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Biomedical subjects

D M Cooper

Publications and source records attributed to D M Cooper.

At least 181 records · Page 10Linked to original sources
PubMed1988

Evidence that maturation of the peripheral chemoreceptors is not complete in childhood.

We examined the hypothesis that the peripheral chemoreceptors contribute a different degree of tone to respiration during exercise in normal young children as compared to adults. To improve resolution of the peripheral chemoreceptor contribution, the studies were conducted during controlled levels of exercise. Peripheral chemoreceptor function was assessed by the hyperoxic (FIO2 = 0.80) switch technique during steady-state, sub-anaerobic threshold exercise during air (FIO2 = 0.21) and midly hypoxic gas (FIO2 = 0.15) breathing in 9 healthy children (mean +/- 1 SD age (years) = 8.2 +/- 1.4) and 10 healthy adults (28.2 +/- 6.5). Ventilation during exercise was significantly greater under hypoxic conditions in both children and adults. During air breathing exercise the mean ventilatory decrease in response to the hyperoxic switch was similar in the two groups (27.9 +/- 10.7% in children and 23.3 +/- 6.3% in adults). In contrast, during hypoxic gas breathing exercise the children demonstrated a much greater decrease in ventilation following the hyperoxic switch (57.9 +/- 3.6%) compared to adults (38.9 +/- 5.5%) (P less than 0.0001). Thus, the peripheral chemoreceptors have a greater role in the exercise hyperpnea during hypoxic exercise in young children as compared to adults, suggesting attenuation of peripheral chemoreceptor function during maturation.

Adult↗
PubMed1988

Control of ventilation during exercise in patients with central venous-to-systemic arterial shunts.

The diversion of systemic venous blood into the arterial circulation in patients with intracardiac right-to-left shunts represents a pathophysiological condition in which there are alterations in some of the potential stimuli for the exercise hyperpnea. We therefore studied 18 adult patients with congenital (16) or noncongenital (2) right-to-left shunts and a group of normal control subjects during constant work rate and progressive work rate exercise to assess the effects of these alterations on the dynamics of exercise ventilation and gas exchange. Minute ventilation (VE) was significantly higher in the patients than in the controls, both at rest (10.7 +/- 2.4 vs. 7.5 +/- 1.2 l/min, respectively) and during constant-load exercise (24.9 +/- 4.8 vs. 12.7 +/- 2.61 l/min, respectively). When beginning constant work rate exercise from rest, the ventilatory response of the patients followed a pattern that was distinct from that of the normal subjects. At the onset of exercise, the patients' end-tidal PCO2 decreased, end-tidal PO2 increased, and gas exchange ratio increased, indicating that pulmonary blood was hyperventilated relative to the resting state. However, arterial blood gases, in six patients in which they were measured, revealed that despite the large VE response to exercise, arterial pH and PCO2 were not significantly different from resting values when sampled during the first 2 min of moderate-intensity exercise. Arterial PCO2 changed by an average of only 1.4 Torr after 4.5-6 min of exercise. Thus the exercise-induced alveolar and pulmonary capillary hypocapnia was of an appropriate degree to compensate for the shunting of CO2-rich venous blood into the systemic arterial circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Hydrodynamic properties of adenosine Ri receptors solubilized from rat cerebral-cortical membranes.

Adenosine Ri receptors and inhibitory guanine-nucleotide-regulatory components were solubilized from rat cerebral-cortical membranes with sodium cholate. (-)-N6-Phenylisopropyl[2,8-3H]adenosine [( 3H]PIA) binds with high affinity to the soluble receptors, which retain the pharmacological specificity of adenosine Ri receptors observed in membranes. The binding is regulated by bivalent cations and guanine nucleotides. Bivalent cations increase [3H]PIA binding by increasing both the affinity and the apparent number of receptors. Guanine nucleotides decrease agonist binding by increasing the dissociation of the ligand-receptor complex. Adenosine agonists stabilize the high-affinity form of the soluble receptor. The hydrodynamic properties of the adenosine receptor were determined with cholate extracts of membranes that were treated with [3H]PIA. Sucrose-gradient-centrifugation analysis indicates that the receptor has a sedimentation coefficient of 7.7 S. The receptor is eluted from Sepharose 6B columns with an apparent Stokes radius of 7.2 nm. Labelling of either sucrose-gradient or gel-filtration-column fractions with pertussis toxin and [32P]-NAD+ reveals that both the 41,000- and 39,000-Mr substrates overlap with the receptor activity. These studies suggest that the high-affinity adenosine-receptor-binding activity in the cholate extract represents a stable R1-N complex.

