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Biomedical subjects

S S Buys

Publications and source records attributed to S S Buys.

12 recordsLinked to original sources
PubMed1994

Phase II evaluation of amonafide in advanced sarcoma: a Southwest Oncology Group study.

Soft tissue sarcomas are generally resistant to most chemotherapeutic agents, and individuals with advanced disease have a poor prognosis. We evaluated amonafide, a new drug that has significant activity against several tumor cell lines, to determine its activity against sarcomas. Amonafide was administered to 18 patients with advanced soft tissue sarcoma (16 of whom had received prior chemotherapy) at a dose of 300 mg/m2 over 60 min daily for 5 days. Courses were repeated every 21 days. Toxicity was mild, but no responses were observed. We conclude that amonafide is not an active agent in previously treated, advanced soft tissue sarcomas in the dose and schedule utilized.

Adenine↗
PubMed1991

Iron absorption in hypotransferrinemic mice.

We used a unique animal model, the hypotransferrinemic (Htx) mouse, to examine the role of transferrin (Tf) in gastrointestinal iron uptake. Despite the absence of Tf, Htx animals hyperabsorb iron. Transfusion of red blood cells sufficient to normalize the hematocrit and reticulocyte count resulted in a return of iron absorption to normal values. These studies indicate that Tf does not play an obligate role in iron absorption, either as a carrier or as a humoral signal regulating absorption. Transfer of plasma or whole blood from Htx mice or from other animal models of iron hyperabsorption to normal mice did not cause an increase in iron absorption in recipient animals. Using the plasma or blood transfer approach, we have been unable to detect a humoral regulator of gastrointestinal iron absorption.

Animals↗
PubMed1990

Effect of osmotic pressure on uptake of chemotherapeutic agents by carcinoma cells.

Intraperitoneal chemotherapy has been used to treat cancers which are confined to the abdominal cavity. Several variables which affect drug delivery into tumor cells have been identified, but the effect of osmotic pressure has not been studied. Tumor cell lines were used to evaluate the effect of fluid tonicity on drug uptake. HeLa cells and a murine teratoma cell line were suspended in solutions of tonicities 154, 308, and 616 mosM, each containing the same quantity of 5-fluorouracil, and uptake of the drug was measured at different intervals over 30 min. At all time points the amount of 5-fluorouracil taken up by cells in solutions of 154 mosM was greater than that in 310 mosM solutions, which was greater than the uptake in 616 mosM solutions, each by an average of 40-50%. Incorporation of drug into tumor cells was also assayed in vivo using a teratoma cell line propagated i.p. in mice. Tumor cell uptake of doxorubicin was increased to a similar extent when this drug was administered in hypotonic solutions of 154 mosM and was decreased by administration in hypertonic solutions of 465 mosM, as compared to solutions of 310 mosM. These results demonstrate that the uptake of chemotherapeutic agents into tumor cells is increased significantly when these drugs are infused in solutions of lower osmolalities, a finding which may be exploited in clinical situations.

Animals↗
PubMed1990

Carotid thrombosis following neck irradiation.

Therapeutic irradiation may accelerate atherosclerosis, increasing the risk of vascular stenosis or occlusion several to many years following radiation. However, intimal damage following irradiation may result earlier in thrombosis without stenosis. This report discusses three cases of carotid occlusion that occurred within 3 years of moderate dose irradiation. Angiographic studies showed that occlusion occurred in the absence of atherosclerotic stenosis. A review of the literature supports the conclusion that people who receive neck irradiation are at risk not only for the delayed development of diffuse atherosclerosis but also for thrombotic occlusion within months to several years. We suggest that patients who develop neurological symptoms or signs following neck irradiation, regardless of age, dose of radiation, or interval since radiation, should be evaluated for carotid or vertebral artery disease.

Adult↗
PubMed1990

Three cases of fatal cardiac tamponade following ventricular endocardial biopsy.

Three patients had perforation of the ventricular free wall and fatal cardiac tamponade following endocardial biopsy to evaluate congestive heart failure. The number of endocardial biopsies at this institution at the time of the third death was 2372, resulting in an overall mortality rate of 0.13%. Of the 2372 biopsies, 2136 (90%) were performed to evaluate cardiac graft rejection and 236 (10%) were performed for other reasons. All the patients who died belonged to the latter group. None of the cardiac transplant patients have had fatal ventricular perforation--a significant difference. At our institution, the frequency of mortality following endocardial biopsy in the noncardiac transplant patients is 1.3%. Patients who have ventricular endocardial biopsy of native hearts rather than transplanted hearts may be at increased risk for fatal perforation.

Adult↗
PubMed1989

Effect of volume and pH on surface receptor number in macrophages.

Incubation of rabbit alveolar macrophages in hypo-osmotic solutions transiently increases cell volume and inhibits membrane internalization, resulting in an increase in surface receptor number. Since recent reports suggest that hypo-osmotic treatment decreases intracellular pH, and that reduced pH inhibits receptor internalization, pH was measured in hypo-osmotically treated macrophages. We found that cells incubated in iso-osmotic solutions of pH less than 7.2 exhibited a decrease in intracellular pH upon exposure to hypo-osmotic solutions, while cells in iso-osmotic solutions of pH greater than 7.2 had an increase in pH upon exposure to hypo-osmotic solutions. The relative increase in surface receptor number was unaffected by the initial pH or by the direction of change in pH. Incubation of cells in high K+/low Na+ hypotonic buffers induced a persistent increase in cell volume and surface receptor number. Cell volume and surface receptor number fell to baseline values after restoration of isotonicity by the addition of hypertonic sucrose. These manipulations had little effect on intracellular pH. We conclude that the inhibition of membrane internalization observed in cells exposed to hypo-osmotic solutions is independent of changes in intracellular pH. The inhibition of internalization observed in this system may be due directly to forces produced as a consequence of cell swelling.

