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Biomedical subjects

M Ennis

Publications and source records attributed to M Ennis.

At least 73 records · Page 4Linked to original sources
PubMed1999

Serum eosinophil cationic protein (ECP): reference values in healthy nonatopic children.

BACKGROUND: Although serum ECP concentrations have been reported in normal children, there are currently no published upper cutoff reference limits for serum ECP in normal, nonatopic, nonasthmatic children aged 1-15 years. METHODS: We recruited 123 nonatopic, nonasthmatic normal children attending the Royal Belfast Hospital for Sick Children for elective surgery and measured serum ECP concentrations. The effects of age and exposure to environmental tobacco smoke (ETS) on the upper reference limits were studied by multiple regression and fractional polynomials. RESULTS: The median serum ECP concentration was 6.5 microg/l and the 95th and 97.5 th percentiles were 18.8 and 19.9 microg/l. The median and 95th percentile did not vary with age. Exposure to ETS was not associated with altered serum ECP concentrations (P = 0.14). CONCLUSIONS: The 95th and 97.5 th percentiles for serum ECP for normal, nonatopic, nonasthmatic children (aged 1-15 years) were 19 and 20 microg/l, respectively. Age and exposure to parental ETS did not significantly alter serum ECP concentrations or the normal upper reference limits. Our data provide cutoff upper reference limits for normal children for use of serum ECP in a clinical or research setting.

Adolescent↗
PubMed1999

Inflammatory mediators in bronchoalveolar lavage samples from children with and without asthma.

BACKGROUND: We investigated whether eosinophils and mast cells, found in the airways of children with wheeze, were activated during relatively asymptomatic periods. METHODS: A nonbronchoscopic bronchoalveolar lavage (BAL) procedure was performed on children presenting for an elective surgical procedure. Eosinophil-derived (eosinophil cationic protein, ECP) and mast cell-derived (histamine/tryptase) mediator concentrations were measured in the BAL fluid. A detailed history and serum immunoglobulin E were used to classify the children into four groups: atopic with and without asthma, viral-associated wheeze and normal controls. RESULTS: The ECP concentrations in BAL from atopic asthmatic subjects were significantly higher than those measured in BAL from normal controls (P < 0.01), no other groups differed significantly. Histamine concentrations were elevated in both the atopic asthmatic and viral-associated wheeze groups compared with controls (P < 0.02) and additionally higher concentrations were obtained in atopics with asthma compared with atopics without asthma (P < 0.03). Tryptase concentrations did not differ between groups, although the tryptase and histamine concentrations correlated significantly (r = 0.78, P < 0.0001). CONCLUSIONS: Elevated histamine concentrations were found in children with wheeze regardless of the aetiology, whereas ECP was only elevated in those asthmatics with atopy. This suggests that even in relatively quiescent periods, there is some on going activation of airway eosinophils in children with atopic asthma.

Adolescent↗
PubMed1999

Serum eosinophilic cationic protein and blood eosinophil counts for the prediction of the presence of airways inflammation in children with wheezing.

BACKGROUND: Serum eosinophilic cationic protein (ECP) concentrations may be useful noninvasive markers of airways inflammation in atopic asthma. However, the usefulness of serum ECP measurement for the prediction of airways inflammation in children with a history of wheezing is unknown. OBJECTIVE: To determine the test accuracy of serum ECP and blood eosinophil percentage as noninvasive markers of eosinophilic airways inflammation. METHODS: Bronchoalveolar lavage (BAL) fluid and peripheral blood samples for eosinophil percentages and serum ECP were obtained from children undergoing elective surgery and who gave a history of wheezing in the previous year. Sensitivity, specificity and likelihood ratios (LH) and the area under the curve (AUC) for the receiver operator characteristic (ROC) curve were calculated for each blood marker for the prediction of airways inflammation defined by a BAL eosinophil percentage > 0.86. Data were analysed on the basis of how recently symptoms had occurred. RESULTS: Seventy-seven children (median age 6.75 years) were studied. An AUC of 0.75 (log serum ECP concentration) and 0.76 (log blood eosinophil percentage) was obtained for predicting airways inflammation. A serum ECP > 13 microg/L yielded a LH of 4.4, whereas using a cutoff blood eosinophils > 4% yielded a LH of 1.9, for the prediction of elevated eosinophils in BAL. Serum ECP and eosinophil percentages in BAL and blood were lowest (not statistically significant) when last symptoms had occurred more than 12 weeks previously. CONCLUSIONS: Serum ECP and blood eosinophil percentages are useful markers for predicting eosinophilic airways inflammation in wheezing children.

