HIV-1-seropositive intravenous narcotic addicts and homosexuals develope syndrome of immunologic thrombocytopenic purpura (ITP) which has become part of the AIDS related complex as well as AIDS. This syndrome is associated with markedly elevated plateletbound IgG, IgM, C3C4, circulating immune complexes and anti-F(ab')2 antibodies suggesting an immune complex etiology. Narcotic addict patients unlike homosexuals, also have specific anti-platelet 75 IgG antibody. We have evidence that HIV-1 related ITP is being spread sexually into the heterosexual community by narcotic addicts. We propose to study the mechanism(s) of ITP in both groups of patients and study the risk of heterosexual transmission of HIV-1 via the semen of narcotic addicts. This would be accomplished by; 1) Examining the role of impaired megakaryocytopoiesis in the etiology of the disorder by looking for CD4 receptors on megakaryocytes, looking for HIV-1 or its products in megakaryocytes; looking for anti-HIV-1 antibody or its complexes on megakaryocytes. 2) Searching for anti-idiotype antibody against anti-HIV-1 (gp120) since this could be responsible for impaired resistance to HIV-1 infection; as well as the decreased number and function of helper 14 cells in these patients despite the very low copy number of proviral HIV-1 DNA in these cells (<1/10,000). An anti-idiotype antibody against anti-HIV-1 (gp120) should simulate the HIV-1 (gp120) epitopes and bind to the CD4 receptor. 3) Examining the role of increased peripheral destruction of platelets by determining the specific platelet antigenic determinants for the 7S anti-platelet antibody of narcotic addicts: determining how immune complexes of both groups of patients bind to platelets; determining whether the 7S anti-platelet IgG or immune complexes stimulate the phagocytosis of platelets by monocytes. 4) Measuring reticulo-endothelial function in thrombocytopenic and non-thrombocytopenic HIV-1 seropositibive patients, to determine whether there is a correlation between reticulo-endothelial function and thrombocytopenia. Reticulo-endothelial blockade could explain the absence of thrombocytopenia in patients with elevated platelet IgG, IgM and C3C4. 5) Studying the semen and peripheral blood of narcotic addicts and the peripheral blood of their non-addict spouses or sexual consorts for integrated HIV-1 proviral DNA. This would provide valuable information regarding the infectivity of narcotic addict semen and spread of AIDS into the heterosexual community.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA004315-05
Application #
3209795
Study Section
Sociobehavioral Subcommittee (DAAR)
Project Start
1986-09-30
Project End
1994-08-31
Budget Start
1990-09-01
Budget End
1991-08-31
Support Year
5
Fiscal Year
1990
Total Cost
Indirect Cost
Name
New York University
Department
Type
Schools of Medicine
DUNS #
004514360
City
New York
State
NY
Country
United States
Zip Code
10012
Wang, Jianhui; Zhang, Wei; Yi, Zanhua et al. (2012) Identification of a thrombin cleavage site and a short form of ADAMTS-18. Biochem Biophys Res Commun 419:692-7
Dang, Suying; Hong, Tao; Wisniewski, Thomas et al. (2011) Dissolution of pre-existing platelet thrombus by synergistic administration of low concentrations of bifunctional antibodies against ?3 integrin. PLoS One 6:e27012
Wang, J; Zhang, W; Nardi, M A et al. (2011) HIV-1 Tat-induced platelet activation and release of CD154 contribute to HIV-1-associated autoimmune thrombocytopenia. J Thromb Haemost 9:562-73
Pan, Ruimin; Wang, Jianhui; Nardi, Michael A et al. (2011) The inhibition effect of anti-GPIIIa49-66 antibody on megakaryocyte differentiation. Thromb Haemost 106:484-90
Wang, Jianhui; Yi, Zanhua; Wang, Shiyang et al. (2011) The effect of decitabine on megakaryocyte maturation and platelet release. Thromb Haemost 106:337-43
Zhang, Wei; Li, Yong-Sheng; Nardi, Michael A et al. (2010) Dissolution of arterial platelet thrombi in vivo with a bifunctional platelet GPIIIa49-66 ligand which specifically targets the platelet thrombus. Blood 116:2336-44
Zhang, Wei; Dang, Suying; Wang, Jianhui et al. (2010) Specific cross-reaction of anti-dsDNA antibody with platelet integrin GPIIIa49-66. Autoimmunity 43:682-9
Li, Zongdong; Nardi, Michael A; Li, Yong-Sheng et al. (2009) C-terminal ADAMTS-18 fragment induces oxidative platelet fragmentation, dissolves platelet aggregates, and protects against carotid artery occlusion and cerebral stroke. Blood 113:6051-60
Hu, Liang; Ibrahim, Sherif; Liu, Cynthia et al. (2009) Thrombin induces tumor cell cycle activation and spontaneous growth by down-regulation of p27Kip1, in association with the up-regulation of Skp2 and MiR-222. Cancer Res 69:3374-81
Nardi, Michael A; Gor, Yelena; Feinmark, Steven J et al. (2007) Platelet particle formation by anti GPIIIa49-66 Ab, Ca2+ ionophore A23187, and phorbol myristate acetate is induced by reactive oxygen species and inhibited by dexamethasone blockade of platelet phospholipase A2, 12-lipoxygenase, and NADPH oxidase. Blood 110:1989-96

Showing the most recent 10 out of 25 publications