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Activated monocytes release a number of substances, including inflammatory cytokines and eicosanoids, that are highly toxic to cells of the central nervous system. Because monocytic infiltration of the central nervous system closely correlates with HIV-1-associated dementia, it has been suggested that monocyte-derived toxins mediate nervous system damage.(More)
Neurological disorders develop in most people infected with human immunodeficiency virus type 1 (HIV-1). However, the underlying mechanisms remain largely unknown. Here we report that binding of HIV-1 transactivator (Tat) protein to low-density lipoprotein receptor-related protein (LRP) promoted efficient uptake of Tat into neurons. LRP-mediated uptake of(More)
Many patients infected with human immunodeficiency virus type-1 (HIV-1) suffer cognitive impairment ranging from mild to severe (HIV dementia), which may result from neuronal death in the basal ganglia, cerebral cortex and hippocampus. HIV-1 does not kill neurons by infecting them. Instead, viral proteins released from infected glial cells, macrophages(More)
Human immunodeficiency virus (HIV) infection of the nervous system is unique when compared with other viral encephalitides. Neuronal cell loss occurs in the absence of neuronal infection. Viral proteins, termed "virotoxins," are released from the infected glial cells that initiate a cascade of positive feedback loops by activating uninfected microglial(More)
Patients infected with HIV-1 often exhibit cognitive deficits that are related to progressive neuronal degeneration and cell death. The protein Tat, which is released from HIV-1-infected cells, was recently shown to be toxic toward cultured neurons. We now report that Tat induces apoptosis in cultured embryonic rat hippocampal neurons. Tat induced caspase(More)
Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HANDs) remain among the most common disorders in people infected with HIV, even in an era when potent antiretroviral therapy is widely deployed. This review discusses the clinical features of HANDs and the implications for more effective treatment. With the improved survival of(More)
Nine cancer patients were treated with adoptive cell therapy using autologous anti-MAGE-A3 T-cell receptors (TCR)-engineered T cells. Five patients experienced clinical regression of their cancers including 2 on-going responders. Beginning 1-2 days postinfusion, 3 patients (#'s 5, 7, and 8) experienced mental status changes, and 2 patients (5 and 8) lapsed(More)
HIV-1 infection commonly leads to neuronal cell death and a debilitating syndrome known as AIDS-related dementia complex. The HIV-1 protein Tat is neurotoxic, and because cell survival is affected by the intracellular calcium concentration ([Ca2+]i), we determined mechanisms by which Tat increased [Ca2+]i and the involvement of these mechanisms in(More)
BACKGROUND Treatment of multiple sclerosis with natalizumab is complicated by rare occurrence of progressive multifocal leukoencephalopathy (PML). Between July, 2006, and November, 2009, there were 28 cases of confirmed PML in patients with multiple sclerosis treated with natalizumab. Assessment of these clinical cases will help to inform future therapeutic(More)