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Biomedical subjects

D M Cooper

Publications and source records attributed to D M Cooper.

At least 253 records · Page 14Linked to original sources
PubMed1978

Inhibition of bovine adrenocortical adenylate cyclase activity by adenosine.

Incubation of bovine adrenocortical membranes with corticotropin and 5-guanylylimidodiphosphate produced a state of adenylate cyclase (ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1) with maximal catalytic activity and an increased sensitivity to inhibition by adenosine. Due to metabolism of adenine nucleotides during adenylate cyclase assays a quantitative assessment of the nature of this inhibition was not possible. However, when determined at 0.2--1.0 mM MgATP2-, half-maximal inhibition of the basal and maximally active states of the enzyme was observed at adenosine concentrations of 210--330 and 70--90 micrometer, respectively. The inhibition appeared to be partially competitive, suggesting that the nucleoside may act as an allosteric negative effector which reduces the affinity of the active site for substrate. Adenosine was 5--6 times more potent as an inhibitor of adrenal adenylate cyclase than 2-chloroadenosine. Adenosine deaminase abolished the inhibitory effect of the nucleoside, whilst theophylline had no effect on activity either in the absence or presence of adenosine.

Adenosine↗
PubMed1978

Adenosine analogs inhibit adipocyte adenylate cyclase by a GTP-dependent process: basis for actions of adenosine and methylxanthines on cyclic AMP production and lipolysis.

Adenylate cyclase in purified membranes from rat adipocytes is inhibited by low concentrations of purine-modified adenosine analogs, particularly those modified in the N6 position. Such inhibition is antagonized competitively by methylxanthines, but not by other cyclic nucleotide phosphodiesterase inhibitors, and it is dependent on "inhibitory" concentrations of GTP in the assay medium. Ribose-modified adenosine analogs inhibit adenylate cyclase through a process that is neither dependent upon the GTP concentration nor antagonized by methylxanthines. These results explain the potent effects of adenosine and methylxanthines on fat cell metabolism and demonstrate the importance of GTP in mediating inhibition by agents that act at cell surface receptors.

Adenosine↗
PubMed1978

Ultrastructure of airways in children with asthma.

This study describes the histopathology and ultrastructure of bronchial mucosa in lung biopsies from two children with bronchial asthma in remission, and compares them with lung samples from two children who died in status asthmaticus. Light microscopy of all samples showed changes typical of bronchial asthma, e.g. mucus plugging, goblet cell hyperplasia, 'thickening of bronchial basement membrane', peribronchial smooth muscle hypertrophy and eosinophilic infiltration. Electron microscopy revealed that the mucus plugs consisted of moderately electron-dense floccular material containing degenerate epithelial cells, macrophages and cell fragments. The luminal surfaces of ciliated cells showed cytoplasmic blebs and abnormal cilia. Mast cells in various stages of degranulation were scattered between bronchial epithelial cells. The subepithelial hyaline layer, commonly referred to as "thickened basement membrane", consisted of collagen fibrils in plexiform arrangement. The basement membrane proper appeared intact. These electron microscopic changes, particularly the presence of mast cells and subepithelial collagen deposits, were also found in autopsy samples. This combined light and electron microscopic study shows that marked, possibly irreversible changes may be present in the lungs of patients with severe bronchial asthma, even when they are asymptomatic. These pulmonary changes could be the direct consequence of mast cell activation and the release of various mediators. No evidence of immune complex deposition was found.

Asthma↗
PubMed1977

Modulation of the response of bovine adrenocortical adenylate cyclase to corticotropin.

An assessment was made of some of the basic parameters responsible for the modulation of adenylate cyclase activity in a bovine adrenocortical plasma-membrane preparation. When determined at 0.1 mM-ATP, basal adenylate cyclase activity increased with increasing MgCl2 concentrations, whereas in the presence of corticotropin activity was essentially maximal at 10mM-MgCl2; high concentrations (25mM) of MgCl2 inhibited adenylate cyclase activity determined in the presence of both corticotropin and GTP. At all MgCl2 concentrations, corticotropin and GTP activated the enzyme in a synergistic fashion. The magnitude of the stimulation of basal activity produced by corticotropin was a function of Mg2+ concentration, whereas that produced by GTP appeared largely independent of Mg2+ concentration. Adenylate cyclase activity in the bovine adrenal membrane was half-maximally stimulated by corticotropin concentrations in the range 0.3--1.0 nM. The concentration of corticotropin evoking half-maximum response was not significantly affected by raising the free Mg2+ concentration from 0.4 to 4.9 mM, nor by the presence of GTP. In the presence of GTP, high concentrations (over 1 micrometer) of corticotropin inhibited adenylate cyclase activity, although no inhibition was apparent in the absence of guanine nucleotide.

Adenosine Triphosphate↗
PubMed1977

Assessing bronchodilator responsiveness.

This report concerns the difficulty in distinguishing variation due to drug effects from the spontaneous daily variation in baseline levels of pulmonary function in the evaluation of bronchodilator responsiveness in asthmatic children. Both prospective and retrospective studies were employed to assess the importance of the influence of the baseline level of function from which change is measured on the degree of responsiveness observed. It was found that for baseline levels up to approximately 90% of the predicted normal value, all patients had the capacity to respond significantly to a bronchodilator. However, there was no limit of baseline function below which a significant response did not occur.

Adolescent↗
PubMed1977

Apparent positive cooperativity of ACTH action on adrenocortical cells: the effect of hormone degradation.

