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Biomedical subjects

A O'Halloran

Publications and source records attributed to A O'Halloran.

11 recordsLinked to original sources

The sigma receptor ligand JO 1784 (igmesine hydrochloride) is neuroprotective in the gerbil model of global cerebral ischaemia.

To assess the effects of the novel sigma receptor ligand JO 1784 ((+)-N-cyclopropyl-methyl-N-methyl-1,4-diphenyl-1-yl-but-3-en-1-ylami ne, hydrochloride or igmesine hydrochloride) on behavioural and histological changes following cerebral ischaemia, the gerbil model of cerebral ischaemia was used. Two experiments were carried out. In the first animals were either sham operated, subjected to 5 min of bilateral carotid occlusion or administered JO 1784 (25, 50, 75 or 100 mg/kg p.o.) 1, 24 and 48 h after 5 min bilateral carotid occlusion and histological evaluation carried out 96 h after surgery. In the second experiment the effects of JO 1784 administered at a dose of 100 mg/kg i.p. 30 min, 6, 24 and 48 h post-surgery on home cage activity and nitric oxide (NO) synthase activity in the cortex, hippocampus, cerebellum and brain stem 4 days after surgery was examined. Extensive neuronal death was observed in the CA1 region of 5 min occluded animals. JO 1784 (50, 75 and 100 mg/kg) provided significant protection against this ischaemia-induced cell death (P < 0.03-0.005). In the second experiment a large increase in home cage activity was observed for 5 min occluded animals for 12 h after surgery (P = 0.0018-0.02). A large increase in NO synthase activity was observed in all brain regions for 5 min occluded animals. Post-administration of JO 1784 attenuated the ischaemia-induced hyperactivity and increased NO synthase activities.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

The Galway Study of Panic Disorder. II: Changes in some peripheral markers of noradrenergic and serotonergic function in DSM III-R panic disorder.

Sixty six patients with panic disorders, fulfilling the DSM III criteria for panic attack, together with a group of age and sex matched controls, were studied for changes in their peripheral noradrenergic and serotonergic status before treatment and during six months treatment with either clomipramine or lofepramine. The results of this study suggest that, despite clinical improvement, the peripheral markers of both adrenergic (platelet aggregation to noradrenaline, platelet alpha 2 receptor density and lymphocyte beta receptor density) and serotonergic (platelet aggregation to serotonin, 3H-ketanserin binding to platelet 5HT2 receptors and 3H-5HT uptake into platelets) function largely remained abnormal. It is concluded that such abnormalities are trait markers of biogenic amine function in patients with panic attack. Further studies are needed to determine whether or not these parameters eventually normalize in those patients showing prolonged remission of symptoms.

Adult

Polarity specific adaptation to motion in the human visual system.

Three experiments investigated polarity specific adaptation to movement. Experiment 1 tested for temporal polarity specific adaptation, using counterphase sawtooth gratings as adapting and test stimuli. Each counterphase grating contained oppositely moving sawtooth components, and was thus balanced for direction, but both components of the adapting grating created only one polarity of luminance change over time, whereas the components of the test grating presented different signs. After adaptation, only the test component containing the unadapted temporal change was visible. A second experiment, using an analogous procedure, found evidence for spatial polarity specific adaptation. Experimental results can be explained by motion detectors which preserve information about spatial and temporal polarity. A third experiment found that spatial and temporal polarity specific adaptation differ in their dependence on temporal frequency.

Adaptation, Ocular

The spacing illusion: a spatial aperture problem?

A geometrical illusion in which the horizontal spacing between adjacent parallel lines in a row is underestimated when the lines are tilted away from vertical in a chevron configuration was investigated in two experiments. The perceived spacing was found to decrease as the tilt angle increased, consistent with the idea that separation judgements are influenced by the normal spacing between lines ie at right angles to the line orientation. It is proposed that this illusion reveals an analogue in spatial perception to the well-known aperture problem in motion perception. In establishing the separation of nearby or overlapping shapes in an image, the visual system cannot only rely upon the normal separation of contours belonging to each shape (as would be visible through small spatial apertures or receptive fields), since this varies with contour orientation. The system is therefore faced with a spatial aperture problem. The spacing illusion may arise because information usually available to solve the problem is absent in the illusion figure, or it may reflect a bias in favour of the orthogonal, which is adopted in the face of the ambiguity.

Adult

Proliferative myositis. An immunohistochemical and ultrastructural study.

