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Biomedical subjects

R A Cooper

Publications and source records attributed to R A Cooper.

At least 325 records · Page 18Linked to original sources
PubMed1969

The role of membrane lipids in the survival of red cells in hereditary spherocytosis.

Red cells in hereditary spherocytosis (HS) have a decreased ratio of membrane surface area to cell volume and therefore a spheroidal shape. This abnormality in shape predisposes them to pooling and destruction in the spleen. Although splenectomy prevents hemolysis in HS, the red cell defect, as manifested by spheroidicity, increased autohemolysis, excesive permeability to sodium, and hypermetabolism, persists. The role of membrane lipids in these manifestations in vitro and in cell survival in vivo was examined. Before splencetomy, and in spite of the presence of a young cell population, the cholesterol and phospholipid content of HS red cells is decreased. After splenectomy lipid values are similar to those obtained in normal subjects with spleens. However, after splenectomy for conditions other than HS the lipid content of red cells is greater than normal. Thus, when compared with the red cells of patients without HS who have also undergone splenectomy, HS cells after splenectomy are deficient in both cholesterol and phospholipid. Obstructive jaundice causes an increase in membrane lipid, primarily cholesterol, and a decrease in the osmotic fragility of normal red cells. When HS red cells are transfused into patients with obstructive jaundice they also become less osmotically fragile. Moreover, when incubated in obstructive jaundice serum, they gain cholesterol. This acquistion of membrane lipid in vitro does not result in a change in their rate of glucose utilization or sodium efflux. However, the transformation to a less spheroidal shape in vivo permits them to traverse better the splenic circulation and survive longer.

Bilirubin↗
PubMed1969

The selective and conjoint loss of red cell lipids.

The pattern of lipid loss from the membrane of red cells incubated in serum is influenced by the availability of glucose. Under homeostatic conditions with respect to glucose, cholesterol alone is lost. This results from esterification of free cholesterol in serum by the serum enzyme, lecithin:cholesterol acyltransferase, and is associated with a proportional decrease in membrane surface area, reflected by an increased osmotic fragility. This selective loss of membrane cholesterol also occurs in hereditary spherocytosis (HS) red cells, even after incubation for 65 hr in the presence of glucose. The loss of free cholesterol from red cells relative to its loss from serum, under these conditions, is greatest at higher hematocrits, similar to those found in the spleen. Although the selective loss of membrane cholesterol increases the spherodicity of normal red cells, it does not lead to a change in their rate of glucose consumption, and both the loss of cholesterol and the increase in osmotic fragility are reversible in vitro. Moreover, normal red cells made osmotically fragile by cholesterol depletion in vitro rapidly become osmotically normal and survive normally after their reinfusion in vivo.In contrast to this selective loss of membrane cholesterol, red cells incubated in the absence of glucose lose both cholesterol and phospholipid. This occurs more rapidly in HS than normal red cells and is followed by a disruption of cation gradients and then by hemolysis. Cholesterol and phospholipid lost under these conditions is not restored during subsequent incubations in vitro. Selective loss of membrane cholesterol is a physiologic event secondary to an altered state of serum lipids. It is reversible both in vitro and in vivo and neither influences cellular metabolism nor impairs viability. Conjoint loss of phospholipid and cholesterol, however, results from intrinsic injury to the red cell membrane which results from prolonged metabolic depletion.

Blood Transfusion↗
PubMed1969

Anemia with spur cells: a red cell defect acquired in serum and modified in the circulation.