The ability of adrenocortical cells to degrade ACTH1--39 and [125I]ACTH has been assessed under various conditions. Under conditions leading to increased hormone degradation there was an elevation of both the ED50 and the value of the Hill coefficient derived from concentration-effect curves for ACTH-stimulated steroidogenesis. Such degradative mechanisms offer a simple explanation for tha apparent positive cooperativity proposed by others for ACTH-receptor-adenylate cyclase interactions.

Adrenal Cortex↗
PubMed1977

Occult pulmonary abnormalities in asymptomatic asthmatic children.

The pulmonary status of 178 asymptomatic asthmatic children with normal time-volume spirograms was further evaluated using flow-volume loops, body plethysmographic studies, and blood gas tensions in arterialized capillary blood. Residual volume (RV) was abnormal in 26%, total lung capacity (TLC) in 33%, RV/TLC% in 41%, and arterial oxygen pressure in 23% of them. All values for expiratory flow measured relative to observed vital capacity (VC), (ie, the forced expiratory volume in one second [FEV1], the mean forced expiratory flow during the middle half of the forced vital capacity [FEF25-75%; FVC], FEV1/VC, and the instantaneous forced expiratory flow after 75% and after 50% of the FVC has been exhaled) were normal, and VC was subnormal in only five instances, but flow rates measured relative to TLC were abnormal in 26% of the patients. Some abnormality of pulmonary function was present in all but 13% of these asymptomatic children. Reliance upon conventional evaluation of pulmonary function by forced expiratory spirograms and freedom from wheezing may frequently give the clinician a false impression of the true conditon of the lungs of the asthmatic child.

Adolescent↗
PubMed1976

Clinical and physiological assessment of asthmatic children treated with beclomethasone dipropionate.

Forty-two perennial asthmatic children were selected for a 12-wk study using beclomethasone dipropionate. The groups included 21 steroid-dependent children (Group I) and 21 patients (Group II) whose disease was of sufficient severity that corticosteroid therapy was contemplated. All children received the drug in a dose of 100 mug 4 times daily. During the study, oral prednisone was withdrawn from the steroid-dependent children while other therapy was essentially unchanged. Group II children underwent a double-blind trial, receiving beclomethasone for 6 wk and placebo for 6 wk. Objective assessment of adrenal and pulmonary function was obtained at regular intervals. For the latter, total lung capacity and its subdivisions, airways resistance, maximum expiratory flow volume, and oxygen tension, were measured in both groups. In Group II static elastic recoil was measured also. For most tests the results were statistically significant. In both groups, 18 of 21 patients demonstrated an excellent clinical response, no evidence of adrenal suppression, and improvement in pulmonary function. Forty of 42 patients were followed for another 12 wk, and 19 of each group did well. After 20-24 wk of therapy, 16% of patients harbored monilia in their oropharynx, and 1 patient had clinical monilial stomatitis. Within the limits of the time of the study, beclomethasone dipropionate appeared to provide adequate clinical control in many chronic, severe, steroid-dependent and nonsteroid-dependent asthmatic children.

17-Ketosteroids↗
PubMed1976

Chronic pulmonary disease in a child with the Ehlers-Danlos syndrome.

The presence of chronic pulmonary disease is an uncommon finding in the Ehlers-Danlos syndrome. The patient discussed herein presented with severe irreversible obstructive pulmonary disease characterized by marked hyperinflation, an increase in static lung compliance, and tracheal dilatation. A largely normal lung biopsy ruled out chronic pulmonary emphysema. Despite the similarity of this patient to those with the Mounier-Kuhn syndrome, the degree of tracheobronchial enlargement was not as great as is usually seen in this disorder although these anatomic changes may develop with time. The findings in this case demonstrate that any site within the tracheobronchial tree may be involved in the Ehlers-Danlos syndrome and further emphasize the need to determine the degree of reversibility of obstructive lung disease in children.

Child↗
PubMed1976

Inhibition of exercise-induced bronchospasm by atropine.

The ability of atropine to inhibit exercise-induced bronchospasm was evaluated in 18 children with chronic, perennial asthma. In 17 of 18 patients, exercise-induced bronchospasm was blocked by prior inhalation of 0.1 mg per kg of atropine sulfate, administered in a randomized single blind fashion. In 14 of these 17 patients, significant bronchodilatation occured after the combination of atropine and exercise. Placebo failed to inhibit exercise-induced bronchospasm in any patient. These results suggest that the parasympathetic nervous system has a role in the mediation of exercise-induced bronchospasm in children.

Adolescent↗
PubMed1976

Inhaled atropine sulfate: dose response characteristics.

Inhaled atropine sulfate is a bronchodilator in man, but its efficacy and optimal dosage are still unknown. In the current study, the dose-response characteristics of this agent were examined in 20 children with chronic perennial asthma, using maximal expiratory flow-volume curves. Inhaled drug was delivered in incremental doses of 0.005 to 0.1 mg per kg. A peak action of atropine on the maximal flow after exhalation of 50 per cent of the forced vital capacity was seen 1 hour after inhalation; significant bronchodilatation was observed for as long as 300 min, depending on the dose. A plateau was observed in the dose-response curve in the dose range, 0.05 to 0.1 mg per kg. Changes in the maximal expiratory flow after exhalation of 75 per cent of the forced vital capacity paralleled those in the maximal expiratory flow after exhalation of 50 per cent of the forced vital capacity. Specific conductance significantly increased, and the ratio of residual volume to total lung capacity significantly decreased in 10 patients examined. In no case could the observed increases in flows be explained by the patient's breathing at a higher lung volume. Considerable intersubject variation was found in the effects of a given dose of atropine. This may be explained by variations in baseline flows. It was concluded that atropine sulfate by inhalation is an effective bronchodilator in children with severe asthma and that reported variations in its efficacy may be related to inadequate dosage.

Adolescent↗