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J W Eaton

Publications and source records attributed to J W Eaton.

At least 145 records · Page 8Linked to original sources
PubMed1981

Abnormal erythrocyte calcium homeostasis in oxidant-induced hemolytic disease.

The processes leading to red cell destruction in oxidant-induced hemolytic disease are not yet fully known. Oxidant damage to hemoglobin per se may be insufficient to explain the process, and the involvement of membrane damage has been suggested. We now report that at least one crucial membrane function-exclusion of calcium-is disrupted by the potent oxidant phenylhydrazine. Phenylhydrazine, both in vitro and when administered to mice in hemolytic doses, causes profound inhibition of red cell calcium ATPase. Coincident with this, red cell calcium content increases very rapidly in mice given phenylhydrazine. These observations suggest that disordered red cell calcium homeostasis may be an important element in oxidant-induced red cell destruction.

Adenosine Triphosphatases↗
PubMed1981

Erythrocyte calcium abnormalities in sickle cell disease.

During a relatively brief tenure in the circulation, sickle erythrocytes may become dehydrated and irreversibly deformed and acquire extensive membrane damage. Abnormally high intracellular calcium concentrations may contribute to these abnormalities, as evidenced by the fact that many of them may be reproduced through ionophoric leading of normal red cells with small amounts of calcium. Sickle erythrocytes have another, possibly related, abnormality; they adhere to cultured vascular endothelium, perhaps due to the disordered (i.e., clumped) negative surface charge present on many Hb SS red cells. This endothelial adherence may have pathophysiologic significance, in that the attendant slowing of erythrocyte circulation may help initiate and propagate vascular occlusions.

Anemia, Sickle Cell↗
PubMed1981

Erythrocyte/endothelial interactions and the vasocclusive severity of sickle cell disease.

Sickle - but not normal - RBC adhere to human endothelial cells. This abnormal behavior requires neither deoxygenation nor frank morphologic distortion of the sickle RBC. Although adherence increases as RBC density increases (presumably paralleling the accumulation of membrane damage), even the least dense sickle and youngest sickle RBC adhere abnormally to endothelium. Data suggest that adherence to endothelium is a consequence of an aberrancy of sickle RBC membrane surface charge topography (clumping of NANA), which it turn may be related - at least in part - to abnormal calcium accumulations in sickle RBC. The propensity for endothelial adherence varies greatly among patients with sickling disorders, and it correlates positively and significantly with clinical vasocclusive severity. The inherent tendency for endothelial adherence of washed sickle RBC from a given patient shows little temporal variation, regardless of the patient's state of health. However, plasma factors which may fluctuate during concurrent illness have an enhancing effect of RBC/endothelial interactions in vitro and may increase the likelihood for vasocclusion by increasing adherence in vivo. It is not yet clear whether adherence is in itself a fully sufficient condition for the development of vasocclusion. It may be that RBC adherence to endothelium initiates vasocclusion by impeding microvascular blood flow and thereby allowing the secondary occurrence of reversible sickling, thus leading to pain crisis and organ infarction.

Adolescent↗
PubMed1981

The red cell: a primer.

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Anion Exchange Protein 1, Erythrocyte↗
PubMed1980

Erythrocyte adherence to endothelium in sickle-cell anemia. A possible determinant of disease severity.

We studied 33 patients with sickle-cell anemia to examine the possible relation between the severity of their disease (frequency of microvascular occlusions) and the abnormal adherence of sickle erythrocytes to cultured human endothelium. Neither clinical severity nor erythrocyte adherence correlates significantly with red-cell indexes, hemoglobin concentration, percentage of irreversibly sickled red cells, level of fetal hemoglobin, or reticulocyte count. However, clinical severity and erythrocyte adherence are strongly correlated (rank correlation coefficient = +0.666; P less than 0.001). These findings are consistent with the hypothesis that abnormal interactions between erythrocytes and endothelium may be the initiating factor in the development of microvascular occlusions in sickle-cell anemia.

Adolescent↗
PubMed1980

Anion channel blockade: effects upon erythrocyte membrane calcium response.

The influx of small amounts of calcium into normal human red cells adversely affects cellular metabolism, shape, ion and water content, and deformability. Because restriction of cation (potassium) efflux moderates these deleterious effects of Ca++ influx, we investigated the possibility that inhibition of anion permeability might be similarly beneficial. Human red cells were treated with 4,4'-diisothiocyano-2,2'-stilbene disulfonate (DIDS), which reacts preferentially with external sites on the transmembrane protein, band 3, and specifically inhibits inorganic anion transport. DIDS-treated and control cells were then exposed to the ionophore A23187 and Ca++. We find that DIDS treatment blocks Ca++-induced K+ and water loss and diminishes changes in osmotic fragility and cellular elasticity. Furthermore, DIDS reduces the "trapping" of hemoglobin by red cell membranes and increases the apparent affinity of the cell membrane for glyceraldehyde-3-phosphate dehydrogenase.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1980

Abnormal adherence of sickle erythrocytes to cultured vascular endothelium: possible mechanism for microvascular occlusion in sickle cell disease.

