Publications by authors named "Clarence Alfrey"

Background: Neocytolysis, the selective hemolysis of young circulating red blood cells (RBCs), contributes to the physiologic control of red cell mass and to pathophysiologic phenomena such as anemia of renal disease, anemia after spaceflight, and blood doping by athletes. Progress in understanding the process is hampered by the lack of established markers to distinguish young from older RBC.

Methods: Twelve potentially informative RBC surface markers were assayed by flow cytometry in normal blood samples, and 4 were preferentially expressed in young RBC.

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Erythropoietin is the major hormone regulator of erythrocyte production promoting the survival, as well as the differentiation and maturation, of erythroid progenitor cells. In addition to these well-characterized effects, it appears that an erythropoietin-responsive non-erythroid mechanism also mediates the selective destruction of young circulating erythrocytes (neocytes) when red cell mass becomes excessive - a process termed 'neocytolysis'. Endothelial cells appear to respond to a rapid decrease in circulating levels of erythropoietin by secreting cytokines (including TGF-alpha), which signal reticuloendothelial phagocytes to destroy neocytes.

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We have uncovered a physiologic process which negatively regulates the red cell mass by selectively hemolyzing young circulating red blood cells. This allows fine control of the number of circulating red blood cells under steady-state conditions and relatively rapid adaptation to new environments. Neocytolysis is initiated by a fall in erythropoietin levels, so this hormone remains the major regulator of red cell mass both with anemia and with red cell excess.

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