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importance of subtype in the immune response to the pre-s(2) region of the hepatitis b surface antigen. i. t cell fine specificity.previous studies of murine t cell recognition of the pre-s(2) region of the hepatitis b surface ag (hbsag) identified high (h-2b,d,q), intermediate (h-2s,k), and low to nonresponder (h-2f) haplotypes. however, these studies utilized the y subtype of hbsag. the purpose of this study was to examine the influence of viral subtype on t cell recognition of the pre-s(2) region and to identify specific t cell recognition sites in a panel of h-2 congenic strains. immunization with pre-s(2) containing hb ...19901691762
importance of subtype in the immune response to the pre-s(2) region of the hepatitis b surface antigen. ii. synthetic pre-s(2) immunogen.one purpose of this study was to examine the influence of viral subtype on in vivo antibody production to the pre-s(2) region of the hepatitis b surface ag. immunization with hepatitis b surface ag particles containing the pre-s(2) region of the d or y subtypes identified the b10.m (h-2f) strain as an antibody nonresponder to the pre-s(2) and s regions after immunization with the y subtype, but as an antibody responder to the pre-s(2) and s regions after immunization with the d subtype. both the ...19901691763
assay of pres epitopes and pres1 antibody in hepatitis b virus carriers and immune persons.the diagnostical significance of the large hepatitis b surface protein with its pres1 attachment site and of anti-pres antibodies are not yet well known. we investigated the epitope of the pres1 attachment site to see whether it is a marker of viremia and whether antibodies against it occur in convalescents and vaccinees. for comparison, sera were also tested for the presence and relative amount of a pres2 epitope. the epitopes were detected by binding to specific monoclonal antibodies (mab ma18 ...19901691815
hepatocarcinogenesis due to chronic liver cell injury in hepatitis b virus transgenic mice.fifty-nine transgenic mice from a lineage that overproduces the hepatitis b virus large envelope polypeptide and accumulates high intrahepatic concentrations of hepatitis b surface antigen were followed for evidence of liver disease throughout their 24-month life span. by 4 months of age all mice displayed biochemical and histological evidence of moderately severe chronic hepatitis which was followed sequentially by the development of regenerative nodules and oval cell hyperplasia (by 6 months), ...19901692259
mapping of b-cell epitopes of the human hepatitis b virus x protein.the immune response to the x protein of human hepatitis b virus (hbv) was studied by epitope mapping by using a set of ms2-hbx fusion proteins and synthetic peptides. antibodies in sera of patients with acute and chronic hbv infection showed a multispecific immune response. each serum contained antibodies to a different set of epitopes, which taken together cover most of the hbx sequence. some of the epitopes were detectable only by immunoblotting with fusion proteins; others were detectable onl ...19901692348
immunohistochemical studies of intrahepatic tumour necrosis factor alpha in chronic liver disease.to determine the intrahepatic production of tumour necrosis factor alpha (tnf alpha) in chronic liver disease three monoclonal antibodies were used against tnf alpha in immunohistochemical studies of liver tissue sections from patients with chronic liver disease. all three monoclonal antibodies stained infiltrating mononuclear cells. monoclonal antibody ii 7c2 also stained the cytoplasm or nucleus, or both, of a varied number of hepatocytes from nine patients with chronic hepatitis b virus infec ...19901692847
presentation and immunogenicity of viral epitopes on the surface of hybrid hepatitis b virus core particles produced in bacteria.we recently reported the enhanced immunogenicity of a peptide epitope when it was presented as a fusion protein with hepatitis b core antigen. in those experiments the fusion protein was expressed in vaccinia virus. we have now refined the system so that large amounts of highly immunogenic particles can be produced using a simple bacterial expression system. we describe the expression of three different viral epitopes as chimeric particles that induce good antibody responses to each epitope afte ...19901693163
epitope-specific antibody response to the surface antigen of duck hepatitis b virus in infected ducks.in order to investigate the immune response to duck hepatitis b virus (dhbv) infection, newly hatched dhbv dna negative ducklings were injected with infectious serum of sufficiently low dhbv-dna titer to allow clearance of viremia. of 20 injected ducklings, 13 (65%) became viremic. of these, 6 (46%) cleared virus from the serum 3 to 22 weeks postinjection. the convalescent sera of these 6 animals were tested for an epitope-specific antibody response in a highly specific competitive inhibition as ...19901693247
discrimination of hepatitis b virus (hbv) subtypes using monoclonal antibodies to the pres1 and pres2 domains of the viral envelope.we report the production and characterization of murine anti-pres2 and anti-pres1 monoclonal antibodies (mab) and demonstrate their utility in discriminating hepatitis b virus (hbv) subtypes. on the basis of western blotting and reciprocal competition binding to hbv virions, at least five distinct epitopes have been identified in the pres domain: two within the pres1 region and three within the pres2 region. all pres2 mab bind m protein (gp33 and gp36) but only one group binds strongly to m and ...19901693248
epitope mapping of the pres1 domain of the hepatitis b virus large surface protein.the large (l) surface glycoprotein of hepatitis b virus is an important component of the virion envelope derived from translation initiation at the 5' end of the pres1 domain of the surface antigen open reading frame. since key roles in virion assembly and infectivity have been postulated for this protein, further understanding of its structure and topology is important. to this end we have mapped the epitopes recognized by a panel of monoclonal antibodies specific for this polypeptide by examin ...19901693249
[synthesis and immunological properties of the peptide fragment of the hepatitis b virus envelope pres-protein].we have synthesized the 24-41 fragment of the pres region of the hepatitis b (subtype ayw) envelope. the peptide was prepared by the solid phase synthesis on perfluoropoly-ethylene polymer grafted with polystyrene. the peptide chain was elongated from c-terminus using pentafluorophenyl- and p-nitrophenyl esters of boc-amino acids. the peptide was cleaved off the solid phase by hbr in cf3cooh, purified by gel filtration, and, after conjugation with serum albumin (bsa), inoculated into mice. the r ...19901693272
