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Biomedical subjects

R I Weed

Publications and source records attributed to R I Weed.

At least 19 recordsLinked to original sources
PubMed1982

Erythrocyte hemighosts: a hallmark of severe oxidative injury in vivo.

Erythrocyte hemighosts and ghosts were found in five patients: two with severe oxidant haemolysis caused by chemicals or drugs, and three G6PD deficient subjects with haemolysis triggered by infection and/or drugs. Scanning and transmission electron-microscopy showed that the hemighost consisted of a thinned-out part with antero-posterior apposition of the membrane and a thicker spheroidal part containing most of the haemoglobin. Heinz bodies were found in both parts of the cell close to the membrane. Large number of hemighosts (30-90%) is an ominous sign as three of our five affected patients died. The removal of these cells by exchange transfusion or the induction of forced diuresis probably saved the life of the other two patients. Experiments in rabbits showed that hemighosts were found only with severe oxidative injury induced by a large dose of acetylphenylhydrazine (50 mg/kg) and the spleen was not required for their formation. The marked congestion in the splenic sinusoids and other microcirculation results from sludging of these damaged rigid cells and is an important pathophysiological mechanism in severe oxidant injury.

Adult↗
PubMed1977

The regulation of the release of granulocytes from normal marrow.

Figure 16 synthesizes the various aspects of marrow egress. The central anatomical relationship of the hematopoietic compartment to vascular sinus is shown above. The hatched blocks represent the sinus wall, capable of developing narrow migration channels. In the marrow, immature granulocytes alter their biophysical characteristics by developing motility, nuclear and cytoplasmic deformability and surfaces which facilitate egress. Humoral factors contribute to proliferation and maturation. Also, other humoral agents, releasing factors, may act on mature cells, for example, as cytoattractants, and on the sinus wall to reduce its adventitial cover and thereby to enhance egress. In the sinus, flow or discharge of sinus contents may be regulated by humoral agents or neural messages which may affect terminal sphincters or other structures. Although the marrow in situ is a difficult organ to study, future innovations are to be expected and our understanding of the delicate balance between hematopoietic cells, stroma and vasculature will be enhanced. Corrections of inferential errors due in part to the semi-quantitative and qualitative nature of much of our current data should be expected.

Animals↗
PubMed1976

Complement-induced ultrastructural membrane lesions: requirement for terminal components.

The step in the complement (C) sequence at which 8- to 11-nm ring-shaped lesions are formed on antibody-coated erythrocytes (EA) has remained controversial. Some workers have concluded that these lesions appear at the C5 step and are not ultrastructural correlates of lysis; others hold that these lesions are formed only after the action of C8 and C9 in association with lysis. We have re-examined this problem by using sheep EA and human sera genetically lacking C5, C6, C7, or C8. Electron micrographs of negatively stained membranes (x 220,000) were read in blind fashion and the results correlated with 125I-C5 binding. Rare structures resemblind C-induced ring lesions were found on EA exposed to C5-deficient (C5D), C6D, C7D and C8D sera or to heated normal serum, with no significant differences among these sera (lesion density 0 to 0.26/mum2). Fresh normal serum (NHS) produced 140 to 220 ring lesions/mum2. C5 binding to EA in C8D serum was 60% of that observed in an NHS control; in C6D and C7D sera C5 binding was 4 to 11% of the normal value. Iodine treatment of sera (to enhance C5 uptake by C2 oxidation) increased C5 binding in C6D serum to 40 to 65% of that seen in native NHS; in iodine-treated C7D and C8D sera C5 binding was 250 and 440%, respectively, of the native NHS value. No increase in ring lesions was observed, however, except in the iodine-treated NHS. Thus, in whole serum, C5 binding is not sufficient to produce ultrastructural membrane rings in the absence of later-acting C components, at least through C8. The formation of ring lesions appears to have C requirements similar to those necessary for lysis.

Binding Sites↗
PubMed1975

Herediatary spherocytosis. A review.

Studies of the clinical features of hereditary spherocytosis since 1871 and laboratory investigation of the cellular abnormalities since 1940 have led to the characterization of hereditary spherocytosis as a prime example of a Mendelian dominant, genetically determined disorder of the erythrocyte membrane. This review of hereditary spherocytosis emphasizes the contributions of Dr. Lawrence Young and many others of out present understanding of the disease and discusses current studies of the protein abnormality in the membrane of hereditary spherocytes.

Adenosine Triphosphate↗
PubMed1975

Slow phase hemolysis in hypotonic electrolyte solutions.

