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Biomedical subjects

D M Cooper

Publications and source records attributed to D M Cooper.

At least 217 records · Page 12Linked to original sources
PubMed1984

Progesterone inhibition of Xenopus oocyte adenylate cyclase is not mediated via the Bordetella pertussis toxin substrate.

Preincubation of intact Xenopus laevis oocytes with islet-activating protein (IAP) stimulates plasma membrane adenylate cyclase activity measured in the presence of either GTP or 5'-guanylyl imidodiphosphate. The toxin appears to act by catalyzing the ADP-ribosylation of a 41,000-D protein in the oocyte plasma membrane that is distinct from the 45,000- and 52,000-D proteins labeled by cholera toxin. Preincubation of intact oocytes with IAP for 2.5 hr inhibits 80% of the ADP-ribosylation of oocyte membranes subsequently prepared and treated in vitro with IAP in the presence of [alpha-32P]NAD. The abilities of progesterone and the P site agonist, 2',5'-dideoxyadenosine, to inhibit plasma membrane adenylate cyclase are not inhibited by IAP treatment, but IAP pretreatment abolishes inhibition by acetylcholine. In addition, IAP pretreatment of oocytes slows the time course of germinal vesicle breakdown induced by suboptimal concentrations of progesterone. This effect of toxin upon oocyte maturation is apparently due to its effect upon basal cyclase activity, since IAP has no effect upon the time course of maturation induced by 10 microM progesterone. These results indicate that, even though the oocyte adenylate cyclase does contain a functional Ni subunit, inhibition of Xenopus oocyte adenylate cyclase by progesterone or 2',5'-dideoxyadenosine is not mediated via the Bordetella pertussis toxin substrate.

Adenosine Diphosphate Ribose↗
PubMed1983

Role of calmodulin in the effect of guanyl nucleotides on rat hippocampal adenylate cyclase: involvement of adenosine and opiates.

The adenylate cyclase activity of rat hippocampal plasma membranes can be stimulated by vasoactive intestinal polypeptide (VIP). Low concentrations (10(-9) to 19(-7) M) of 5'-guanylyl-imido diphosphate (GppNHp) evoke a transient inhibition of the enzyme, which is followed by stimulation with increasing GppNHp concentrations (10(-6) to 10(-4) M). Inclusion of Inclusion of ethyleneglycol-bis-(beta-aminoethylether)-N,N'-tetraacetic acid (EGTA) during incubation abolishes the GppNHp inhibition while preserving GppNHp activation. The stimulation induced by GppNHp is amplified by VIP, but the inhibition is unaffected. Adenosine analogs and opiates are inhibitory ligands in the presence of GTP, and their effects can be reversed by the appropriate receptor antagonists, 3-isobutyl-1-methylxanthine and naloxone. Treatment of membranes with trypsin abolishes the GppNHp-induced inhibition without affecting the GppNHp stimulation. The inhibition induced by GppNHp is also abolished by EGTA treatment followed by washing, which coincides with a reduction in the adenosine- and opiate-mediated, GTP-dependent inhibition. The GppNHp inhibition can be restored in EGTA-treated but not in trypsin-treated membranes by addition of calcium-calmodulin but not by Ca2+ or Mg2+. Calcium-calmodulin-depleted membranes lack calcium stimulation as well as GppNHp-induced inhibition, whereas untreated membranes and calcium-calmodulin-depleted membranes plus exogenous calcium-calmodulin showed calcium stimulation and GppNHp inhibition. These results suggest that calmodulin is involved in both Ca2+ stimulation and guanine nucleotide-mediated inhibition of rat hippocampal adenylate cyclase.

Adenosine↗
PubMed1983

Ventilation distribution and density dependence of expiratory flow in asthmatic children.

Of 114 asthmatic children, 21% had abnormally steep phase III slopes from a modified single-breath oxygen (SBO2) procedure. We hypothesized that the steep slopes reflect inequality of time constants caused by obstruction of peripheral airways and tested this by using a bronchodilator to reduce overall time constants in subgroups of 10 children with steep slopes (SS) and 20 children with normal slopes (NS). Maximum expiratory flow increased by equivalent degrees (0.65-0.70 l/s) in both groups, but slope decreased significantly only in the SS group. Moreover, the single-breath mixing efficiency of inspired oxygen with resident nitrogen was normal in the NS group but significantly low in the SS group. Density dependence of maximum expiratory flow (DD) was abnormally small in the SS group [15 +/- 6% (SD) increase compared with 57 +/- 13% increase in a separate group of normal children] and was independent of the anatomical dead space. In contrast, DD was normal and varied inversely with anatomical dead space (r = 0.62, P less than 0.01) in the NS group. These results indicate that 1) steep SBO2 slopes found in asthmatic children between acute episodes reflect unequal time constants caused by obstruction of peripheral airways and 2) part of the variation in DD among asthmatic children is caused by variation in convective accelerative pressure losses in major airways.