alpha-fetoprotein in the woodchuck model of hepadnavirus infection and disease: immunochemical analysis of woodchuck alpha-fetoprotein and measurement in serum by quantitative monoclonal radioimmunoassay.woodchuck hepatitis virus infection of the eastern woodchuck represents a useful model for the study of hepatitis b virus infection and disease in humans, including hepatocellular carcinoma. in man, hepatocellular carcinoma is frequently detected and monitored using assays for serum alpha-fetoprotein. to study the relationship between alpha-fetoprotein and woodchuck hepatitis virus-induced hepatocellular carcinoma in the woodchuck model, we produced a monoclonal antibody to woodchuck alpha-fetop ...19901693355
stable expression of hepatitis delta virus antigen in a eukaryotic cell line.the gene encoding the hepatitis delta virus structural antigen (hdag) was linked to a neomycin resistance gene in a retrovirus expression vector, and human hepg2 cells were transfected with the recombinant plasmid. a stable cell line was cloned that expressed hdag in the nuclei of 100% of cells, in a pattern indicating a close relationship with cell nucleoli. analysis of partially purified recombinant hdag by hplc showed an mr in the range of 7 x 10(5) to 2 x 10(6), which appeared to contain con ...19901693665
[treatment of chronic hepatitis caused by hepatitis b virus]. 19901694296
[a new approach for explaining viral organotropism: fusion of hbv transfected cells with hepatocytes]. 19901694375
growth-factor independence of a new differentiated hepatitis b virus dna-negative human hepatoma cell line.the establishment of a new, differentiated, hepatitis b virus dna-negative, human hepatoma cell line (named plc/an/2) is described. neoplastic liver tissue was obtained during hepatectomy in an hbsag-negative man. the established cell line is negative for alpha-fetoprotein and carcinoembryonic antigen; it has retained in vitro some of the differentiated functions of normal hepatocytes. additionally, it presents a distinctive rearrangement (translocation) at the long arm of chromosome 4. the high ...19901694812
adhesive molecules in liver disease. immunohistochemical distribution of thrombospondin receptors in chronic hbv infection.the distribution of the thrombospondin-receptor was studied in 26 cases of inflammatory hepatitis b virus (hbv) related liver disease and twelve non-inflammatory controls using monoclonal antibody (mcab) okm5. okm5 reacted in all cases with sinusoidal lining cells, portal vessel endothelium, and scattered mononuclear inflammatory cells. in 16 of the 26 cases with inflammation, one or more clusters of okm5 positive (okm5+) hepatocytes were found in areas of periportal or intralobular inflammation ...19901694875
hepatitis b surface antigen particles with all four subtypic determinants: point mutations of hepatitis b virus dna inducing phenotypic changes or double infection with viruses of different subtypes.hepatitis b surface antigen (hbsag) particles carry the common determinant, a, as well as d or y and w or r subtype determinants, and are classified into the four major subtypes, i.e., adw, adr, ayw and ayr. rare sera contain hbsag particles with all four subtype determinants (adywr). target sequences (nucleotides 38-550) in the s gene of hepatitis b virus (hbv) dna in two such sera were amplified by the polymerase chain reaction. individual amplification products were cloned in an m13 phage vec ...19901694959
mechanism of translation of the hepadnaviral polymerase (p) gene.unlike many other reverse transcriptase genes, the polymerase (p) gene of the hepatitis b viruses is expressed by translational initiation from its own aug codon rather than by ribosomal frameshifting during translation of the overlapping core gene (c). to explore the mechanism of its translation, we have fused the p gene of duck hepatitis b virus to the bacterial lacz gene at a point 3' to the c-p overlap; this allows detection of the products of p translation with antisera to the lacz-encoded ...19901695011
fulminant hepatitis. 19901695027
nature and display of hepatitis b virus envelope proteins and the humoral immune response. 19901695029
hepatitis b surface antigen-specific cd8-positive t cell clones. antigen specificity and interleukin-2 production.clones of hepatitis b surface antigen-reactive cd8+ and cd4+ t cells were obtained from peripheral blood mononuclear cells (pbm) of a hepatitis b immunized individual whose pbm proliferated when cultured with hepatitis b surface antigen (hbsag). lymphocytes were activated by culturing for 2 weeks with hbsag and high concentrations of interleukin-2 (il-2), then cloned in the presence of irradiated hbsag-activated pbm and autologous epstein-barr virus (ebv)-transformed b cells, together with antig ...19901695132
in situ hybridization: application to the study of gene expression during experimental hepatocarcinogenesis and human hepatocellular carcinoma.the possibility of detecting specific mrna directly within tumor cells offered by the in situ hybridization (ish) technique has provided a new dimension to the study of experimental and human hepatocarcinogenesis. the combination of ish and immunocytochemical techniques on the same or adjacent tissue sections provides a more complete picture of the various changes in gene expression. ish may also detect posttranscriptional abnormalities of gene expression at the cellular level, such as expressio ...19901695388
antiviral therapy: hepatitis b.antiviral therapy for chronic hepatitis b virus infection can result in clearance of replicating virus from the liver and prevention of progression to cirrhosis in a substantial proportion of patients. adenosine arabinoside monophosphate, a potent inhibitor of hbv replication, is of limited usefulness because it causes significant neuromuscular toxicity. acyclovir alone is relatively nontoxic, but is clinically ineffective in eliminating hbv from the liver. lymphoblastoid or recombinant alpha-in ...19901696158
acute exacerbation in patients with liver cirrhosis: a clinicopathological study.the incidence, clinicopathologic features and etiology of acute exacerbation occurring in patients with liver cirrhosis were assessed prospectively among 332 hepatitis b surface antigen (hbsag) positive and 71 hbsag negative patients. during an 11-year period and a mean follow-up duration of 26.8 months, 148 acute exacerbation occurred in 107 hbsag positive patients and 32 episodes occurred in 18 hbsag negative patients. the calculated annual incidence was 11.5%. the clinical, laboratory and his ...19901696678
assessment of pattern and treatment of intrahepatic recurrence after resection of hepatocellular carcinoma.from 1980 to 1988, 161 patients underwent total extirpation of primary hepatocellular carcinoma. there were 18 operative or hospital deaths. recurrence of tumor was diagnosed in 69 of the remaining 143 patients during follow-up treatment with monthly serum alpha-fetoprotein measurements and imaging studies that were performed every three months. there were 61 men and eight women whose ages ranged from 33 to 78 years. the histologic factors noted were cirrhosis of the liver in 60 patients and chr ...19901696750