When a population of erythrocytes is partially hemolyzed the time course of hemolysis can be divided into a fast phase and a slow phase. The slow phase occurs with both rapid and gradual addition of the hypotonic medium (rapid and gradual hemolysis). There is no difference in the osmotic fragility of erythrocytes remaining at 60 minutes after rapid or gradual hemolysis. Erythrocytes near their critical hemolytic volume have an equimolar ouabaininsensitive sodium-potassium exchange. Critical non-hemolytic swelling with resulting stress on the membrane appears requisite to slow phase hemolysis since more non-penetrant sucrose is required to prevent slow phase lysis rather than that which would be predicted from the intracellular colloid osmotic pressure due to hemoglobin. Sucrose protection from slow phase hemolysis thus depends not only on counter-balancing the colloid osmotic pressure, but also removal of sufficient intracellular water to prevent critical membrane strain. This model is consistent with that proposed by Katchalsky. Irreversible membrane changes associated with hypotonic stress manifested by persistent stomatocytic shape change and membrane wrinkling on return of cells to isotonicity appear to be due to critical changes in membrane components. Such cells, having normal indices and specific gravity are less deformable than control cells in 2.8 mum pore size polycarbonate filters.

Cell Membrane↗
PubMed1975

Calcium and magnesium ATPases of the spectrin fraction of human erythrocytes.

Using a rapid method of preparation, spectrin has been isolated from human erythrocytes and its ATPase activity investigated. The ATPase activity with calcium has two distinct components, one with optimal activity when calcium and ATP are of equal concentration (low-Ca-ATPase) and another which is activated above 1 mM CaCl2 and is maximal at 100 mM CaCl2. There is also a Mg-ATPase with maximal activity at 10 mM MgCl2. The high-Ca-ATPase of spectrin, but not the low-Ca-ATPase, is inhibited by magnesium, while the Mg-ATPase is inhibited by Ca in excess of ATP. None of these activities exhibits the calcium-stimulated magnesium-dependent activity characteristic of the red cell calcium pump.

Adenosine Triphosphatases↗
PubMed1975

Bone marrow sinus cell packing: a determinant of cell release.

Ultrastructural studies of erythropoietin effects on the bone marrow of control and hypertransfused (65 hct) mice revealed a decrease in adventitial cell cover of the sinus apertures in erythropoietin-treated animals. A more striking finding, however, was the marked inhibition of erythropoietin-induced reticulocytosis by hypertransfusion itself. Hypertransfusion of the erythropoietin-treated animals appeared to decrease the reticulocyte response by inhibiting reticulocyte response by marrow cords in addition to inhibiting erythroid proliferation. This inhibition of reticulocyte response was associated with clustering of reticulocytes around the marrow sinuses which were packed with red cells. Acute lowering of the hematocrit of erythropoietin-treated, hypertransfused animals to normal at the time of maximal reticulocyte response in control animals resulted in more than a twofold increase in reticulocytosis with 2 hr. It is suggested that (1) elevated levels of erythropoietin are associated with a diminution of the normal marrow-peripheral blood barrier, thereby contributing to the premature release of marrow elements and (2) the hematocrit is an important determinant of cell release from the marrow into the peripheral circulation.

Animals↗
PubMed1975

Membrane structure and its relation to haemolysis.

Advances in our understanding of the biochemistry, physiology and ultrastructure of the normal erythrocyte membrane have opened up the possibility of characterising congenital or acquired membrane defects in various haemolytic anaemias. The normal red cell membrane can undergo reversible disc-echinocytic or disc-stomatocytic shape changes in response to a wide variety of chemical agents and conditions. These shape changes may become irreversible and, in fact, they may be encountered in different types of haemolytic disease, suggesting that the echinocytic and stomatocytic shape changes represent two fundamental ways in which red cells react to intrinsic and extrinsic insults. Membrane alterations in haemolytic disease can be divided into disorders in which the defect appears to be a primary membrane abnormality, e.g. hereditary spherocytosis and disorders in which membrane damage occurs secondary to internal or external influences, e.g. the membrane alteration in sickled cells. The normal of deformability of the red cell is one of the prime determinants of survival in vivo and thus the geometric relationship of the erythrocyte surface area to cell volume, if decreased, can contribute to haemolysis. Intrinsic changes in membrane deformability or membrane deformability secondary to alterations in the cell haemoglobin may also compromise passage through the microcirculation, particularly through the spleen. Finally, abnormalities of cation permeability and/or lipid composition are found in certain haemolytic states. In each case it is essential to attempt to relate the abnormality described to the manner in which cell properties critical to in vivo survival are compromised in order to understand the pathophysiology.

Abetalipoproteinemia↗