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Biomedical subjects

A M Robertson

Publications and source records attributed to A M Robertson.

30 records · Page 2Linked to original sources
PubMed1978

Morphological aspects of glucocorticoid-induced cell death in human lymphoblastoid cells.

Morphological aspects of cell death associated with a cytolethal concentration of methylprednisolone sodium succinate (500 micrograms/ml) on the BLA1 lymphoblastoid cell line were studied over a 48-hr incubation period by light, transmission and scanning electron microscopy. Studies revealed two distinctive morphological changes induced by the steroid from 1 hr onwards after treatment. One showed contortion and "blebbing" of the cytoplasm and nucleus accompanied or followed by nuclear pyknosis, resulting in the formation of membrane-bounded bodies containing apparently normal cytoplasmic organelles with or without nuclear fragments. The other showed "rounding up" of the cell with loss of cytoplasmic protrusions and long slender surface processes, aggregation of well-preserved cytoplasmic organelles, accompanied by nuclear pyknosis and fragmentation. In both cases many of the features are typical of apoptosis. The subsequent degeneration of cells and fragments not unexpectedly resembled in vitro autolysis. This in-vitro system is suitable for studying the early biochemical events and intracellular control mechanisms of apoptosis.

Cell Line↗
PubMed1977

Cytolethal effects of glucocorticoids in human lymphoblastoid cell lines.

Glucocorticoid hormones penetrate rapidly into intact lymphoblastoid cells and are retained with the same high affinity and specificity as with cytoplasmic extracts. Optimal conditions for lethal glucocorticoid responses in vitro were determined for a series of human lymphoblastoid cell lines by using different glucocorticoid preparations, and steroid solvents and by varying the cell density. Kinetic studies revealed that lethal glucocorticoid effects are dose-dependent and that continuous exposure of cells to steroid is necessary for progression of lethal effects to occur. Even under optimal conditions, human lymphoblastoid cells only exhibit a marked cytolethal response to glucocorticoids at concentrations which greatly exceed both physiological and therapeutically attainable steroid levels. They are also greatly in excess of steroid levels required to saturate the cytoplasmic receptors of intact or disrupted lymphoblastoid cells. It is suggested that either lethal steroid mechanisms in vitro differ fundamentally from those in vivo or the pharmacological activity of glucocorticoids in vivo does not involve a direct cytolethal action.

Burkitt Lymphoma↗
PubMed1975

Cytoplasmic receptor levels and glucocorticoid response in human lymphoblastoid cell lines.

The cytolethal response to treatment with prednisolone was investigated in vitro in eight human lymphoblastoid cell lines containing varying concentrations of specific cytoplasmic glucocorticoid receptors. A similar response was observed in seven of the lines irrespective of their concentration of cytoplasmic receptors and pharmacological doses of steroid, well above those required to saturate receptors in cell-free extracts, were required for a massive lethal response. One cell line derived from Burkitt's lymphoma was refractory to lethal effects even with pharmacological doses of steroid. A similar unresponsiveness to the cytolethal effect of prednisolone in vitro was observed in fresh lymphoblasts derived from patients with acute lymphoblastic leukaemia despite evidence of a satisfactory clinical response to therapy which included steroid. The resistance of human lymphoblastoid cells to treatment with glucocorticoids in vitro may result from a defect in activation subsequent to the binding of steroid to cytoplasmic receptors.

Burkitt Lymphoma↗
PubMedDate not supplied

Bacterial glycosulphatases and sulphomucin degradation.

The presence of a high bacterial population in a region of the gastrointestinal tract is usually associated with the secretion of sulphomucins into the mucus gel covering that region. The term 'sulphomucin' is a histochemical description of the staining properties of mucin. At present this term can only be qualitatively related to the percentage of sulphate in the mucin molecule, which makes the term difficult to use in a biochemical and functional sense. Sulphomucins are thought to carry out the normal functions attributed to mucins; in addition, heavy sulphation rate-limits the degradation of mucins by bacterial mucin-degrading glycosidases. A number of mucin-specific glycosulphatases have been reported in bacteria, although only two such enzymes have been purified. These enzymes remove part of the sulphate content from sulphomucins and make them more susceptible to further enzymic degradation. The variety of chain locations and sugar attachment sites of sulphate esters on the mucin oligosaccharides, taken together with the data on the enzymes, suggest there will be a spectrum of bacterial glycosulphatases, with different properties, cellular locations and substrate specificities. Bacterial glycosulphatases have the potential to modify sulphated glycoconjugates at mucosal surfaces and should prove useful as biochemical tools for the study of sulphated glycoconjugates.

Animals↗