antiviral strategies in chronic hepatitis b virus infection: ii. inhibition of duck hepatitis b virus in vitro using conventional antiviral agents and supercoiled-dna active compounds.primary duck hepatocyte (pdh) cultures, congenitally infected with the duck hepatitis b virus (dhbv), were grown on feeder cell layers of irradiated human embryonic lung fibroblasts and then exposed to a number of compounds with recognized or potential antiviral activity. these compounds included conventional antiviral agents, reverse transcriptase inhibitors, compounds with activity to supercoiled-dna, and dna-binding agents. twenty-three compounds were evaluated, and 13 were found to inhibit s ...19901696959
vaccine-induced escape mutant of hepatitis b virus.in southern italy, 44 contacts of hepatitis b virus carriers, including infants of carrier mothers, became hbsag positive despite passive and active immunisation according to standard protocols. in 32 of these vaccinees infection was confirmed by the presence of additional markers of viral replication. in 1 infant, serious disease occurred. the virus from this patient is an escape mutant with a different sequence from that of the isolate from the mother. a point mutation from guanosine to adenos ...19901697396
[immune modulating effect of isoprinosine in patients with post-alcoholic liver cirrhosis].immunomodulating effect of isoprinosine was estimated in group of 10 patients with postalcoholic liver cirrhosis and compared with another group of 10 patients with postinflammatory liver cirrhosis with infection of hepatitis b virus. disturbances of immunologic reactivity in the patients with postalcoholic liver cirrhosis mainly concerned increased immunoglobulin g, a concentrations in the blood serum, decreased percentage values of lymphocytes t and their subpopulations (lymphocytes t4 and t8) ...19901697438
synthetic oligopeptides bearing a common or subtypic determinant of hepatitis b surface antigen.two determinants of hepatitis b surface ag (hbsag), identified by mab raised against polypeptide components, were characterized immunochemically. one was expressed on hbsag irrespective of the four major subtypes, i.e., adw, adr, ayw, and ayr, whereas the other was subtypic but not identical to any of d, y, w, and r determinants. the common determinant was generated by a synthetic pentadecapeptide with a sequence of thr-thr-ser-thr-gly-pro-cys-lys-thr-cys-thr-ile-pro-ala-gln representing amino a ...19901697880
[subclasses of antibodies to hepatitis b core antigen in chronic hbv infections: changes during treatment with interferons and predictors of response].response to interferon therapy in chronic hepatitis b virus (hbv) carrier is preceded by the appearance of igm class anti-hbc (antibody to hepatitis b core antigen). the temporal relationship and magnitude of the igm anti-hbc response is variable, suggesting that the antibody is not directly involved in hepatocyte lysis, but is merely a marker of a changed state of immunity to the nucleocapsid proteins induced by interferon. igg 1, 2, 3 and 4 did not change during therapy. igg anti-hbc of all su ...19901698593
effects of insertional and point mutations on the functions of the duck hepatitis b virus polymerase.the polymerase (p) gene of hepadnaviruses encodes a large polypeptide that appears to participate in several steps in the viral life cycle: packaging of viral rna, providing the primer for synthesis of minus-strand dna, synthesizing minus-strand dna from an rna template and plus-strand dna from a dna template, and degrading viral rna in rna-dna hybrids. to assist in the assignment of these functions to domains of the duck hepatitis b virus polymerase protein, we have constructed a series of subs ...19901698997
antigenic mimicry of an immunoglobulin a epitope by a hepatitis b virus cell attachment site.the pres(21-47) sequence of the hepatitis b virus (hbv) envelope protein is involved in binding of the virus to cell receptors. a protein similarity search revealed a partial homology between this sequence and a segment of the human immunoglobulin a (iga) heavy chain constant region, suggesting that the cell attachment site for hbv might be located on secretory component representing a receptor for polymeric iga. data presented herein do not support this hypothesis but provide evidence for immun ...19901699350
combined immunoprophylaxis in the prevention of perinatal transmission of hepatitis b and hepatitis d virus infections in saudi children.the efficacy of the combined immunoprophylaxis approach (passive plus active immunization) was evaluated in babies born to 52 hbsag-carrier saudi mothers, of whom seven (13.5%) were hbeag-positive and seven were anti-hdv-positive. newborns were given 100 iu of hepatitis b immune globulin (hbig) from the hepuman berna-swiss serum and vaccine institute, berne, and hepatitis b vaccine (5 micrograms) within 12 hours of birth, and the vaccine was given again at 1 and 6 months of age (5 micrograms/inj ...19901699476
immunological studies before and during interferon therapy in chronic hbv infection: identification of factors predicting response.lymphoblastoid interferon is effective therapy in some but not all patients with chronic hepatitis b virus infection. to assess whether immunological parameters were predictive of response to interferon therapy, we determined the human leukocyte antigen type, cd4/cd8 ratio, natural killer cell activity, igm anti-hbc antibody levels and concanavalin a-induced lymphocyte proliferative response in 30 patients before treatment. in addition, to investigate the mechanisms of action of interferon in pr ...19901699861
virological examinations of patients with aids-related complex/walter-reed 5 enrolled in a double-blind placebo-controlled study with intravenous gammaglobulin administration. prognostic value of anti-p24 determination. the arc-ivig study group.thirty patients with aids-related complex/walter-reed 5 enrolled in a placebo-controlled double-blind study with high-dose intravenous gammaglobulin administration were tested by quantitating hiv western blot and other serological tests for viral antibodies. furthermore, conventional virus isolation attempts were performed. absence or loss of p24 antibodies during the study period was associated with progression to aids (p = 0.01) and thereby was an earlier prognostic parameter of a poor prognos ...19901700551