Adolescent↗
PubMed1999

A Huntington's disease CAG expansion at the murine Hdh locus is unstable and associated with behavioural abnormalities in mice.

Huntington's disease (HD) is a dominant disorder characterized by premature and progressive neurodegeneration. In order to generate an accurate model of the disease, we introduced an HD-like mutation (an extended stretch of 72-80 CAG repeats) into the endogenous mouse Hdh gene. Analysis of the mutation in vivo reveals significant levels of germline instability, with expansions, contractions and sex-of-origin effects in evidence. Mice expressing full-length mutant protein display abnormal social behaviour in the absence of acute neurodegeneration. Given that psychiatric changes, including irritability and aggression, are common findings in HD patients, our data are consistent with the hypothesis that some clinical features of HD may be caused by pathological processes that precede gross neuronal cell death. This implies that effective treatment of HD may require an understanding and amelioration of these dysfunctional processes, rather than simply preventing the premature death of neurons in the brain. These mice should facilitate the investigation of the molecular mechanisms that underpin the pathway from genotype to phenotype in HD.

Animals↗
PubMed1999

Current-source density analysis in the rat olfactory bulb: laminar distribution of kainate/AMPA- and NMDA-receptor-mediated currents.

The one-dimensional current-source density method was used to analyze laminar field potential profiles evoked in rat olfactory bulb slices by stimulation in the olfactory nerve (ON) layer or mitral cell layer (MCL) and to identify the field potential generators and the characteristics of synaptic activity in this network. Single pulses to the ON evoked a prolonged (>/=400 ms) sink (S1ON) in the glomerular layer (GL) with corresponding sources in the external plexiform layer (EPL) and MCL and a relatively brief sink (S2ON) in the EPL, reversing in the internal plexiform and granule cell layers. These sink/source distributions suggested that S1ON and S2ON were generated in the apical dendrites of mitral/tufted cells and granule cells, respectively. The kainate/AMPA-receptor antagonist CNQX (10 microM) reduced the early phase of S1ON, blocked S2ON, and revealed a low amplitude, prolonged sink at the location of S2ON in the EPL. Reduction of Mg2+, in CNQX, enhanced both the CNQX-resistant component of S1ON and the EPL sink. This EPL sink reversed below the MCL, suggesting it was produced in granule cells. The NMDA-receptor antagonist APV (50 microM) reversibly blocked the CNQX-resistant field potentials in all layers. Single pulses were applied to the MCL to antidromically depolarize the dendrites of mitral/tufted cells. In addition to synaptic currents of granule cells, a low-amplitude, prolonged sink (S1mcl) was evoked in the GL. Corresponding sources were in the EPL, suggesting that S1mcl was generated in the glomerular dendritic tufts of mitral/tufted cells. Both S1mcl and the granule cell currents were nearly blocked by CNQX (10 microM) but enhanced by subsequent reduction of Mg2+; these currents were blocked by APV. S1mcl also was enhanced by gamma-aminobutyric acid-A-receptor antagonists applied to standard medium; this enhancement was reduced by APV. ON activation produces prolonged excitation in the apical dendrites of mitral/tufted cells, via kainate/AMPA and NMDA receptors, providing the opportunity for modulation and integration of sensory information at the first level of synaptic processing in the olfactory system. Granule cells respond to input from the lateral dendrites of mitral/tufted cells via both kainate/AMPA and NMDA receptors; however, in physiological concentrations of extracellular Mg2+, NMDA-receptor activation does not contribute significantly to the granule cell responses. The glomerular sink evoked by antidromic depolarization of mitral/tufted cell dendrites suggests that glutamate released from the apical dendrites of mitral/tufted cells may excite the same or neighboring mitral/tufted cell dendrites.

