[Significance of HBe antigen in acute HBs antigen-positive hepatitis (author's transl)].
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Biomedical subjects
Publications and source records attributed to F Deinhardt.
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The tumour-promoting agents 12-0-tetradecanoylphorbol-13-acetate (TPA) and phorbol-12, 13-dibutyrate (PDB) I are potent mitogens for human peripheral blood lymphocytes. In contrast, the non-cocarcinogenic substance phorbol lacks lymphocyte-activating properties. Non-toxic levels of retinoic acid (RA) or retinyl acetate (RAt) inhibit the phorbol-ester-stimulated lymphocyte blastogenesis required the near-concurrent addition of retinoids. Differences in the sensitivity of phorbol-ester-stimulated lymphocyte subpopulations to the antagonistic action of RA or RAt, respectively, suggest that the inhibitory effect of retinoids may not be due to a common mode of action. Lymphocyte cultures may provide a useful model system for studies of the mechanisms of action of both phorbol esters and retinoids.
Sera from 1966 Bavarian blood donors were investigated by radioimmunoassay for serological markers of past hepatitis A and B infections. The prevalence of hepatitis A antibody increased with age and was higher in the urban than in rural populations. More than 80% of persons above 40 years of age had antibody whereas only few young adults showed previous exposure to hepatitis a virus. 20 of 1093 random persons (1.8%) were HBsAg positive at first blood donation. In all age groups anti-HBc was the best marker for previous hepatitis B exposure. There was no correlation between the frequency of hepatitis A and B markers.
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The interrelations of 1) antibody to hepatitis B core antigen (HBcAg)--anti-HBc; 2) single-stranded DNA-binding antibodies (anti-DNA); and 3) the e-antigen/antibody system--hepatitis B e antigen (HBeAg) and antibody (anti-HBe), were studied in 150 hepatitis B surface antigen (HBsAg) carriers, in 43 of whom diagnostic liver biopsies had been performed. There was a good correlation between titers of anti-HBc and anti-DNA, regarded as indicators of viral and pathological activity, respectively, as well as between levels of these two antibodies and the presence of HBeAg or anti-HBE as detected by radio-immune assay (RIA). In general, HBeAg-positive carriers showed high anti-HBc and high anti-DNA titers, while the carriers positive for anti-HBe had low titers of both. These findings were in accord with the histopathological results. The three serologic parameters, anti-HBc, anti-DNA, and e-antigen/antibody, should together prove useful for the evaluation of the clinical status of chronic HBsAg carriers.
Three methods were compared for determining anti-HAV of the IgM class. In the first method flat-bottomed microtiter plates coated consecutively with anti-HAV of the IgG class and HAAg were incubated with patient serum and, after washing, peroxidase conjugated anti-mu was added. After subsequent incubation with substrate the enzymatic reaction was stopped and the optical density was measured. In the second method the solid phase was coated first with antibodies to IgM and after incubation with patient serum and subsequent incubations with HAAg and 125I anti-HAV of the IgG class radioactivity was counted. These two methods were compared with reorienting sucrose gradient ultracentrifugation, an established method for demonstrating specific IgM antibodies. The persistence of IgM anti-HAV in 103 sera drawn at different times after onset of jaundice was evaluated. Sera drawn up to 30 days after onset of hepatitis A were IgM anti-HAV positive with both of the first two methods. Forty-one to 90 days after onset of illness IgM anti-HAV could be demonstrated with the first method in 47% of the patients, in 94% with the second method, and in 82% with gradient centrifugation. The second method was most sensitive and could be adjusted so that at a serum dilution of 1:10(4) anti-HAV IgM was detected only up to six months after infection. In contrast to the first method, nonspecific reactions caused by rheumatoid factor were not detected with the second method. During a one-year period about 15,000 sera of patients with clinical diagnoses of acute hepatitis were tested; the positive results correlated well with the clinical data, and there was no indication of nonspecific positive results.
Hepatitis B e antigen (HBeAg) and its antibody (anti-HBe) were evaluated using a sensitive radioimmunoassay (RIA) in weekly serum samples obtained from nine chimpanzees experimentally infected with hepatitis B virus (HBV). In two chimpanzees with HBV infection with detectable hepatitis B surface antigen (HBsAG) for less than five weeks, and in one chimpanzee with documented HBV infection with no detectable HBsAg, HBeAg was not detected; in all three, anti-HBe became detectable early in the infection. In six chimpanzees in which HGsAg was detected for 16 weeks or longer, HBeAg was detected early in the infection; in five, anti-HBe became detectable and HBeAg undetectable prior to the clearance of HBsAg. The sixth remained HGsAg-positive and HBeAg-positive for more than two years and never developed anti-HBe. These results confirmed the sensitivity of this RIA and its value in predicting the course of HBV infections.
A virus-transformed marmoset lymphoblastoid cell line (LCL) with T-cell characteristics was used for the production of rabbit anti-marmoset T-cell globulin (RAMTG). Exhaustive absorption of the crude antiserum with kidney-liver homogenate and pooled marmoset B-LCL yielded a T-cell-specific antibody. Specificity of the absorbed RAMTG was evidenced by plateau formation in the cytotoxic activity on marmoset peripheral blood lymphocytes (PBL) and clear discrimination between marmoset T-LCL and B-LCL. Unexpectedly, the absorbed RAMTG was not cytotoxic for human PBL. Assays for mitogenic activity showed that unabsorbed RAMTG exhibited mitogenic activity on marmoset, but not on human or baboon PBL. Unabsorbed rabbit anti-human T-cell globulin (RAHTG) induced cellular proliferation in human and baboon PBL, whereas marmoset or Saimiri sciureus PBL showed no response. Absorbed RAMTG did not stimulate DNA synthesis of marmoset PBL. In conclusion, the specific RAMTG may be useful for studies on the functional role of T-lymphocytes in the marmoset immune response to organ allografts or infectious agents.
