


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