Adolescent↗
PubMed1983

Control of breathing at the start of exercise as influenced by posture.

It has been suggested that the initial phase of the ventilatory response to exercise is governed by a mechanism which responds to the increase in pulmonary blood flow (Q)--cardiodynamic hyperpnea. Because the initial change in stroke volume and Q is less in the supine (S) than in the upright (U) position at the start of exercise, we hypothesized that the increase in ventilation would also be less in the first 20 s (phase I) of S exercise. Ten normal subjects performed cycle ergometry in the U and S positions. Inspired ventilation (VI), O2 uptake (VO2), CO2 output (VCO2), corrected for changes in lung gas stores, and end-tidal O2 and CO2 tensions were measured breath by breath. Heart rate (HR) was determined beat by beat. The phase I ventilatory response was markedly different in the two positions. In the U position, VI increased abruptly by 81 +/- 8% (mean +/- SE) above base line. In the S position, the phase I response was significantly attenuated (P less than 0.001), the increase in VI being 50 +/- 6%. Similarly, the phase I VO2 and VO2/HR responses reflecting the initial increase in Q and stroke volume, were attenuated (P less than 0.001) in the S posture, compared with that for U; VO2 increased 49 +/- 5.3 and 113 +/- 14.7% in S and U, respectively, and VO2/HR increased 16 +/- 3.0 and 76 +/- 7.1% in the S and U, respectively. The increase in VI correlated well with the increase in VO2, (r = 0.80, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1982

Impaired adenylate cyclase activity of phenylhydrazine-induced reticulocytes.

A method which involves Percoll gradient centrifugation, is described for separating rabbit reticulocytes from other blood cells, including erythrocytes. This permits a quantitative comparison of the adenylate cyclase activity of reticulocyte membranes which had been induced either by bleeding (30% reticulocytosis) or by repeated injections of phenylhydrazine (90% reticulocytosis). Adenylate cyclase activity was greatly impaired on exposure to the hemolytic agent; total activity was reduced about 20-fold. However, a more selective loss was observed in terms of hormonal stimulation. Prostaglandin E1 was 2-fold more effective than either sodium fluoride or Forskolin in stimulating the enzyme from bled reticulocytes, whereas it was 3-fold less effective than either fluoride or Forskolin in the case of membranes from animals which had been exposed to phenylhydrazine. A stimulatory adenosine receptor was detectable only in reticulocytes which had not been treated with the hemolytic agent. These studies suggest that purified reticulocytes from bled animals represent the most suitable model system in which to study the maturation of red blood cells.

1-Methyl-3-isobutylxanthine↗
PubMed1982

Catecholamines and the kinetics of lipolysis in isolated rat adipocytes. Statistical analysis and handling of day-to-day variability in dose-response curves: a general procedure for assessing and manipulating dose-response data.

(1) As a first step in studying the kinetics of the lipolytic system of rat adipocytes, the day-to-day variation between dose-response curves has been analysed. (2) Methods are described for the evaluation of large quantities of data relating noradrenaline to lipolysis. (3) A 'clustering' technique is presented which can be used both to estimate and minimise differences between curves along the response axis. Criteria are outlined to determine whether clustering is appropriate. (4) Our findings indicate that the basic form of the relationship between lipolysis and noradrenaline concentration is relatively stable and consequently that the data can be utilized to study the relationship in greater detail. (5) The techniques described should be applicable to all hormone-mediated responses and may therefore provide the first step towards a meaningful analysis of the relationship between hormone concentrations and response in many systems.

Adipose Tissue↗
PubMed1982

A kinetic analysis of the actions of L-noradrenaline and its related agonists and antagonists on in vitro lipolysis in rat adipose tissue.

(1) Iterative non-linearising optimisation techniques have been used to fit three alternative models to relationships between beta-adrenergic effector concentrations and the lipolytic response which they elicit in dispersed adipocytes derived from rat epididymal fat pads. (2) The models, which consist of a simple hyperbolic relationship, a Hill-type functions and a rational quadratic formulation, were fitted to data obtained with agonists, "partial" agonists and antagonists both alone and in combination. (3) Whereas the hyperbolic relationship was inadequate in all circumstances, the hill-type function accommodated dose-response curves which exhibit no "auto-inhibitory" hook or bell-shaped feature. However, the rational quadratic function could be satisfactorily fitted to the data whether or not the auto-inhibitory phase was apparent. (4) The mechanisms that govern the steepness of the dose-response relationships and their bell-shaped feature are discussed. Evidence is presented that the latter originates at the level of adenylate cyclase.

Adipose Tissue↗
PubMed1982

Analysis of apparent co-operativity in the catecholamine-stimulated lipolysis of rat adipose tissue.

