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Biomedical subjects

R S Tedder

Publications and source records attributed to R S Tedder.

At least 145 records · Page 8Linked to original sources

Prevalence of antibody to human T-lymphotropic virus type III in AIDS and AIDS-risk patients in Britain.

2000 persons in the UK were examined serologically for antibodies to human T-lymphotropic virus type III (HTLV-III). Sera reacting in a membrane immunofluorescence assay (IFA) to HTLV-III were also positive when tested against cells infected with lymphadenopathy virus (LAV-1), and cross-adsorption tests indicated that these retroviruses are probably identical. A competitive radioimmunoassay (RIA), which was wholly concordant with IFA, was used to screen the sera. 30/31 patients with the acquired immunodeficiency syndrome (AIDS) were seropositive, as were 89% patients with persistent generalised lymphadenopathy (PGL), 17% symptomless homosexual men, 34% haemophiliacs receiving pooled clotting factors, and 1.5% intravenous drug abusers. None of more than 1000 unselected blood donors was seropositive. These data confirm the close association between HTLV-III and AIDS and PGL and show that infection with HTLV-III is also prevalent in the populations in whom these syndromes are most likely to develop. However, it would be unwise to presume that AIDS will necessarily develop in seropositive subjects.

Acquired Immunodeficiency Syndrome↗

Clinical findings and serological evidence of HTLV-III infection in homosexual contacts of patients with AIDS and persistent generalised lymphadenopathy in London.

Between 1980 and 1984 28 homosexual men who had had ano-genital intercourse with patients with either acquired immunodeficiency syndrome (AIDS) or persistent generalised lymphadenopathy (PGL) were followed up. The pattern of the sexual links indicated that within this group there were two clusters, one consisting of 7 men and the other of 13.17 of the 28 contacts became ill with either AIDS or PGL; among those in the clusters, 4 died of AIDS and 11 had PGL, and of the rest 2 had PGL. 16 of the 19 men in the clusters who were tested for HTLV-III antibodies were seropositive, as were 7 of those not in the clusters. 111 men attending a genitourinary medicine clinic who had not had known contact with either AIDS or PGL patients and who were being screened for syphilis served as controls. Of these, 19/86 who were homosexual and 0/25 who were heterosexual were positive for HTLV-III antibodies. None of the 4 who died of AIDS had had contact with each other. The 2 in the first cluster seemed to have been linked by a symptomless HTLV-III-negative man, who was also probably the link between the two clusters, while in the second cluster the chief "carrier" seemed to be a seropositive man in whom PGL developed. These findings are consistent with the hypothesis that HTLV-III is the sexually transmitted causative agent of AIDS and PGL.

Acquired Immunodeficiency Syndrome↗

Low prevalence in the UK of HTLV-I and HTLV-II infection in subjects with AIDS, with extended lymphadenopathy, and at risk of AIDS.

Antibodies reacting selectively with human T-cell leukaemia virus type I (HTLV-I) were detected in approximately 5% patients with extended lymphadenopathy syndrome (ELAS) and in less than 1% of unselected homosexual patients and drug abusers. None of 22 patients with acquired immunodeficiency syndrome (AIDS) had HTLV-I antibodies and neither did 85 haemophiliacs and 940 blood donors. 3 out of 113 drug addicts had high titres of antibodies to human T-cell leukaemia virus type II (HTLV-II). A T-cell line was derived from 1 of the seropositive ELAS patients. This line was found to be infected with, and releasing, HTLV-I. Infection by HTLV-I and HTLV-II retroviruses thus occurs more frequently in ELAS patients and drug addicts than in the UK population as a whole, but the low prevalence of these infections in ELAS and AIDS patients indicates that these two strains of lymphotropic retroviruses have no aetiological role in ELAS and AIDS.

Acquired Immunodeficiency Syndrome↗

Antibody assays for varicella-zoster virus: comparison of competitive enzyme-linked immunosorbent assay (ELISA), competitive radioimmunoassay (RIA), complement fixation, and indirect immunofluorescence assays.

The competitive ELISA test was compared with competitive RIA, complement fixation, and indirect fluorescent antibody test for the detection of antibody to varicella-zoster virus (VZV). ELISA and RIA were the most sensitive tests, being tenfold as sensitive as indirect immunofluorescence and 20 times as sensitive as complement fixation, which was surprisingly inadequate for detecting anti-VZV in sera from regular haemodialysis patients. The ELISA test was found to be the most suitable assay, employing a routine complement fixation test (CFT) grade viral antigen and not requiring radiolabelling and counting facilities, which are unavailable in most virology laboratories.

