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Biomedical subjects

J M Elliott

Publications and source records attributed to J M Elliott.

At least 73 records · Page 4Linked to original sources
PubMed1993

The lymphoblast beta-adrenergic receptor in bipolar depressed patients: characterization and down-regulation.

beta-Adrenergic receptor binding and adenylyl cyclase activity were examined in lymphoblast cell lines established from 12 patients with bipolar disorder and 10 unrelated healthy control subjects. No significant differences were found in [125I]iodocyanopindolol binding affinity or capacity or in isoprenaline-stimulated cAMP response. Incubation of lymphoblasts with isoprenaline (1 nM) for 24 h prior to assay reduced both receptor number and adenylyl cyclase activity. The extent of receptor down-regulation was significantly less in cells of bipolar disorder patients (20 +/- 5%) compared to controls (40 +/- 4%). Desensitization of adenylyl cyclase, however, was reduced to a similar degree in bipolar (65 +/- 14%) and control (68 +/- 20%) subjects. We conclude that basal beta-adrenergic receptor characteristics are not altered in bipolar disorder but that agonist down-regulation of receptor number may be less efficient than in control cells. The functional implications of this effect are discussed.

Adenylyl Cyclases↗
PubMed1993

Non-invasive diagnosis of arterial patency after thrombolytic treatment and its relation to prognosis.

OBJECTIVE: To validate a simple noninvasive method with serial creatine kinase measurements for diagnosis of early patency of the infarct related artery after thrombolytic treatment with streptokinase. To investigate the relation between early patency of the infarct related artery and prognosis. DESIGN: Patients under 76 years of age and seen within six hours of the start of prolonged chest pain and ST segment elevation were treated with streptokinase (1.5 x 10(6) U) intravenously over 30-60 minutes. Blood for measurement of total creatine kinase activity was taken at baseline and at 1, 2, 3, 4, 8, 12, 16, 20, and 24 hours after starting treatment. The rise in enzyme activity at each time from baseline was expressed as a proportion of the total rise from baseline to peak. PATIENTS: Patients studied were in the following groups: (a) Sixty patients took part in a validation study with angiographic determination of patency of the infarct related coronary artery at 2.6 (0.3) hours (mean (SD)) after starting streptokinase. (b) A further 258 patients did not have early arteriography, but data were added to those from the 60 validation patients to find the relation between enzymatically determined early patency of the infarct related artery and 30 day mortality. (c) A further subset of 232 patients with first infarctions (including patients from groups (a) and (b) had angiocardiography at three weeks after infarction, and data were used to investigate the relation between early patency of the infarct related artery and left ventricular function. MAIN OUTCOME MEASURES: Normalised rate of rise of creatine kinase activity at three hours after starting streptokinase in relation to angiographic patency of the infarct related coronary artery at 2.5 hours; 30 day cardiac mortality; and left ventricular function at three weeks in survivors of first infarction. RESULTS: In the validation study, a rise in three hour creatine kinase activity of > 20% of peak occurred in 34/37 patients with initially patent infarct related coronary arteries (sensitivity 92%), and a rise to < 20% of peak occurred in 21/23 patients with initially occluded arteries (specificity 91%). In the prognostic study, 30 day mortality was 2.1% in the 191 patients with three hour creatine kinase > 20% of peak and 8.7% in the 127 patients with three hour creatine kinase < 20% of peak (p < 0.01). Angiocardiography in three week survivors of anterior infarction (n = 95) showed better left ventricular function when three hour creatine kinase was > or = 20% than when it was < 20% of peak (mean (SEM) end systolic volume 71 (5) v 96 (9) ml, p < 0.02; ejection fraction 56% (2%) v 51% (2%), NS). CONCLUSION: Non-invasive determination of early patency of the infarct related artery by the normalised rate of rise of creatine kinase activity at three hours seems to be reliable, and may be prognostically important and of value for use in clinical trials.

Adult↗
PubMed1992

Streptokinase and lifestyle outcome in survivors of myocardial infarction.

