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A O'Halloran

Publications and source records attributed to A O'Halloran.

14 recordsLinked to original sources
PubMed2000

Activation of apoptotic and inflammatory pathways in dysfunctional donor hearts.

BACKGROUND: Myocardial dysfunction is common after brain death, but the mechanisms remain unclear. Apoptosis is tightly regulated by enzymes termed the caspases. We have investigated the caspases involved in the terminal part of the apoptotic pathway in dysfunctional (nontransplanted) donor hearts and their relation to inflammatory markers and compared them to hearts with good ventricular function (transplanted donors). METHODS: Thirty-one donor hearts assessed for transplantation were examined. Western blotting was used to measure pro-caspase-9, caspase-3, DFF45, the activated nuclease CPAN and poly (ADP-ribose) polymerase, a DNA repair enzyme inactivated by caspase-3. Caspase-3 activity was also measured. Histologic and immunocytochemical analysis for HLA Class II and Real Time polymerase chain reaction for tumor necrosis factor-alpha and interleukin 6 were performed to detect inflammatory activation. RESULTS: Cleaved caspase-9 was higher (5.53+/-0.6 vs. 3.64+/-0.4 O.D. units, P<0.01) in nontransplanted compared with transplanted donors and there was a trend for higher pro-caspase-9 (5.20+/-1.0 vs. 4.22+/-0.4 O.D. units, P=NS). Levels of pro-caspase-3 were higher in nontransplanted (9.66+/-0.5 vs. 5.15+/-0.5 O.D. units, P<0.00001) donors and cleavage products of caspase-3 were elevated in 14 of 14 nontransplanted and 2 of 17 transplanted donors. Intact DFF-45 (8.94+/-0.36 vs. 6.14+/-0.30 O.D. units, P<0.000005), its spliced product (2.38+/-0.35 vs. 0.4+/-0.21 O.D. units, P=0.0001) and the nuclease caspase-activated nuclease (2.01+/-0.3 vs. 0.66+/-0.16 OD units, P=0.001) were higher in nontransplanted donors. The caspase-3 substrate poly (ADP-ribose) polymerase was higher in nontransplanted (1.16+/-0.13 vs. 0.61+/-0.22 O.D. units, P=0.57) donors. CONCLUSIONS: The caspases are elevated in dysfunctional donor hearts compared with hearts with good ventricular function with a possible link to inflammatory activation supporting the concept that brain death causes inflammatory activation which can lead to apoptosis with a possible important effect on function.

Adult↗
PubMed2000

Aortic root characteristics of human pulmonary autografts.

BACKGROUND: After pulmonary autograft replacement of the aortic valve and root, the pulmonary artery (PA) wall is subjected to higher pressures. Concern exists that this may lead to structural and functional changes in the implanted autograft and subsequent aortic root dilatation and neoaortic regurgitation. We therefore assessed root dimensions and neoaortic regurgitation, morphological structure, and mechanical behavior in patients who underwent the Ross operation. METHODS AND RESULTS: Seventy-four patients who were randomized to undergo aortic valve replacement with an aortic homograft or a pulmonary autograft were followed up echocardiographically for up to 4 years and had their aortic root dimensions measured at the level of the annulus, sinuses, and sinotubular junction. In a separate series of 18 patients who underwent pulmonary autograft surgery and 8 normal organ donors, samples from the PA and aorta were analyzed for medial wall thickness, distribution of the staining of collagen and elastin, and elastin fragmentation. Finally, stress-strain curves were obtained from samples of the PA and aorta from 9 patients who underwent pulmonary autograft surgery and from 1 patient in whom a 4-month-old autograft was explanted. No patient in either group had aortic dilatation at any level of >20% or more than mild aortic regurgitation at up to 4 years of follow-up. The aortic media was thicker in both autografts and normal donors (P:<0.01), and there was a trend for the PA media to be thicker in the autograft group. Elastic fiber in all aortas showed little or no variation, whereas in the PA, there was considerable variation in fragmentation. Patients with higher preoperative PA pressures tended to have lower fragmentation scores (chi(2) P:<0.01). The lower stiffness modulus, higher stiffness modulus, and maximum tensile strength of the aorta was 34% to 38% higher than that of the PA (P:<0.01); however, the 4-month-old autograft appeared to show adaptation in mechanical behavior. CONCLUSIONS: In our series of patients, there was no significant progressive dilatation of the aortic root. We demonstrated differences in the anatomic structure and mechanical behavior of the PA in vitro and highlighted histological and mechanical modes of adaptation.

Adolescent↗
PubMed1998

Effect of antibiotic pretreatment on immunogenicity of human heart valves and component cells.

BACKGROUND: For many years valves have been sterilized with high-dose antibiotics before implantation, but now there is an increasing trend to using "homovital" valves, which have been exposed to very low dose antibiotics. METHODS: To investigate the immunogenicity of valve tissue, before and after exposure to high- and low-dose antibiotics, peripheral blood mononuclear cells and human allogenic T cells were cocultured with antibiotic-treated valve discs, cultured valve endothelial cells, and fibroblasts. Proliferation was measured by uptake of thymidine labeled with hydrogen 3. RESULTS: Untreated tissue pieces stimulate peripheral blood mononuclear cells (4,080+/-980 cpm) at day 0 with similar results after 1 day in Hank's balanced salt solution (4,272.4+/-1,307 cpm) reducing to 2,442+/-926 cpm after 3 days and 1,111+/-255 cpm after 5 days; antibiotic-treated pieces are less immunogenic after 1 (2,560+/-403 cpm), 3 (1,550+/-60 cpm), 5 (717+/-295 cpm), and 7 days (633+/-174 cpm) in homovital solution, whereas sterilized pieces are not immunogenic (184+/-96 cpm) after only 1 day in strong antibiotics. Histologic analysis showed that this corresponds to a reduction of class I and class II expression by human valve endothelial cells. Human valve endothelial cells but not fibroblasts are capable of causing direct stimulation of CD4+ T cells. However, human valve endothelial cells poorly stimulate CD4+ T cells after incubation in homovital solution for 24 hours. CONCLUSIONS: This study shows that valve tissue is immunogenic and this immunogenicity is mediated mainly by endothelial cells. However, the immunostimulatory potential of the valve can be reduced by incubating the solution in an antibiotic cocktail.

Anti-Bacterial Agents↗
PubMed1995

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↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1990

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↗
PubMed1986

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↗
PubMed1986

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↗
PubMed1985

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↗
PubMedDate not supplied

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↗