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Biomedical subjects

H S Jacob

Publications and source records attributed to H S Jacob.

At least 181 records · Page 10Linked to original sources
PubMed1973

Chlorinated urban water: a cause of dialysis-induced hemolytic anemia.

Unexplained acute hemolytic anemia is sometimes seen in uremic patients undergoing hemodialysis. Chloramines, which are oxidant compounds made up of chlorine and ammonia and are widely used as bactericidal agents in urban water supplies, have been found responsible for two recent epidemics, in dialyzed uremic patients, of acute hemolytic anemia characterized by Heinz bodies. Chloramines produce denaturation of hemoglobin, both by their direct oxidizing capacity and their ability to inhibit red cell reductive (hexose monophosphate shunt) metabolism.

Anemia, Hemolytic↗
PubMed1971

Abnormal membrane protein of red blood cells in hereditary spherocytosis.

We present evidence that the hereditable hemolytic disease, hereditary spherocytosis (HS), involves an abnormality in protein of the red cell membrane. Unlike that from normal red cells, lipid-free proteins extracted from HS red cell membranes fail to increase in sedimentation rate when treated with cations; such treatment of normal membrane proteins has been shown by others to cause the formation of microfilaments. That microfilament formation might be defective in HS red cell membranes is supported by observations with vinblastine. This compound, a potent precipitant of filamentous, structure proteins throughout phylogeny, precipitates significantly less HS membrane protein than normal. The resistance of HS membrane protein to changes in conformation by cations is observable at the cellular level as well. That is, both normal and HS red cells agglutinate after repeated washing and suspension in electrolyte-free media. Tiny concentrations of Ca(++) (5 x 10(-5) M) changes the surfaces of normal cells in such a way as to cause disagglutination; HS red cells resist this change and remain agglutinated unless Ca(++) concentrations are increased many-fold. We conclude that membrane ("structure") proteins of HS red cells are genetically altered in such a way as to interfere with their proper conformation, perhaps into fibrils. Potentially many mutations in membrane proteins might preclude this alignment, with the result that normal erythrocyte biconcavity and plasticity is prevented and the clinical syndrome of hereditary spherocytosis is manifest.

Blood Protein Disorders↗
PubMed1970

The role of hemoglobin heme loss in Heinz body formation: studies with a partially heme-deficient hemoglobin and with genetically unstable hemoglobins.

A number of mutant hemoglobins are inordinately unstable, denaturing in circulating red cells into Heinz bodies, resulting in congenital Heinz body hemolytic anemia (CHBHA). We have emphasized that most such hemoglobins involve amino acid substitutions at sites neighboring the heme group of the beta-polypeptide chain, and have shown that heme binding to globin is diminished thereby. Thus, hemes were progressively lost from four unstable hemoglobins (Köln, Hammersmith, San Francisco, and Zürich) as they precipitated into Heinz bodies at 50 degrees C. The role of heme loss, especially from beta chains, in Heinz body formation was supported by studies with a hemoglobin synthesized to contain hemes only on its alpha chains (alpha(2) (heme)beta(2) (0)). The behavior of this compound, postulated to be an intermediary in the formation of Heinz bodies, mimicked that of the genetically unstable hemoglobins in several ways: (a) it precipitated at 50 degrees C into typical coccoid Heinz bodies; (b) as also observed with CHBHA hemoglobins this denaturation was virtually prevented by the heme ligands, cyanide or carbon monoxide, which inhibit further heme loss; it was potentiated by oxidation of hemes to the ferri- state, which accentuates heme loss; (c) the thiol groups of alpha(2) (heme)beta(2) (0) were hyperreactive, forming mixed disulfides with glutathione and membrane sulfhydryls at rates similar to those of CHBHA hemoglobins and 10 or more times that of normal hemoglobin A; (d) heme repletion of the protein molecules by the addition of crystalline hemin to either alpha(2) (heme)beta(2) (0) or to the genetically unstable hemoglobins, prevented their precipitation into Heinz bodies and normalized their aberrant electrophoretic behaviors; and (e) during Heinz body formation at 50 degrees C both alpha(2) (heme)beta(2) (0) and the genetically unstable hemoglobins released free alpha(heme)-chains into solution, suggesting that the bulk of the whitish, Heinz body precipitate is naked beta(8)-chains. We conclude that heme loss from mutant beta chains is an early step in Heinz body formation in several of the unstable hemoglobinopathies. The resulting hemedepleted compounds, of which synthetic alpha(2) (heme)beta(2) (0) is a prototype, are unstable, cleaving into beta(0)-chain precipitates (the bulk of the Heinz body material) and soluble, free alpha(heme)-chains (demonstrated previously in hemolysates from many patients with CHBHA).

Anemia, Hemolytic, Congenital↗