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Science 13 December 1996:
Vol. 274. no. 5294, pp. 1917 - 1921
DOI: 10.1126/science.274.5294.1917
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Reports

Immunologic NO Synthase: Elevation in Severe AIDS Dementia and Induction by HIV-1 gp41

D. Cory Adamson, * Brigitte Wildemann, *dagger Masayuki Sasaki, Jonathan D. Glass, ddagger Justin C. McArthur, Vesselin I. Christov, Ted M. Dawson, Valina L. Dawson §

Indirect mechanisms are implicated in the pathogenesis of the dementia associated with human immunodeficiency virus-type 1 (HIV-1) infection. Proinflammatory molecules such as tumor necrosis factor alpha  and eicosanoids are elevated in the central nervous system of patients with HIV-1-related dementia. Nitric oxide (NO) is a potential mediator of neuronal injury, because cytokines may activate the immunologic (type II) isoform of NO synthase (iNOS). The levels of iNOS in severe HIV-1-associated dementia coincided with increased expression of the HIV-1 coat protein gp41. Furthermore, gp41 induced iNOS in primary cultures of mixed rat neuronal and glial cells and killed neurons through a NO-dependent mechanism. Thus, gp41-induced NO formation may contribute to the severe cognitive dysfunction associated with HIV-1 infection.

D. C. Adamson, B. Wildemann, M. Sasaki, V. I. Christov, T. M. Dawson, V. L. Dawson, Departments of Neurology, Neuroscience, and Physiology, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Pathology 2-210, Baltimore, MD 21287, USA.
J. D. Glass, Departments of Neurology and Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
J. C. McArthur, Department of Neurology, Johns Hopkins University School of Medicine, and Department of Epidemiology, Johns Hopkins University School of Hygiene and Public Health, Baltimore, MD 21287, USA.
*   These authors contributed equally to this work.

dagger    Present address: Department of Neurology, University of Heidelberg, Im Neuenheimer Feld 400, D-69120 Heidelberg, Germany.

ddagger    Present address: Department of Neurology, Emory University School of Medicine, Atlanta, GA 30322, USA.

§   To whom correspondence should be addressed. E-mail: valina.dawson{at}qmail.bs.jhu.edu

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