[evolution and prognosis in patients with primary liver cancer. i. the effect of individual factors on the survival of patients with primary liver cancer].the data of the frequency, evolution and prognosis of 63 patients with primary liver carcinoma which had developed on the basis of liver cirrhosis are presented. an attempt is made to assess the importance of the etiologic factors, type of liver cirrhosis, macroscopic type of the tumor, histologic pattern of the cancer, sex and age for the evolution and prognosis of the disease. the patients with primary liver carcinoma without cirrhosis have a better prognosis. as high risk factors may be accep ...19901700554
[clinical studies of the specificity of detecting viral dna in non-a, non-b hepatitis in liver tissue and lymphocytes].the clinical specifity of an intraparticular virus-dna of 5001 bp associated with non-a, non-b hepatitis (hnanb) was evaluated. investigations were done in liver biopsies and lymphocytes in 173 patients having acute or chronic hnanb (n = 107) or liver diseases of other etiology (n = 66). the sensitivity of the test system (polymerase chain reaction, southern-transfer, dna-hybridisation with synthetic oligonucleotides) was less than 100 virus particles per probe. in all patients with acute hnanb ...19901700557
[effective synthesis of oligo(poly)deoxyribonucleotides using an h-phosphonate method in plastic microcolumn].a facile technique of manual oligonucleotide synthesis via h-phosphonate approach is developed. syntheses carried out in pipette tips with siliconised glasswool filters take 3-3.5 min per cycle with 97-98% yields per condensation. the method was used to synthesize 12-55-mers: t7 and pl promoter regions, gene of the signal peptide of the e. coli ompa protein, oligonucleotides coding for amino acid sequences 94-105 of pres1- and 133-143 of pres2-regions of hepatitis b virus, hybridisation probes, ...19901700717
non-a, non-b hepatitis specific antibodies directed at host-derived epitope: implication for an autoimmune process.a cdna clone (gor47-1) bearing an epitope with an aminoacid sequence grrgqkaksnpnrpl (gor epitope) was isolated from the plasma of a laboratory chimpanzee infected with human non-a, non-b hepatitis (nanbh) agent. the epitope was not encoded by reported sequences of hepatitis c virus (hcv) but instead was coded for by a host cellular sequence. an enzyme-linked immunosorbent assay (elisa) was developed for antibodies to the gor epitope (anti-gor). a patient with acute nanbh produced both igm and i ...19901701012
alpha-fetoprotein in the woodchuck model of hepadnavirus infection and disease: normal physiological patterns and responses to woodchuck hepatitis virus infection and hepatocellular carcinoma.persistent infection of the eastern woodchuck (marmota monax) with the woodchuck hepatitis virus (whv) produces disease sequelae similar to those observed in humans with persistent hepatitis b virus infection, including hepatocellular carcinoma (hcc). to further characterize serological markers of hcc in the woodchuck, serum alpha-fetoprotein (afp) was measured under normal physiological conditions and following infection with whv. serum afp was elevated in association with whv-induced hepatitis ...19901701355
integration of hepatitis b virus dna into cells of six established human hepatocellular carcinoma cell lines.the authors successfully established 5 hepatocellular carcinoma cell lines, jhh-1, 2, 4, 5 and 6, derived from hepatitis b surface antigen seronegative patients and one line. jhh-7, from a patient considered to be a hepatitis b virus carrier. in the culture media of any of the jhh cell lines, including jhh-7, hepatitis b surface antigen was not detected by radioimmunoassay. however, in jhh-7, integration of hepatitis b virus dna was confirmed at two sites on the chromosomes of this line by south ...19901701409
hepatitis b virus: the houdini of hepatology? 19911702078
[synthesis of hepatitis b virus core antigen (hbcag) particles by recombinant vaccinia virus]. 19901702184
diagnostic aspects and follow-up of 174 cases of hepatocellular carcinoma. second report.from june 1981 to june 1989 we diagnosed 174 cases of hepatocellular carcinoma (hcc) at our institution (piacenza, northern italy). average age was 65.6 years; male to female ratio 3.4. 149 patients were cirrhotic (85.6%); alcohol abuse was present in 88/169 (52.1%); in 53/145 patients all hepatitis b virus markers were negative. alpha-fetoprotein showed a low diagnostic sensitivity (values above 500 ng only in 49/169 or 29.0%). we used ultrasound (us) examination with a very high identification ...19911702884
hepg2 cell binding activities of different hepatitis b virus isolates: inhibitory effect of anti-hbs and anti-pres1(21-47).the antigenic relationships among different hepatitis b virus (hbv) isolates were investigated by using monoclonal antibodies (mabs) specific for hbs, pres2 (phsa binding site), and pres1 (hepatocyte receptor-binding site) epitopes in a double immunoradiometric assay. in order to define possible functional differences resulting from structural and antigenic differences in the hbv env protein, the hbv isolates were compared in an in vitro cell-binding assay based on the attachment of 125i-labeled ...19911703368
[hepatitis c virus antibodies (hcv) in patients treated with chronic hemodialysis].patients undergoing chronic hemodialysis are frequently affected by nosocomial viral infections, as indicated by the high prevalence of hbv antibodies. the question, to what extent hcv is transmitted by blood transfusions (nanb-pth), or acquired in a nosocomial manner, is still unanswered. we therefore evaluated the hcv antibody rate of 387 sera of dialysis patients on the "eurotransplant" waiting list. the hcv antibody reactivity ranged from 5.4 to 12.0% between different dialysis centers. in h ...19901703848
specific uptake of asialofetuin-tacked liposomes encapsulating interferon-gamma by human hepatoma cells and its inhibitory effect on hepatitis b virus replication.asialofetuin-tacked liposomes (af-liposomes) encapsulating interferon (ifn)-gamma were bound and internalized into a human hepatoma cell line, hepg2 cells, selectively through asialoglycoprotein receptor, but not non-tacked liposomes (n-liposomes). af-liposomal ifn-gamma was more effective for inhibition of viral dna replication in hepatitis b virus (hbv)-producing clone from hepg2 cells transfected with hbv-dna than n-liposomal ifn-gamma. af-liposomes may increase the therapeutic potential of i ...19911704230
expression of leukocyte adhesion molecules in the liver of patients with chronic hepatitis b virus infection.virus-specific t-cell responses are believed to be involved in the pathogenesis of liver cell injury secondary to hepatitis b virus infection. in this study, liver biopsy specimens from patients with chronic hepatitis b virus infection were analyzed for expression of two major pathways of adhesion used by cytotoxic t cells to interact with target cells. the lymphocyte function-associated antigen 3 was found preferentially expressed on hepatocytes of patients with active hepatitis b virus replica ...19911704328