Adenosine↗
PubMed1987

Adenosine receptor agonists inhibit inositol phosphate accumulation in rat striatal slices.

The accumulation of inositol-1-phosphate in rat striatal slices was inhibited by the adenosine analogues 5'-N-ethylcarboxamide-adenosine and N6-phenylisopropyladenosine. Maximal inhibition (approximately 20%) was achieved by micromolar concentrations of either compound. Both basal and stimulated values could be inhibited, and the inhibition was reversible by the adenosine receptor antagonist 8-phenyltheophylline (10 microM). The results suggest that adenosine may exert a tonic inhibitory influence on inositol phospholipid-derived second messenger production in the striatum in vivo.

Adenosine↗
PubMed1987

Beneficial effect of sulfamethoxazole and trimethoprim on accelerated coagulation.

We have shown that the drug combination of sulfamethoxazole and trimethoprim has a radio protective effect in mice. Since radiation injury is due in part to microvascular thrombosis produced by the release or action of thromboplastin, we evaluated the effect of these drugs individually on thromboplastin-accelerated coagulation. Sulfamethoxazole at a final concentration of 0.05 microgram/ml and trimethoprim at concentrations of 0.005 and 0.05 microgram/ml significantly prolonged the recalcification times of human plasma. Whether these drugs have an anticoagulant effect when employed clinically remains to be determined.

Anticoagulants↗
PubMed1987

Evaluation of normal prosthetic valve function by Doppler echocardiography.

Previous investigations have suggested that Doppler echocardiography is useful in detecting dysfunction in aortic (AVR) and mitral prostheses (MVR). However, to diagnose abnormalities, the spectrum of normal velocities through these valves must be established. Therefore, we used Doppler echocardiography to study 100 patients with 105 prosthetic valves that had no clinical evidence of valve dysfunction 9 +/- 8 days postoperatively. There were 66 Carpentier-Edwards (C-E), 23 St. Jude (S-J), and 16 Ionescu-Shiley (I-S) valves. In 70 AVR, the peak instantaneous gradient was 26.4 +/- 8.2 Hg, mean systolic gradient was 15.6 +/- 5 mm Hg, and gradients varied inversely with valve size, although differences were significant only when comparing the smallest vs the largest valve sizes (p less than or equal to 0.03). Peak instantaneous gradients greater than 36 mm Hg occurred only in AVR size 23 or smaller. There were no significant differences in gradients among C-E, S-J, and I-S AVR. In 35 MVR, mean gradient was 6.9 +/- 2.3 mm Hg and valve area was 2.7 +/- 0.8 cm2; neither varied significantly with valve size. However, S-J MVR group had smaller mean gradients and larger effective valve area than C-E bioprosthetic MVR (p = 0.01 and p = 0.05, respectively). Regurgitation was more common in AVR (26%) than in MVR (9%), p = 0.04, although all instances were mild and clinically silent. We conclude that normal AVR and MVR of a given size and type have a predictable range of Doppler echocardiographic parameters. Doppler evidence of mild regurgitation is a frequent finding in normal AVR and MVR.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Ca2+/calmodulin distinguishes between guanyl-5'-yl-imidodiphosphate- and opiate-mediated inhibition of rat striatal adenylate cyclase.