The presence of the hepatitis B e antigen (HBeAg) and antibody to HBeAg (anti-HBe) was studied by a solid-phase radioimmunoassay in 70 patients with acute hepatitis positive for hepatitis B surface antigen. HBeAg was found in 15 of 16 patients studied within two weeks after onset of symptoms. In total, 45 patients were found positive for HBeAg. The prevalence of this antigen declined constantly during the first 10 weeks after onset of symptoms. Chronic liver disease was demonstrated or suspected in 10 patients, including the five patients who had HBeAg for more than 10 weeks after onset of symptoms. In 33 patients with seroconversion from HBeAg to anti-HBe, 27 (82%) developed anti-HBe within two weeks after the clearance of HBeAg. Among the 58 patients who were or became HBeAg-negative, 53 (91%) had or developed anti-HBe. Thus HBeAg seems to be present regularly in early acute hepatitis B. The persistence of HBeAg may be of prognostic value for the development of a chronic carrier state with hepatitis B surface antigen and/or a chronic liver disease.
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The presence of hepatitis B e antigen (HBeAg) and its antibody (anti-HBe) was studied in 249 asymptomatic carriers of hepatitis B surface antigen (HBsAg) of different ethnic origin and clinical course. Among male homosexuals, renal transplant recipients, and hemodialysis patients, > 90% were HBeAg-positive. In contrast, anti-HBe was present in > 85% of HBsAg-positive Danish pregnant women and blood donors. In presumably immunologically intact persons, significantly elevated levels of transaminases were found in the HBeAg-positive group as compared with the anti-BHe group (P < 0.0001). Among persons with Down's syndrome, males showed a tendency toward clearing of HBeAg and development of anti-BHe as compared with females. In Eskimos a correlation was found between presence of hepatitis B e markers, age of the HBsAg carrier, and geographic origin of the carrier. A similar age relationship was found in Vietnamese refugees. It is proposed that in the general population a correlation may exist between the prevalence of HBsAg carriers and the percentage of HBeAg-positive HBsAg carriers.
Canine thymus cells infected with virus (HL-23V) produced by human acute myelogenous leukaemia cells in culture were shown in previous reports to produce transforming and non-transforming type C virus similar or identical to the simian sarcoma virus complex SSV(SSAV) and to induce tumours in marmoset monkeys (Bergholz et al. 1977a). In these earlier studies the appearance of breakthrough foci at low dilutions of antiserum in neutralization tests with high-titred anti-SSV(SSAV) serum suggested the presence of another virus, distinct from SSV-(SSAV). We now report the isolation of this component and, by comparative neutralization analysis, demonstrate that it is most closely related to gibbon ape leukaemia virus (GALV). It is distinguished from SSV(SSAV) by kinetics of neutralization and molecular hybridization experiments. This component was readily cloned both from virus produced by HL-23V chronically-infected canine thymus cells established by Teich et al. (1975) when HL-23V was first isolated and from virus produced by HL-23V-induced marmoset tumour cells in culture. The presence of this component in the original leukaemic cell cultures is discussed.
Cells producing endogenous and exogenous type-C retroviruses of murine, feline and primate origin were evaluated for expression of those virus-specific cell-surface antigens which cross-react with antibodies to interspecies determinants of mammalian type-C viral polypeptides. Surface polypeptides of cells replicating endogenous and exogenous type-C retroviruses were iodinated by the lactoperoxidase method. Labelled antigens were immunoprecipitated and analyzed in polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. This method detected gp71 and less frequently p15E/p12E on the surface of virus-producing cells; in addition, p27 was found on F422 cells replicating feline leukemia virus. Antibodies to the membrane protein p15E displayed the broadest cross-reactivity but only antibodies to gp71 mediated complement-dependent interspecies cell lysis. The pattern of cross-reactivity reflected known genetic relationships among these mammalian viruses. Although antiserum to the simian sarcoma virus complex (SSV) was strongly cytotoxic to some human tumor cell lines, this reactivity could not be attributed to antibodies cross-reacting with SSV gp71.
Attempts were made to transform human cervical cells and nonhuman primate cells with herpes simplex virus (HSV). None of 129 cervical cell cultures obtained from 29 patients and infected in vitro with various strains of HSV became transformed. Established cell lines of marmoset cells infected with HSV showed no characteristics of malignant transformation. Parallel cultures of rat embryo cells maintained under similar experimental conditions became malignant.
Nontoxic concentrations of retinoic acid enhance DNA synthesis of human peripheral blood lymphocytes in response to phytohemagglutinin or rabbit-antihuman thymocyte globulin, whereas the response to concanavalin A or pokeweed mitogen remained unaffected. Retinoic acid-induced stimulation of lymphocyte reactivity to phytohemagglutinin or antithymocyte globulin was most evident in T cell-enriched subpopulations and required the near-concurrent addition of retinoic acid and mitogens. Retinoic acid-mediated enhancement of lymphocyte proliferation in response to phytohemagglutinin or antithymocyte globulin was paralleled by a concomitant suppression of immune interferon production of lymphocytes stimulated with these mitogens. These findings allow further studies on the immunoregulatory action of retinoids in vitro.
The tumour promoting phorbol ester TPA induces the production of lymphocyte-activating factors (LAF) by human peripheral blood lymphocytes. The noncocarcinogenic and nonmitogenic agent phorbol lacks LAF-inducing properties. Production of LAF by TPA-stimulated lymphocytes occurs independent of the presence of macrophages in cultures and shows a correlation to the dose of TPA used for lymphocyte activation. The possible implications of these observations for the in vitro interaction of phorbol esters and cells of the haemopoietic system are discussed.