peptide mapping of neutralizing and nonneutralizing epitopes of duck hepatitis b virus pre-s polypeptide.antibodies to the envelope proteins of duck hepatitis b virus neutralize viral infection in vitro. using a library of murine monoclonal antibodies (mabs) against the envelope proteins, we previously identified four neutralizing and two non-neutralizing epitopes on the pre-s region of the large envelope proteins. in this study we report the localization of all but one of these epitopes at the amino acid level. all but 28 nucleotides of the pre-s and s genes were cloned in puc vectors and expresse ...19911704654
mutations affecting hepadnavirus plus-strand dna synthesis dissociate primer cleavage from translocation and reveal the origin of linear viral dna.hepadnaviruses replicate their circular dna genomes via reverse transcription of an rna intermediate. the initial product of reverse transcription, minus-strand dna, contains two copies of a short direct repeat (dr) sequence, termed dr1 and dr2. plus-strand dna synthesis initiates at dr2 on minus-strand dna, using as a primer a short, dr1-containing oligoribonucleotide derived by cleavage and translocation from the 5' end of pregenomic rna. to clarify the sequence requirements for plus-strand pr ...19911704925
development and application of an in vitro model for screening anti-hepatitis b virus therapeutics.the development of effective anti-hepatitis b virus agents has been hampered by the lack of reliable in vitro systems for the screening of new therapeutics. in an effort to circumvent this problem, we have developed an in vitro system for screening anti-hepatitis b virus drugs using hepatitis b virus dna-transfected hep g2 cells. the cell line designated 2.2.15 produces replicative viral dna intermediates, mature dane particles and high levels of viral antigens. subconfluent 2.2.15 cells were tr ...19911705531
characterization and genetic analysis of alternatively spliced transcripts of hepatitis b virus in infected human liver tissues and transfected hepg2 cells.the transcriptional map of hepatitis b virus (hbv) has been expanded recently by the discovery of a singly spliced transcript in hepatoma cell lines transfected with cloned viral dna and a doubly spliced one in naturally infected human liver tissues. by the use of reverse transcription and a subsequent polymerase chain reaction, the two spliced hbv rnas were shown to be present in both types of cells. as further evidence, an hbv mutant was constructed and found to exclusively express the singly ...19911705988
the hepatitis b virus and the host response.the clearance of hepatitis b virus infected cells from the liver is probably dependent on an interplay between the interferon system and the cellular limb of the host immune response. although the importance of the nucleocapsid proteins as targets for sensitized cytotoxic t cells is established in chronic hepatitis b infection, further studies are needed during the early phase of acute infection. the relative importance of pre-s sequences as inducers and targets of the virus neutralizing humoral ...19901706740
possible prevention of chronic hepatitis b by early interferon therapy.a study is currently underway to investigate the efficacy of interferon therapy in patients with prolonged (greater than or equal to 10 weeks but less than 6 months) hepatitis b infection. to date, a total of 15 patients have been enrolled in the study and randomly assigned to receive either placebo for 24 weeks (n = 8) or interferon 5 million units subcutaneously 3 times a week for 24 weeks (n = 7), with follow up for 1 year. thirteen patients have completed the follow-up period: seven patients ...19901706741
[exposition of epitopes of transmembrane protein gp41 of the human immunodeficiency virus on surface capsids of the hepatitis b virus core antigen]. 19901706924
immune response of peripheral blood mononuclear cells to hbx-antigen of hepatitis b virus.the hepatitis b virus genome encodes a transcriptional transactivator protein designated hbxag. we have investigated whether this antigen is a target structure for human t-lymphocytes. using recombinant hbxag protein, we found hbxag-specific stimulation of peripheral blood mononuclear cells in patients with acute hepatitis b virus infection (6 of 6) and chronic hepatitis b virus infection (6 of 17) but not in healthy individuals. with hbxag-specific synthetic polypeptides, several t-cell epitope ...19911707027
expression of insulin-like growth factor ii, alpha-fetoprotein and hepatitis b virus transcripts in human primary liver cancer.insulin-like growth factor ii is a fetal growth factor structurally and functionally related to insulin and insulin-like growth factor i. its mrna expression is developmentally regulated in human liver, the reexpression of insulin-like growth factor ii fetal transcripts being often observed in primary liver cancer. insulin-like growth factor ii and alpha-fetoprotein mrnas were studied in 16 human primary liver cancers, most of which were highly differentiated. hepatitis b virus transcripts were ...19911707028
kinetics of antibody response to hepatitis b virus determinants and to recombinant vaccines in italy.the kinetics of antibody response to the group determinant a and subdeterminants d and y of hepatitis b virus were studied after infection and following immunisation with two recombinant dna yeast-derived hepatitis b vaccines. the initial antibody response was to the subdeterminant epitopes, whereas anti-a antibody, which provides protection against different subtypes of the virus, was not detected for some weeks or months. the delay in the development of anti-a antibody after active immunisatio ...19901707087
expression of the terminal protein region of hepatitis b virus inhibits cellular responses to interferons alpha and gamma and double-stranded rna.constructs expressing the core, surface, x, or polymerase proteins of hepatitis b virus were transfected into human cells. in transient assays, only the polymerase inhibited the responses to interferons alpha and gamma (ifn-alpha and -gamma). stable expression of the polymerase was achieved in the cell line 2ftgh, which carries an ifn-inducible marker gene, by growth under conditions that select for inhibition of the response to ifn-alpha, but the clones grew poorly. when expressed alone, the te ...19911707174
gamma-interferon production in response to hepatitis b core protein and its synthetic peptides in patients with chronic hepatitis b virus infection.the nucleocapsid of hepatitis b virus (hbv) is an efficient immunogen in activating t cells to produce interferon-gamma (ifn-gamma) in patients with chronic hbv infection. we investigated hepatitis b core antigen (hbcag)-specific t cell recognition, which seems to be implicated in the pathogenesis of chronic liver disease. ifn-gamma production by peripheral-blood mononuclear cells of patients with chronic hbv infection [25 patients with chronic active hepatitis (cah) and 14 asymptomatic carriers ...19901707382