Adult↗

The immunoglobulin M response to rubella vaccine in young adult women.

Rubella vaccination histories were taken from 333 young women working in the head office of a retail organization: 29% said they had had vaccine and 47% said they had not. The remainder did not know. Forty-six per cent of those less than or equal to 25 years old (who should have been offered vaccine at school), and 6% of those greater than 25 years old, said they had been vaccinated. When screened for immunity to rubella by radial haemolysis (RH) 3% had a low level of antibody (less than 15 i.u./ml) and 11% had no antibody. After immunization with Cendevax the specific rubella IgM response was measured by an IgM antibody capture radioimmunassay (MACRIA). It was only detectable in the group without RH antibody, and was present in 26/31 of them. The IgM response to Cendevax was strongest in specimens taken 20-39 days after immunization, but in 10 out of 11 cases tested was still present at around 71 days. The specific IgM responses to Cendevax were very similar to those in women given Almevax in an earlier study, when measured in parallel tests. Taking both vaccines together, specific IgM was present in 35 out of 36 vaccinees without pre-existing antibody tested between 40 and 77 days post-immunization. Detection of specific IgM by MACRIA would therefore be an effective means of determining susceptibility retrospectively in rubella vaccinees found to be pregnant.

Adult↗

Monoclonal antibodies to hepatitis Be antigen (HBeAg) derived from hepatitis B core antigen (HBcAg): their use in characterization and detection of HBeAg.

A panel of mouse hybridomas secreting monoclonal antibody to serum hepatitis Be antigen (HBeAg) was produced from mice immunized with denatured hepatitis B core antigen (HBcAg). This panel could be divided broadly into two groups. Within each group, the monoclonal antibodies recognized a single antigenic site, designated either e-alpha or e-beta, and generally exhibited a high degree of cross-inhibition. In contrast, between the two groups of antibodies there was little or no cross-inhibition. The antigens of serum HBeAg and denatured HBcAg appeared to be very similar. Both behaved as molecules carrying only a single e-alpha or e-beta site, in spite of native serum HBeAg having an apparent molecular weight of 300 000. It is inferred that e-alpha and e-beta sites may be involved in the polymerization of HBeAg into HBcAg and that during this process mutual masking of antigenic sites may occur.

Animals↗

Immunological characterisation of rubella virion polypeptides.

Antibodies specific for rubella virion polypeptide, VPI, secreted by clones of hybridoma cells or produced in rabbits in response to specific antigenic stimulation, located determinants for haemagglutination inhibiting (HI) and neutralising (Nt) antibodies on this envelope component.

Antibodies, Viral↗

Homosexual men in London: lymphadenopathy, immune status, and Epstein-Barr virus infection.

By November 7, 1983, 24 cases of AIDS in the United Kingdom had been reported to the Communicable Disease Surveillance Centre. At the same time an increasing number of homosexual men with unexplained lymphadenopathy syndrome (LAS) have been seen in our department. Between December 1982 and July 1983, 14 homosexual men with LAS and 11 healthy homosexual men were studied. Patients with LAS had a high number of lifetime episodes of sexually transmitted diseases, a history of recent sexual activity in the United States (9 of 14), sexual contact with British AIDS patients or other persons with LAS (7 of 14), and hypergammaglobulinemia. Low T-helper/T-suppressor ratios (less than 0.8), due mainly to a decrease in T-helper cells, were found in both groups. Lymph node biopsies showed follicular hyperplasia and hypocellular pattern. All 25 patients studied had antibodies to Epstein-Barr virus capsid antigen (anti-VCA) and 11 had antibodies to early antigen (anti-EA); 13 of 17 were excreting the virus; and two showed no Epstein-Barr-virus-specific regression. Peripheral blood immunoglobulin-producing B-cells from six patients with hypergammaglobulinemia were negative for the Epstein-Barr virus nuclear antigen (EBNA). Five lymph node biopsies showed no EBNA-positive cells. Epstein-Barr virus reactivation is common in the patients with LAS and healthy homosexual men in London, but would not seem to be the cause of the polyclonal B-cell activation or lymphadenopathy.

Adult↗

Acute anterior uveitis and hepatitis B virus infection.

