We propose to build a research program of interdisciplinary studies on human schistosomiasis mansoni and Chagas' disease in Minas Gerias, Brazil. The disciplines will include immunology, molecular biology, biochemistry, pathology, epidemiology and clinical medicine. This program is rooted in the collaborative research being pursued in schistosomal immunoregulation by 3 of the senior investigators on this application. Our goals are to understand the pathogenesis of these diseases, and develop vaccines or other modalities to control the morbidity and mortality of these infections. Studies on the immunoregulation of schistosomiasis: comparisons of T cell clones/hybridomas from patients with different clinical forms, and their abilities to induce/regulate in vitro granuloma formation; comparisons of multi/monoclonal anti-schistosome idiotypes (Ids) from patients in clinical groups. Schistosomal pathogenesis: ability of patients to stimulate/regulate fibrogenesis, and to produce fibrogenic extracellular matrix proteins, at the protein and gene activation levels. Studies on the immunology of Chagas' disease: cellular immune responses and regulation in patients with different clinical forms of Chagas' disease; Id analysis of patients' anti-T. cruzi antibodies and retrospective and longitudinal studies of maternal/perinatal immune effects on subsequent responsiveness, morbidity and mortality; autoimmune studies and HLA-typing, with analysis in relationship to clinical patterns. Studies of the Molecular Biology of S. mansoni: identification, cloning and production of parasite encoded antigens useful in both diagnosis and immunoregulatory studies of schistosomiasis. Studies of the Molecular Biology of T cruzi: identification, cloning and production of parasite encoded antigens related to patients' cellular immunity and useful in diagnosis of Chagas' disease, and potentially involved in cross-reactivity and autoimmune reactions with host tissues.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI026505-05
Application #
3091899
Study Section
Special Emphasis Panel (SRC (50))
Project Start
1989-05-01
Project End
1994-08-31
Budget Start
1993-05-01
Budget End
1994-08-31
Support Year
5
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
d'Avila Reis, D; Lemos, E M; Silva, G C et al. (2001) Phenotypic characterization of the inflammatory cells in chagasic megaoesophagus. Trans R Soc Trop Med Hyg 95:177-8
Lane, J E; Olivares-Villagomez, D; Vnencak-Jones, C L et al. (1997) Detection of Trypanosoma cruzi with the polymerase chain reaction and in situ hybridization in infected murine cardiac tissue. Am J Trop Med Hyg 56:588-95
Singh, P K; Jones, M M; Lane, J E et al. (1997) Synthesis and in vitro trypanocidal activity of some novel iron chelating agents. Arzneimittelforschung 47:311-5
Jones, M M; Singh, P K; Lane, J E et al. (1996) Inhibition of Trypanosoma cruzi epimastigotes in vitro by iron chelating agents. Arzneimittelforschung 46:1158-62
Ribeiro-Rodrigues, R; Colley, D G; Correa-Oliveira, R et al. (1996) Antibodies reactive to Trypanosoma cruzi epimastigotes or amastigotes express different idiotypic patterns if from patients with different clinical forms of Chagas' disease. Scand J Immunol 43:671-9
Lane, J E; Ribeiro-Rodrigues, R; Suarez, C C et al. (1996) In vitro trypanocidal activity of tetraethylthiuram disulfide and sodium diethylamine-N-carbodithioate on Trypanosoma cruzi. Am J Trop Med Hyg 55:263-6
Rodrigues, R R; Lane, J E; Carter, C E et al. (1995) Chelating agent inhibition of Trypanosoma cruzi epimastigotes in vitro. J Inorg Biochem 60:277-88
Oliveira, G C; Kemp, W M (1995) Cloning of two actin genes from Schistosoma mansoni. Mol Biochem Parasitol 75:119-22
Jones, E M; Colley, D G; Tostes, S et al. (1993) Amplification of a Trypanosoma cruzi DNA sequence from inflammatory lesions in human chagasic cardiomyopathy. Am J Trop Med Hyg 48:348-57
Swanson, P M; Carter, C E; Hager, C et al. (1992) Identification and characterization of an alpha-mannosidase from Trypanosoma cruzi. Glycobiology 2:563-9

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