[establishment and characterization of a human hepatocellular carcinoma cell line jhh-7 producing alpha -fetoprotein and carcinoembryonic antigen--changes in secretion of afp and cea from jhh-7 cells after heat treatment].a human hepatocellular carcinoma cell line, jhh-7, was established from resected liver tumor of a 53 year old male with hepatitis b virus infection. jhh-7 was composed of polygonal epithelial cells and functionally synthesized and secreted human albumin, afp, cea and ferritin. no hbsag was detected in the culture supernatant of jhh-7 cells. changes of secretion of afp and cea from jhh-7 cells after heat treatment was studied using a temperature gradient incubator. secretion of afp decreased alon ...19901707654
influence of hepatitis b virus infection and age on mode of growth of hepatocellular carcinoma.according to the extent of hepatic involvement of the tumor and that of portal vein invasion at the time of initial diagnosis, patients with hepatocellular carcinoma (hcc) were grouped into three or four groups. correlations among the extent of hepatic involvement, extent of portal vein invasion, and prevalence of hepatitis b surface antigen (hbsag) and age distribution were examined. the extent of hepatic involvement of the tumor and that of portal vein invasion were significantly greater in pa ...19911707748
hepatitis c virus seroprevalence in italian haemophiliacs injected with virus-inactivated concentrates: five year follow-up and correlation with antibodies to other viruses.the overall prevalence of anti-hcv antibody in a group of 125 haemophiliacs was 62%. four patients who had never received replacement therapy were anti-hcv negative. of the 121 patients injected regularly with commercial concentrates, 76 were already anti-hcv seropositive in 1985 and remained so throughout the follow-up. two patients seroconverted in 1987 without obvious signs or symptoms of hepatitis. our patients were treated with dry heat-treated concentrates since 1985 and with wet heat- or ...19911707952
evidence that less-than-full-length pol gene products are functional in hepadnavirus dna synthesis.duck hepatitis b virus mutants containing frameshift or stop codon mutations in a portion of the viral pol gene separating the terminal protein and reverse transcriptase domains had a leaky phenotype and, depending on the location and type of mutation, synthesized up to 10% as much viral dna as did the wild type. this region of the pol gene had previously been reported to be refractory to missense mutations; in fact, the leakiness of most of our mutants appeared attributable to translational sup ...19911707980
recognition of a hepatitis b virus nucleocapsid t-cell epitope expressed as a fusion protein with the subunit b of escherichia coli heat labile enterotoxin in attenuated salmonellae.two overlapping t-cell sites of the nucleocapsid antigen (hbc) of hepatitis b virus (hbv) (amino acids (aa) 120-140) and a b-cell epitope of the pre-s(2) region of the hbv surface antigen (aa 133-140) were expressed as a fusion protein with the subunit b of escherichia coli heat labile enterotoxin (lt-b) in attenuated salmonellae (aroa salmonella dublin sl1438). when balb/c (haplotype h-2d) mice were fed salmonellae expressing lt-b or the lt-b/hbv fusion protein they developed serum igg anti-lt- ...19901708183
differentiating effect of sodium butyrate on human hepatoma cell lines plc/prf/5, hcc-m and hcc-t.the in vitro effect of sodium butyrate (sb) on human hepatoma cell lines plc/prf/5, hcc-m and hcc-t was investigated. sb was added at the non-toxic but cytostatic concentration of 1 mm. in all these cell lines, sb reduced cell proliferation and changed the morphology of the cells into a fibroblast-like shape. in plc/prf/5, alpha-fetoprotein production and c-myc expression were inhibited. in contrast, gene expression of albumin, one of the normal liver-cell products, and that of integrated hepati ...19911708367
detection of polyadenylated rna in hepatitis b virus-infected peripheral blood mononuclear cells by polymerase chain reaction.polymerase chain reaction (pcr) with a reverse transcriptase step characterized a specific transcription activity in hepatitis b virus (hbv)-infected peripheral blood mononuclear cells (pbmc) in two patients (1 and 2) with chronic hepatitis positive for antibody to hepatitis b core antigen (hbc). patient 1 was also coinfected with human hepatitis delta virus. a patient who cleared hbv replication after antiviral treatment with vidarabine served as negative control. hbv-specific rna poly a sequen ...19911708401
identification of a binding site in the hepatitis b virus rna pregenome for the viral pol gene product.the hepatitis b virus, although containing a dna genome, replicates by reverse transcription of an rna pregenome. the viral pol gene encodes the reverse transcriptase which catalyzes viral dna synthesis. to study the interaction of this protein with hbv rna, the entire pol gene product was expressed except its eight amino-terminal codons in escherichia coli as fusion protein with beta-galactosidase. in the absence of competing nucleic acids full-length expression products were able to nonspecifi ...19911708931
interactions of hepatitis b virus with hepatocytes: mechanism and clinical relevance.a receptor for hepatitis b virus (hbv) on hepatocytes has been postulated. there is increasing evidence that the binding of the virus to the target cell surface is mediated by epitopes of the pre-s proteins of the hbv envelope. in contrast to vaccination with hbsag, passive immunization for the prevention of hbv infection is less effective. using antibodies against the pre-s proteins, representing the putative attachment site for hbv binding to hepatocytes, a more efficient means of protection m ...19911709133
morbidity and mortality from chronic hepatitis b virus infection in family members of patients with malignant and nonmalignant hepatitis b virus-related chronic liver diseases.three-hundred forty-one hbsag-positive family members of 152 patients with chronic hepatitis b virus infection (47 asymptomatic carriers, 59 with chronic hepatitis, 17 with cirrhosis and 29 with hepatocellular carcinoma) were prospectively studied to determine the morbidity and mortality from chronic hepatitis b virus infection in the family members of patients with malignant and nonmalignant hepatitis b virus-related chronic liver diseases. most of the family members had no history of acute hep ...19911709410
direct evidence for cytotoxicity associated with expression of hepatitis delta virus antigen.it has been postulated that hepatocyte injury resulting from infection with hepatitis d virus may be caused by a direct virus cytotoxicity in contrast to immune-mediated injury associated with hepatitis b virus. we have transfected hela and hepg2 continuous cell lines with a recombinant plasmid containing the hepatitis d antigen gene under the inducible control of the human metallothionein promoter. the addition of zinc to the cell culture medium then led to the expression of hepatitis d antigen ...19911709411