Algorithms↗
PubMed1999

Dendrodendritic recurrent excitation in mitral cells of the rat olfactory bulb.

Most neuronal interactions within the olfactory bulb network are mediated by dendrodendritic synapses. Dendritic transmitter release potentially could affect the parent dendrite as well as local neuronal elements that have receptors for the released transmitter. Here we report that under conditions that facilitate N-methyl-D-aspartate (NMDA) receptor activity (reduced GABAA inhibition and extracellular Mg2+), a single action potential evoked by brief intracellular current pulses in mitral cells is followed by a prolonged depolarization, which is blocked by an NMDA receptor antagonist. This depolarization also is evoked by a presumed calcium spike in the presence of tetrodotoxin. A similar NMDA-receptor-dependent prolonged depolarization is elicited by stimulation of the lateral olfactory tract at current intensities subthreshold for antidromic activation of the recorded neuron. These observations suggest that glutamate released from the dendrites of mitral cells excites the same and neighboring mitral cell dendrites. Further evidence suggests that both the apical and lateral dendrites of mitral cells participate in this recurrent excitation. These dendrodendritic interactions may play a role in the prolonged, NMDA-receptor-dependent depolarization of mitral/tufted cells evoked by olfactory nerve stimulation.

2-Amino-5-phosphonovalerate↗
PubMed1999

Bronchoalveolar lavage findings in patients with chronic nonproductive cough.

Mast cells and eosinophils may play a role in the pathophysiology of chronic cough in nonasthmatics. It is unknown, however, whether degranulation of these cells occurs in the airways of such patients. Thirty-five nonsmoking patients referred with a chronic nonproductive cough (mean cough duration 76.2 months) were evaluated using a comprehensive diagnostic protocol. Bronchoalveolar lavage (BAL) cell differentials and BAL histamine, tryptase and eosinophilic cationic protein (ECP) concentrations were determined. Ten nonsmoking healthy volunteers served as controls. Diagnostic subgroups were identified: eight postnasal drip syndrome (PNDS), seven cough variant asthma (CVA), seven gastro-esophageal reflux (GOR), seven dual aetiology and six idiopathic. Nonasthmatic coughers (NAC) were characterized as those patients without bronchial hyperresponsiveness on histamine challenge and whose cough had either responded to therapy for PNDS or GOR or failed to improve with antiasthma therapy. There was a significant increase in both eosinophil and mast cell numbers (p<0.05) and in histamine levels (p = 0.027) when NAC patients were compared with controls. Tryptase and ECP levels were elevated in 7 of 23 and 6 of 23 NAC patients, respectively. In conclusion, airway inflammatory cell numbers are not only increased but also activated, suggesting an important role for airways inflammation in the pathophysiology of chronic nonproductive cough.

Adult↗
PubMed1999

Adjuvant treatment and onset of menopause predict weight gain after breast cancer diagnosis.

PURPOSE: Weight gain is common during the first year after breast cancer diagnosis. In this study, we examined clinical factors associated with body size at diagnosis and weight gain during the subsequent year. PATIENTS AND METHODS: An inception cohort of 535 women with newly diagnosed locoregional breast cancer underwent anthropometric measurements at baseline and 1 year. Information was collected on tumor- and treatment-related variables, as well as diet and physical activity. RESULTS: Mean age was 50.3 years; 57% of women were premenopausal. Mean baseline body mass index (weight [kg] divided by height [m] squared) was 25.5 kg/m2. Overall, 84.1% of the patients gained weight. Mean weight gain was 1.6 kg (95% confidence interval, 1.2 to 1.9 kg), 2.5 kg (95% confidence interval, 1.8 to 3.2 kg) in those receiving chemotherapy, 1.3 kg (95% confidence interval, 0.7 to 1.8 kg) in those receiving tamoxifen only, and 0.6 kg (95% confidence interval, 0.01 to 1.3 kg) in those receiving no adjuvant treatment. Menopausal status at diagnosis (P = .02), change in menopausal status over the subsequent year (P = .002), axillary nodal status (P = .009), and adjuvant treatment (P = .0002) predicted weight gain in univariate analysis. In multivariate analysis, onset of menopause and administration of chemotherapy were independent predictors of weight gain (all P < or = .05). Caloric intake decreased (P < .01) and physical activity increased (P < .05) during the year after diagnosis; these factors did not explain the observed weight gain. CONCLUSION: Weight gain is common after breast cancer diagnosis; use of adjuvant chemotherapy and onset of menopause are the strongest clinical predictors of this weight gain.

