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Biomedical subjects

R H Purcell

Publications and source records attributed to R H Purcell.

At least 271 records · Page 15Linked to original sources
PubMed1983

Primate animal models and titered inocula for the study of human hepatitis A, hepatitis B, and non-A, non-B hepatitis.

Although many primate species have been inoculated with the agents of human hepatitis A, B, and non-A, non-B, only a small number of species have been shown to be susceptible, and only the chimpanzee (Pan troglodytes) has been shown to be reproducibly susceptible to all three types of human hepatitis. Infectious inocula containing each agent have been identified in different laboratories and the end-point titers of infectivity determined, in most cases by inoculation of chimpanzees. These inocula and the nonhuman primate models have permitted investigators to study the inactivation of these agents and to evaluate passive and active immunization against the agents.

Animals↗
PubMed1983

New approaches to hepatitis B vaccines.

Current HBV vaccines are composed of subviral forms of HBsAg purified from pooled human plasma, inactivated and absorbed to alum. These vaccines have established an excellent record of safety and efficacy in clinical trials to date. Economic factors and theoretical safety problems associated with the plasma donor population, however, have stimulated an intense interest in the development of alternative vaccines for HBV. The recombinant DNA and synthetic peptide approaches appear to offer the greatest potential for future generations of HBV vaccines. Such vaccines would be free of the potential safety problems associated with plasma source material and could assure the continued supply of uniform HBsAg for vaccine use.

Animals↗
PubMed1983

Live attenuated vaccine for hepatitis A.

The successful development of hepatitis B vaccines has stimulated interest in the active immunoprophylaxis of type A hepatitis. The development of hepatitis A vaccines has been simplified by the ability to propagate HAV in tissue culture systems and the availability of animal model systems, including the chimpanzee and certain species of marmosets in which to evaluate safety and efficacy of candidate vaccines. Both inactivated and live, attenuated hepatitis A vaccines are possible, but the limited replicative ability of HAV in tissue culture makes the former impractical at present. However, HAV appears to be rapidly attenuated by serial passage in tissue culture and such attenuated strains are candidates for a live, attenuated vaccine similar to the Sabin polio vaccine. The HM-175 strain of HAV, recovered from the stool of a patient with type A hepatitis in Melbourne, Australia, was isolated directly in primary African green monkey kidney (AGMK), a cell substrate suitable for vaccine development. This strain has been serially passaged over 20 times in AGMK. The parent strain (stool extract) and virus at tissue culture passages 10 and 20 were evaluated for infectivity and virulence in seronegative chimpanzees. The parent strain produced evidence of liver damage (elevated liver enzymes) at all dilutions of infectious virus tested. In contrast, tissue culture-passaged virus was fully infectious for chimpanzees, but did not produce biochemical evidence of hepatitis. Similarly, hepatitis A viral antigen could not be detected in liver biopsies and little or no viral antigen could be detected in acute phase stool samples.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

The woodchuck animal model of hepatitis B-like virus infection and disease.

As a model of virus-induced disease, the WHV/woodchuck system is at an early stage of development; yet, much progress has been made and there now exists considerable evidence that WHV causes serious liver disease with major parallels to HBV infection of man. The relatively short interval (4-5 yrs) from infection to end-stage disease in this model provides unique opportunities for definition of the natural history of HBV disease and the evaluation of various intervention strategies (e.g., vaccine prophylaxis and anti-viral therapy). Such studies are currently in progress in a number of laboratories.

Animals↗
PubMed1982

Natural and experimental infection of woodchucks with woodchuck hepatitis virus, as measured by new, specific assays for woodchuck surface antigen and antibody.

Solid-phase radioimmunoassays for woodchuck hepatitis virus (WHV) surface antigen (WHsAg) and antibody to it (anti-WHs) were developed. The test for WHsAg could detect as little as 10 ng/ml. In both tests it was necessary to employ radiolabeled WHsAg instead of anti-WHs as the probe because the latter appeared to be labile to the conditions of labeling. The tests were used to characterize naturally acquired and experimental WHV infections of woodchucks. Forty-three of 72 wild-caught woodchucks had serological evidence of WHV infections; 16 of these resulted in chronic infection, and the remainder were self-limiting. All chronically infected animals were positive for WHsAg and DNA polymerase activity. During 3 years of observation, 11 of the 16 WHsAg-positive animals and 3 of the 27 anti-WHs-positive animals, but none of the 21 uninfected animals developed hepatocellular carcinoma. Seroconversion, possibly resulting from infection with WHV, was documented in a chimpanzee inoculated with WHV. An immune adherence hemagglutination test for WHsAg was also developed by using anti-WHs of chimpanzee origin as a reagent, but the test was not useful for detecting anti-WHs of woodchuck origin because of the lability of the latter.

Animals↗
PubMed1981

Donor transaminase and recipient hepatitis. Impact on blood transfusion services.

To assess the relationship of donor alanine aminotransferase (ALT) level to recipient hepatitis, 283 transfused patients were prospectively followed up after open heart surgery; hepatitis developed in 12.7%, of which 97% was non-A, non-B. The ALT tests of 3,359 donors to these patients indicated that risk of hepatitis was significantly associated with the level of donor ALT; 29% of 52 patients receiving at least 1 unit of blood with an ALT level greater than 53 IU/L had hepatitis develop (20.7 cases per 1,000 units), compared with 9% of 231 recipients of only blood with an ALT level of 53 IU/L or less (7.8 cases per 1,000 units). Calculation of corrected efficacy predicts that, at an exclusion level equivalent to 2.25 SDs above the mean log for normal subjects, ALT testing of donors could prevent 29% of posttransfusion hepatitis at the loss of 1.6% of donor units.

