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Biomedical subjects

R A Cooper

Publications and source records attributed to R A Cooper.

At least 253 records · Page 14Linked to original sources

Morphological and functional characteristics of cells infiltrating and destroying tumor multicellular spheroids in vivo.

EMT6 mammary sarcoma cells were grown in vitro as multicellular spheroids to model for the heterogeneity of microenvironments and structural changes which develop in many tumors, including micrometastases. Spheroids of 700-900 micron diameter were implanted into and recovered at different times from the peritoneal cavities of sensitized or nonsensitized allogeneic and syngeneic mice. The colony forming efficiency of spheroid tumor cells recovered at 24 and 48 h from sensitized allogeneic mice was markedly decreased as compared with those from nonsensitized allogeneic or syngeneic animals. These recovered spheroids were extensively infiltrated by both lymphocytes and macrophages, which ultrastructurally had very close membrane associations with tumor cells. Host cells recovered from spheroids exhibited cytotoxic activity in an in vitro 51Cr release assay. Thus, multicellular spheroids in vivo provide a unique experimental model to study the functional capacity of host cells within a spheroical tumor. Although lacking the stroma and the vasculature of in vivo solid tumors, this model does have many similarities to in vivo tumors and is thus suitable for studying the tumor cell-host cell interactions within the tumor microenvironment. In addition, the system offers the potential for quantitative study of the effects of treatment modalities on tumor cell-host cell interactions.

Animals↗

Prostatic mucinous carcinoma.

Four criteria are proposed for establishing the pathologic diagnosis of prostatic mucinous carcinoma. Twenty-one reported cases of this rare tumor are reviewed, and a new case is presented. The clinical and pathologic features of 16 authentic features of 16 authentic cases are analyzed.

Adenocarcinoma, Mucinous↗

Hereditary stomatocytosis: association of low 2,3-diphosphoglycerate with increased cation pumping by the red cell.

The levels of glycolytic intermediates have been measured in red cells from patients with both overhydrated and dehydrated varieties of the hereditary stomatocytosis syndrome. Red cell 2,3-diphosphoglycerate was reduced by 33% below normal in all patients with either stomatocyte or target cell morphologies (i.e. over or under hydrated varieties respectively). The relative decrement in 2,3-diphosphoglycerate was even greater when abnormal cells were compared with control cells with similar reticulocytosis. Red cell ADP concentrations in stomatocytosis were significantly increased above normal but ATP concentrations were not significantly changed. Whole blood oxygen affinity in stomatocytosis was increased in proportion to the lowered content of diphosphoglycerate. Some new parameters of membrane transport in hereditary stomatocytosis have been measured. Platelet K+ and Na+ concentrations and platelet K+ permeability were normal in stomatocytosis. The number of 3H-uridine transport sites in stomatocytes were increased by 9-39% above normal and this increment was the same as the increment in red cell lipids (0-38%). Hereditary stomatocytes contain 2-10-fold more cation pumps than normal and the increased active cation pumping may explain the high ADP, the low 2,3-diphosphoglycerate concentration and the increased oxygen affinity in this syndrome.

Adenosine Diphosphate↗

Feasibility and efficacy of 5-azacytidine used early in the therapy of adult acute nonlymphocytic leukemia: an ECOG pilot study.

Ten of 19 adult patients (53%) with acute non-lymphocytic leukemia achieved a complete remission (CR) after receiving combination therapy with daunorubicin and cytosine arabinoside. The early administration of 5-azacytidine to treatment failures did not enhance the CR rate. Patients gaining CR received six monthly cycles of single-agent chemotherapy (5-azacytidine, daunorubicin, and cytosine arabinoside) sequentially as consolidation therapy over the next 7 months and no subsequent maintenance therapy. The median duration of CR is 10 months which is similar to previous studies. The early administration of 4-azacytidine did not increase the duration of remission, but was not associated with significant toxicity.

Adult↗

Influence of increased membrane cholesterol on membrane fluidity and cell function in human red blood cells.