Age of Onset↗
PubMed1999

Risk of menopause during the first year after breast cancer diagnosis.

PURPOSE: Premenopausal women with breast cancer often enter a premature menopause during initial treatment of their malignancy, with resulting loss of childbearing capacity, onset of menopausal symptoms, and subsequent prolonged exposure to long-term risks of menopause. Adjuvant therapy is believed to contribute to this early menopause. PATIENTS AND METHODS: One hundred eighty-three premenopausal women with locoregional breast cancer (tumor-node-metastasis staging system classification, T1-3 N0-1 M0) who had undergone surgical treatment and provided information on menopausal status at diagnosis and 1 year later were enrolled. Systemic adjuvant therapy was recorded. Univariate and multivariate predictors of menopause were examined. RESULTS: Age, weight gain, tumor stage, nodal stage, and systemic adjuvant therapy (chemotherapy, tamoxifen) were all significant univariate correlates of menopause. In multivariate analysis, age, chemotherapy, and hormone therapy (tamoxifen) made significant independent contributions to the onset of menopause. CONCLUSION: Age and systemic chemotherapy are the strongest predictors of menopause in women with locoregional breast cancer. They independently contribute to menopause. A graphic representation of our multivariate model allows an estimation of risk of menopause according to patient age and planned adjuvant treatment, and it may facilitate clinical decision-making.

Adult↗
PubMed1999

Adenosine induces histamine release from human bronchoalveolar lavage mast cells.

Previous studies have shown that in vitro adenosine enhances histamine release from activated human lung mast cells obtained by enzymic dispersion of lung parenchyma. However, adenosine alone has no effect on histamine release from these cells. Given the evidence for direct activation of mast cells after endobronchial challenge with adenosine and previous studies indicating that mast cells obtained at bronchoalveolar lavage are a better model for asthma studies than those obtained by enzymic dispersion of lung tissue, the histamine-releasing effect of adenosine was examined on lavage mast cells. Bronchoalveolar lavage fluid was obtained from patients attending hospital for routine bronchoscopy (n=54). Lavage cells were challenged with adenosine or adenosine receptor agonists (20 min, 37 degrees C) and histamine release determined using an automated fluorometric assay. Endogenous adenosine levels were also measured in lavage fluid (n=9) via an HPLC method. Adenosine alone caused histamine release from lavage mast cells in 37 of 54 patients with a maximal histamine release of 20.56+/-2.52% (range 5.2-61%). The adenosine receptor agonists (R)-N6-(2-phenylisopropyl)adenosine, 5'-N-ethylcarboxamidoadenosine and CGS21680 also induced histamine release from lavage mast cells. Preincubation of lavage mast cells with the adenosine receptor antagonist xanthine amine congener caused significant inhibition of the response to adenosine (P=0.007). There was an inverse correlation between endogenous adenosine levels in the lavage fluid and the maximal response to in vitro adenosine challenge of the lavage cells. The findings of the present study indicate a means by which adenosine challenge of the airways can induce bronchoconstriction and support a role for adenosine in the pathophysiology of asthma. The results also suggest that cells obtained from bronchoalveolar lavage fluid may provide the ideal model for the testing of novel, adenosine receptor, targeted therapies for asthma.

Adenosine↗
PubMed1998

Glutamate and synaptic plasticity at mammalian primary olfactory synapses.

