Virus-like antigen, antibody, and antigen-antibody complexes in hepatitis measured by complement fixation.

Complement fixation techniques are described for measuring a virus-like antigen associated with viral hepatitis. Antigen was found in the blood of 98 percent of 130 patients, with the serum form of hepatitis, from whom multiple samples were obtained. Antibodies arising during hepatitis are usually combined with antigen and cause anticomplementary activity in the serum, which is reversible with excess antigen or antibody. Tests for antigen and specific anticomplementary activity can be used diagnostically and to screen blood donors for hepatitis carriers.

Hepatitis B virus infection and primary hepatocellular carcinoma.

Ninety-three patients with biopsy-proven primary hepatocellular carcinoma (PHC) from Uganda, Zambia, and the United States were examined for serologic evidence of hepatitis B virus (HBV) infection. Patients were tested for hepatitis B surface antigen (HBsAg) and its antibody (anti-HBs), antibody to the hepatitis B core antigen (anti-HBc), hepatitis B e antigen (HBeAg), and its antibody (anti-HBe). Active HBV infection, as indicated by positive tests for HBsAg (with or without anti-HBs) and anti-HBc (without anti-HBs), was present in 62% of PHC patients (58 of 93), in contrast with 10% of African controls (9 of 90), and less than 1% of most United States adult populations reported in the literature. The presence of HBeAg or anti-HBe was rare among PHC patients and controls.

Development of a pollution prevention and energy efficiency clearinghouse for biomedical research facilities.

This is the report of the National Association of Physicians for the Environment Committee on Development of a Pollution Prevention and Energy Efficiency Clearinghouse for Biomedical Research Facilities from the Leadership Conference on Biomedical Research and the Environment held at the National Institutes of Health in Bethesda, Maryland, on 1--2 November 1999. A major goal of the conference was the establishment of a World Wide Web-based clearinghouse, which would lend tremendous resources to the biomedical research community by providing access to a database of peer-reviewed articles and references dealing with a host of aspects of biomedical research relating to energy efficiency, pollution prevention, and waste reduction. A temporary website has been established with the assistance of the U.S. Environmental Protection Agency (EPA) Regions III and IV, where a pilot site provides access to the EPA's existing databases on these topics. A system of peer review for articles and promising techniques still must be developed, but a glimpse of topics and search engines is available for comment and review on the EPA Region IV-supported website (http://wrrc.p2pays.org/).

Comparative evaluation of radioimmunoassay kits used for testing blood for hepatitis B surface antigen.

A comparative evaluation of six licensed radioimmunoassay kits for the detection of hepatitis B surface antigen (HBsAg) has been performed. Each method met the federal licensure requirements for the test. The performance of the kits varied considerably, however, when they were challenged to the limits of their sensitivities. During the period December 1978 through March 1979, four kits were judged to be of equivalent high sensitivity, whereas two were less sensitive. Three of the kits, including two of those with high sensitivity, generated a high (6%--7%) proportion of false reactive results. The sensitivities of all kits decreased during the shelf lives of the reagents.

Evaluation of hepatitis B antigen testing in federally licensed blood banks in the United States.

Between August 1972 and January 1974, the Burear of Biologics distributed four panels of 20 coded serum samples to all federally licensed blood banks for hepatitis B antigen testing. Initially, all but six blood banks reported results by counterelectrophoresis (CEP) only, but by January 1974, 152 of 247 banks reported results by radioimmunoassay (RIA). On the four panels distributed, correct results were reported for 63 to 83% of all potentially detectable samples by CEP and for 98 to 100% of all samples potentially detectable by RIA. Perfect scores were obtained by only 5 to 25% of blood banks using CEP but by 77 to 100% using RIA. Nonreproducible results on duplicate reactive samples, included to evaluate internal consistency, ranged from 0.5 to 25% by CEP and from zero to 5% by RIA. These results demonstrate greater reliability in addition to greater sensitivity of "third generation" RIA testing in comparison with "second generation" CEP testing.

Liver cell dysplasia: a premalignant condition.

Liver cell dysplasia is defined as cellular enlargement, nuclear pleomorphism, and multinucleation of liver cells occurring in groups or occupying whole cirrhotic nodules. The prevalence, natural history, and relationship to the Australia or hepatitis-associated antigen (HAA) have been studied in 552 Ugandan African patients with normal, cirrhotic, and cancerous livers. Liver cell dysplasia was found in only two of 200 (1%) patients with normal livers, in three of 43 (6.9%) of patients with normal livers bearing primary liver cell carcinoma, 35 of 175 (20.3%) patients with cirrhosis, and 80 of 124 (64.5%) of patients with cirrhosis and primary liver cell carcinoma. Cirrhotic patients without dysplasia were, on average, ten years younger than those with dysplasia and the latter were on average six years younger than those with cirrhosis and carcinoma. Liver cell dysplasia occurred more frequently in males than in females. It was found in all but one instance in macronodular or mixed forms of cirrhosis only. There was a strong relationship between dysplasia and the presence of HAA in 104 patients that suggests a possible carcinogenic mechanism for the longincubation (serum or B) hepatitis virus in liver cell carcinoma. It is concluded that the presence of liver cell dysplasia identifies a group of patients with a high risk of liver cell carcinoma and that they should be followed up by serial alpha-fetoprotein estimations.

Polychlorinated biphenyls (PCBs) selectively disrupt serotonergic cell growth in the developing Spisula embryo.

Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants that exert neurotoxic effects during embryonic development. The present study demonstrates that early embryonic exposure to a mixture of PCBs (Aroclor 1254) results in a decrease in serotonergic cell growth. Using a novel, marine invertebrate embryo model, Spisula solidissima, immunocytochemistry, and confocal microscopy techniques, a dose-dependent decrease in serotonergic cell number was quantified within 24 h of exposure. This effect was seen with doses as low as 1 ppm Aroclor 1254. These findings demonstrate that environmentally relevant doses of Aroclor 1254 impair development of the serotonergic nervous system.

Evaluation of an extensive tuberculosis contact investigation in an urban community and jail.

SETTING: Urban community and jail. OBJECTIVES/DESIGN: Evaluate outcome and process of an extensive tuberculosis contact investigation, including completion of treatment of latent TB infection (TLTBI). RESULTS: Between April 2000 and September 2001, 18 epidemiologically-linked tuberculosis cases were identified; 15 were culture-confirmed, all with a matching 14-band DNA fingerprint pattern. The source case had cavitary pulmonary disease and had been incarcerated 4 months prior to diagnosis. Sixty-six of 67 (99%) community contacts and 221/344 (64%) jail contacts were evaluated. The presumed new infection rate was 56% for community contacts (11 cases, 25 tuberculin skin test [TST] positive) and 20% for jail contacts (6 cases, 32 TST converters). Screening results for 113 (33%) jail contacts were obtained in the jail TST registry upon rearrest. All identified cases completed treatment. Of 22 community contacts initiating TLTBI, 11 completed (44% of infected, 50% of initiators). Of 32 infected jail contacts, 12 initiated TLTBI (all who remained incarcerated), and 10 completed (31% of infected, 83% of initiators). None of 20 additional in-fected jail contacts, all of whose TST conversions were identified with re-arrest data, were subsequently located. Two additional related cases have been identified as of October 2003. CONCLUSIONS: Close health department/corrections collaboration facilitated this extensive contact investigation, which identified high Mycobacterium tuberculosis transmission rates and controlled the outbreak. Numerous contacts were identified and screened, but rates of treatment completion for infected contacts were low. Novel strategies are needed to maximize the number of infected contacts who are not only identified and evaluated, but completely treated.

Antibody to hepatitis B core antigen.

Two distinct antigen-antibody systems are associated with the hepatitis B virus (HBV): hepatitis B surface antigen (HBs Ag) and antibody (anti-HBs) and the more recently described hepatitis B core antigen (HBc Ag) and antibody (anti-HBc). Testing of serial serum samples from patients with type B hepatitis demonstrates the regular occurrence of anti-HBc during the course of this disease. In general, highest titers of anti-HBc are seen with prolonged circulation of HBs Ag as in the chronic carrier state. Titers of anti-HBc begin to fall with recovery from HBV infection and anti-HBc appears to be shorter lived than anti-HBs. As such, anti-HBc testing is important in documenting the occurrence of infection with HBV and is of great value in epidemiologic studies and in evaluating the safety and efficacy of hepatitis B immune globulin and HBV vaccines.

Review of infectivity studies in nonhuman primates with virus-like particles associated with MS-1 hepatitis.

Using the technique of immune electron microscopy we have conducted hepatitis A infectivity studies in marmoset monkeys and chimpanzees. Marmosets inoculated with human serum containing the MS-1 strain of hepatitis A virus have developed hepatitis and seroconverted to 27 nm virus-like particles isolated from stools of humans in the early acute stages of hepatitis. Similar results have been observed through several marmoset subpassages, and the virus-like particles have been recovered from the liver of animals in the acute phase of hepatitis. Chimpanzees inoculated with stool filtrates containing the virus-like particles develop hepatitis with concomitant excretion of the particles in early acute phase stools and subsequent development of serum antibody to the particles. These studies provide evidence that the above particles constitute the virus of hepatitis A of the MS-1 prototype.

Viral hepatitis, type B, in experimental animals.

Evidence of natural infection with hepatitis B virus (HBV) in chimpanzees was followed by demonstration that this species provides a highly sensitive animal model system for experimental type B hepatitis. With rare exceptions, inoculation of sero-negative chimps with materials containing infectious HBV produces serologic evidence of infection including appearance of circulating hepatitis B surface antigen (HBs Ag) and subsequently development of antibody to HBs Ag and hepatitis B core antigen. Serum enzyme elevations indicative of liver damage occurred in 31 of 46 aminals infected to date. The antigenic subtypes of HBV in the inocula breed true in the infected animals, and HBV titers of sera containing the adw and ayw subtypes have been established as 10(7.5) infectious units/ml. Rhesus monkeys also provide a valuable animal model for type B hepatitis, but they appear to be less sensitive than chimps, and they do not develop evidence of liver damage.

Serologic and animal inoculation studies of a communal outbreak of viral hepatitis, type A.

Sera from individuals in an outbreak of viral hepatitis in a multifamily household, probably spread by contaminated food, were studied for antibodies to hepatitis A virus (anti-HAV), and selected acute phase sera were inoculated into marmosets. Significant rises in anti-HAV titers between acute and convalescent sera occurred in all of 15 individuals in the outbreak who experienced serum enzyme elevations and in one of 14 individuals whose serum enzyme levels remained normal. The remaining 13 individuals in the latter group had antibody levels in both early and late sera compatible with residual immunity from prior HAV infections and correlating with resistance to reinfection. Groups of marmosets were infected with acute phase sera from two of the cases; in both instances the inoculated sera contained substantial levels of anti-HAV. The marmosets developed specific anti-HAV seroconversions as well as enzyme elevations.