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Bryostatin is a unique lead in the development of potentially transformative therapies for cancer, Alzheimer's disease and the eradication of HIV/AIDS. However, the clinical use of bryostatin has been hampered by its limited supply, difficulties in accessing clinically relevant derivatives, and side effects. Here, we address these problems through the(More)
N-acetylcysteine (600 mg/day) was given to patients by mouth for five days before bronchoscopy and bronchoalveolar lavage to determine whether N-acetylcysteine could increase the concentrations of the antioxidant reduced glutathione in plasma and bronchoalveolar lavage fluid. Bronchoalveolar lavage was performed 1-3 hours (group 2, n = 9) and 16-20 hours(More)
Highly active antiretroviral therapy (HAART) can potently suppress human immunodeficiency virus (HIV) replication and prevent progression to AIDS. However, HAART does not cure infected patients. Instead, HIV persists in latently infected CD4+ T cells and various cryptic cellular reservoirs. Hence, under current therapy regimens, patients must continue(More)
BACKGROUND Oxidant/antioxidant imbalance may occur in the lungs of patients with chronic obstructive pulmonary disease (COPD). Glutathione is an important extracellular and intracellular thiol oxidant in the lungs. These studies were carried out to determine the effect of N-acetyl cysteine on thiol concentrations in plasma, bronchoalveolar lavage fluid, and(More)
Many important aspects of human retroviral infections cannot be fully evaluated using only in vitro systems or unmodified animal models. An alternative approach involves the use of humanized mice, which consist of immunodeficient mice that have been transplanted with human cells and/or tissues. Certain humanized mouse models can support robust infection(More)
Interferons (IFN) are essential antiviral cytokines that establish the cellular antiviral state through upregulation of hundreds of interferon-stimulated genes (ISGs), most of which have uncharacterized functions and mechanisms. We identified cholesterol-25-hydroxylase (CH25H) as a broadly antiviral ISG. CH25H converts cholesterol to a soluble antiviral(More)
Even after extended treatment with powerful antiretroviral drugs, HIV is not completely eliminated from infected individuals. Latently infected CD4(+) T cells constitute one reservoir of replication-competent HIV that needs to be eliminated to completely purge virus from antiretroviral drug-treated patients. However, a major limitation in the development of(More)
Antiretroviral therapy is currently only capable of controlling HIV replication rather than completely eradicating virus from patients. This is due in part to the establishment of a latent virus reservoir in resting CD4+ T cells, which persists even in the presence of HAART. It is thought that forced activation of latently infected cells could induce virus(More)
Evidence is presented that the elastase-specific inhibitor of Mr 2500 (Sallenave, J.-M. & Ryle, A.P. (1991) Biol. Chem. Hoppe-Seyler 372, 13-21) is a biologically active fragment of a larger molecule described in the skin of patients with psoriasis (Wiedow, O., Shroder, J.-M., Gregory, H., Young, J.A. & Christophers, E. (1990) J. Biol. Chem. 265,(More)
Quiescent T lymphocytes containing latent human immunodeficiency virus (HIV) provide a long-lived viral reservoir. This reservoir may be the source of active infection that is reinitiated following the cessation of antiretroviral therapy. Therefore, it is important to understand the mechanisms involved in latent infection to develop new strategies to(More)