The sera and red cells of three patients with severe liver disease and "spur cells" were studied. In each case the per cent of serum cholesterol which was free (unesterified) was elevated, and the serum lecithin: cholesterol acyltransferase activity was depressed. Lipoproteins with beta mobility were increased, but exhibited immune reactivity with antisera to both alpha- and beta-lipoproteins. Serum bile salt concentrations were markedly elevated and consisted primarily of chenodeoxycholic acid, with small amounts of lithocholic acid present as well.SPUR CELLS MANIFESTED A STRIKING INCREASE IN CHOLESTEROL CONTENT AND IN THE CHOLESTEROL: phospholipid ratio, but a normal osmotic fragility. When incubated in heated normal serum, spur cells lost their excess cholesterol and became spherocytic and osmotically fragile. Conversely, sera from patients with spur cells readily transferred up to one-third of their free cholesterol to normal red cells, causing normal cells to become resistant to osmotic lysis. In addition, these sera caused normal red cells to acquire thorny membrane projections. Cholesterol transfer to normal cells also occurred from normal serum which had previously been incubated with spur cells. Changes in cell cholesterol were induced by all of the lipoprotein fractions of spur serum. When transfused into a patient with spur cells, normal red cells became more resistant to osmotic lysis over the course of 24 hr. However, over the subsequent 7 days they underwent a progressive increase in osmotic fragility. These normal cells, as well as the patient's own cells, had a shortened survival. Correlating with the moderate decrease in the filterability of red cells spurred in vitro, red cell destruction occurred predominently in the spleen. Red cells in this disorder appear to serve as repositories for free cholesterol loosely bound to serum lipoproteins. Cholesterol acquisition by the red cell membrane increases its surface area and causes the red cell to be resistant to osmotic lysis. The associated alteration in red cell shape leads to further changes in the cell membrane during circulation in vivo resulting in the loss of membrane surface area and culminating in the cell's premature destruction in the spleen.

Anemia↗
PubMed1968

Bile salts and cholesterol in the pathogenesis of target cells in obstructive jaundice.

Free cholesterol is in rapid equilibrium between serum lipoproteins and red cells. The level of red cell cholesterol is influenced by bile salts, which shift the serum/cell partition of free cholesterol to the cell phase and which inhibit the cholesterol-esterifying mechanism. During incubation in normal serum possessing an active cholesterol-esterifying mechanism, red cells lose cholesterol and surface area and thereby become more spheroidal and less resistant to osmotic lysis. When exposed to serum from patients with obstructive jaundice or to normal serum with added bile salts, red cells accumulate cholesterol and increase their surface area, thereby acquiring a flattened shape and an increased resistance to osmotic lysis. The described gains and losses of red cell cholesterol and surface area do not involve metabolic injury and occur with no significant change in phospholipid content. The red cells of patients with obstructive jaundice are flat and osmotically resistant and have an increased cholesterol:phospholipid ratio. When transfused into normal subjects these "target cells" rapidly lose their osmotic resistance. Similarly, normal cells acquire osmotic resistance in the circulation of patients with obstructive jaundice. These reversible changes in shape occur with half-times of about 9 and 24 hr, respectively, and occur without impairing cell viability. These studies indicate that the red cell membrane accumulates cholesterol in obstructive jaundice as a consequence of the elevated levels of bile salts. The resulting increment in red cell surface area is responsible for the physical properties and appearance of target cells. These observations substantiate Murphy's findings in vitro indicating that cholesterol is an important determinant of red cell shape and that its content in the cell membrane may vary independently from the phospholipids. Presumably any process or disorder affecting cholesterol exchange in vivo is capable of critically modifying the shape and behavior of red cells.

Bile Acids and Salts↗
PubMed1967

Dermatopathic lymphadenopathy a clinicopathologic analysis of lymph node biopsy over a fifteen-year period.

Forty cases of dermatopathic lymphadenopathy were found in a series of 906 consecutive lymph node biopsies (4.8 per cent). The histologic development and progression of the disease was correlated with the clinical state of the patient. In 35 of 40 cases the patients had active skin disease at the time of the biopsy; one of the remaining five patients had Hodgkin's disease, one had multiple myeloma and one had secondary syphilis. In the other two, no organic cause was found. In nine cases (22.5 per cent), the histological pattern typical of dermatopathic lymphadenopathy was associated with malignant lymphoma. Except for two biopsies, which showed coexisting malignant lymphoma and dermatopathic lymphadenopathy, no histologic features were found which distinguished patients with malignant lymphoma from the remainder. While the pathogenesis of the lymph node changes remains obscure, the histologic features suggest that it is at least in part an immune response, although the nature of the responsible antigen is unknown.

Biopsy↗