Antiviral action & tissue uptake of AZT-sterol dicarboxylates.
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Biomedical subjects
Publications and source records attributed to M Lightfoote.
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In an effort to develop an assay which would rapidly detect and analyze circulating immune complexes, we have adapted the Raji cell radioimmunoassay (RIA) to a flow cytometric (FCM) analysis. The advantages of immune complex analysis by FCM are many. Foremost is the effectiveness and efficiency of the FCM method relative to the radioimmunoassay (RIA) method. The data demonstrated that FCM detection is three times more sensitive than RIA detection. Only populations of viable Raji cells bearing immune complexes are analyzed because parameters of the FCM analysis permitted the elimination (gating out) of dead cells. The determinations are rapid and the data are immediately available for several additional analyses. Because of the availability of many fluorescent monoclonal antibodies to complement components, viral antigens, light chains and immunoglobulin isotypes, it is possible to detect many components that might be present in the Raji cell bound complexes. Finally, the Raji cells can be characterized in different stages of their cell cycle to generate information about the state of the cells and the density of the receptors involved in binding the complexes.
Leu-3- cells that survive infection with the acquired immune deficiency syndrome (AIDS) retrovirus can be induced with IUdR to express infectious virus. A cellular clone (8E5), isolated by limiting dilution of a mass culture of survivor cells, was found to contain a single, integrated provirus that was constitutively expressed. Although IUdR treatment of 8E5 cells failed to induce infectious virus, cocultivation with Leu-3+ cells generated the characteristic syncytia associated with acute AIDS retrovirus infection. The single integrated copy of proviral DNA directs the synthesis of all major viral structural proteins except p64, as monitored by immunoblotting. The relationship of the 8E5 clone to viral latency and persistence is discussed.
The acquired immunodeficiency syndrome (AIDS) is epidemic in Central Africa. To determine the prevalence of AIDS virus infection in East Africa, we studied 90 female prostitutes, 40 men treated at a clinic for sexually transmitted diseases, and 42 medical personnel in Nairobi, Kenya. Antibody to human T-cell lymphotropic virus Type III (HTLV-III) was detected in the serum of 66 percent of prostitutes of low socioeconomic status, 31 percent of prostitutes of higher socioeconomic status, 8 percent of the clinic patients, and 2 percent of the medical personnel. The presence of the antibody was associated with both immunologic and clinical abnormalities. The mean T-cell helper/suppressor ratio was 0.92 in seropositive prostitutes and 1.82 in seronegative prostitutes (P less than 0.0001). Generalized lymphadenopathy was present in 54 percent of seropositive prostitutes and 10 percent of seronegative prostitutes (P less than 0.0001). No constitutional symptoms, opportunistic infections, or cases of Kaposi's sarcoma were present. Our results indicate that the epidemic of AIDS virus infection has, unfortunately, spread extensively among urban prostitutes in Nairobi, Kenya. Sexual exposure to men from Central Africa was significantly associated with HTLV-III antibody among prostitutes, suggesting transcontinental spread of the epidemic.
We have developed a continuous human T-cell line (A3.01) for the study of acquired immunodeficiency syndrome (AIDS)-associated retrovirus that mimics normal peripheral blood lymphocytes in susceptibility to viral cytopathic effect without the need for cell activation or conditioned medium. Following infection, substantial quantities of virus are produced during a 3- to 5-day period; the associated killing of cells can be monitored in a microtiter assay as a function of virus input. Southern blot hybridization of infected cellular DNAs indicated that no gross alteration occurred in the restriction maps of the proviral DNA during the transfer of virus to and its passage in A3.01 cells. This cell system offers an alternative to other AIDS retrovirus cell systems because it permits the monitoring of viral cytopathic effects.
Immune responses to Epstein-Barr herpesvirus (EBV) and EBV-related antigens were studied serially in 18 patients with heterophil antibody-positive infectious mononucleosis and in 18 control subjects. Enhanced cellular immune responses to EBV particles and to EBV intracellular soluble antigens were found in the patients at convalescence, suggesting that the development of specific cellular immune responses was associated with apparent control of the virus infection. In addition, a correlation between severity of disease and specific cellular immune response was found. Patients with severe clinical signs were found to have a more active cellular immune response to EBV intracellular soluble antigens early in the infection compared with patients with mild disease. This suggests that an increased immune reactivity to intracellular antigens during the early part of the illness is related to the severity of clinical manifestations in infectious mononucleosis. Serum antibody to viral capsid antigen and early antigen was not related to the severity of clinical disease.