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In Asia, Africa, and other tropical areas, primary hepatic carcinoma (PHC) is associated with liver cirrhosis of the postnecrotic (macronodular) type. Chronic viral hepatitis is likely to be the cause of this cirrhosis in many patients from regions where chronic infection with the hepatitis B virus (HBV) is common. More than 95% of patients with hepatoma (in Mali and Senegal) have evidence of infection with HBV, a much higher frequency than in controls. Thirty-nine of 62 patients with PHC had hepatitis B surface antigen (HBsAg) (controls, 8 of 98) and 56 of 63 (controls, 26 of 100) had antibody against hepatitis B core antigen (anti-HBc). In earlier studies, we demonstrated a maternal effect of HBsAg. If the mother has the antigen and the father does not, the children are much more likely to also have HBsAg than if the father has the antigen and the mother does not (93/161 = 57.8% when mother is positive vs. 28/135 = 20.7% when father is positive; P = 0.6 X 10(-10)). Studies in Greece and in the Solomon Islands show that presence of HBsAg in parents affects the sex ratio of the offspring of the mating. This implies that the presence of the agent in a parent can affect the fetus early in life. Parental studies in the west African hepatoma patients showed that there is a very high frequency of HBsAg in mothers (71.6%), while the frequency in fathers (18.5%) is significantly less. This suggests that the development of hepatoma in offspring is related to infection in parents. Several years ago, we described a vaccine which may be useful in preventing infection with hepatitis B. Strategies are discussed which might be effective in preventing the development of carriers with, it is hoped, a consequent decrease in the frequency of HBV carriers, chronic hepatitis, and primary hepatic carcinoma. The strategy would employ methods for decreasing the frequency of the agent in the environment by the application of public health methods including the vaccination of appropriate newborns and other members of the population.

A sensitive method for the detection of hepatitis B surface antigen (HBsAg) is described whereby the separation of specific antibody by affinity chromatography is incorporated into one of the assay reagents. HBsAg, which may be obtained from tissue culture fluids of a human hepatoma cell line, is first reacted with polystyrene beads. Unoccupied spaces on the plastic are next covered with a non-specific protein (e.g. albumin). The plastic is then reacted with either whole antiserum or an IgG fraction of anti-HBs. Care must be taken to cover all of the reacting sites of the first layer of HBsAg with sufficient anti-HBs. This results in a reagent capable of detecting antigen. No affinity purified antibody was necessary because the reagent, at this stage, contains only specific antibody on the surface. Antigen reacting with this reagent can be detected by the addition of radioactively labeled IgG fraction of anti-HBs, which will complete the ‘sandwich’. This assay has been evaluated and found to be as sensitive as those commercially available.

Sera from 588 woodchucks were assayed for woodchuck hepatitis virus (WHV) markers using hepatitis B virus (HBV) reagents which have cross-reactivity with WHV markers. Twenty per cent of these woodchucks, trapped in Delaware, Maryland and Pennsylvania, had WHsAg; 50% of these had DNA polymerase. There are areas of high and low endemicity within these states. Female woodchucks may have a higher incidence of WHV markers than do males. Woodchuck hepatitis surface antigen (WHsAg) and anti-WHc often occur together but less commonly than HBsAg and anti-HBc do in human HBV infection. Experimental infection of woodchucks with WHV produced a prolonged infection (up to 40 weeks). WHsAg and DNA polymerase appeared to be more reliable indicators of infectivity than anti-WHc, woodchuck hepatitis e antigen (WHeAg) or anti-WHe. WHeAg was not detected throughout this period of infection, while anti-WHe appeared late in two of three experimentally infected animals. Four male and four female woodchucks which developed primary hepatocellular carcinoma in captivity were analyzed for WHV markers throughout their period of confinement. Seven were WHsAg and anti-WHc positive when captured. The animal that was free of WHV markers on capture converted to the WHsAg and anti-WHc positive state prior to the development of primary hepatocellular carcinoma. One primary hepatocellular carcinoma animal produced WHeAg and none anti-WHs or anti-WHe.

