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Biomedical subjects

S B Shohet

Publications and source records attributed to S B Shohet.

At least 109 records · Page 6Linked to original sources
PubMed1978

Marked reduction of spectrinin hereditary spherocytosis in the common house mouse.

In contrast to the disease in humans, hereditary spherocytosis in the common house mouse produces an extreme spherocytosis. The cells show a broad distribution in size ranging from microcytic to macrocytic. Of particular interest is the finding of a substantial reduction in the major membrane polypeptide called spectrin, supporting a critical role for this protein in the control of erythrocyte shape and membrane stability.

Animals↗
PubMed1978

Monovalent cation composition and ATP and lipid content of irreversibly sickled cells.

Discontinuous Stractan gradients were used to separate heterogeneous populations of sickle cells into discrete subpopulations containing varying proportions of reticulocytes, mature discoid cells, and irreversibly sickled cells (ISC). The improved homogeneity of these preparations, together with an enhanced yield of ISC, allowed us to distinguish effects of cell maturation from those of irreversible sickling. With these cell preparations we have begun to define physical properties of ISC. We confirmed the marked abnormalities in cation composition of native ISC. Measurements of ATP in ISC did not substantiate prior reports of ATP deficits. Finally, no evidence for substantial loss of membrane lipids during the process of ISC formation could be demonstrated.

Adenosine Triphosphate↗
PubMed1978

The spectrin phosphorylation reaction in human erythrocytes.

Phosphorylation of spectrin in whole cells occurs on a single tryptic peptide and indicates a specific and limited modification of spectrin. Phosphorylation of spectrin in soluble extracts and isolated membranes is less specific. Diamide is an inhibitor of erythrocyte spectrin kinase and casein kinase. This agent also inhibits the restoration of biconcave morphology to metabolically depleted erythrocytes reincubated with adenosine.

Adenosine Triphosphate↗
PubMed1977

Abnormalities in granule formation in acute myelogenous leukemia.

Granule formation was investigated in differentiating neutrophils of a patient with acute myelogenous leukemia (AML) by means of the combined techniques of electron microscopy and peroxidase cytochemistry. Two important pathologic features were observed: first, an abnormal concentration and packaging of peroxidase into Auer rods in leukemic promyelocytes, and second, the presence of Auer rods surrounded by single-unit membranes in some mature polymorphonuclear leukocytes (PMN). An additional unexpected finding was the discovery of two distinct populations of PMN circulating concurrently; a minor (less than 5%) normal one that contained both peroxidase-positive azurophilic and peroxidase-negative specific granules and a major abnormal one characterized by the absence of specific granules. None of these abnormalities was observed during the two remissions of this patient's disease. During relapse a "hiatus leukemicus" occurred, which also revealed two populations of cells, a majority population of leukemic blasts, and a minority population of a few normal PMN. These findings documented several developmental abnormalities in the differentiating cells of myelogenous leukemia and also suggested that concurrent normal and abnormal populations of PMN may be a helpful diagnostic feature of a leukemic process.

Adult↗
PubMed1976

Water proton magnetic resonance studies of normal and sickle erythrocytes. Temperature and volume dependence.

The temperature and cell volume dependence of the NMR water proton line-width, spin-lattice, and spin-spin relaxation times have been studied for normal and sickle erythrocytes as well as hemoglobin A and hemoglobin S solutions. Upon deoxygenation, the spin-spin relaxation time (T2) decreases by a factor of 2 for sickle cells and hemoglobin S solutions but remains relatively constant for normal cells and hemoglobin A solutions. The spin-lattice relaxation time (T1) shows no significant change upon deoxygenation for normal or sickle packed red cells. Studies of the change in the NMR linewidth, T1 and T2 as the cell hydration is changed indicate that these parameters are affected only slightly by a 10-20% cell dehydration. This result suggests that the reported 10% cell dehydration observed with sickling is not important in the altered NMR properties. Low temperature studies of the linewidth and T1 for oxy and deoxy hemoglobin A and hemoglobin S solutions suggest that the "bound" water possesses similar properties for all four species. The low temperature linewidth ranges from about 250 Hz at -15 degrees C to 500 Hz at -36 degrees C and analysis of the NMR curves yield hydration values near 0.4 g water/g hemoglobin for all four species. The low temperature T1 data go through a minimum at -35 degrees C for measurements at 44.4 MHz and -50 degrees C for measurements at 17.1 MHz and are similar for oxy and deoxy hemoglobin A and hemoglobin S. These similarities in the low temperature NMR data for oxy and deoxy hemoglobin A and hemoglobin S suggest a hydrophobically driven sickling mechanism. The room temperature and low temperature relaxation time data for normal and sickle cells are interpreted in terms of a three-state model for intracellular water. In the context of this model the relaxation time data imply that type III, or irrotationally bound water, is altered during the sickling process.

Anemia, Sickle Cell↗
PubMed1976

Hemolytic anemias. Failure of the red cell membrane.

The normal erythrocyte membrane is composed of nearly equivalent amounts of lipid and protein. The lipid portion of the membrane has been well studied. Even though de novo synthesis of lipid does not occur in human red cells, many biochemical pathways exist which facilitate detoxification of lipid breakdown products and lipid renewal. Rare defects in these processes are associated with hemolytic disorders. Recent studies have revealed that the membrane proteins are diverse and suggest that protein dysfunction may also account for clinical disease. Protein and lipid are entwined in a physicochemical relationship which is probably best depicted by the classic lipid bilayer with interspersed proteins in both the inner and outer surfaces and also spanning the bilayer. Membrane failure results in hemolytic anemia. This failure can be intrinsic, caused by abnormal lipid or protein constituents; or extrinsic, with a normal membrane being unable to counteract physical, chemical or immunologic stress. Clinical examples of membrane failure and hemolytic anemia can be separated into three groups according to the predominant mechanism of the hemolysis: fragmentation, whole-cell lysis, and filtration and entrapment. Although these mechanisms can act separately or in concert, the final hemolytic destruction of the cell can usually be traced to a failure of membrane function.