The abnormal shape and poor deformability of the sickled erythrocyte (RBC) have generally been held responsible for the microvascular occlusions of sickle cell disease. However, there is no correlation between the clinical severity of this disease and the presence of sickled RBC. In searching for additional factors that might contribute to the pathophysiology of sickle cell disease, we have investigated the possibility that sickle RBC might be less than normally repulsive of the vascular endothelium. After RBC suspensions are allowed to settle onto plates of cultured human endothelial cells, normal RBC are completely removed by as few as six washes. In contrast, sickle RBC remain adherent despite multiple washes. On subconfluent culture plates, normal RBC are distributed randomly, whereas sickle RBC cluster around endothelial cells. Sickle RBC adherence is not enhanced by deoxygenation but does increase with increasing RBC density. The enzymatic removal of membrane sialic acid greatly diminishes the adherence of sickle RBC to endothelial cells, suggesting that sialic acid participates in this abnormal cell-cell interaction. Although net negative charge appears normal, sickle RBC mainfest an abnormal clumping of negative surface charge as demonstrated by localization of cationized ferritin. These abnormalities are reproduced in normal RBC loaded with nonechinocytogenic amounts of calcium. We conclude that sickle RBC adhere to vascular endothelial cells in vitro, perhaps caused by a calcium-induced aberration of membrane topography. This adherence may be a pathogenetic factor in the microvascular occlusions characteristic of sickle cell disease.

Anemia, Sickle Cell↗
PubMed1980

Evaluation of the role of diacyglycerol in calcium-induced erythrocyte shape change and rigidity.

The intrusion of micromolar amounts of calcium into the calcium-poor interior of the human erythrocyte initiates a series of cataclysmic changes in cellular metabolism and morphology. These include (1) cellular shrinkage (elevated mean cell hemoglobin concentration), (2) loss of water and potassium, (3) rapid and near-total hydrolysis of intracellular ATP, (4) conversion of cell shape from biconcave disc to echinocyte and spheroechinocyte, (5) greatly diminished cellular deformability and elasticity, and (6) the accumulation of DAG. It has been suggested that this latter of phenomenon may account for the changes in cell shape and, perhaps, membrane viscoelastic properties. In the present study we have tested the hypothesis that DAG accumulation is important in the evolution of calcium-induced erythrocyte damage. Our results indicate that (1) calcium-loaded lamb erythrocytes become misshapen and inelastic but do not produce detectable DAG; (2) human red cells suspended in potassium-rich buffer do accumulate DAG after exposure to calcium and A23187 but do not become echinocytic or inflexible; (3) human erythrocytes artificially loaded with DAG are morphologically and elastically normal; and (4) human erythrocytes which have "naturally" accumulated DAG after prolonged incubation in the presence of calcium will retain this DAG after energy repletion. Despite marked elevations of DAG, these cells resume normal morphology and deformability. In aggregate, our data fail to support any direct role for DAG accumulation in the occurrence of calcium-induced damage to human erythrocytes.

Adenosine Triphosphate↗
PubMed1980

Calcium-induced erythrocyte rigidity: the roles of cellular metabolism, hydration, and ionic balance.

Previous investigations have shown that incubation of human erythrocytes with the ionophore A23187 and calcium causes accumulation of the cation, losses in potassium, water, and cellular volume, hydrolysis of adenosine triphosphate (ATP), conversion of biconcave discocytes to echinocytes and spheroechinocytes, and marked increases in erythrocyte resistance to micropipette aspiration. Subsequent studies demonstrated that prevention of water and potassium loss blocked the influence of calcium loading on erythrocyte stiffness without affecting calcium uptake by the cells or hydrolysis of ATP. In the present study erythrocytes were exposed to conditions that permitted individual or coordinate manipulation of cellular ATP, water, potassium, and calcium in order to determine which factors developing as a result of calcium loading were responsible for the calcium-induced changes in erythrocyte viscoelastic properties. Results of the study demonstrate that volume loss, ATP hydrolysis, and potassium depletion do not individually or in combination cause increases in erythrocyte stiffness. However, all of these changes are essential and must develop in conjunction with calcium loading in order for erythrocytes to develop diminished deformability and elasticity.

Adenosine Triphosphate↗
PubMed1979

Generation of hydroxyl radical by enzymes, chemicals, and human phagocytes in vitro. Detection with the anti-inflammatory agent, dimethyl sulfoxide.

Methane (CH(4)) production from the anti-inflammatory agent, dimethyl sulfoxide (DMSO), was used to measure .OH from chemical reactions or human phagocytes. Reactions producing .OH (xanthine/xanthine oxidase or Fe(++)/EDTA/H(2)O(2)) generated CH(4) from DMSO, whereas reactions yielding primarily O-(2) or H(2)O(2) failed to produce CH(4). Neutrophils (PMN), monocytes, and alveolar macrophages also produced CH(4) from DMSO. Mass spectroscopy using d(6)-DMSO showed formation of d(3)-CH(4) indicating that CH(4) was derived from DMSO. Methane generation by normal but not chronic granulomatous disease or heat-killed phagocytes increased after stimulation with opsonized zymosan particles or the chemical, phorbol myristate acetate. Methane production from DMSO increased as the number of stimulated PMN was increased and the kinetics of CH(4) production approximated other metabolic activities of stimulated PMN. Methane production from stimulated phagocytes and DMSO was markedly decreased by purportedly potent .OH scavengers (thiourea or tryptophane) and diminished to lesser degrees by weaker .OH scavengers (mannitol, ethanol, or sodium benzoate). Superoxide dismutase or catalase also decreased CH(4) production but urea, albumin, inactivated superoxide dismutase, or boiled catalase had no appreciable effect. The results suggest that the production of CH(4) from DMSO may reflect release of .OH from both chemical systems and phagocytic cells. Interaction of the nontoxic, highly permeable DMSO with .OH may explain the anti-inflammatory actions of DMSO and provide a useful measurement of .OH in vitro and in vivo.

Cells, Cultured↗