Australia antigen was found in clams contaminated by drainage of untreated sewage from a coastal hospital. In closed-system aquariums, the antigen was ingested by clams and transmitted to previously uninfected clams. In opensystem aquariums, the titer of Australia antigen decreased with time, suggesting viral concentration rather than replication.

Summary1) Various microorganisms were studied for ability to metabolize myricyl palmitate (beeswax), tubercle wax, and tributyrin. All cultures except one produced positive results varying only in rate and extent to which they attacked these substrates. A pronounced lag phase in utilization of substrate by 3 microorganisms tested was attributed to saturation of enzyme sites with endogenous substrates. 2) With the exception of Candida albicans intact cells did not show esterase activity. However, positive results were obtained with extracts which suggested that deesterification was an initial step in utilization of waxes as sources of energy for the various microorganisms tested.

SummaryNine different human anti-Australia antigen antisera were compared to each other using population and immunologic methods. Six of the antisera fell into the same category (Philadelphia I) and included specificities detected by the previously described anti-Au(1) antisera. There were three antisera, each of which contained specificities different from those in the anti-Au(1) category. They are to be examined to see whether they identify forms of hepatitis or other conditions different from those detected by anti-Au(1).

Subtypes of hepatitis B antigen (HBAg, Australia antigen) were investigated in 29 HBAg positive sera of asymptomatic carriers and hepatitis patients, living in different areas of Peru. Ethnically, 10 of them were from Indians and 19 from Mestizos. All of these HBAg sera were found to be subtype adw.

(1971). Australia Antigen and Hepatitis: A Comprehensive Review. CRC Critical Reviews in Clinical Laboratory Sciences: Vol. 2, No. 3, pp. 473-528.

SummaryAntibodies to the Australia antigen were shown to be present in the ascitic fluid of mice hyperimmunized with Australia antigen-Freund's adjuvant mixtures. As much as 100 ml can be removed from individual mice if they are restimulated by intraperitoneal injections of adjuvant-saline mixtures. The antibodies contained in these ascitic fluids were shown to be both of the gamma G and gamma M types. The specificities of the antibodies contained in the mouse ascitic fluid were shown to be similar but not identical to human antibody to Australia antigen.

SummaryMycobacterium tuberculosisvar. hominisstrains H37Rv, H37Ra and H37RaN; Mycobacterium tuberculosisvar. bovisstrain BCG-4; and Mycobacterium smegmatiswere ground in a ball mill and fractionated according to the methods outlined earlier(2). Enzymes aconitase. fumarase. DPNH oxidase, catalase. cytochrome oxidase, isocitric, alpha-ketoglutaric, malic and succinic dehydrogenase were localized in one or more fractions using the two criteria established by Alexander and Wilson(12a. b). Cytochrome oxidase. DPNH oxidase and succinic dehydrogenase were found to be particulate bound by both criteria. However, the locus of other enzymes determined by one criterion did not always coincide with that determined by the second criterion. A modified criterion was then established and this was discussed. With the new criterion most of the enzymes of the tricarboxylic acid cycle and terminal electron transport system could be localized. The particles found within the various fractions were electron opaque and labile to...

BLUMBERG and his colleagues have published data on the relation of Australia antigen, Au(1), to hepatitis1,2. While existing antisera, either of human or rabbit sources3, frequently can be used to detect this antigen in patients with hepatitis by either immunodiffusion4 or complement fixation5 it is probable that the antigen is undetectable in some patients. One possible reason for this may be the neutralization of antigen by antibody. Sera may manifest the presence of antigen at one time and antibody at another time2. In such a case, a precipitin band forms between sera from early and later bleedings from the same patient.

Excerpt The association of Australia antigen (Au(1)) with viral hepatitis led to the hypothesis that it is a hepatitis virus. We have published clinical, epidemiologic, immunologic, and electron mi...

Endemic hepatitis occurred among the personnel of a research laboratory working with human blood and tissues in the study of Australia antigen (Au(1)). All individuals were tested for seru...