prevalence of antibody against the core protein of hepatitis c virus in patients with hepatocellular carcinoma.we have cloned the whole structural region of the hepatitis c virus (hcv) genome and transiently expressed the nucleocapsid protein in animal cells. since the nucleotide sequences of this region of the hcv genome has been shown to be highly conserved among different hcv isolates, the assay detecting the antibody to this expressed protein is useful for studying the pathogenicity of hcv. in this work, we investigated the presence of antibodies to hcv nucleocapsid protein (p22) in patients with hep ...19911710205
pregenomic rna encapsidation analysis of eleven missense and nonsense polymerase mutants of human hepatitis b virus.we characterized 11 dna polymerase mutants of human hepatitis b virus (hbv) which contain single missense or nonsense mutations in the various domains within this gene. except for mutant 738, a tight association between dna replication and rna packaging of these missense pol mutants was observed. further analysis of hbv core particle-associated rna indicated that only the 3.5-kb core-specific rna, but not the precore-specific rna, is selectively packaged in this tissue culture system. previously ...19911710285
protection against lethal cytomegalovirus infection by a recombinant vaccine containing a single nonameric t-cell epitope.the regulatory immediate-early (ie) protein pp89 of murine cytomegalovirus induces cd8+ t lymphocytes that protect against lethal murine cytomegalovirus infection. the ie1 epitope is the only epitope of pp89 that is recognized by balb/c cytolytic t lymphocytes (ctl). using synthetic peptides, the optimal and minimal antigenic sequences of the ie1 epitope have been defined. to evaluate the predictive value of data obtained with synthetic peptides, recombinant vaccines encoding this single t-cell ...19911710286
cellular immune responses to hepatitis b virus antigens in man. 19911710754
hepatitis c virus antibodies among different groups at risk and patients with suspected non-a, non-b hepatitis.4000 sera were tested for antibodies against hepatitis c virus (hcv) by means of an elisa using the c100-3 antigen. 38.9% of patients with non-a, non-b hepatitis following blood transfusion (n = 108) had hcv antibodies. among patients with chronic liver damage of unknown origin (n = 316) 30.4% were anti-hcv positive, and in 2,506 patients with transitional or chronic elevation of transaminases 14.8% showed hcv antibodies. haemophiliacs (n = 26) with 65.4% anti-hcv positives and drug addicts (n = ...19911711018
detection of pre-s1 proteins in peripheral blood mononuclear cells from patients with hbv infection.the presence of pre-s1 proteins in peripheral blood mononuclear cell (pbmc) samples from 115 patients with different forms of hepatitis b virus (hbv) infection was investigated by western blot. among 67 chronic hbsag carriers, hbv antigens were detected in the pbmc in 80% for hbsag, 27% for hbc/e ag and 34% for pre-s1 proteins. the detection of pre-s1 proteins in pbmc was significantly associated with the presence of serum markers of hbv replication (hbv dna and/or dna polymerase). in the group ...19911711065
[seroepidemiology of hepatitis b in pediatric age. studies conducted in the city of rome]. 19901711334
identification of immunodominant t cell epitopes of the hepatitis b virus nucleocapsid antigen.several lines of experimental evidence suggest that inclusion of core sequences in the hepatitis b vaccine may represent a feasible strategy to increase the efficacy of the vaccination. in order to identify immunodominant core epitopes, peripheral blood t cells purified from 23 patients with acute hepatitis b and different hla haplotypes were tested with a panel of 18 short synthetic peptides (15 to 20 amino acids [aa]) covering the entire core region. all patients except one showed a strong t c ...19911711541
horizontal transmission of hepatitis b virus amongst british 2nd world war soldiers in south-east asia.infection with hepatitis b virus (hbv) is much more common in tropical than in temperate countries. visitors to the tropics are thus at risk from hbv, though the degree of risk, and the routes of infection involved are uncertain. we report serological markers of hbv in two groups of 2nd world war soldiers, who served in the thai/burma jungles. the groups comprised 100 ex-prisoners of the japanese (pow), and 100 burma campaign veterans (bcv). surface antigen to hbv (hbsag) was positive in 0% of p ...19911711690
monitoring of serum alpha-fetoprotein levels in children with chronic hepatitis b virus infection.changes in serum alpha-fetoprotein (alpha fp) levels were investigated by radioimmunoassay during the follow-up (17 +/- 12 months, two to three times per year) of 50 children with chronic hepatitis b virus infection (mean age of 8 years, 30 males) and of 35 healthy age- and sex-matched controls. eleven of 50 were healthy carriers; 7 had chronic persistent hepatitis, 29 had chronic active hepatitis, and 3 had cirrhosis-associated chronic active hepatitis. serum alpha fp levels in controls were fo ...19911712035
inhibitory activity of monoclonal antibody f35.25 on the interaction between hepatocytes (hepg2 cells) and pres1-specific ligands.the capacity of a pres1-specific monoclonal antibody (mcab) f35.25 to block the attachment of pres1-specific ligands to human hepatoma hepg2 cells was studied. in order to define more precisely the fine epitope specificity of mcab f35.25, its reaction with synthetic peptides derived from the pres1 sequence (12-53) was investigated. mcab f35.25 was found to recognize better synthetic peptide pres(21-47) from the adw 2 and ayw sequences than the synthetic peptide pres(32-53) adw 2. the shortest se ...19911712075
physicochemical and immunological properties of the hepatitis b surface antigen containing the pres2 9 amino acid sequence produced by a recombinant yeast.the hepatitis b virus surface antigen containing the pres2 nine amino acid sequence produced by a recombinant saccharomyces cerevisiae (yhbsag) was purified and its physicochemical properties were determined. ultrastructurally, the yhbsag was found to be a homogeneous spherical particle with a diameter of 24 +/- 4 nm. the homogeneity of the yhbsag particles was also demonstrated by analyses of their buoyant density and isoelectric point. they consisted of protein (53%), lipid (36%) and carbohydr ...19911712147