The aetiology of acute anterior uveitis (AAU) in the great majority of cases is unclear. Various infective agents have been postulated, however, as playing a direct or indirect part in the disease process, possibly via an immune-complex vasculitis. In an earlier study we concluded that, contrary to a previous report, hepatitis B virus (HBV) played only a small role, if any, in the pathogenesis of uveitis in Great Britain. Since we did not look for other markers of HBV infection other than hepatitis B surface antigen (HBsAg), it is possible that some cases of recent HBV infection may have been missed. In the present study 49 patients with AAU were tested for markers of hepatitis B infection. Sera from all patients tested were found to be negative for HBsAg and for antibody to the HBV core (anti-HBc), excluding HBV as a significant cause of AAU in this country. Since the quest for an infective agent in AAU may remain unproductive, future research on the aetiopathogenesis of AAU should include the study of tissue 'vulnerability' and the local and systemic immunoregulatory factors which modulate inflammatory responses.

Adult↗

Viral infections transmitted by blood and its products.

Modern transfusion practice is associated with an increased risk of transmitting viral agents because of the changing nature of the patients and of the therapeutic blood products. More immunosuppressed patients are receiving blood released faster and with more elaborate blood components. In addition to the classically recognized importance of hepatitis B virus (itself disseminated most efficiently by contamination of products derived from large pools of plasma containing many donations) other agents are assuming increasing importance. They frequently display one or more of the predisposing characteristics of prolonged viraemia, inapparent infections and a carrier or latent state. Some of these infections like cytomegalovirus and the human T-cell leukaemia virus are transmitted only by the cellular component of blood. Others like B and non-A, non-B hepatitis and the putative agent(s) of the newly recognized acquired immune deficiency syndrome can also be transmitted in the plasma or its products. Not all the agents transmitted cause severe illness, however; human parvovirus appears to cause no clinical illness when transmitted by transfusion and infections with non-A, non-B hepatitis are largely detected only by elevations in transaminase levels. Screening tests for the presence of these agents in donor blood or for evidence of infection by them in donors continue to be studied. Other approaches, related in particular to the selection of donors, are becoming increasingly important where serological screening tests are not available.

Acquired Immunodeficiency Syndrome↗

Rubella-specific IgM reactivity in sera from cases of infectious mononucleosis.

Eight sera from 125 cases of infectious mononucleosis (IM) were reactive for rubella-specific IgM in an M-antibody capture radioimmunoassay. The reactivity of individual sera varied depending upon the source of the rubella antigen used in the assay. One serum gave strongly positive results with some rubella haemagglutinating antigens but negative results with others and may have contained an IgM antibody which was capable of distinguishing between strains of rubella virus. If the diagnosis of rubella is based solely on detection in solid-phase immunoassay of rubella-specific IgM, IM should be excluded.

Adult↗

Production of monoclonal antibodies to hepatitis B surface and core antigens, and use in the detection of viral antigens in liver biopsies.

Hybridomas secreting monoclonal antibodies to HBsAg and HBcAg were prepared from immunized mice. An antibody capture radioimmunoassay was used to detect and select appropriate hybrids for propagation and cloning. The advantages of this assay were discussed. The resulting monoclonal antibodies were compared with conventional polyclonal antisera for the detection of virus antigens in liver tissue and found to give excellent results.

Antibodies, Monoclonal↗

Serological markers in fulminant hepatitis B.

Serological markers for hepatitis B virus infection have been examined in 34 patients with acute hepatitis B, 17 of whom developed fulminant hepatic failure. Hepatitis B surface antigen concentrations were significantly lower and hepatitis Be antigen was less frequently detectable in patients with fulminant hepatic failure compared with those with acute hepatitis (median 0.64 micrograms, range 16-0 and median 32 micrograms and range 100-4 micrograms respectively, p less than 0.001; HBeAg detected in 12% and 88% respectively, p less than 0.001). The IgM component of hepatitis B core antibody was significantly higher in the patients with fulminant hepatic failure with median values of 500 IU/ml compared with those with uncomplicated hepatitis (median 202 IU/ml, p less than 0.05 Wilcoxon's rank test). Three patients who developed a fulminant course had detectable levels of either anti-HBs or anti-HBe. These results are consistent with enhanced antibody responses to all three hepatitis B virus antigens and more rapid clearance of the latter during fulminant hepatic failure.

Acute Disease↗