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S Charache

Publications and source records attributed to S Charache.

At least 145 records · Page 8Linked to original sources
PubMed1970

Electron paramagnetic resonance studies of spin-labeled hemoglobins and their implications to the nature of cooperative oxygen binding to hemoglobin.

The spin label technique has been used to study human hemoglobins A, F, Zürich, and Chesapeake as a function of carbon monoxide saturation. The experimental results suggest that the changes in the electron paramagnetic resonance spectra of hemoglobin labeled with N-(1-oxyl-2,2,6,6-tetramethyl-4-piperidinyl)iodoacetamide depend on the state of ligation of more than one heme group. For those hemoglobins with full or large cooperative ligand binding (such as A, F, and Zürich), there is a lack of isosbestic points in the spectra as a function of CO saturation. However, for those hemoglobins with little or no cooperative ligand binding (such as Chesapeake and methemoglobins), there is a sharp set of isosbestic points. These findings confirm and extend the early work of McConnell and co-workers. The absence of a set of isosbestic points in those hemoglobins with full cooperative ligand binding is consistent with the sequential model of Koshland, Némethy, and Filmer for cooperative oxygen binding to hemoglobin. The present results, with hemoglobin variants having known amino acid substitutions, also focus on the importance of the interactions among the amino acid residues located at alpha(1)-beta(2) or alpha(2)-beta(1) subunit contacts for the functioning of hemoglobin as an oxygen carrier. In addition, the resonance spectra of the spin label are very sensitive to small structural variations around the heme groups in the beta- or gamma-chains where the labels are attached. The results of the spin label experiment are discussed in relation to recent findings on the mechanism of oxygenation of hemoglobin from the nuclear magnetic resonance studies of this laboratory and the x-ray crystallographic analysis of Perutz and co-workers.

Amides↗
PubMed1970

Effect of 2,3-diphosphoglycerate on oxygen affinity of blood in sickle cell anemia.

Blood of patients with sickle cell anemia (SS) exhibits decreased affinity for oxygen, although the oxygen affinity of hemoglobin S is the same as that of hemoglobin A. SS red cells contain more 2,3-diphosphoglycerate (DPG) than normal erythrocytes. The oxygen affinity of hemolyzed red cells is decreased by added DPG, and hemolysates prepared from SS red cells do not differ from normal hemolysates in this regard. Reduction of oxygen affinity to the levels found in intact SS red cells required DPG concentrations in excess of those found in most SS patients. The same was true of oxygen affinity of patients with pyruvate kinase deficiency. Other organic phosphates, as well as inorganic ions, are known to alter the oxygen affinity of dilute solutions of hemoglobin. These substances, the state of aggregation of hemoglobin molecules, and cytoarchitectural factors probably play roles in determining oxygen affinity of both normal and SS red cells.

Anemia, Sickle Cell↗
PubMed1969

Nuclear magnetic resonance studies of hemoglobins. 3. Evidence for the nonequivalence of alpha- and beta-hains in azide derivativeof methemoglobins.

Nuclear magnetic resonance spectroscopy (100-MHz proton) was used to study the low-spin (S = 1/2) azide derivatives of human adult (alpha(2)beta(2)), human fetal (alpha(2)gamma(2)), Zürich (alpha(2)beta(2) (63 His --> Arg)), and horse (alpha(2)'beta(2)') methemoglobins, as well as whale metmyoglobin in 0.1 M deuterated phosphate at pD 7 and at 31 degrees C. The experimental results indicate that the azide-bound heme groups of the alpha- and beta-chains in human adult methemoglobin and of the alpha- and gamma-chains in fetal methemoglobin are not equivalent. The affinity of the beta- or gamma-chain for azide ion appears larger than that of the alpha-chain. The nuclar magnetic resonance spectrum of hemoglobin Zürich shows that the environment of the azide-heme complex in the abnormal beta-chain is altered by the substitution of arginine for histidine in the beta-63 position, while the alpha-heme environment remains unaffected.

Animals↗
PubMed1969

Hemoglobin Hasharon (alpha-2-47 his(CD5)beta-2): a hemoglobin found in low concentration.

Hemoglobin Hasharon (alpha(2) (47 his)(CD5)beta(2)) was found to comprise only 16-19% of hemolysates of carriers. These heterozygotes appeared to have mild, compensated, hemolytic anemia. Hb Hasharon was more heat-labile than hemoglobins A, S, or C. Its specific activity was higher than that of Hb A after administration of (59)Fe to two carriers. When hemoglobin synthesis by bone marrow cells was studied in vitro, about 18% of incorporated leucine appeared in the Hb Hasharon fraction. It is suggested that Hb Hasharon is unstable in vivo, and that mild hemolytic anemia and a relatively small decrease in its concentration in hemolysates result from its denaturation within red cells. Decreased synthesis, which appears to be the major cause of the small amount of abnormal hemoglobin, may protect heterozygotes from clinically significant hemolytic anemia.

Aged↗
PubMed1967

Pathogenesis of hemolytic anemia in homozygous hemoglobin C disease.

Hemoglobin C is less soluble than hemoglobin A in red cells, in hemolysates, and in dilute phosphate buffer. Its relative insolubility may be explained by electrostatic interactions between positively charged beta6-lysyl groups and negatively charged groups on adjacent molecules. Red cells from patients with homozygous hemoglobin C (CC) disease exhibit aberrant physical properties which suggest that the cells are more rigid than normal erythrocytes. They pass through membrane filters less readily than normal red cells do, and their viscosity is higher than that of normal cells. Differences from normal cells are exaggerated if mean corpuscular hemoglobin concentration (MCHC) is increased, by suspension in hypertonic salt solution. Increased rigidity of CC cells, by accelerating their fragmentation, may be responsible for formation of microspherocytes. These small dense cells are exceptionally rigid, and probably are even more susceptible to fragmentation and sequestration. Rigidity of CC cells can be attributed to a "precrystalline" state of intracellular hemoglobin, in which crystallization does not occur, although the MCHC exceeds the solubility of hemoglobin in hemolysates.

Anemia, Hemolytic↗
PubMedDate not supplied

One view of the pathogenesis of sickle cell diseases.

A single amino acid substitution in the beta chain of hemoglobin (beta 6 glutamic acid leads to valine) is responsible for polymerization of deoxyhemoglobin S, and the sickling of red blood cells containing that hemoglobin. Sickled cells are rigid and inflexible, causing obstruction of small blood vessels, which in turn causes obstruction of small blood vessels, which in turn causes ischemic injury. Organs most frequently damaged include the spleen, bone marrow, liver, and kidney. Sickled cells also have a shortened survival; the hemolytic anemia they produce is responsible for aplastic crises, megaloblastic anemia, ankle ulcers, gallstones and gout. "Sickle cell lung disease" is a serious problem, since distinction between infection and infarction is difficult or impossible, and impaired oxygenation of the blood makes further sickling likely. Since the entire patient, not just his blood, is affected by the disease, treatment must go beyond transfusion and drug administration. Each patient presents a new constellation of problems, and therapy must be individualized if it is to be optimal.

Anemia, Aplastic↗