Glutamate is the transmitter at synapses from the olfactory nerve (ON) to mitral (Mi)/tufted cells, but very little is known about the functional properties of this synapse. This report summarizes in vitro physiological and computational modeling studies investigating glutamatergic neurotransmission at ON-->Mi cell synapses. Single ON shocks in rat main olfactory bulb (MOB) slices elicit distinct early and late spiking components triggered, respectively, by (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)/kainic acid (KA) and N-methyl-D-aspartate (NMDA) receptor activation. Modeling simulations showed that the placement of both AMPA/KA and NMDA receptors on Mi apical dendrites replicates the experimentally observed early and late Mi spiking responses to ON shocks. Brief, tetanic ON stimulation in vitro induced robust, selective long-term potentiation (LTP) of NMDA receptor-dependent spiking. Modeling experiments disclosed several potential mechanisms underlying the selective LTP of NMDA receptor-dependent spiking. These findings demonstrate that ON-->Mi cell transmission exhibits a novel form of plasticity whereby high frequency synaptic activity induces selective LTP of NMDA receptor-dependent spiking.

Animals↗
PubMed1998

A comparison of statistical learning methods on the Gusto database.

We apply a battery of modern, adaptive non-linear learning methods to a large real database of cardiac patient data. We use each method to predict 30 day mortality from a large number of potential risk factors, and we compare their performances. We find that none of the methods could outperform a relatively simple logistic regression model previously developed for this problem.

Databases as Topic↗
PubMed1998

Nerve gas-induced seizures: role of acetylcholine in the rapid induction of Fos and glial fibrillary acidic protein in piriform cortex.

Soman (pinacolymethylphosphonofluoridate), a highly potent irreversible inhibitor of acetylcholinesterase (AChE), causes seizures and rapidly increases Fos and glial fibrillary acidic protein (GFAP) staining in piriform cortex (PC). This suggests that the inhibition of AChE by soman leads to increased acetylcholine (ACh) and neuronal excitability in PC. The sole source of cholinergic input to PC is from the nucleus of the diagonal band (NDB). To investigate the role of ACh in soman-induced seizures, we lesioned cholinergic neurons in NDB unilaterally with 192-IgG-saporin. By 10 d, saporin eliminated staining for choline acetyltransferase (ChAT), the synthetic enzyme for ACh, in NDB ipsilateral to the lesion. Staining for AChE, the degradative enzyme for ACh, was eliminated in PC ipsilateral to the lesioned NDB. By 45-60 min after soman, increased Fos and GFAP staining in PC was evident only ipsilateral to the unlesioned NDB. By 90-120 min after soman, Fos and GFAP staining increased bilaterally in PC. In a second experiment, electrical stimulation electrodes were implanted unilaterally in the NDB to activate focally the projections to PC in unanesthetized rats. Within 5 min of NDB stimulation, there were clear behavioral and EEG signs of convulsions. After 45-60 min of NDB stimulation, there was increased Fos and GFAP staining in layer II of PC ipsilateral to the stimulation site. Pretreatment with the selective muscarinic receptor antagonist scopolamine blocked the convulsions and prevented increased Fos and GFAP staining in PC. These results suggest that ACh release in PC triggers the initiation of seizures and gliosis after soman administration, predominantly by the activation of muscarinic receptors.

Acetylcholine↗
PubMed1998

Fos expression in rat pontine tegmental neurons following activation of the medial preoptic area.

Fos immunohistochemistry was used to map the distribution of pontine neurons excited by activation of the medial preoptic area (MPO). Although we have previously shown that Barrington's nucleus receives a very dense focal input from the MPO, electrical stimulation of the preoptic area unexpectedly induced very little Fos expression in Barrington's neurons. These results suggest that the MPO-->Barrington's projection utilizes a transmitter(s) that does not involve transduction of the Fos protein; alternatively, MPO afferents to Barrington's nucleus may be inhibitory in nature. As Barrington's nucleus plays a critical role in micturition, MPO projections to Barrington's nucleus may regulate voiding reflexes during sexual behavior. Interestingly, while the locus coeruleus (LC) proper receives only a sparse projection from the MPO, extensive Fos expression was present in LC. The finding of Fos immunoreactive LC neurons suggests that the excitatory influence of MPO may regulate LC neuronal activity and NE release during reproductive behaviors.