Abetalipoproteinemia↗
PubMed1976

Hybrid erythrocytes for membrane studies in sickle cell disease.

A hybrid erythrocyte model for membrane studies in sickle cell disease has been developed. The model consists of normal red cell membranes containing hemoglobin S and sickle cell membranes containing hemoglobin A. In hybrids, complete hemoglobin exchange has been achieved together with restoration of low membrane permeability to potassium. Normal membranes containing HbS sickle upon deoxygenation and assume the characteristic appearance of irreversibly sickled cells (ISC) after prolonged anoxia. It is suggested that the hybrid model will be useful in defining further the process of ISC formation and in studying the influence of sickle hemoglobin upon the function of the surrounding membrane.

Anemia, Sickle Cell↗
PubMed1976

The measurement of circulating red cell volume using nonradioactive cesium and fluorescent excitation analysis.

Nonradioactive cesium, as an analogue of potassium, has been used to label autologous red blood cells for determination of the red cell volume in man. The initial and the equilibration concentrations of cesium are assayed by fluorescent excitation analysis (FEA), using a 600 mCi 241Americium source and a Si(Li) detector with a 1024-channel analyzer. Comparative studies with 51Chromium in 13 rabbits showed good correlation, but the intracellular cesium concentration achieved by simple incubation with 2.6 per cent cesium chloride solution was too low to be of practical value in humans. Incubation of the human red blood cells with 50 mug per milliliter of Nystatin in 2.6 per cent cesium chloride opened reversible "pores" in the red cell membrane which permitted high intracellular cesium labeling without demonstrable red cell damage. The cesium red cell volumes in 11 random human subjects differed from the 51Chromium red cell volumes by only 0.2 +/- 4.5 per cent and 2.5 +/- 7.6 per cent at blood sampling times of 10 minutes and 40 minutes, respectively. Blood cesium levels fell with a clearance half-time of 31.5 hours in 4 rabbits, and 2.4 days in 1 normal human. Fluorescent excitation analysis of cesium-labeled autologous red blood cells permits accurate determination of the red cell volume in man without associated patient radiation, thus making the procedure much more acceptable for children, pregnant women, normal volunteers, and for repeated studies in the same individual.

Blood Volume Determination↗
PubMed1976

Lipid membrane peroxidation in beta-thalassemia major.

The composition of membrane lipids was studied in 17 splenectomized and eight unsplenectomized patients with beta-thalassemia major and compared to normal controls. The results showed a nearly twofold increase in total cell lipids; a reduction in the percentage, but not the absolute amount of phosphatidylethanolamine, and a corresponding increase in phosphatidylcholine in the lipids; a considerable increase in the percentage of the saturated fatty acid, palmitic acid, and a reciprocal decrease in the polyunsaturated fatty acid, arachidonic acid; a twofold increase in the amount of malonyldialdehyde (MDA) generated after peroxide threat to the RBC when calculated either per gram hemoglobin or per cell; no change in the amount of MDA generated when calculated per microgram of membrane phosphorus at risk per cell; and a considerable decrease in serum alpha-tocopherol (vitamin E) levels. Thalassemic erythrocytes contain more lipid per cell which is susceptible to peroxidation. In addition, the distribution of fatty acids in these cells suggests that autooxidation of that lipid may have occurred. Autooxidation may be initiated by free radicals, which are constantly formed in the normal red cell, and may be especially prevalent when unstable hemoglobins are present. The low MCHC or some other intracellular defect of thalassemic cells may allow such potent oxidants to find their way to the cell membrane. Vitamin E, a biologic antioxidant is decreased in these patients, and clinical supplementation may be indicated to prevent some of the membrane damage in thalassemia.

Adolescent↗
PubMed1976

Phosphorylation in erythrocyte membranes from abnormally shaped cells.

Erythrocyte protein phosphorylation was examined in membrane preparations of 25 patients with hereditary spherocytosis (HS). Reduced phosphorylation in substrate polypeptides was observed in 22 HS erythrocyte membranes for both splenectomized and nonsplenectomized patients. A reduction in labeling was also observed in a polypeptide which was labeled only in the presence of cAMP. No reduction was observed in membranes from immunologically acquired spherocytosis cells or from cells from patients with hereditary elliptocytosis. Heating membranes to 45 degrees C caused negligible inhibition of membrane protein phosphorylation, while heating to 50 degrees C extensively inhibited phosphorylation. Dephosphorylation of membrane protein that occurred in isolated membranes was not dependent upon cAMP.

Cyclic AMP↗
PubMed1976

Stabilization of the shape of sickled cells by calcium and A23187.

Evaluation of the role of calcium in irreversible sickling has been approached by treating sickled cells with calcium and the ionophore A23187. A calcium-dependent stabilization of the sickled cell shape was observed after reoxygenation of cells in the presence of ionophore. At low calcium concentrations, this retention of sickled shape was maintained for periods up to 1 hr. However, the morphology of the oxygen-stable sickled cells was like that of deoxygenated sickle cells and significantly different from the characteristic morphology of native irreversibly sickled cells (ISCs). Because the stabilized cells did not fulfill the morphological criterion for ISCs, the shape-stabilizing effect of calcium in this system did not provide additional support for the hypothesis that calcium accumulation was the determining factor in ISC generation.

Anemia, Sickle Cell↗