Cholesterol and phospholipid are the two major lipids of the red cell membrane. Cholesterol is insoluble in water but is solubilized by phospholipids both in membranes and in plasma lipoproteins. Morever, cholesterol exchanges between membranes and lipoproteins. An equilibrium partition is established based on the amount of cholesterol relative to phospholipid (C/PL) in these two compartments. Increases in the C/PL of red cell membranes have been studied under three conditions: First, spontaneous increases in vivo have been observed in the spur red cells of patients with severe liver disease; second, similar red cell changes in vivo have been induced by the administration of cholesterol-enriched diets to rodents and dogs; third, increases in membrane cholesterol have been induced in vitro by enriching the C/PL of the lipoprotein environment with cholesterol-phospholipid dispersions (liposomes) having a C/PL of greater than 1.0. In each case, there is a close relationship between the C/PL of the plasma environment and the C/PL of the red cell membrane. In vivo, the C/PL mole ratio of red cell membranes ranges from a normal value of 0.09--1.0 to values which approach but do not reach 2.0. In vitro, this ratio approaches 3.0. Cholesterol enrichment of red cell membranes directly influences membrane lipid fluidity, as assessed by the rotational diffusion of hydrophobic fluorescent probes such as diphenyl hexatriene (DPH). A close correlation exists between increases in red cell membrane C/PL and decreases in membrane fluidity over the range of membrane C/PL from 1.0 to 2.0; however, little further change in fluidity occurs when membrane C/PL is increased to 2.0--3.0. Cholesterol enrichment of red cell membranes is associated with the transformation of cell contour to one which is redundant and folded, and this is associated with a decrease in red cell filterability in vitro. Circulation in vivo in the presence of the spleen further modifies cell shape to a spiny, irregular (spur) form, and the survival of cholesterol-rich red cells is decreased in the presence of the spleen. Although active Na-K transport is not influenced by cholesterol enrichment of human red cells, several carrier-mediated transport pathways are inhibited. We have demonstrated this effect for the cotransport of Na + K and similar results have been obtained by others in studies of organic acid transport and the transport of small neutral molecules such as erythritol and glycerol. Thus, red cell membrane C/PL is sensitive to the C/PL of the plasma environment. Increasing membrane C/PL causes a decrease in membrane fluidity, and these changes are associated with a reduction in membrane permeability, a distortion of cell contour and filterability and a shortening of the survival of red cells in vivo.

Biological Transport↗

Morphology and physiology of the McLeod erythrocyte. I. Scanning electron microscopy and electrolyte and water transport properties.

The McLeod phenotype is a rare condition characterized by deficiencies in the Kell blood group antigens of erythrocytes. The present study has defined some of the morphological and physiological characteristics of these red cells. Scanning electron microscopy reveals that approximately 27% of McLeod cells are morphologically abnormal. These aberrant forms resemble the acanthocytes of abetalipoproteinemia. Incubation experiments indicate that the morphology of McLeod erythrocytes is not due to a plasma factor. Biochemical studies reveal that the lipid composition and microviscosity of these erythrocytes are normal. In addition, isotopic tracer experiments indicate that electrolyte transport is also within the normal range. However, osmotic water permeability is approximately 30% below normal. The absence of a lipid abnormality and other experimental data suggest that the abnormal morphology and reduced H2O permeability of the McLeod erythrocyte may be due to defective membrane protein.

Biological Transport, Active↗

Computerized tomography (body scan) of Baker's cyst.

Computerized tomography (CT scan or body scan) has never been applied to the diagnosis of Baker's cysts. There cases of Baker's cyst evaluated by both CT scanning and arthrography are presented. The CT scan appears to be of no value.

Adult↗

Ectopic gallstone as a cause of gastric outlet obstruction.

Gallstone ileus is, of course, a well known cause of small bowel obstruction. A gallstone, however, is a very rare cause of gastric outlet obstruction. Three cases illustrating this phenomenon are exhibited. Radiographs were diagnostic in two of the studies. All three patients did well postoperatively.

Aged↗