Clinical and lifestyle parameters were assessed in 145 patients who were randomised in a double blind study comparing streptokinase or placebo given within four hours of the onset of ischaemic chest pain. Sixty-six percent of patients were in paid employment at the time of their infarct and 79% returned to paid employment. Patients who received streptokinase returned to work 17 days earlier (p less than 0.05) and returned to sport and leisure activities 33 days earlier (p less than 0.05) than those who received placebo. Those who had received streptokinase also tended to leave hospital earlier (0.8 days, p = 0.07). There were no differences in angioplasty or coronary surgery rates or the incidence of reinfarction in the first year (8%). Total community costs were reduced in the patients who received thrombolytic therapy. These findings have important implications in the benefit:cost analysis of thrombolytic therapy.

Activities of Daily Living↗
PubMed1991

Effects of chronic alpha 2-adrenoceptor blockade on platelet and lymphocyte adrenoceptor binding in normal volunteers.

Platelet and lymphocyte adrenoceptor binding was measured in 12 healthy male volunteers before and after 22 days treatment with the alpha 2-adrenoceptor antagonist idazoxan 40 mg tds. Platelet alpha 2-adrenoceptor number assessed by the agonist 3H-UK 14304 [correction of UK 14303] was significantly increased following idazoxan, with a smaller increase in antagonist binding (3H-rauwolscine). Lymphocyte beta-adrenoceptor number was unaltered by idazoxan, although the variance within the sample was significantly increased. Plasma MHPG levels were significantly reduced by chronic idazoxan. These data indicate upregulation of the platelet alpha 2-adrenoceptor in response to chronic blockade and suggest that this may reflect a similar change in presynaptic alpha 2-adrenoceptors which regulate norepinephrine release.

Adrenergic alpha-Antagonists↗
PubMed1991

Contribution of perceptual fluency to recognition judgments.

Following a shallow (count vowels) or deep (read) study task, old and new words were tested for both fluency of perception and recognition memory. Subjects first identified a test word as it came gradually into view and then judged it as old or new. Old words were identified faster than new words, indicating implicit, perceptual memory for old words. Independently of this effect, words judged old were identified faster than words judged new, especially after shallow study. Eight experiments examined the possible causal relationship between perceptual fluency and recognition judgements. Experiments 1 to 4 showed that fast identifications per se do not promote old judgments. Accelerating the identification of test items by semantically priming them or making them come more quickly into view did not affect recognition judgments. Experiment 5 showed that the usual association of fast identifications with old judgments is not an artifact of item selection because the association disappeared when the identifications and judgements were segregated into different phases of the test task. Experiments 6 and 7 showed tha the likelihood of old judgments increases directly with the pretested perceptibility of test words, but only after shallow study. Experiment 8 showed that the dependency of recognition judgments on perceptual fluency continues to hold when the requirement to identify the words before judging them is eliminated. We conclude that fluency of perception contributes to recognition judgments, but only when the fluency is produced naturally (e.g., through perceptual memory) and explicit memory is minimal.

Adult↗
PubMed1990

Attention capture by novel stimuli.

In several experiments, observers were given glimpses of 4-word arrays. Accuracy of word localization was tested after each array. Some words, called familiar, appeared many times across the series of arrays; others, called novel, appeared only once. The ratio of novel to familiar words in an array ranged from 0:4 to 4:0. When familiar and novel words were not intermixed (in 0:4 and 4:0 arrays), localization accuracy was higher for familiar words. However, when they were intermixed, especially in 1:3 arrays, accuracy tended to be higher for the novel words. This novel popout effect was the outcome of the suppressed localizability of the familiar words (relative to the 0:4 baseline) and the enhanced localizability of the novel words (relative to the 4:0 baseline). Novel popout may reflect an automatic orientation of attention away from more fluently unfolding regions of the perceptual field (familiar objects) and toward less fluently unfolding regions (novel objects).

Adolescent↗
PubMed1989

Comparison of [125I]iodolysergic acid diethylamide binding in human frontal cortex and platelet tissue.