The inhibition of adenylate cyclase from rat striatal plasma membranes by guanyl-5'-yl-imidodiphosphate [Gpp(NH)p] and morphine was compared to determine whether Gpp(NH)p-mediated inhibition accurately reflected hormone-mediated inhibition in this system. Inhibition of adenylate cyclase activity by Gpp(NH)p and morphine was examined with respect to temperature, divalent cation concentration, and the presence of Ca2+/calmodulin (Ca2+/CaM). Gpp(NH)p-mediated inhibition was dependent on the presence of Ca2+/CaM at 24 degrees C; the inhibition was independent of Ca2+/CaM at 18 degrees C; and inhibition could not be detected in the presence, or absence, of Ca2+/CaM at 30 degrees C. In contrast, naloxone-reversible, morphine-induced inhibition of adenylate cyclase was independent of both temperature and the presence of Ca2+/CaM. Mg2+ dose-response curves also reinforced the differences in the Ca2+/CaM requirement for Gpp(NH)p- and morphine-induced inhibition. Because Gpp(NH)p-mediated inhibition was independent of Ca2+/CaM at low basal activities (i.e., 18 degrees C, or below 1 mM Mg2+) and dependent on the presence of Ca2+/CaM at higher basal activities (24 degrees C, or above 1 mM Mg2+), the inhibitory effects of Gpp(NH)p were examined at 1 mM Mg2+ in the presence of 100 nM forskolin. Under these conditions, both Gpp(NH)p- and morphine-induced inhibition of adenylate cyclase were independent of Ca2+/CaM. The results demonstrate that the requirement for Ca2+/CaM to observe Gpp(NH)p-mediated inhibition depends on the basal activity of adenylate cyclase, whereas hormone-mediated inhibition is Ca2+/CaM independent under all conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclase Inhibitors↗
PubMed1987

Coupling of ventilation and CO2 production during exercise in children.

The purpose of this study was to determine how ventilation (VE) and CO2 production (VCO2) in response to exercise change during the growth process in children and teenagers. Dynamic gas exchange responses were measured in two types of studies: 128 healthy children ranging in age from 6 to 18 yr performed progressive exercise tests ("ramp" type protocol) for measurement of the slope of the relationship between VE and VCO2--delta VE/delta VCO2; and the response characteristics of VE and VCO2 in the transition between rest and exercise were measured in 11 teenagers and 11 younger children. Gas exchange was measured breath by breath. We found a small but significant decrease in delta VE/delta VCO2 with increasing body weight (r = -0.46, p less than 0.05), height, or age (mean slope of 27 in the youngest in 21 in the oldest subjects). The response characteristics of VE and VCO2 (measured as the time constant of the best-fit exponential response) were longer than for VO2 in both younger children and teenagers; but the time constants for VE and VCO2 were each approximately 30% faster in younger children compared to teenagers. In addition, end-tidal PCO2 during exercise was significantly lower in the younger subjects (mean value of 39.6 torr) compared to the teenagers (mean value of 43.5 torr). The results suggest that the process of respiratory control in exercise matures to a small degree during childhood in that PCO2 may be regulated at lower levels in younger children and there may be growth-related differences in the relative amounts of CO2 that can be stored in tissues.

Adolescent↗
PubMed1987

Calmodulin may play a pivotal role in neurotransmitter-mediated inhibition and stimulation of rat cerebellar adenylate cyclase.

Adenylate cyclase activity was stimulated 2.5-fold by exogenous Ca2+/calmodulin (CaM) (1 microM) in rat cerebellar plasma membranes which had been depleted of endogenous Ca2+/CaM. In EGTA-washed membranes, phenylisopropyladenosine (an adenosine receptor agonist) was unable to inhibit adenylate cyclase activity unless exogenous Ca2+/CaM was included in the assay. Conversely, isoproterenol (a beta-adrenergic receptor agonist) was able to stimulate adenylate cyclase activity only in the absence of Ca2+/CaM. The regulation of adenylate cyclase activity by guanyl-5'-yl-imidodiphosphate [Gpp(NH)p, a nonhydrolyzable guanine nucleotide analog, used to monitor interactions between guanine nucleotide-binding proteins and the catalytic unit of adenylate cyclase] was similar to that of phenylisopropyladenosine and isoproterenol; i.e., Gpp(NH)p produced inhibition exclusively in the presence of Ca2+/CaM, whereas only stimulation was observed in the absence of Ca2+/CaM. These results suggest that changes in intracellular Ca2+ concentrations may determine whether adenylate cyclase can be stimulated or inhibited by neurotransmitters.

Adenylyl Cyclases↗
PubMed1987

Antagonism of calmodulin-stimulated adenylate cyclase by trifluoperazine, calmidazolium and W-7 in rat cerebellar membranes.

