Abstract

The present project intends to advance the understanding of the molecular basis of the polymerization of Hb S. We intend to investigate the pregelling events, the role of non-Hb S molecules, and the supramolecular structure of the polymer. We intend to pursue the kinetics of sickling, the ligand kinetics of Hb S containing red cells and the basis of the changes in the oxygen equilibrium curve in these cells. We will continue the development of nitrogen mustards and alkylureas as antisickling agents. We will also inquire into the basis of the stimulation of the synthesis of Hb F in some pathological states, with the hope of understanding its operative control.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL021016-12
Application #
3097798
Study Section
Heart, Lung, and Blood Research Review Committee B (HLBB)
Project Start
1982-06-01
Project End
1992-05-31
Budget Start
1988-06-01
Budget End
1989-05-31
Support Year
12
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
Albert Einstein College of Medicine
Department
Type
Schools of Medicine
DUNS #
009095365
City
Bronx
State
NY
Country
United States
Zip Code
10461

  Publications

Hirsch, R E; Witkowska, H E; Shafer, F et al. (1997) HbC compound heterozygotes [HbC/Hb Riyadh and HbC/Hb N-Baltimore] with opposing effects upon HbC crystallization. Br J Haematol 97:259-65
Ducrocq, R; Bennani, M; Bellis, G et al. (1994) Hemoglobinopathies in the Dogon Country: presence of beta S, beta C, and delta A' genes. Am J Hematol 46:245-7
Hirsch, R E (1994) Front-face fluorescence spectroscopy of hemoglobins. Methods Enzymol 232:231-46
Lew, V L; Etzion, Z; Bookchin, R M et al. (1993) The distribution of intracellular calcium chelator (fura-2) in a population of intact human red cells. Biochim Biophys Acta 1148:152-6
Bookchin, R M; Balazs, T; Lew, V L (1993) Composition of the hemoglobin S polymer. Am J Hematol 42:118-21
Etzion, Z; Tiffert, T; Bookchin, R M et al. (1993) Effects of deoxygenation on active and passive Ca2+ transport and on the cytoplasmic Ca2+ levels of sickle cell anemia red cells. J Clin Invest 92:2489-98
Kaul, D K; Nagel, R L; Chen, D et al. (1993) Sickle erythrocyte-endothelial interactions in microcirculation: the role of von Willebrand factor and implications for vasoocclusion. Blood 81:2429-38
Shear, H L; Roth Jr, E F; Fabry, M E et al. (1993) Transgenic mice expressing human sickle hemoglobin are partially resistant to rodent malaria. Blood 81:222-6
Hirsch, R E; Lin, M J; Pulakhandam, U R et al. (1993) Hemoglobin oxygen affinity is increased in erythropoietic protoporphyria. Photochem Photobiol 57:885-8
Shear, H L (1993) Transgenic and mutant animal models to study mechanisms of protection of red cell genetic defects against malaria. Experientia 49:37-42

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