The human platelet contains a functional 5-hydroxytryptamine (5-HT) receptor that appears to resemble the 5-HT2 subtype. In this study, we have used the iodinated derivative [125I]iodolysergic acid diethylamide ([125I]iodoLSD) in an attempt to label 5-HT receptors in human platelet and frontal cortex membranes under identical assay conditions to compare the sites labelled in these two tissues. In human frontal cortex, [125I]iodoLSD labelled a single high-affinity site (KD = 0.35 +/- 0.02 nM). Displacement of specific [125I]iodoLSD binding indicated a typical 5-HT2 receptor inhibition profile, which demonstrated a significant linear correlation (r = 0.97, p less than 0.001, n = 17) with that observed using [3H]ketanserin. However, [125I]iodoLSD (Bmax = 136 +/- 7 fmol/mg of protein) labelled significantly fewer sites than [3H]ketanserin (Bmax = 258 +/- 19 fmol/mg of protein) (p less than 0.001, n = 6). In human platelet membranes, [125I]iodoLSD labelled a single site with affinity (KD = 0.37 +/- 0.03 nM) similar to that in frontal cortex. The inhibition profile in the platelet showed significant correlation with that in frontal cortex (r = 0.96, p less than 0.001, n = 16). We conclude that the site labelled by [125I]iodoLSD in human platelet membranes is biochemically similar to that in frontal cortex and most closely resembles the 5-HT2 receptor subtype, although the discrepancy in binding capacities of [125I]iodoLSD and [3H]ketanserin raises a question about the absolute nature of this receptor.

Binding, Competitive↗
PubMed1989

Sex-related differences in central adrenergic function and responsiveness to repeated administration of desipramine or electroconvulsive shock.

1. Clonidine induces hypoactivity in rodents. Male rats were found to be markedly more susceptible to the sedative effects of this alpha 2-adrenoceptor agonist than females. Thus to obtain identical hypoactivity responses for subsequent experiments, clonidine was administered to male and female rats at doses of 0.2 and 0.5 mg kg-1, respectively. 2. The clonidine-induced hypoactivity response of female rats was not affected by the oestrous cycle. 3. Repeated injection of desipramine (DMI; 5 mg kg-1 b.d.) for up to 14 days progressively attenuated clonidine-induced hypoactivity in both male and female rats. However, in males the attenuation was more rapid in onset and a greater overall reduction was obtained. This alpha 2-adrenoceptor-mediated response was also progressively reversed by repeated daily administration of an electroconvulsive shock (ECS; 110 V, 1 s). In this case, although the maximum decrease was greater in males, the time of onset was identical in both sexes. 4. There were no sex-related differences in either the number or affinity of alpha 2- and beta-adrenoceptors in rat cortex. Cortical alpha 2-adrenoceptors were decreased by 14 days of DMI injection or 10 days of ECS treatment (ECS x 10) and these effects were identical in both sexes. These receptors were not altered by 2 days administration of DMI or ECS. Cortical beta-adrenoceptors were reduced in male and female rats by 2 and 14 days of DMI injection and by ECS x 10, but not ECS x 2. 5. Viewed overall, the data show differences in alpha 2-adrenoceptor function between the sexes, as determined by clonidine-induced hypoactivity and the responsiveness of this paradigm to repeated administration of DMI and ECS. In contrast, no differences were observed in complementary alpha 2- and beta-adrenoceptor binding experiments using rat cortical tissue.

Animals↗
PubMed1988

Human platelet 5-hydroxytryptamine receptors: binding of [3H]-lysergic acid diethylamide (LSD). Effects of chronic neuroleptic and antidepressant drug administration.

