PubMed · 9846554
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R F Itzhaki, M Wozniak, C Dobson, W R Lin. 1998. ApoE-viral interactions.. https://doi.org/10.1038/3908
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The interleukin (IL)-4 -589-C/T polymorphism has been reported to protect against human immunodeficiency virus type 1 (HIV-1)-related disease progression in white adults. In the present study, the effect of the IL-4 -589 polymorphism on HIV-1-related disease progression was evaluated in a seroprevalent cohort of 1043 children. The IL-4 -589-T allele was more prevalent in Hispanic and in black, non-Hispanic children, compared with white, non-Hispanic children. We found that the IL-4 -589-C/T polymorphism does not affect the risk of HIV-1-related disease progression or central nervous system impairment in children, and this did not differ by race/ethnicity. Our findings suggest that the IL-4 -589-C/T polymorphism is not an important determinant of HIV-1 disease progression in children.
Human immunodeficiency virus type-1 (HIV-1) infection is commonly associated with neuronal loss, as well as, cognitive and motor deficits collectively termed HIV-1-associated dementia (HAD). Function of the HIV-1 transcription factor Tat, activation of N-methyl-D-aspartate (NMDA)-type glutamate receptors, and subsequent rapid rises in free intracellular Ca2+ have been implicated in the development of this neurological disorder. However, the role of specific NMDA receptor modulatory sites in mediating effects of Tat has not been examined. The present studies examined the ability of two variants of Tat protein (1-100 nM), Tat 1-72 and Tat 1-86, to produce rapid rises in intracellular Ca2+ in organotypic slice cultures of rat hippocampus. Further, these studies evaluated the role of an NMDA receptor polyamine-sensitive site in mediating Tat-induced elevations in intracellular Ca2+. Brief exposure (10 min) to each variant of Tat protein (>1 nM) markedly increased levels of intracellular Ca2+ in each region of the hippocampus to as much as 145% of controls. In contrast, exposure of cultures to a deletion mutant of Tat protein devoid of amino acids 31-61 (Tat Delta31-61) did not produce changes in intracellular Ca2+ levels. Most significantly, exposure to the NMDA receptor antagonist dizocilpine (MK801 20 microM) and the polyamine site antagonist arcaine (10 microM) significantly attenuated increases in intracellular Ca2+ levels when co-administered with either the Tat 1-72 or Tat 1-86 amino acid variant of Tat. Thus, exposure of the hippocampus to Tat produces increases in intracellular Ca2+ levels that require function of an NMDA receptor polyamine-sensitive site and this may well contribute to the neurotoxic effects of HIV-1 infection. Polyamine-sensitive portions of this receptor may then represent novel therapeutic targets in the pharmacologic treatment of HAD-related neurotoxicity.
Neuroimaging technology continues to unfold in a very exciting way, providing almost limitless information about the structural and functional integrity of the nervous system. In patients with an immunocompromised state such as those infected with human immunodeficiency virus (HIV) and subsequently developing acquired immunodeficiency syndrome (AIDS), neurologic complications represent an important manifestation requiring vigilance. Many of the central nervous system (CNS) disorders related to HIV and AIDS are treatable and without prompt diagnosis and treatment, will lead to significant morbidity or death. Neuroimaging plays an increasingly pivotal role in the early diagnosis and longitudinal monitoring of these conditions. The author intends to provide an overview of neuroimaging technology and its applications including various magnetic resonance imaging (MRI) and functional imaging techniques in the evaluation of patients with HIV and AIDS related CNS disorders. The role of neuroimaging in this population includes early detection of direct HIV infection, opportunistic infections, neoplasia, or cerebrovascular diseases. In addition, through a wide breadth of imaging techniques, the pathology, neurochemistry and metabolism of lesions can be studied to clarify the differential diagnosis, such as discriminating infection vs. neoplasia.