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Biomedical subjects

F B Hollinger

Publications and source records attributed to F B Hollinger.

153 records · Page 9Linked to original sources

Current tests for antibody to hepatitis b core antigen used to screen donors for non-A, non-B hepatitis are comparable to the original radioimmunoassay for hepatitis B core antigen.

Prospective studies have shown a relationship between the transfusion of donor blood which is positive for antibodies to hepatitis B core antigen (anti-HBc) and an increased incidence of non-A, non-B hepatitis. The anti-HBc test was selected on the assumption that epidemiologic circumstances predisposing donors to hepatitis B infection also might favor exposure to non-A, non-B hepatitis. Current radioimmunoassays (RIA) and enzyme-linked immunoassays (EIA) for anti-HBc utilize hepatitis B core antigen (HBcAg) prepared by recombinant DNA technology, whereas the original RIA anti-HBc assay used HBcAg derived from hepatitis B virions. In the current study, 1329 sera were evaluated of which 23.3 percent were anti-HBc positive. The results indicate that sensitivity, specificity, and positive and negative predictive values of the current EIA and RIA tests for anti-HBc (Abbott Diagnostic Laboratories) are virtually identical to the original RIA test kit. In addition, all donor samples (128 specimens) administered to 57 cases of non-A, non-B hepatitis that were prospectively followed at Baylor College of Medicine for the Transfusion-Transmitted Viruses (TTV) Study group were retested with the EIA-recombinant anti-HBc assay. All 21 samples which were reactive in the original RIA anti-HBc test also were positive by the current EIA procedure. One sample was EIA positive/RIA negative, and 106 other samples were negative by both assays. Thus, commercial anti-HBc kits based on HBcAg derived by recombinant DNA technology, should retain their predictive value for reducing the incidence of non-A, non-B hepatitis as described in the prospective studies.

Antibodies, Viral↗

Infectious liver diseases in three groups of Copenhagen workers: correlation of hepatitis A infection to sewage exposure.

Three groups of Copenhagen municipality male employees-77 sewer workers, 81 gardeners, and 79 clerks-matched for age and duration of employment, were studied for clinical and serological evidence of infection with viral hepatitis types A and B and pathogenic leptospires. "Antibody against hepatitis A virus" (anti-HAV) was found significantly more often among sewer workers (80.5%), than among gardeners (60.5%) or clerks (48.1%). The anti-HAV prevalence rates correlated with age rather than duration of employment. Of all the 11 cases of jaundice reported, only 3 cases (sewer workers) occurred while employed for the city. One case of the 11 resulted from leptospirosis. Anti-HAV was detected in the other 10 subjects and was assumed to be of etiological importance. Hepatitis B serological markers were similar in each group. It is concluded that exposure to metropolitan sewage provides a limited risk of enteric infections, such as hepatitis A, while the hepatitis B virus apparently is not successfully transmitted by this route.

Adult↗

Biophysical and biochemical properties of purified preparations of hepatitis B surface antigen (HBs Ag).

Two antigenically distinct subtypes, adw and ayw, of hepatitis B surface antigen (HBs Ag), have been purified from the plasma of anicteric hepatitis patients. Biophysical studies of these purified preparations revealed considerable heterogeneity in their overall surface charge, morphology and molecular weights. Chemical studies revealed that the composition of the particles is complex in that four to six different polypeptides and three glycoproteins were identified. In addition, cholesterol, three polar lipids, and two glycolipids were detected in purified HBs Ag preparations. Antisera, prepared in guinea pigs to individual polypeptides derived from HBs Ag subtypes adw and ayw, reacted with both the group- and type-specific antigenic determinants associated with the intact particles. The potential of these purified preparations of HBs Ag and of the individual subunits derived from them as possible vaccines is discussed. Specific antipolypeptide sera will be utilized to determine whether HBs Ag components are synthesized as specific viral products or are composed of components of modified host-cell molecules.

Amino Acids↗

Hbc ag, anti-HBC, and DNA polymerase activity in transfused recipients followed prospectively.

Hepatitis B core antigen, antibody to core antigen, and DNA polymerase activity were measured in sera from a select group of post-transfusion hepatitis B patients who had been followed prospectively following blood transfusion. Preliminary results of this study have revealed (1) that RIA testing of blood would not eliminate but would reduce post-transfusion hepatitis B infections by about 50 per cent; (2) that infection with HB virus is modified or aborted in the presence of pre-existing antibody to HB surface antigen; and (3) that transfusion of blood containing anti-HBs does not increase the risk of post-transfusion hepatitis B. HBc Ag and/or DNA polymerase activity were observed in the sera of all recipients tested who developed liver enzyme abnormalities along HBs Ag and anti-HBc. DNA polymerase activity usually occurred in the early stages of incubation before the transaminase became abnormal, whereas HBc Ag was more often associated with increasing enzymatic evidence of liver damage, suggesting release of core structures from the hepatocytes. The presence of DNA polymerase without detectable HBc Ag may be due to the presence of intact Dane particles in the sera, preventing recognition of the core antigen. No serological evidence of hepatitis B was observed in the sera of 24 other recipients who developed abnormal transaminases. Immunoelectron microscopy of these same sera revealed evidence of exposure to hepatitis A antigen following transfusion in at least two recipients.

Antibodies↗

Endogenous DNA polymerase-positive core particles from hepatitis-infected hepatocytes.

The purification is described of liver-derived hepatitis B core antigen (HBc Ag) from human hepatocytes demonstrating only intranuclear particles by electron microscopy. The purified preparation contained 5 x 10(11) particles per ml. The particles were mono-dispersed and relatively free of background material. DNA-dependent polymerase activity was present and had greater activity than an equal number of cores derived from Dane particles isolated from plasma. Specificity of the polymerase reaction was confirmed by precipitation of the activity with specific anti-HBc antiserum. A proportion of the liver-derived core particles was nonreactive for DNA polymerase activity. The polymerase-positive population of particles had a larger size than the polymerase-negative population of liver-derived cores as evidenced by gel filtration in Sepharose 4B.

DNA-Directed DNA Polymerase↗

Agarose gel filtration of concentrated fecal extracts containing virus-like particles associated with hepatitis A.

Virus-like particles shown to be associated with hepatitis A infection were recently visualized by immune electron microscopy in human and chimpanzee acute-phase fecal extracts. Agarose gel filtration of concentrated chimpanzee fecal extracts containing those 27-nm diameter particles separated more than 99% of the high molecular weight fecal impurities into two major peaks as determined by absorbance at 280 and 260 nm. The hepatitis A-associated particles were found between these two peaks by both immune electron microscopy and a new immunoradiometric assay.

Animals↗