Lisa Ho & Praise Austin Dr. Robin W. Briehl Albert Einstein College of Medicine
Red Blood Cell Round disc shape Transports oxygen Sickle Cell Trait Sickle Cell Disease Abnormal sickle shape Rigidity Cell Damage & Cell-Cell Adhesion Hemolysis & Anemia
Glutamic Acid Valine Deoxygenation Hydrophobic Interaction Polymerization into Stiff Fibers Distorts shape & rigidifies cells Induces Vaso-Occlusion
Video camera Zeiss light microscope DIC Optics Epi-illumination light source for photolysis of HbCO Potassium Phosphate buffer (pH 7.2 at 0.1 M concentration) Blood or Hb solution sample Gel sample
Fiber Visualization using 546nm light source Differential Interference Contrast Microscopy Can visualize objects smaller than diffraction limitation size Splits the light into two different light beams Wollaston prism The phase image facilitates visualization of the fibers.
Image Video VCR Processor Camera Barrier Filter Analyzer Dichroic mirror 436nm photolysis 546nm Hg arc observation Exciter Filter Field Wollaston prism CO Diaphragm Slide Wollaston prism Polarizer Hg arc
Help decipher how polymers grow and dissolve Aim: Inhibit growth Facilitate dissolution
Increase the delay time Conduct Rheological tests on Lab grown Gels Clinical Studies on various therapeutic treatments
Enbury, S. H., Hebbel, R. P., Mohandas, N. & Steinberg, M. H. (1994). Sickle cell disease: basic principles and clinical practice. New York: Raven Press Ltd. Dickerson, R. E. & Geis, I. (1983). Hemoglobin . California: The Benjamin/ Cummings Plublishing Company, Inc. Wang, J. C., Turner, M. S., Agarwal, G., Kwong, S., Josephs, R., Ferrone, F. A. & Breihl, R. W. (2002). Micromechanics of isolated sickle cell hemoglobin fibers: bending moduli and persistence lengths. Journal of Molecular Biology, 315, 601-612. Agarwal, G., Wang, J. C., Kwong, S., Cohen, S. M., Ferrone, F. A., Josephs, R. & Breihl, R. W. Sickle hemoglobin fibers: mechanisms of depolymerization. Journal of Molecular Biology, 322, 395-412. Ferrone, F. A. (2004). Polymerization and sickle cell disease: a molecular view. Microcirculation, 11:2, 115-128 Breihl, R. W. (1997). Sickle cell hemoglobin. Encyclopedia of human biology, (Second Edition, Vol. 8, pp. 1-20). New York, Academic Press Inc. Anfinsen, C. B., Edsall, J. T., Richards, F. M. & Eisenberg, D. S. (1987). Advances in protein chemistry. New York, Academic Press Inc.
Professor Robin W. Briehl, MD Jiang Cheng Wang Suzanna Kwong Albert Einstein College of Medicine & Staff Dr. Sat Bhattacharya Harlem Children Society The audience
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