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R G Morris

Publications and source records attributed to R G Morris.

At least 235 records · Page 13Linked to original sources

Hormone-induced cell death. 2. Surface changes in thymocytes undergoing apoptosis.

In vivo, apoptotic cells are swiftly recognized by phagocytes, presumably because of changes on their surface. This article describes surface changes in rat cortical thymocytes undergoing apoptosis induced by glucocorticoid treatment in vitro. Homogeneous populations of thymocytes early in apoptosis were prepared by isopyknic centrifugation. These cells were compared with purified nonapoptotic cells in terms of several surface characteristics, including binding to macrophages, surface ultrastructure, microelectrophoretic mobility (a measure of surface charge density), and ability to bind four lectins and four monoclonal antibodies to thymocyte antigens. Apoptotic cells bound to macrophages more avidly than did nonapoptotic cells by a process not dependent upon serum factors. Their surfaces lost microvilli and became " blistered ," apparently through fusion of vesicles of endoplasmic reticulum with the plasma membrane. The surface charge density of apoptotic cells was less than that of nonapoptotic cells. Surface antigens and lectin-binding sites were less abundant on apoptotic than on normal cells, in proportion to the general reduction in cell size observed in apoptosis. Differences between apoptotic and normal cells were not detected, however, in the relative quantities of exposed galactose, N-acetyl galactosamine, N-acetyl glucosamine, N-acetyl neuraminic acid, or of several surface antigens, including the major sialoglycoproteins of the thymocyte membrane. It appears that although several changes occur in the surface of apoptotic cells, many cell membrane structures remain intact. The changes responsible for the recognition of apoptotic cells by phagocytes are more subtle than those detectable by the binding of lectin and antibody probes, but preliminary data suggest that a lectin-sugar interaction is involved.

Animals↗

The effects of central catecholamine depletions on spatial learning in rats.

The role of forebrain catecholamine systems in spatial learning was assessed using a recently described place navigation task. Rats were required to learn the spatial location of a platform hidden 1 cm below the surface in order to escape from a large pool filled with opaque water. Circumscribed destruction of dopamine or noradrenaline neurones was achieved with bilateral stereotaxic injections of 6-hydroxydopamine. Rats with neostriatal dopamine depletions showed regulatory impairments, mild akinesia and increased latencies to escape during training on both the spatial task and on a non-spatial control task. However their normal transfer test performance indicated that their deficit was not due to impaired spatial learning. Similarly, spatial learning and transfer test performance were unimpaired by mesocorticolimbic dopamine depletions or by extensive noradrenaline loss in cortex and hippocampus following dorsal noradrenergic bundle lesions. These findings suggest that considerable spatial learning can occur in the absence of each of the major telencephalic catecholamine systems.

Afferent Pathways↗

Hippocampal electrical activity and gamma-aminobutyrate metabolism in brain tissue following administration of homocysteine.

The concentration of gamma-aminobutyrate (GABA) and the activity of glutamate decarboxylase and GABA-transaminase were measured in extracts of mouse brain before the onset and during the course of generalized seizures induced by systemic administration of homocysteine thiolactone. The results indicate that whole brain GABA metabolism is unaffected by subconvulsive and convulsive doses of homocysteine at all stages of the generalized seizure. Electroencephalographic monitoring of rat brain electrical activity via hippocampal electrode implantation allowed the course homocysteine-induced seizures to be followed and afforded a means of quantifying such seizures.

4-Aminobutyrate Transaminase↗

Hormone-induced cell death. Purification ad properties of thymocytes undergoing apoptosis after glucocorticoid treatment.

A high proportion of cortical thymocytes obtained from suckling rats undergo apoptosis on exposure in vitro to the glucocorticoid methylprednisolone. The apoptotic cells can be separated from apparently normal thymocytes by isopyknic centrifugation on Percoll gradients. This experimental system provides homogeneous populations of apoptotic cells and thus permits a more incisive study of this physiologic mode of cell death than has been hitherto possible. It is shown that apoptosis involves a sharp but transient increase in buoyant density, concomitant with the appearance of characteristic morphologic changes in nucleus and cytoplasm. More than 80% fo the chromatin of apoptotic cells has a molecular weight sufficiently low to resist sedimentation at 27,000g and consists of short oligonucleosome chains, apparently as a result of endogenous endonuclease activity. By contrast, the chromatin of thymocytes that retain normal density (whether treated or control) is of high molecular weight. Apoptotic cells, unlike those of normal density, show little or no incorporation of nucleosides and amino acids into macromolecules. These investigators were unable to detect populations of cells intermediate between apoptotic and normal in buoyant density, morphologic characteristics, chromatin cleavage, or leucine incorporation, but evidence is presented suggesting that thymidine and uridine incorporation may fall prior to development of apoptosis.

Animals↗

Changes in plasma catecholamine concentrations during endotracheal intubation.

The changes in arterial pressure and arterial concentrations of noradrenaline, adrenaline and dopamine were monitored in 16 patients undergoing endotracheal intubation. Significant increases in mean arterial pressure and plasma noradrenaline were noted. The increases in arterial pressure were associated with increases in noradrenaline concentrations. Adrenaline and dopamine concentrations did not change significantly following intubation. The results suggest a predominantly sympathetic response during intubation and the need for prophylaxis in patients at risk.

Adult↗

Set shifting in anorexia nervosa: an examination before and after weight gain, in full recovery and relationship to childhood and adult OCPD traits.

Deficits in set shifting tasks are present in anorexia nervosa (AN), but it is not known whether these deficits are traits independent of current disease or nutritional status or merely a temporary consequence of starvation or psychopathology. The aims of the present study were to determine if set-shifting sub-optimal performance are state or trait-related by examining set shifting in patients with current or past AN, and the extent of association of these deficits with obsessive compulsive traits and behaviours. To achieve this we examined set shifting abilities in three groups of subjects: (a) AN patients with current illness, prior to receiving treatment (AN); (b) people with past AN currently in long term recovery (ANRec) and a healthy comparison group (HC). We also longitudinally followed up a subset for the AN group who showed weight recovery in response to in patient treatment (ANWR). We administered a group of set shifting tests, which included cognitive, perceptual and motor shifting tasks. A semi-structured interview was obtained to ascertain obsessive compulsive personality disorder (OCPD) traits as a child and adult. Set-shifting difficulties were observed in the AN group, but to a lesser extent in the ANRec group. In the AN group these difficulties did not show any improvement follow re-testing after weight recovery. Performance on set shifting tasks was associated with childhood rigidity and inflexibility. Some aspects of set shifting sub-optimal performance in AN appear to be a trait rather than a state marker.

Adult↗