Search PubMed⌕ Search

Biomedical subjects

J M Oliver

Publications and source records attributed to J M Oliver.

At least 163 records · Page 9Linked to original sources
PubMed1977

Mechanisms of microtubule diassembly in vivo: studies in normal and chronic granulomatous disease leucocytes.

Microtubule assembly in human polmorphonuclear leucocytes is a dynamic process that can be initiated by binding of the plant lectin Concanavalin A to surface receptors. Colchicine inhibits lectin-induced microtubule assembly and promotes the movement of Concanavalin A into surface caps. Inhibition of microtubule assembly and enhanced Concanavalin A cap formation also follow treatment of normal leucocytes with two specific glutathione-oxidizing agents, 'diamide' and tertiary butylhydroperoxide. Our objective here was to determine if microtubule inhibition is mediated via glutathione disulphide or via hydrogen peroxide that is generated in Concanavalin A-treated leucocytes and may accumulate when cells are depleted of reduced glutathione. We show that exogenous hydrogen peroxide induces Concanavalin A capping on normal polymorphonuclear leucocytes but only at concentrations that simultaneously oxidize glutathione. We also show that 'diamide' and tertiary butylhydroperoxide cause Concanavalin A cap formation in leucocytes from patients with chronic granulomatous disease. These cells cannot generate significant amounts of superoxide or hydrogen peroxide. Thus, it seems likely that the reversible inhibition of microtubule assembly and function caused by glutathione oxidants requires only increased glutathione disulphide and is not dependent on subsequent accumulation of other metabolites.

Child↗
PubMed1976

Carbamycholine prevents giant granule-formation in cultured fibroblasts from beige (Chediak-Higashi) mice.

Primary embryonic fibroblasts isolated from beige (Chediak-Higashi) mice develop pathognomonic giant granules in vitro. Inclusion in the culture medium of carbamylcholine (carbachol) or phorbol myristate acetate (PMA) results in the generation of morphologically normally granules. Chediak-Higashi fibroblasts are highly susceptible to shape changes induced by colchicine. This abnormal property is also corrected by carbachol and PMA.

Atropine↗
PubMed1976

Changes in number, mobility, and topographical distribution of lectin receptors during maturation of chick erythroid cells.

Plant lectins have been used to probe changes in cell surface characteristics that accompny differentiation in a complete series of chick erythroid cells. Dramatic differences in lectin receptor mobility were observed between the most immature cells of the series, the proerythroblasts, and cells at the next stage of maturation, the erythroblasts. Both concanavalin A and Ricinus communis agglutinin form caps on proerythroblasts, whereas they develop a patchy distribution on erythroblasts. Erythroid cells at later developmental stages show a homogeneous distribution of surface-bound R. communis agglutinin. Concanavalin A also shows a uniform distribution on the cell periphery, but appears to be concentrated in a ring above the perinuclear region of the cell. In addition to changes in mobility of lectin receptors, a large reduction (50-70%) in the number of lectin receptors per cell accompanies maturation of proerythroblasts to erythroblasts. Pretreatment of the cells with neuraminidase results in enhanced binding of R. communis agglutinin to proerythroblasts. The number of additional R. communis agglutinin receptors exposed by enzyme treatment remains relatively constant during subsequent cell maturation.

Animals↗
PubMed1976

Effects of glutathione-oxidizing agents on microtubule assembly and microtubule-dependent surface properties of human neutrophils.

In human peripheral blood polymorphonuclear leukocytes and lymphocytes, GSH-oxidizing agents promote the movement of surface-bound concanavalin A (Con A) into caps and inhibit the assembly of microtubules (MT) that is normally induced by Con A binding. Con A capping and inhibition of MT assembly occur when GSH levels in cell suspensions are decreased by 30-70%, and return to GSH to control levels is accompanied by the appearance of cytoplasmic MT and by inhibition of the capping response with Con A. Oxidation of GSH markedly stimulates the hexose monophosphate shunt, and regeneration of GSH occurs rapidly. The data indicate that MT cannot be assembled or maintained in the face of decreased GSH levels. Thus, GSH homeostasis becomes critical during physiological events such as phagocytosis which simultaneously induce the assembly of MT and the production of agents like H2O2 that can oxidize GSH.

Azo Compounds↗
PubMed1976

Correction of characteristic abnormalities of microtubule function and granule morphology in Chediak-Higashi syndrome with cholinergic agonists.

