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Previous Volume 337:762-769 September 11, 1997 Number 11 Next

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In 1949, the discovery that sickle hemoglobin (₂ ^S₂) has an abnormal electrophoretic mobility prompted Linus Pauling and his colleagues to christen sickle cell anemia "a molecular disease."¹ The ensuing five decades have produced a wealth of information on the mechanisms by which a single base substitution in the gene encoding the human -globin subunit, with the resulting replacement of 6 glutamic acid by valine, leads to the protean and devastating clinical manifestations of sickle cell disease. Until recently there was a disappointing lag in the application of this knowledge to the design of safe and effective forms of therapy. . . . [Full Text of this Article]

Molecular Pathogenesis

Kinetics of Hemoglobin S Polymerization

Dysregulation of Red-Cell Volume

Interaction of SS Red Cells and Vascular Endothelium

Approaches to Therapy

Inhibition of Hemoglobin S Polymerization

Reduction of the Intracellular Hemoglobin Concentration

Induction of Hemoglobin F

Future Prospects

Source Information

From the Division of Hematology, Brigham and Women's Hospital, Harvard Medical School, Boston.

Address reprint requests to Dr. Bunn at Hematology Research, Rm. 223 LMRC, 221 Longwood Ave., Boston, MA 02115.

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