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Biomedical subjects

R S Tedder

Publications and source records attributed to R S Tedder.

At least 109 records · Page 6Linked to original sources

The cloning and expression in Escherichia coli of sequences coding for p24, the core protein of human immunodeficiency virus, and the use of the recombinant protein in characterizing a panel of monoclonal antibodies against the viral p24 protein.

The sequences encoding the p24 core protein of human immunodeficiency virus type 1 were identified in a cDNA library made from infected CEM cells. The nucleotide sequence of the DNA coding for p24 was shown to be very similar but not identical to the sequences of lymphadenopathy virus and human T-cell leukaemia virus type IIIb. These sequences were expressed in Escherichia coli at the amino terminus of beta-galactosidase and used to screen a panel of monoclonal antibodies raised against virus-expressed p24. Regions containing the epitopes of five of the monoclonal antibodies were located using a series of amino- and carboxy-terminal deletion mutants of the recombinant p24 protein.

Blotting, Western↗

The expression in Escherichia coli of sequences coding for the p18 protein of human immunodeficiency virus and the use of the recombinant protein in characterizing a panel of monoclonal antibodies against the viral p18 protein.

The sequences coding for the p18 protein of CBL-1, a British human immunodeficiency virus (HIV) type 1 isolate, were expressed in Escherichia coli as beta-galactosidase fusion proteins. The recombinant proteins were used to screen a panel of five monoclonal antibodies (MAbs) raised against p18 expressed in CBL-1-infected cells. The regions containing the epitopes for four of the MAbs were located using carboxy deletion mutants and synthetic peptides. The epitope of one of the MAbs (1D9) was reconstructed as part of an unfused, E. coli-expressed p18 protein using the polymerase chain reaction technique. Four different HIV strains and one lymphadenopathy virus type 2 strain were analysed by fluorescence-activated cell sorting of live infected cells using the p18-reactive MAbs.

Amino Acid Sequence↗

Inoculation of New World primates with the human immunodeficiency virus.

The susceptibility of common marmosets and cotton-top tamarins to infection by HIV-2 in vivo was tested. One year and 19 months, respectively, post-inoculation, sera taken from three of four animals from each species are reactive for HIV-2 antibodies and HIV-specific nucleotide sequences were demonstrated in short-term cultures of PBL from two cotton-top tamarins. The animals remain in good health.

Acquired Immunodeficiency Syndrome↗

Envelope cross-reactivity in Western blot for HIV-1 and HIV-2 may not indicate dual infection.

Serological identification of infection with human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) by western blot alone may not be sufficient to diagnose dual infection. Extensive cross-reactions (eg, to envelope glycoprotein antibody) are seen on heterologous western blots. The use of other techniques, in this case competitive enzyme-linked immunosorbent assays, indicates that blot patterns previously thought to demonstrate simultaneous dual infections should be interpreted with caution.

Acquired Immunodeficiency Syndrome↗

Human retroviral infections in The Gambia: prevalence and clinical features.

The prevalence of infection with human immunodeficiency virus type 1 (HIV 1) is lower in west Africa than in other parts of Africa. Human immunodeficiency virus type 2 (HIV 2) has been isolated from west African patients and may be transmitted by heterosexual contact. The prevalence of antibodies to HIV 1 and HIV 2 was studied by enzyme linked immunosorbent assay (ELISA) among various groups of subjects in The Gambia, west Africa--namely, prostitutes, blood donors, patients with suspected infection with HIV, patients attending clinics for sexually transmitted diseases, and patients with tuberculosis. Four cases of the acquired immune deficiency syndrome (AIDS) due to infection with HIV 1 were detected, of which three had been acquired abroad. No other subject was found to be positive for antibodies to HIV 1. The prevalence of antibodies to HIV 2 among the patients attending clinics for sexually transmitted diseases was found to have increased from 0/117 in 1984 to 10/185 (5%) in the last six months of 1986. One out of 278 blood donors was positive for antibodies to HIV 2 as were 10 out of 80 patients with suspected AIDS. HIV 2 seems to be transmitted sexually, and, although it has been present for only a short time, it seems to be endemic in The Gambia and is pathogenic.

Acquired Immunodeficiency Syndrome↗

Incidence of retroviruses in some Brazilian groups.

The prevalence of human T lymphotropic virus type I (HTLV-I) and human immunodeficiency virus (HIV) antibodies was evaluated in Brazil among 116 aboriginal Indians living in a pre-Amazonian region, and in 44 patients with haematological malignant disorders being treated in Rio de Janeiro. Screening for the presence of antibodies to HIV was performed routinely for 17,224 blood donors at the National Cancer Institute, Rio de Janeiro, from January 1986 to May 1987. The results demonstrated that HIV infection was not endemic among Brazilian Indians, as none of them had antibodies to HIV, in contrast with the population of Rio de Janeiro, which showed a high prevalence (0.34%) of positivity among normal individuals. In a small group of patients with haematological disease only one with acute lymphoblastic leukaemia proved to be HIV-positive, the infection having been acquired through previous blood transfusion. None of the serum samples reacted with HTLV-I, including those of 17 non-Hodgkin's lymphoma patients. HTLV-I infection does not seem to be endemic in this country, but further large scale studies are necessary, especially in patients with haematological disorders, homosexual individuals and drug users.

