In general, the studies described in this proposal are designed to further our understanding of platelet and leukocyte function in health and disease. Most of the experiments are designed to translate metabolic, biochemical and biophysical data into mean- ingful morphologic concepts. Thus, we wish to determine what membrane changes occur when platelets adhere, aggregate or degranulate, and how integral membrane proteins/lipids are rearranged. Elucidation of the mechanism(s) of secretion, endocytosis and intracellular transport form part of the objective. Although the emphasis will be on surface membranes, intracellular proteins and organelles which play a role in specific cell functions will also be investigated. Similar studies will be carried out on leukocytes to explain the transduction of stimuli which eventuate in migration or mitosis. The methodologies will include conventional fluorescence and electron microscopy, immunohistochemistry on the light microscopic and ultrastructural level, freeze-fracture, cell fractionation and tissue culture. Three new techniques will be introduced: 1) Low-icryl low temperature embedding, which permits detection of intracellular antigens at higher resolution than previously possible, 2) label- fracture, which permits delineation of surface molecules coincident with proteins anchored in the outer leaflet of the plasma membrane and 3) in situ hybridization, which permits a correlation of subcellular topography with higher order gene expression. Specimens obtained from patients with abnormal platelet or leukocyte function will be compared with those obtained from healthy subjects, and with cells that have been experimentally modified in vitro. The morphologic information derived from such studies seems important because, in the future, it may become possible to selectively alter structure e.g., by insertion of molecules into membranes which may restore normal function to pathologic cells. At all times, the ultimate goal is to help our understanding of aberrant blood cell function, which is a prerequisite for the rational management of patients with hematologic disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK012274-25
Application #
3224851
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
1978-01-01
Project End
1993-06-30
Budget Start
1992-07-01
Budget End
1993-06-30
Support Year
25
Fiscal Year
1992
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
Leelawattana, R; Ziambaras, K; Roodman-Weiss, J et al. (2000) The oxidative metabolism of estradiol conditions postmenopausal bone density and bone loss. J Bone Miner Res 15:2513-20
Zucker-Franklin, D (1996) Megakaryocyte and platelet structure in thrombocytopoiesis: the effect of cytokines. Stem Cells 14 Suppl 1:1-17
Zucker-Franklin, D; Fraig, M; Grusky, G (1995) Interaction of human immunodeficiency virus type 1, human T-cell leukemia/lymphoma virus type I (HTLV-I), and HTLV-II with in vitro-generated dendritic cells. Clin Diagn Lab Immunol 2:343-8
Pancake, B A; Zucker-Franklin, D; Coutavas, E E (1995) The cutaneous T cell lymphoma, mycosis fungoides, is a human T cell lymphotropic virus-associated disease. A study of 50 patients. J Clin Invest 95:547-54
Zucker-Franklin, D; Pancake, B A; Friedman-Kien, A E (1994) Cutaneous disease resembling mycosis fungoides in HIV-infected patients whose skin and blood cells also harbor proviral HTLV type I. AIDS Res Hum Retroviruses 10:1173-7
Zucker-Franklin, D; Pancake, B A (1994) The role of human T-cell lymphotropic viruses (HTLV-I and II) in cutaneous T-cell lymphomas. Semin Dermatol 13:160-5
Zucker-Franklin, D (1994) The effect of viral infections on platelets and megakaryocytes. Semin Hematol 31:329-37
Zucker-Franklin, D; Huang, Y Q; Grusky, G E et al. (1993) Kaposi's sarcoma in a human immunodeficiency virus-negative patient with asymptomatic human T lymphotropic virus type I infection. J Infect Dis 167:987-9
Stahl, C P; Zucker-Franklin, D; Evatt, B L et al. (1991) Effects of human interleukin-6 on megakaryocyte development and thrombocytopoiesis in primates. Blood 78:1467-75
Lavie, G; Zucker-Franklin, D (1989) Cell surface-associated proteinases in NK cell-mediated cytotoxicity: enhancement of enzyme expression is unique to activation with interferon-alpha. Cell Immunol 124:202-11

Showing the most recent 10 out of 12 publications