hbxag in the liver from carrier patients with chronic hepatitis and cirrhosis.formalin-fixed, paraffin-embedded specimens from 110 cases of chronic hepatitis and 108 cases of cirrhosis were stained for hbxag by the avidin-biotin complex technique using specific antisera made against full-length hbxag polypeptide or derived synthetic peptides. these tissues were also stained for the hbsag and hbcag by the peroxidase-anti-peroxidase method. among patients with chronic hepatitis, 86% were hbsag positive in liver cells, 60% were surface antigen positive and 32% were core anti ...19911712339
minor role of hepatitis b virus in the causation of chronic liver disease in somalia indicated by a case-control study.chronic liver disease (cld) is frequent in somalia. in a case-control study, 116 in-patients with cld were compared with the same number of age and sex matched controls. demographic variables, use of drugs, symptoms and signs, serological markers for hepatitis b virus (hbv) and serum alpha-foetoprotein (afp) were assessed. hepatitis b surface antigen (hbsag) was found in 44 cases of which 17 had antibodies to hepatitis d virus (anti-hd) and 7 had hepatitis b e antigen (hbeag). twenty-three contr ...19911712517
characterisation of a linear binding site for a monoclonal antibody to hepatitis b core antigen.the complete amino acid (aa) sequence of the hepatitis b virus (hbv) core protein (hbcag), ayw subtype, was synthesized as decapeptides with five overlapping aas. the peptides were tested for reactivity with monoclonal antibodies (mabs) to hbcag (35/312, 37/275, and 7/275). all the mabs specifically inhibited human anti-hbc by cross competition in assays for anti-hbc and anti-hbe. the mab 35/312 recognised a peptide covering residues 76-85 of the hbcag sequence. the other two mabs did not react ...19911713264
human and murine b-cells recognize the hbeag/beta (or hbe2) epitope as a linear determinant.the complete amino acid (aa) sequence of the hepatitis b virus (hbv) core protein (hbcag), deduced from the genome of the hbv ayw subtype, was synthesized as decapeptides with five overlapping aas. the peptides were tested for reactivity with monoclonal antibodies (mabs) to the beta (or hbe2) epitope of hepatitis b e antigen (hbe/b mabs; 57/8, 78/3, 141/158 and 141/207). cross-competition between the mabs with a mab to the hbe/alpha epitope (or hbe1) and an anti-hbc mab showed that all the hbe/b ...19911713295
[current view on the anti-hepatitis b therapy]. 19911713808
immunogenicity of foreign peptide epitopes expressed in bacterial envelope proteins.we have used two bacterial proteins from escherichia coli to express heterologous peptides. both proteins are situated in the e. coli cell envelope but have different properties: lamb is an integral outer membrane protein, and male a soluble periplasmic protein. the peptides were expressed as genetic inserts within "permissive sites" of these recipient proteins, i.e. sites which allow the insertion of foreign peptides without affecting the biological properties of the host protein. in this paper ...19901714094
[treatment of chronic hepatitis b and c with alpha interferon]. 19911714130
export of intracellular hbsag in chronic hepatitis b virus infection is related to viral replication.serum and liver hbsag bear an inverse relation to each other during the evolution of chronic hepatitis b virus infection and the quantity of hbsag in tissue rises gradually with time. in this study, intracellular and extracellular levels of hbsag were measured by radioimmunoassay in primary culture of hepatocytes from 30 patients with chronic hepatitis b virus infection to determine a possible relationship with hepatitis b virus replication. serum levels of hbsag correlated with markers of activ ...19911714871
hepatitis c virus in patients with polyarteritis nodosa. prevalence in 38 patients.in order to assess the prevalence of hepatitis c virus (hcv) in polyarteritis nodosa (pn), 38 patients with systemic necrotizing angiitis were retrospectively tested for the presence of anti-hcv antibodies (ab). twenty-one patients were hepatitis b virus (hbv) positive, comprising group a, and 17 were hbv negative, comprising group b. two patients from group a had anti-hcv ab (2/21: 9.5%). one was treated unsuccessfully with corticosteroids, then with vidarabine and plasma exchanges; hbe/anti-hb ...19911715249
[prevalence of hepatitis virus (hbv and hcv) and hiv-1 infections in a prison community]. 19901715727
inhibition of human hepatocellular carcinoma and hepatoblastoma cell lines by deferoxamine.inhibition of human hepatocellular carcinoma (plc/prf/5 and hep3b) or hepatoblastoma (hep g2) cell lines by inclusion of deferoxamine mesylate (desferrioxamine) (dfx) in the culture medium was evaluated. when plc/prf/5 cells were maintained for 7 days in 30 or 60 microm dfx, the cell number was decreased by 30-60%, little or no alpha-fetoprotein (afp) was produced, and supernatant endpoint dilution titers of hepatitis b surface antigen (hbsag) were reduced 1-2 logs. plc/prf/5 cells maintained fo ...19911715897
a cell culture assay for compounds which inhibit hepatitis b virus replication. 19911716089
therapy of chronic viral hepatitis.chronic infection with hepatitis b virus (hbv), the delta agent (hdv) or hepatitis c virus (hcv) carries high risks of chronic liver disease which can result in cirrhosis and hepatocellular carcinoma. many antiviral agents have been tried to inhibit viral replication and thereby limit infectivity and the risks of eventual serious liver disease. interferon offers a 30-40% chance of viral clearance to the hepatitis b carrier, offers a good chance of clinical response in parenterally acquired chron ...19911716277
transcriptional control of hepadnavirus gene expression. 19911716544
molecular heterogeneity of e antigen polypeptides in sera from carriers of hepatitis b virus.hepatitis b e ag (hbeag) was isolated from pooled sera of carriers, without abnormalities in liver function, by affinity column chromatography with mab against hbeag. hbeag polypeptide with an estimated molecular size of 20,000 da (p20e) was detected, in addition to regular hbeag polypeptides (p17e/p18e). p20e, as well as p17e/p18e, did not bind with mab against the carboxyl-terminal domain of the c-gene product. p20e disclosed an n-terminal sequence of mqlfhlxlii- (x unknown), whereas p17e had ...19911717588
phosphorylation in the carboxyl-terminal domain of the capsid protein of hepatitis b virus: evaluation with a monoclonal antibody.the capsid protein of hepatitis b virus (p21c) is made of 183 amino acids coded for by the c gene. by using p21c isolated from dane particles (hepatitis b virus) as an immunogen, a monoclonal antibody (no. 2212) which recognized an epitope dependent on the phosphorylation of p21c was raised. the binding of no. 2212 antibody to authentic p21c was completely inhibited by a synthetic undecapeptide with a sequence of rrrsqsprrrr, representing amino acids 165 to 175 of p21c, only when the peptide was ...19911717713
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