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Biomedical subjects

D Whitby

Publications and source records attributed to D Whitby.

44 records · Page 3Linked to original sources

Soluble CD4 blocks the infectivity of diverse strains of HIV and SIV for T cells and monocytes but not for brain and muscle cells.

The CD4 antigen has been subverted as a receptor by the human and simian immunodeficiency viruses (HIV-1, HIV-2 and SIV). Several groups have reported that recombinant, soluble forms of the CD4 molecule (sCD4) block the infection of T lymphocytes by HIV-1, as CD4 binds the HIV envelope glycoprotein, gp120, with high affinity. We now report that sCD4 blocks diverse strains of HIV-1, HIV-2 and SIV, but is less effective for HIV-2. The blocking effect is apparent even after adsorption of virions to CD4 cells. Soluble CD4 prevents HIV infection of T-lymphocytic and myelomonocytic cell lines, but neither sCD4 nor anti-CD4 antibodies inhibit infection of glioma and rhabdomyosarcoma cell lines.

Antigens, Surface↗

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↗

Human immunodeficiency virus infection of monocytic and T-lymphocytic cells: receptor modulation and differentiation induced by phorbol ester.

The monocytic leukemic cell line U937 can be infected with human immunodeficiency virus type 1 (HIV-1) to become permanently infected virus producers. Uninfected U937 cells express T4 (CD4) antigen and form syncytia when mixed with HIV-1 producing cells. Anti-T4 monoclonal antibodies block syncytium formation indicating that the HIV-1 receptors on U937 cells include T4 antigen. The promyelocytic leukemic cell line HL60, while expressing only low amounts of surface T4 and not forming syncytia on exposure to HIV-1, can be infected by HIV-1 at lower efficiency than U937 and T-cell lines. 12-O-Tetradecanoylphorbol-13-acetate (TPA) treatment induces the differentiation of U937 cells into macrophages. HIV-infected U937 cells retain the ability to differentiate, though less efficiently, as shown by the appearance of monocyte/macrophage surface markers. T4 antigen on both U937 and T-cell lines is down regulated by TPA treatment. Functional receptors for HIV-1, assayed by syncytium induction and pseudotype plating, are lost concomitantly with T4 antigen following TPA treatment of U937 cells and T cells.

Antigens, Differentiation, T-Lymphocyte↗

The scapular flap--an anatomical and clinical study.

The scapular flap is a medium-sized flap combining many of the good qualities of others, such as thinness and minimal donor site deficit, with the potentialities of a consistently long pedicle that allows combination with other adjacent flaps. The anatomy of the flap and its application in nine clinical cases is described.

Adolescent↗

Identification of a major latent nuclear antigen, LNA-1, in the human herpesvirus 8 genome.

OBJECTIVES: Human herpesvirus 8 (HHV-8) is strongly associated with all forms of Kaposi's sarcoma (KS) and with primary effusion lymphomas (PEL). KS patients' sera are immunoreactive against discrete nuclear localizing antigens in PEL cell lines. This study sought to identify and characterize these nuclear localizing proteins. STUDY DESIGN/METHODS: KS patients' sera were used to screen a cDNA expression library derived from a PEL cell line (BCP-1) latently infected with HHV-8. RESULTS: An HHV-8-specific cDNA clone was isolated. It encoded one partial and two complete open reading frames (ORFs): ORF 73, ORF 72 (v-cyclin), and K13, respectively. The immunodominant epitope was mapped to the C-terminal domain of ORF 73. Analysis with the KS patients' sera of HEK 293 cells transfected with a clone encompassing the complete coding region of ORF 73, ORF 72, and K13 gave a nuclear immunofluorescence pattern similar to that observed in BCP-1 cells. Western blot analysis with KS patients' sera of transfected HEK 293 cells revealed an immunoreactive protein of 220 to 230 kD that was similar to that observed previously in PEL cell lines. After induction of lytic replication of HHV-8 in BCP-1 cells with n-butyrate, we observed a major reduction in the expression of an ORF 73-specific 6.6-kb mRNA, indicating that this region is under latent control. CONCLUSIONS: These data identify a region of HHV-8 encoding for a major immunoreactive latent nuclear antigen (LNA-1), analogous to the Epstein-Barr virus latent nuclear antigens.

Amino Acid Sequence↗

Kaposi's sarcoma in the Gambia, West Africa is less frequent in human immunodeficiency virus type 2 than in human immunodeficiency virus type 1 infection despite a high prevalence of human herpesvirus 8.

OBJECTIVES: To investigate the distribution of Kaposi's sarcoma (KS) cases in patients with human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) infection in the Gambia; to document the prevalence of human herpesvirus 8 (HHV-8) infection in various population groups in the Gambia. STUDY DESIGN/METHODS: A retrospective analysis of KS cases in hospital records at the Medical Research Council (MRC) hospital was performed, along with a cross-sectional survey of HHV-8 prevalence in hospital-based and community-based study population with polymerase chain reaction (PCR) and serologic assays. RESULTS: After adjusting for gender and CD% at the first visit, HIV-1-positive patients were 12.4 times more likely to have KS than were HIV-2-positive patients. The prevalence of antibodies to HHV-8 and the HHV-8 genome was high in both HIV-1-positive and HIV-2-positive patients without KS. The prevalence of antibodies was also high in pregnant women who were HIV-1-positive, HIV-2-positive, or HIV-negative (73%, 83%, and 79%, respectively). CONCLUSIONS: HHV-8 infection is widespread in the Gambia. In addition to immunosuppression and HHV-8 infection, other cofactors specifically related to HIV-1 rather than HIV-2 appear to be involved in the development of KS.

AIDS-Related Opportunistic Infections↗