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Biomedical subjects

H Jacob

Publications and source records attributed to H Jacob.

At least 91 records · Page 5Linked to original sources

Membrane microfilaments of erythrocytes: alteration in intact cells reproduces the hereditary spherocytosis syndrome (vinblastine-colchicine-strychnine-electron microscopy-cell rigidity).

Membrane microfilaments are found throughout the animal world in situations suggesting that they fulfill a critical role in providing normal cell shape and plasticity. We have hypothesized that hereditary spherocytosis, a congenital hemolytic anemia associated with intrinsically rigid and mishapen erythrocytes, might result from genetically defective microfilaments in erythrocyte membranes. By using three different drugs (vinblastine, colchicine, and strychnine) that share one common attribute-that of potently precipitating purified microfilamentous protein-we have provided support for this hypothesis. Thus, all the known in vitro and in vivo characteristics of hereditary spherocytes are reproduced in normal erythrocytes briefly exposed to these precipitating agents.

Blood Proteins↗

Unstable hemoglobins: the role of heme loss in Heinz body formation.

Mutant, unstable hemoglobins precipitate as Heinz bodies in circulating red blood cells resulting in their premature hemolysis. We stress that generally these hemoglobins contain amino acid substitutions in the beta-chain of globin near the heme pocket, and demonstrate that heme binding suffers thereby. Four genetically unstable hemoglobins lost roughly half their heme content while precipitating into Heinz bodies. Conversely, repletion of hemes in vitro corrected the characteristically aberrant electrophoretic mobilities of these hemoglobins and concomitantly prevented their excessive denaturation into Heinz bodies. From the finding that heme-containing alpha-chains accumulate in solution during Heinz body formation, we propose that heme loss occurs predominantly from mutant beta-chains, which then precipitate. This mechanism of Heinz body formation is valid in most, but not all, the unstable hemoglobinopathies.

Blood Protein Electrophoresis↗