We studied four cases of proliferative myositis by the avidin-biotin-peroxidase complex technique, using a panel of 12 antibodies, and by electron microscopy. The aim was to clarify the nature of their constituent cells, specifically the giant ganglion-like cells and spindle cells, and to discuss the implications for histogenesis. In all cases, both cell types showed positive cytoplasmic staining with antibodies to vimentin, actin (C4), and alpha-smooth muscle actin-1, but in only one was there positive staining with desmin. No staining was obtained with factor XIIIa, muramidase, alpha-1-antitrypsin, myoglobin, S-100 protein, CAM 5.2, factor VIII-related antigen, or neuron-specific enolase. By electron microscopy, both types of cells were seen to contain numerous thin filaments, dense bodies, coated and pinocytotic vesicles, active and dilated rough endoplasmic reticulum, few microvilli, and incomplete desmosomal junctions. Our findings imply a myofibroblastic nature for the giant ganglion-like cells and spindle cells. Our observations also support the hypothesis that they are derived from a pericytic cell.

Actins

Changes in platelet 5-hydroxytryptamine uptake in mania.

[3H]5-Hydroxytryptamine (5HT) platelet uptake was examined in a small group of hospitalised drug-free manic patients and in a larger group of drug-treated manic and schizophrenic patients compared to controls. 5HT platelet uptake was significantly higher in the manic group at the beginning of the illness episode than in either schizophrenics or controls. No difference was found in the uptake rates between the schizophrenics and controls. At discharge, manic patients had 5HT uptake values similar to control subjects. Manic patients with no previous history of either mania or depression had highly significant increases in 5HT platelet uptake compared to either schizophrenics, controls or manic patients with a previous history of manic-depression. No correlation was found between the initial increased 5HT uptake rate in the manic patient and the severity or duration of the illness episode, the length of hospitalisation or the gender of the patient.

Adult

Variations in platelet 5-hydroxytryptamine in control and depressed populations.

Platelet 5-hydroxytryptamine uptake was measured in a group of 28 endogenously depressed patients at three points during the day, before, during and after treatment and in 20 controls at the same three times. Uptake rates varied in control subjects in a manner consistent with the presence of a circadian rhythm in uptake. This variation was absent in depressed subjects. Normal variation was restored in those patients showing a clinical response, irrespective of the effects of treatment on the affinity of the uptake system. This restoration was not found in nonresponders or acutely after treatment was commenced. These findings suggest that depression is associated with a disruption of circadian rhythms, that abnormalities of platelet 5-hydroxytryptamine uptake are secondary to such a disruption and that antidepressants may act to correct this disruption.

Adult

Increases in platelet 5HT uptake rates following treatment with "uptake inhibiting" drugs.

A kinetic analysis of 5HT uptake into platelets and its inhibition by antidepressants is the most commonly used method of assessing the effects of antidepressants on 5HT uptake in humans. This study suggests that there is a naturally occurring variation in the uptake rates for 5HT into platelets, consistent with the presence of a circadian rhythm in uptake. There appears to be a derangement of this variation in depressed patients, which is reversed by effective treatment. Antidepressants may have effects both at the 5HT transport site and on the overall degree of variation. In view of this variation and its disruption in depression, it is suggested that measurement of the effects of "uptake inhibiting" drugs in depressed patients may yield different results to those obtained from controls. This difference is most apparent when uptake is measured at several time points. Furthermore, results from in vitro and ex vivo assays may yield distinctly different findings.

Adult

Peripheral adrenoceptors and serotonin receptors in depression. Changes associated with response to treatment with trazodone or amitriptyline.

Changes in platelet and lymphocyte adrenoceptor densities, platelet serotonin uptake and aggregatory response to serotonin were assessed in a group of moderately depressed patients before and during treatment with either trazodone or amitriptyline. Platelet serotonin receptor activity and uptake were lower before the start of treatment in all patients than in those patients responding to treatment. The densities of alpha 2- and beta-adrenoceptors tended to be higher in the patients before treatment and returned to control values after effective therapy. There were no major differences in the biochemical changes between the patients treated with trazodone or amitriptyline. When the biochemical data was correlated with the clinical history of the patients, it was found that only endogenously depressed patients, and not those with non-endogenous depression, had a significantly reduced platelet serotonin uptake rate. In addition, female depressives had a slightly lower platelet 5-HT aggregatory response than males irrespective to the type of depression.

Adolescent

Platelet 5-HT uptake in delusional and nondelusional depressions.

Platelet 5-hydroxytryptamine (5-HT) uptake was measured in a group of 28 endogenously depressed patients, at three points during the day, before, during and after treatment. It was also measured in 20 controls at the same three times. Uptake rates varied in control subjects in a manner consistent with the presence of a circadian rhythm in uptake. This variation was absent in depressed subjects. Deluded and nondeluded depressives showed a similar absence of variation but differed in the absolute values for their uptake rates. In particular deluded depressives did not show the lowering of platelet uptake rates, which has been widely reported for endogenous depression. This difference between the two groups was maintained after treatment was started but was not present after clinical recovery, suggesting a state-rather than trait-dependent marker. These differences between deluded and nondeluded depressives have implications for the investigation of platelet 5-HT uptake in other psychiatric illnesses.

Adult