Publications

To determine whether neurological and neuropsychological abnormalities are associated with clinical manifestations of human immunodeficiency virus type 1 (HIV-1) infection in men who do not have acquired immunodeficiency syndrome (AIDS), we performed a historical prospective and cross-sectional study. One hundred HIV-1 seropositive homosexual or bisexual men, of whom 26 had AIDS-related complex, 31 had generalized lymphadenopathy, and 43 had no signs or symptoms of HIV-1 infection, and 157 HIV-1 seronegative men were enrolled from a cohort of 6,701 men who were originally recruited between 1978 and 1980 for studies of hepatitis B virus infection. Evaluation included medical history, physical examination, and neuropsychological tests. Of 26 HIV-1 seropositive subjects with AIDS-related complex, 11 (42%) reported neurological, cognitive, or affective symptoms compared with 30 (19%) of 157 HIV-1 seronegative subjects (relative risk = 2.2, p = 0.02). On neuropsychological testing, subjects with AIDS-related complex performed at a significantly lower level than the HIV-1 seronegative group (p = 0.001). A significantly higher percentage of subjects with AIDS-related complex (8[31%]of 26) than HIV-1 seronegative subjects (19 [12%] of 157) had abnormal results on two or more neuropsychological tests (rate ratio = 2.5, p = 0.03). Symptoms and impairment on neuropsychological tests were correlated only within the group who had AIDS-related complex. Subjects with generalized lymphadenopathy and subjects who had no signs or symptoms of HIV-1 infection were not different from HIV-1 seronegative subjects with respect to symptoms or performance on neuropsychological tests.(ABSTRACT TRUNCATED AT 250 WORDS)

We have investigated the biochemical basis for negative regulation of interleukin 2 receptor alpha-chain (IL-2R alpha) gene expression. Transient transfection studies employing internally deleted forms of the IL-2R alpha promoter localized a negative regulatory element (NRE) between nucleotides -400 and -368 relative to the major distal transcription start (cap) site. This 31-base-pair (bp) element is involved in the attenuation of both basal and inducible IL-2R alpha promoter activity. Comparison of this IL-2R alpha NRE with other known regulatory motifs revealed an 11-bp core element (TTCATCCCAGG) that was strikingly similar to a protein-binding domain within the long terminal repeat of the type 1 human immunodeficiency virus (HIV-1). This viral domain has been previously implicated in the negative control of HIV-1 gene expression. In vitro protein-DNA binding studies demonstrated that the same constitutively expressed approximately 50-kDa protein (SP-50) specifically bound to both the IL-2R alpha and HIV-1 NRE core elements. Mutation of the 11-bp IL-2R alpha NRE core element, which disrupted protein binding, significantly augmented basal as well as Tax protein- or phorbol ester-induced IL-2R alpha promoter activity in vivo, suggesting that SP-50 functions as a transcriptional silencer.