Chediak-Higashi (CH) syndrome is a genetic disorder of children and certain animal species including the beige mouse. We have previously described a membrane abnormality in CH mouse polymorphonuclear leukocytes (PMH). Whereas normal mouse PMN do not form surface caps with concanavalin A except after treatment with agents such as colchicine that inhibit microtubule assembly, CH mouse PMN show spontaneous cap formation. This capping is inhibited by 3',5 cyclic guanosine monophosphate and by the cholinergic agonists carbamylcholine and carbamyl beta-methylcholine that increase 3',5' cyclic guanosine monophosphate generation. These data suggested that microtubule function may be impaired in CH syndrome perhaps secondary to an abnormality in 3',5' cyclic guanosine monophosphate generation. The cholinergic agonists were also shown to prevent development of the giant granules that are pathognomonic of CH syndrome in embryonic fibroblasts isolated from CH mice and cultured in vitro. In this report it is shown that an extreme degree of spontaneous concanavalin A cap formation is also characteristic of peripheral blood PMN from two patients with CH syndrome. This indicates an abnormality of microtubule function in CH syndrome in man. 3',5' cyclic guanosine monophasphate, carbamylcholine, and carbamyl beta-methylcholine reduce spontaneous capping in CH cells. In addition, it is shown that monocytes isolated from the patients' blood and incubated in tissue culture generate a large complement of abnormal granules. When the same cells mature in vitro in the presence of carbamylcholine or carbamyl beta-methylcholine, the proportion of cells containing morphologically normal granules is significantly increased. These responses can be reproduced in vivo in the beige (CH) mouse. Animals treated for 3 wk and longer with carbamylcholine or carbamyl beta-methylcholline show normal granule morphology and a normal degree of concanavalin A cap formation in peripheral blood PMN leukocytes.

Adult↗
PubMed1976

Impaired microtubule function correctable by cyclic GMP and cholinergic agonists in the Chediak-Higashi syndrome.

The Chediak-Higashi (CH) syndrome of man and several animal species is characterized by the presence of abnormal giant granules in all granule-containing cells and by defects in chemotaxis and lysosomal degranulation during phagocytosis in polymorphonuclear leukocytes (PMNs). Since similar functional abnormalities have been reported in normal PMNs following exposure to colchicine and other agents that disrupt microtubles it was proposed that microtubule function may be impaired in the CH syndrome. The mobility of concanavalin A (con A)-receptor complexes on PMN membranes was used to test microtubule integrity. Normal PMNs showed a uniform distribution of membrane-bound con A. By contrast, con A was aggregated into surface caps on both colchicine-treated normal PMNs and untreated PMNs from mice and a patient with CH syndrome. This result is consistent with impaired microtubule function in the CH cells. The spontaneous capping response of CH PMNs was inhibited by cyclic GMP and by cholinergic agonists that can elevate cyclic GMP levels in neutrophils. This raised the possibility that the microtubule defect in CH cells may be correctable by treatments that increase cyclic GMP generation. Direct evidence for both the absence of microtubule assembly in con A-treated PMNs from the CH patient and for normal microtubule assembly in CH PMNs incubated with cyclic GMP and cholinergic agonists prior to con A treatment was obtained by electron microscopy. In addition, evidence for a direct relationship between the microtubule defect and the development of giant lysosomes in CH cells was obtained. Thus, CH fibroblasts grown in vitro developed abnormal lysosomes in the majority of cells. However, the same cells cultured in the presence of cholinergic agonists developed a majority of lysosomes that were morphologically normal at the level of the light microscope. Similarly, granule morphology appeared normal in peripheral blood leukocytes from mice treated chronically in vivo with cholinergic agonists.

Animals↗
PubMed1975

The cell surface.

Explore the source record for details and available documents.

Agglutination↗
PubMed1975

Uptake and supply of purine compounds by the liver.

We have analyzed for purine compounds entering and leaving the liver in lightly anesthetized rabbits and rats and for the export of utilizable purine from liver perfused with oxypurine. The in vivo results indicate that roughly 80% of hypoxanthine, xanthine, and urate is removed in a single passage of blood through liver. Conversely, the adenosine concentration of hepatic venous blood is increased 10-fold over portal or arterial levels. When the liver is isolated and perfused with hypoxanthine there is significant release of adenosine, whether measured quantitatively by microbiological assay or qualitatively by analysis of the radioactive purines released from liver that has been prelabeled with [14C]hypoxanthine. These results provide direct evidence for the clearance of hydroxylated purines and the release of utilizable adenine derivatives by liver.

Adenosine↗
PubMed1974

Effects of phagocytosis and colchicine on the distribution of lectin-binding sites on cell surfaces.

The effect of phagocytosis on lectin binding to plasma membranes of polymorphonuclear leukocytes was examined. The specific activities of binding sites of concanavalin A and Ricinus communis agglutinin (defined as mug of lectin bound per 100 mug of membrane protein) were measured on isolated membranes; they decreased in parallel with phagocytosis. Our data suggest that this removal occurs by concentration of binding sites into internalized membrane. Colchicine and vinblastine, which did not inhibit phagocytosis, prevented the selective removal of lectin-binding sites from the surface. It was also shown that at 37 degrees lectins induce their own internalization. This property was used to define operationally three classes of lectin receptors, one of which is most extensively removed from plasma membrane during phagocytosis. Based on other morphological studies in which it is shown that before phagocytosis the surface distribution of concanavalin-binding sites is random, it is inferred that phagocytosis alters surface topography by inducing the selective movement of binding sites into membrane undergoing internalization and that colchicine-sensitive proteins are essential for this imposed topographical reorganization.

Animals↗