(1) The methods available for assessment of the regulatory features of dose-response relationships that do not conform to the Hill equation are considered, and the sensitisation index Si introduced (2) The value of determining Si is assessed using lipolytic dose-response relationships yielded by beta-adrenergic agonists both alone and in the presence of their specific antagonists [D. M. F. Cooper and J. I Davies, Biochem. Pharmac. 31, 721 (1982)]. (3) It is shown that where the Hill equation is fitted to relationships between L-noradrenaline concentration and lipolysis, the high value obtained for the Hill coefficient (1.69) is artefactual (4) By fitting a rational quadratic model and evaluating Si, a solution is obtained (Si(max), 1.02) which is free of this artefact. (5) The relationship between the results obtained by analysis of dose-response curves and direct binding of catecholamine analogues to membrane receptors is discussed.

Adipose Tissue↗
PubMed1982

Opiate receptor-mediated inhibition of adenylate cyclase in rat striatal plasma membranes.

Plasma membranes from rat striatum contain adenylate cyclase activity that is subject to dual regulation by GTP. Low concentrations (up to 30 nM) of the nucleotide increase activity whereas higher concentrations evoke a steady decline in activity; such behavior characterizes dually regulated adenylate cyclase systems. The opiates, morphine sulfate and D-Ala-Met-enkephalin, produce naloxone-reversible inhibition of the enzyme that is dependent on "inhibitory concentrations" of GTP (above 50 nM). In the absence of GTP no inhibition is observed. Sodium ions decrease the inhibition of activity promoted by GTP alone, but amplify the degree of inhibition seen in the presence of the opiates and GTP. The potencies of the opiates in mediating these effects mirror their affinities for delta opiate receptors in striatum. It is suggested that this action of the opiates may represent their primary action in striatum.

Adenylyl Cyclase Inhibitors↗
PubMed1981

Laryngomalacia and inspiratory obstruction in later childhood.

Pulmonary function and symptoms were reviewed in 20 children in whom laryngomalacia had been diagnosed by direct laryngoscopy in infancy. Most children developed stridor in the first 2 weeks, but 3 children did not develop it until age 3 months. The mean duration of stridor was 4 years 2 months, with a range of 4 months to 12 years 7 months. Six children had marked posseting as infants. Airway dynamics were assessed by flow volume loops. All except one had normal expiratory flow volume curves. Inspiratory abnormalities were detected in 7 children; 6 were assessed as having variable extrathoracic inspiratory obstructions and 1 had a fixed obstruction consistent with subglottic stenosis. The mean ratios of maximal inspiratory flow at 50% of vital capacity divided by forced vital capacity in the laryngomalacia and control groups differed significantly, as did the mean ratios of maximal expiratory flow to maximal inspiratory flow at 50% of forced vital capacity. Laryngomalacia is not necessarily a benign disorder of limited duration; there may be persisting inspiratory obstruction in later childhood.

Age Factors↗
PubMed1981

Changes in distribution of ventilation with lung growth.

We systematically studied the effects of varying preinspiratory lung volumes and expiratory flow rates on the alveolar plateau of the single-breath oxygen test in children and adults. With inhalations of oxygen beginning at functional residual capacity (FRC) compared with residual volume (RV), the slope of phase III increased in 52 of 54 children and 6 of 6 adults (mean increase 29.2%, P less than 0.001) but then decreased at preinspiratory volumes greater than FRC. With maximal expiratory flows, the slopes were smaller than slopes from conventional maneuvers in 14 of 15 children by a mean 24.1%, P less than 0.001. These data suggest that apex-to-base differences in regional lung volume are a major determinant of the slope. Slopes (FRC maneuver) decreased as a function of the height of the children (r = -0.73, P less than 0.001), but differences in nitrogen concentration over the alveolar plateau increased with height (r = 0.70, P less than 0.001). This indicates that the apex-to-base differences in regional lung volume increase with lung size. An estimate of mixing efficiency between resident and inspired gas derived from the alveolar plateau increased with height for both RV (r = 0.40, P less than 0.005) and FRC maneuvers (r = 0.45, p less than 0.005) and was greater for FRC than RV (P less than 0.001). These increases in mixing efficiency are consistent with previously demonstrated decreases in closing volume with growth.

Adult↗
PubMed1981

The progression of Duchenne muscular dystrophy: clinical trial of allopurinol therapy.

A 12-month clinical study of Duchenne muscular dystrophy was carried out during a double-blind trial of allopurinol therapy. The disease was monitored by assessment of muscle power and function, pulmonary function tests, and electrocardiography. Biochemical assessments were made of plasma creatine kinase, pyruvate kinase, uric acid, and urinary excretion of 3-methylhistidine and creatinine. Allopurinol did not alter the progression of the disease.

Adolescent↗