Chronic treatment with phenothiazines and thioxanthenes has been found to enhance 5-HT-induced aggregation of human platelets. A method has been developed to study 5-HT2 receptor binding sites on platelets utilising [3H]-LSD and more recently 125I/LSD. Results are presented which suggest that the LSD binding site is indeed the 5-HT2 binding site and that the LSD binding characterises the specific receptor responsible for 5-HT-induced shape change and aggregation. In a group of patients receiving phenothiazines or thioxanthenes, the Bmax of LSD binding was increased. The mean binding affinity was decreased possibly due to a persistence of neuroleptic in the platelet membrane preparation. Analysis showed that this was not the reason why the mean binding capacity was increased. The results show that chronic phenothiazine and thioxanthene delta treatment 'up-regulates' platelet 5-HT2 binding sites and that this may be accompanied by increased sensitivity to platelet aggregation by 5-HT. In normal subjects desipramine treatment increased the Bmax of platelet LSD binding and this was accompanied by an increased prolactin response to tryptophan which is thought to be mediated by central 5-HT function.

Antidepressive Agents↗
PubMed1988

The influence of injection of oestradiol to female rats on changes in alpha 2- and beta-adrenoceptor function induced by repeated administration of desipramine or electroconvulsive shock.

Repeated daily administration to female rats of either an electroconvulsive shock (110 V, 1 sec) or desipramine (DMI; 5 mg/kg x 2) caused a progressive decrease in presynaptic alpha 2-adrenoceptor function assessed by the hypoactivity (sedation) response to clonidine (0.5 mg/kg). This reduction was maximal after approximately seven electroshocks or 8-12 days of injection of DMI. Daily administration of oestradiol (100 micrograms s.c.), starting one day prior to the commencement of administration of DMI or treatment with electroshock, markedly accelerated the onset of decreased hypoactivity responses to clonidine, but did not alter the maximum reduction induced by repeated injection of DMI or administration of electroshock. Injection of oestradiol alone had no effect on the responses to clonidine. Administration of DMI for 14 days decreased the number of both alpha 2- and beta-adrenoceptors in the cortex. Cortical beta-, but not alpha 2-adrenoceptors, were also decreased after 4 days of injection of DMI. Two and ten electroshocks moderately increased and decreased cortical alpha 2-adrenoceptors, respectively. beta-Adrenoceptors were also decreased by ten electroshocks, but two were without effect. Simultaneous administration of oestradiol had little influence on the changes in the binding of alpha 2- or beta-adrenoceptors induced by repeated administration of DMI or treatment with electroshock. Oestradiol increased the numbers of cortical alpha 2- and beta-adrenoceptors 3 and 15 days after injection, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Binding of tritiated yohimbine to platelets in women with maternity blues.

Platelet alpha 2-adrenoceptor binding was measured in 108 women in the 36th week of pregnancy, at ten and twenty days and at three and six months post-partum. An age matched non-pregnant control group of women (N = 25) was also studied. The number (Bmax) of alpha 2-adrenoceptors was elevated antepartum but fell to control values on the tenth post-partum day. At three and six months post-partum, however, alpha 2-adrenoceptor Bmax was again increased. Women who developed maternity blues (N = 59) had significantly more platelet alpha 2-adrenoceptors than those who did not (N = 49) at both ten and twenty days post-partum. In addition their alpha 2-adrenoceptor Bmax was greater than controls at all time points measured except the tenth post-partum day. In contrast, the alpha 2-adrenoceptor Bmax of women without the blues did not differ from controls at any stage. It is suggested that women who develop maternity blues may have a relatively enduring abnormality in alpha 2-adrenoceptor sensitivity which is associated with psychological symptoms when concentrations of circulating sex-steroids suddenly change.

Blood Platelets↗
PubMed1988

Development of kinaesthetic sensitivity and motor performance in children.

Kinaesthetic acuity of 100 children, aged from four to 13 years, was assessed and a developmental trend is described. The relationship between kinaesthetic acuity and motor performance on a range of motor tests commonly used for assessing children was also examined, and contrary to expectation no evidence of a relationship was discovered. There is little reported evidence for this relationship in the literature, and some possible reasons for this are discussed. A staircase procedure for threshold estimation was used and is described in detail.