Animals↗
PubMed1998

Functional organization of rat olfactory bulb glomeruli revealed by optical imaging.

The functional organization and synaptic physiology of olfactory bulb glomeruli were studied in rat in vitro slice preparations stained with the voltage-sensitive dye RH-155. Optical signals were recorded with a 100-element photodiode array at high temporal resolution. Pharmacological and ionic manipulations were used to investigate synaptic responses to stimulation of the olfactory nerve layer (ONL). ONL stimulation evoked a sodium-mediated compound action potential that propagated across the ONL and invaded individual glomeruli. This presynaptic volley evoked calcium-dependent synaptic responses the amplitudes of which were largest within the glomerular layer (GL); smaller amplitude responses were recorded in deeper layers of the olfactory bulb. Synaptic responses in the GL were attenuated by the non-NMDA ionotropic glutamate receptor antagonist CNQX; the residual component was suppressed by the NMDA glutamate receptor antagonist AP-5. The GABAA receptor antagonist bicuculline methiodide had little effect, whereas the GABAB receptor agonist baclofen dramatically attenuated ONL-evoked synaptic responses. The effects of baclofen were reversed by the GABAB receptor antagonist CGP35348. Paired-pulse depression of ONL-evoked synaptic responses in the GL was partially reversed by CGP35348. These findings suggest that olfactory nerve axons release glutamate to activate both NMDA and non-NMDA receptors on GL neurons, that GABAA receptor-mediated inhibition has little effect on these responses, and that GABAB receptor-mediated inhibition may act presynaptically on olfactory nerve axons to modulate their inputs to olfactory bulb neurons.

2-Amino-5-phosphonovalerate↗
PubMed1998

Histamine release from bronchoalveolar lavage cells from asthmatic subjects after allergen challenge and relationship to the late asthmatic response.

BACKGROUND: Metachromatic cells obtained from asthmatic subjects demonstrate increased spontaneous and stimulated histamine release in vitro. Their ability to synthesize and store proinflammatory cytokines has focused renewed interest on their role in asthma. OBJECTIVE: The late asthmatic response provides a useful model of clinical asthma. The aim of the study was to examine metachromatic cell derived mediators and histamine releasability in vitro after in vivo allergen exposure in atopic subjects with and without asthma and relate them to the type of physiological response observed. METHODS: Bronchoalveolar lavage (BAL) cells were obtained 4 h after challenge from asthmatics exhibiting a single early response (EAR, n = 5), a dual response (LAR, n = 7), unchallenged (basal, n = 5), atopic non-asthmatic (ANA, n = 6) and non-atopic non-asthmatics (normal, n = 5). BAL histamine and tryptase concentrations and in vitro histamine release (HR) after stimulation with anti-IgE, allergen, A23187, conconavalin A and substance P were compared. RESULTS: Metachromatic cell numbers were lower in normal controls compared with all asthmatic groups and in LAR compared with EAR. Metachromatic cell derived mediators were higher in asthmatic compared with normal subjects. Spontaneous HR in LAR (20.5 +/- 5.0%) was lower than EAR (29.5 +/- 3.9%) and ANA (30.2 +/- 1.4%) (P < 0.05). No differences were seen in stimulated HR between EAR and LAR. HR in ANA stimulated with anti-IgE was greater than LAR (P < 0.05). HR in ANA stimulated with anti-IgE was greater than LAR (P < 0.05). After stimulation with ionophore A23187 (1 microM), release was greater in LAR compared with basal (P < 0.05) and no different at 5 microM. All subject groups responded to substance P (SP) but was significantly more in the asthmatic subjects compared to normal controls (P < 0.05). Allergen challenge did not modify the response of asthmatic subjects to SP. CONCLUSION: Functional differences in metachromatic cell reactivity are present in atopic subjects 4h after in vivo allergen exposure which relate to the physiological response observed after this time and suggest that there is ongoing metachromatic cell degranulation subjects who subsequently develop LAR.

Adolescent↗