Animals↗
PubMed1988

Effect of hypo-osmotic incubation on membrane recycling.

Incubation of alveolar macrophages in hypo-osmotic media causes a time-and temperature-dependent increase in the number of surface receptors for three different ligands. Exposure of cells to solutions of 210 mOsM or less, at 37 degrees C but not at 0 degree C, resulted in an increase in the number of surface receptors for diferric transferrin, alpha-macroglobulin-protease complexes, and mannose-terminated glycoproteins. Upon media dilution at 37 degrees C, surface receptor number reached a maximum within 5 min and returned to near-normal values by 30 min. The increase in surface receptor number was the result of a decrease in the rate of internalization of receptors, either occupied or unoccupied. The rate of receptor exteriorization was unaltered by hypo-osmotic incubation of cells. The rate of fluid-phase pinocytosis was also inhibited upon incubation in hypo-osmotic solution. In experiments in which both receptor-mediated endocytosis and fluid phase pinocytosis were measured on the same samples, inhibition of both processes occurred with the same kinetics and to a similar extent. The rate of receptor-mediated endocytosis recovered to normal rates after 60 min in hypo-osmotic solutions, whereas the rate of fluid phase pinocytosis did not recover to the same extent.

Animals↗
PubMed1988

Regulatory volume decrease in alveolar macrophages: cation loss is not correlated with changes in membrane recycling.

Alveolar macrophages regain their normal volume after swelling in hypo-osmotic solutions. This process, termed regulatory volume decrease (RVD), is initiated 3-5 minutes after exposure of cells to hypo-osmotic solutions, and by 30 min, near-normal volumes are attained. Volume decrease does not occur at 0 degrees C or in solutions in which Na+ has been replaced by K+, or Cl- by the impermeant anion gluconate. These results, as well as direct measurement of intracellular cations, indicate that decreases in cell volume result primarily from the loss of K+ and Cl- and are similar to RVD in lymphocytes. Kinetic analysis of cation loss, both by directly measuring changes in intracellular cation content and by assaying rubidium efflux, showed that cation loss occurred immediately upon media dilution. The rate of cation loss fit first-order kinetics and preceded both the initiation of volume decrease and the maximum increase in surface receptor number. These results suggest that the cation transporters responsible for RVD are located at the cell surface and that regulation of activity is not dependent on alterations in membrane movement.

Animals↗
PubMed1987

Phorbol esters and calcium ionophores inhibit internalization and accelerate recycling of receptors in macrophages.

Exposure of macrophages to phorbol esters or the calcium ionophore A23187 increases the number of several surface receptors due to recruitment of receptors from internal pools (Buys, S. S., Keogh, E. A., and Kaplan, J. (1984) Cell 38, 569-576). We have examined the mechanism by which these agents increase surface receptor number. Cells which were preloaded with either fluid phase or receptor-mediated ligands did not lose ligand following exposure to ionophore or phorbol ester. The rate of movement of ligands to the lysosome was also unaffected. These results suggest that A23187 does not induce the fusion of ligand-containing compartments with the cell surface. Ionophore treatment did, however, produce a severalfold increase in the rate at which unoccupied receptors reappear on the cell surface. These results suggest that the compartment of receptors affected by the ionophore formed subsequent to the dissociation of ligand from receptor. The altered rate of receptor reappearance was transitory (90 s), and the increase in receptor number was subsequently maintained by a decrease in the rate of internalization. Changes in the rate of receptor internalization did not correlate with changes in the rate of fluid phase pinocytosis, suggesting that the effect on receptor internalization was selective.

Animals↗
PubMed1987

Effect of phagocytosis on receptor distribution and endocytic activity in macrophages.

Phagocytosis requires the internalization of a significant fraction of the plasma membrane and results in the intracellular deposition of large particles. We evaluated the effect of phagocytosis on the cellular distribution of recycling receptors and uptake of ligand to determine whether phagocytosis affects receptor behavior. Phagocytosis of zymosan, latex particles, or IgG-coated red blood cells by rabbit alveolar macrophages did not decrease the number of cell surface receptors for transferrin, alpha 2-macroglobulin X protease complexes, maleylated proteins, or mannosylated proteins. The number of surface receptors for transferrin was also unaltered in J774 cells, a macrophage-like cell line. In both cell types extensive phagocytosis did not affect the rate of receptor-mediated endocytosis or the distribution of receptors between the endosome and the cell surface. However, fluid phase pinocytosis was reduced by phagocytosis. The major reduction appeared to be not in the rate of internalization but rather in the delivery of fluid to the lysosome. These results demonstrate that internalization of a significant amount of the plasma membrane during phagocytosis does not diminish the number of receptors on the cell surface and has no effect on receptor-mediated ligand uptake.

Animals↗
PubMed1984

Fusion of intracellular membrane pools with cell surfaces of macrophages stimulated by phorbol esters and calcium ionophores.

Mouse tumor macrophages (J774) exposed to phorbol myristate acetate (PMA) exhibited a marked increase in cell spreading. Correlated with this phenomenon was an increase in the number of cell surface transferrin (Tf) receptors and a corresponding decrease in the number of Tf receptors located intracellularly in membrane-bound endosomes. Similar effects were noted when J774 cells were exposed to the calcium ionophore A23187. Rabbit alveolar macrophages did not respond to PMA but did respond to A23187 by increasing cell spreading, which was accompanied by increases on the cell surface of four different receptors. These results demonstrate that phorbol esters and calcium ionophores can induce a redistribution of cellular receptors.

Animals↗