Adolescent↗
PubMed1987

Behavioural and biochemical evidence for the release of noradrenaline in mouse brain by TRH and some of its biologically stable analogues.

Small doses of clonidine probably induce hypoactivity (a distinct form of sedation) by stimulating presynaptic alpha 2-adrenoceptors. This was attenuated by injection of 0.1-10 mg/kg of thyrotropin releasing hormone (TRH) or its biologically stable analogues, CG3509, CG3703 and RX77368, when these were given 10 min before clonidine. This effect was dose-dependent in all cases, but the analogues were more potent than TRH. The TRH metabolites, TRH acid and histidyl-proline diketopiperazine (10 mg/kg) were without effect. This response was still attenuated by the analogues, but not TRH, when these were given 1 hr before clonidine. The results, therefore, suggested that it was the basic tripeptide structure which was active and TRH was less potent than its analogues because of rapid metabolism. Attenuation of hypoactivity by TRH and analogues was not due to increased dopaminergic function because apomorphine (5 mg/kg) was ineffective. Thyrotropin releasing hormone (20 mg/kg), CG3509 (10 mg/kg) and CG3703 (1 mg/kg) also induced locomotor activity and produced various other behavioural changes. This was inhibited by prazosin (3 mg/kg) and haloperidol (0.5 mg/kg) but not by yohimbine (1 mg/kg). Apomorphine (5 mg/kg)-induced activity was inhibited by haloperidol and yohimbine but not by prazosin. This indicated that the activity produced by the TRH compounds, but not apomorphine, was partly mediated by alpha 1-adrenoceptors. Both CG3509 (10(-5) and 10(-4) M) and RX77368 (10(-4) M) evoked the release of endogenous noradrenaline from slices of hypothalamus in vitro. The TRH analogues, however, had no affinity for alpha 1- or alpha 2-adrenoceptors in ligand-receptor binding experiments. Viewed overall, the data showed that TRH and its analogues induced the release of noradrenaline in the brain. In addition, a comparison of the behavioural effects of TRH compounds with dopamine and alpha 1-adrenoceptor agonists suggested that in mice these behavioural responses resulted from stimulation of both noradrenergic and dopaminergic function.

Adrenergic alpha-Antagonists↗
PubMed1987

The influence of L-triiodothyronine (T3) on the effects of repeated administration of desipramine or electroconvulsive shock on alpha 2- and beta-adrenoceptor function in the brain of the rat: implications for the potentiation of antidepressant therapy by T3.

Repeated, daily administration of either an electroconvulsive shock (ECS; 110 V, 1 sec) or desipramine (DMI; 5 mg/kg X 2) to rats caused a progressive decrease in the function of presynaptic alpha 2-adrenoceptors, assessed by the hypoactivity (sedation) response to clonidine (0.2 mg/kg). This attenuation required approximately 7 days' administration of either treatment for maximum effect. A single injection of triiodothyronine (T3; 100 micrograms/kg) on day 1 of the treatment markedly accelerated the decreased responses to clonidine induced by DMI or electroconvulsive shock, but did not alter the maximum attenuation. By itself T3 did not affect the hypoactivity responses. alpha 2-Adrenoceptors, measured by the binding of [3H]idazoxan in the cortex, which are believed to be predominantly postsynaptic, were decreased by 14 days of DMI or electroconvulsive shock for 10 days, but not 2 days of either treatment. Triiodothyronine did not influence the decreased number of alpha 2-adrenoceptors induced by DMI or electroconvulsive shock but may have delayed the onset produced by DMI. Binding to beta-adrenoceptors in the cortex was measured using [3H]dihydroalprenolol. This was significantly decreased by 14 days administration of DMI, but not significantly by electroconvulsive shock for 10. Down-regulation of beta-adrenoceptors, induced by DMI was rapid, being observed after 1 day of treatment. Injection of T3 did not influence the final decreases produced by DMI or electroconvulsive shocks but moderately delayed their onset. Triiodothyronine alone caused a 25% reduction in cortical beta-adrenoceptors 24 hr after injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