Alanine Transaminase↗
PubMed1981

Serodiagnosis of viral hepatitis A by a solid-phase radioimmunoassay specific for IgM antibodies.

A solid-phase radioimmunoassay for detecting specific IgM antibodies to hepatitis A virus (HAV) was developed and characterized. The test utilized microtiter plates coated with anti-IgM to specifically absorb the IgM antibodies from the test serum. The anti-hepatitis A IgM antibodies are measured by the specific consecutive binding of hepatitis A antigen and radiolabelled anti-hepatitis A antibodies (anti-HA). In 6 chimpanzees infected with HAV, IgM anti-HA was detected from about the first date of elevated transaminases and was positive for about 3 months. The usefulness of the test was confirmed by testing acute phase sera of 30 patients from a common source outbreak of epidemic hepatitis, and negative sera from 2 control groups. A collection of serum specimens from 190 patients with sporadic HBsAg-negative hepatitis in Brazil was also tested and an etiologic association with HAV was confirmed in the majority of these cases.

Alanine Transaminase↗
PubMed1981

Non-A, non-B hepatitis after experimental transmission of malaria by inoculation of blood.

In a 1969 prisoner volunteer study of malaria transmission by blood inoculation, six persons were subinoculated sequentially, and acute hepatitis occurred in the last four (sequential study). Subsequently, another 15 volunteers receiving malaria-rich blood from 14 different donors were followed prospectively (prospective study), and hepatitis developed in six. Incubation periods were shorter but serum transaminase levels were higher for the cases of hepatitis occurring in the sequential study than in the prospective study. Although the illnesses were clinically mild, elevations in transaminase levels persisted for more than six months in five and fluctuating transaminase activities were observed in nine of the 10 affected persons. In addition, an 11th prisoner developed sporadic hepatitis. Neither known human hepatitis viruses nor malaria could be implicated in these cases, which were classified as non-A, non-B (NANB) hepatitis. The data suggested that the viremia of short-incubation NANB hepatitis may begin within the first week after inoculation, confirmed that NANB hepatitis may be transmitted either percutaneously or nonpercutaneously, and provided further evidence that there is more than one NANB agent.

Adult↗
PubMed1981

Non-A, non-B hepatitis in chimpanzees and marmosets.

Nine of 15 specimens of human origin thought to contain non-A, non-B hepatitis agents caused hepatitis in recipient chimpanzees. Two have been further characterized. One inoculum, designated strain F, has been reported to produce unique cytoplasmic changes detected by electron microscopy in liver biopsy specimens; the other, strain H, produced distinctive nuclear changes. It is not yet clear whether these two changes result from infection by different agents; they have been useful markers of non-A, non-B hepatitis in chimpanzees. Strain F was serially passaged six times in chimpanzees, and the infectivity titer of the strain F plasma was estimated to be less than 10(2)/ml. Strain H had an infectivity titer in chimpanzees of at least 10(6)/ml. Both the strain F and strain H agents have been successfully transmitted and serially passaged in marmosets. Although hepatitis was detected in a lower percentage of marmosets than chimpanzees given either the strain F or H inoculum, the infectivity titer of the strain H agent appeared to be greater than or equal to 10(8) marmoset infectious doses/ml.

Acute Disease↗
PubMed1981

Propagation of human hepatitis A virus in African green monkey kidney cell culture: primary isolation and serial passage.

Human hepatitis A virus (HAV) was propagated in primary African Green Monkey (Cercopithecus aethiops) kidney (AGMK) cell cultures. Three strains of HAV were used: MS-1, SD-11, and HM-175. Cells were inoculated with marmoset-passaged material or human clinical specimens and were stained by direct immunofluorescence to establish the identity of the virus. Both clinical samples and marmoset-passaged material produced immunofluorescence. HAV antigen was found scattered throughout the cytoplasm of inoculated cultures. The HM-175 strain produced the most intense immunofluorescence. This strain of HAV had been serially passaged in cell culture seven times. Blocking experiments with paired human sera from naturally acquired HAV infections and hyperimmune chimpanzee serum from an experimentally infected animal established that the immunofluorescence was specific. The viral antigen was found to be exclusively intracellular. The interval to maximum HAV antigen expression was decreased by serial passage. The HAV strain described herein, which was recovered directly from the stool specimen of a patient with HAV in primary AGMK cell culture, may prove useful as a source of antigen for serological tests and as a candidate vaccine strain.

Animals↗
PubMed1981

Microbiological, serological, and histopathological features of experimental Chlamydia trachomatis urethritis in chimpanzees.

A laboratory-passaged genital strain of Chlamydia trachomatis and two unpassaged genital strains from patients with nongonococcal urethritis were inoculated intraurethrally into three young male chimpanzees. Chlamydia were recovered from the urethra of two animals and specific antibody responses were detected in all of them. Furthermore, a urethral polymorphonuclear leucocyte response, but not an overt discharge, occurred in all the chimpanzees about 1-2 weeks after inoculation. None of these events occurred in a chimpanzee inoculated with medium only. At necropsy three months after inoculation the submucosa of the urethra of one chimpanzee was densely infiltrated with small round cells. This suggests that a similar chronic lymphocytic response may occur in human chlamydial infection of the urethra.

Animals↗