Adolescent↗

Comparison of a monoclonal anti-HIV 1 gag solid phase with a polyclonal anti-HIV solid phase for detecting anti-HIV 1 in a competition ELISA.

An anti-HIV 1 competitive ELISA was developed using a monoclonal anti-HIV 1 gag to capture viral antigen to the solid phase. This format of assay was compared with a competitive ELISA where a polyclonal human anti-HIV 1 was used, to capture the viral antigen. Several benefits were observed using the monoclonal-antibody form of the assay. Firstly, less viral antigen was needed on solid phase to give an equivalent test in terms of positive and negative optical density 450 nm values. Secondly, a slight increase in sensitivity was also gained without any loss of specificity and finally, as a result of the murine nature of the antibody on the solid phase, no cross-reaction with the labelled human antibody in the test conjugate was observed. Such cross-linking has been observed with the polyclonal form of the assay and can lead to false-negative reactions.

AIDS-Related Complex↗

HIV-2 antisera cross-neutralize HIV-1.

The neutralization properties of three independent HIV-2 isolates were examined in comparison with four diverse HIV-1 strains. Human sera containing antibodies specific to HIV-2 can cross-neutralize HIV-1. By contrast, HIV-1 sera are group-specific and have no neutralizing effect on HIV-2. Therefore, HIV-2 antigens may be important components for the development of broadly cross-protective AIDS vaccines.

Antibodies, Viral↗

Hepatitis B virus reactivation or reinfection associated with HIV-1 infection.

Following acute hepatitis B virus (HBV) infection, most individuals develop antibodies to HBV surface (anti-HBs) and core antigen (anti-HBc). Prevalence studies have shown that 10-18% develop anti-HBc in the absence of detectable anti-HBs. We report four such cases, all with persistence of serum anti-HBc, who had evidence of a second period of active HBV replication as demonstrated by the reappearance of serum hepatitis B surface antigen (HBsAg). In one patient, an HBsAg subtype difference indicated that the second period of HBsAg-positivity was due to a reinfection. In the other cases, reactivation may also explain the findings. All cases were anti-HIV-1 seropositive at the time of reappearance of HBsAg. There is experimental evidence that anti-HBc has a protective effect against HBV infection; however, this may require intact cell-mediated immunity to be effective. HIV-1 infection may render such patients susceptible to reinfection. Alternatively, some patients with anti-HBc, but without detectable anti-HBs may have latent HBV infection. Immunosuppression associated with HIV-1 infection may allow reactivation.

Acquired Immunodeficiency Syndrome↗

HIV-2 in UK.

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Antibodies, Viral↗

Impaired responsiveness of homosexual men with HIV antibodies to plasma derived hepatitis B vaccine.

Thirty five homosexual men (17 positive for antibody to the human immunodeficiency virus (HIV) and 18 consistently negative) were vaccinated against hepatitis B virus infection. Eight of the 17 seropositive patients failed to develop detectable hepatitis B surface antibody within three months of the third injection compared with only one of the 18 seronegative patients (p less than 0.01). HIV infection is prevalent in the developed world in groups at risk for hepatitis B infection and in certain Third World countries where widespread vaccination programmes exist. This study shows the impact that coincident HIV infection may have on an otherwise efficacious vaccine. The efficacy of this and other vaccines in patients infected with HIV needs to be studied urgently.

Antibodies, Viral↗

Prevalence of antibodies to human immunodeficiency virus, gonorrhoea rates, and changed sexual behaviour in homosexual men in London.

The prevalence of antibody against human immunodeficiency virus (anti-HIV), which rose among British homosexual/bisexual men attending a London sexually-transmitted-disease clinic from 3.7% (4/107) in March, 1982, to 21% (26/124) in July, 1984, was 18.1% (17/94) in April/May 1985, 24.5% (61/249) in January, 1986, and 25.3% (25/99) in November/December, 1986. This slower rise in anti-HIV prevalence coincided with a fall in the annual gonorrhoea rate from 15.3% in 1982 to 5.1% in the first half of 1986 in the same male homosexual clinic population. Over the same period a reduction in the number of sexual partners and a change to safer sexual practices has been documented among homosexual and bisexual men taking part in a prospective study of the natural history of HIV infection. These data support the value of continuing preventive efforts to control viral spread in the absence of an effective vaccine or therapy.

Acquired Immunodeficiency Syndrome↗

Human immunodeficiency virus infection in two cohorts of homosexual men: neutralising sera and association of anti-gag antibody with prognosis.

Sequential sera from 48 subjects infected with human immunodeficiency virus type I (HIV-I) were examined over 36 months for the presence of neutralising antibodies, and for specific anti-gag (p24) and anti-env (gp41) antibodies to HIV-I. Results were interpreted in terms of clinical outcome during the period 1982/3 to 1985/6. HIV-I-infected subjects who remained symptom-free, by comparison with those who manifested AIDS or AIDS-related complex (ARC), had a significantly higher titre of anti-p24 antibodies throughout the 3 years, as measured by competitive enzyme-linked immunosorbent assay and radioimmunoprecipitation. The symptomless subjects also showed a trend towards an increasing neutralising antibody titre with time. There was no relation between anti-gp41 titre and clinical outcome, nor an independent relation between anti-p24 and neutralising titre. A lower or falling titre of anti-p24 antibody was associated significantly with clinical progression, up to 27 months before development of AIDS/ARC.

AIDS-Related Complex↗