The Neuropathology Core was developed to provide on-going support to the major investigators in the Drug Discovery project that is working to find a treatment for toxoplasmosis in the AIDS patient. The critical element served by this Core is to provide a means of measuring successful drug therapy by histologic methods so that there is not total reliance on survival data for evaluation of efficacy of a particular drug regime. The histologic changes in the brain and heart of immune-competent mice infected with toxoplasma are well known and characterized. Extensive experience with toxoplasma infection in immune-compromised mice and humans with AIDS or organs transplant has permitted us to delineate a continuum of histologic changes that correlate well with the clinical course of infection in a particular patient or mouse. The assessment of degree of involvement by infection in a particular patient or mouse. The assessment of degree of involvement by infection in a particular organ is always done in a blinded fashion so that identity of treated groups as well as the particular drug regime under investigation are not known to the person reading histological slides. In our past studies, true differences in various drug therapy on efficacy of containing the toxoplasma infection are easily discerned by evaluating the histology, particularly that of the brain. Immunoperoxidase staining for toxoplasma antigen will be of increasing importance as these studies continue because in the immunocomprised patient eradication of infection rather than simple control is essential, and this staining allows identification of dormant organisms in infected tissues.

Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
1996
Total Cost
Indirect Cost
Saeij, J P J; Boyle, J P; Coller, S et al. (2006) Polymorphic secreted kinases are key virulence factors in toxoplasmosis. Science 314:1780-3
McFadden, D C; Tomavo, S; Berry, E A et al. (2000) Characterization of cytochrome b from Toxoplasma gondii and Q(o) domain mutations as a mechanism of atovaquone-resistance. Mol Biochem Parasitol 108:12-Jan
McFadden, D C; Boothroyd, J C (1999) Cytochrome b mutation identified in a decoquinate-resistant mutant of Toxoplasma gondii. J Eukaryot Microbiol 46:81S-82S
Liesenfeld, O; Kang, H; Park, D et al. (1999) TNF-alpha, nitric oxide and IFN-gamma are all critical for development of necrosis in the small intestine and early mortality in genetically susceptible mice infected perorally with Toxoplasma gondii. Parasite Immunol 21:365-76
Boothroyd, J C; Hehl, A; Knoll, L J et al. (1998) The surface of Toxoplasma: more and less. Int J Parasitol 28:3-9
Black, M W; Boothroyd, J C (1998) Development of a stable episomal shuttle vector for Toxoplasma gondii. J Biol Chem 273:3972-9
Neyer, L E; Kang, H; Remington, J S et al. (1998) Mesenteric lymph node T cells but not splenic T cells maintain their proliferative response to concanavalin-A following peroral infection with Toxoplasma gondii. Parasite Immunol 20:573-81
Manger, I D; Hehl, A B; Boothroyd, J C (1998) The surface of Toxoplasma tachyzoites is dominated by a family of glycosylphosphatidylinositol-anchored antigens related to SAG1. Infect Immun 66:2237-44
Manger, I D; Hehl, A; Parmley, S et al. (1998) Expressed sequence tag analysis of the bradyzoite stage of Toxoplasma gondii: identification of developmentally regulated genes. Infect Immun 66:1632-7
Subauste, C S; Fuh, F; de Waal Malefyt, R et al. (1998) Alpha beta T cell response to Toxoplasma gondii in previously unexposed individuals. J Immunol 160:3403-11

Showing the most recent 10 out of 55 publications