Ca++-calmodulin (CaM)-dependent stimulation of adenylate cyclase in rat cerebellar plasma membranes was demonstrated by removal of endogenous Ca++ and CaM and addition of exogenous Ca++ and CaM to the membranes. This CaM-dependent adenylate cyclase activity could be inhibited by calmidazolium and trifluoperazine in an apparently competitive manner, whereas the inhibition produced by W-7 was not competitive. The potency of the antagonists was strictly dependent upon the concentration of exogenous CaM present in the assay. Preincubation of membranes with exogenous CaM, followed by addition of anti-CaM agents, greatly reduced the inhibition of CaM-dependent adenylate cyclase activity. The potency of the anti-CaM agents was further decreased in membranes that had not been depleted of endogenous Ca++ and CaM (native membranes). The results suggest that optimal inhibition of CaM-dependent adenylate cyclase activity occurs upon simultaneous addition of exogenous CaM and anti-CaM agents to membranes depleted of endogenous Ca++ and CaM. Association of CaM with the catalytic unit of adenylate cyclase before introduction of CaM antagonists results in a CaM-C complex that is relatively refractory to inhibition by these anti-CaM agents. This CaM-catalytic unit complex probably exists in native membranes, rendering the antagonism of adenylate cyclase activity supported by endogenous Ca++-CaM essentially insensitive to low concentrations of CaM antagonists.

Adenylyl Cyclases↗
PubMed1987

Calmodulin stimulation of the rat cerebral cortical adenylate cyclase is required for the detection of guanine nucleotide- or hormone-mediated inhibition.

Functional interactions between the inhibitory guanine nucleotide-regulatory component (Ni) and the adenylate cyclase catalytic subunit (C) from cerebral cortex have been investigated. The inhibition of adenylate cyclase activity by guanosine 5'-(beta, gamma-imido)triphosphate [Gpp(NH)p] was used as a functional measurement of Ni-C interactions in membranes and cholate extracts. Calmodulin stimulation of C activity was required for the detection of Gpp(NH)p inhibition in these preparations. A similar calmodulin requirement was observed for adenosine receptor-mediated inhibition in membranes. The requirement for calmodulin was demonstrated directly in membranes from which calmodulin had been removed by washing and centrifugation. Adenylate cyclase activity in these preparations was not stimulated by free Ca2+ (1 microM). However, upon the readdition of calmodulin (1 microM), these preparations were stimulated 4-fold by Ca2+. Under these assay conditions, Gpp(NH)p- and adenosine receptor-mediated inhibition was absolutely dependent on Ca2+-calmodulin stimulation. However, forskolin stimulation of activity also restored Gpp(NH)p-mediated inhibition. The following experiments were used to implicate the role of calmodulin in detergent-solubilized preparations: (i) by demonstrating that free Ca2+ was required to observe Gpp(NH)p-mediated inhibition, and (ii) by demonstrating that the calmodulin antagonist, calmidazolium, abolished Gpp(NH)p-mediated inhibition while concomitantly decreasing basal activity. As observed in membranes, detection of guanine nucleotide-mediated inhibition required calmodulin stimulation of the detergent-solubilized adenylate cyclase. These results suggest that stimulation of cerebral cortical C activity by either calmodulin or forskolin is required for Ni-mediated inhibition.

Adenylyl Cyclase Inhibitors↗
PubMed1987

Assessment of nutrient intake of patients with cystic fibrosis compared with healthy children.

The food intakes of 40 patients with cystic fibrosis (CF) (0.7 to 23 years) on low-fat diets were assessed in relation to the appropriate recommended dietary allowance (RDA) and intakes of healthy children. Mean energy intakes of the subjects with CF were similar to the control groups but fell well short of the frequently cited goal of 120-150 per cent of the RDA. Failure to achieve this may account for their marked growth failure. The study highlights the inability of CF patients to maintain a high energy intake despite nutritional counselling when dietary fat is restricted. When energy per kg body weight was considered, children with CF ate more than their peers and it may be unrealistic to expect them to increase their spontaneous oral intake above this level.

Adolescent↗
PubMed1986

Target size of the adenosine Ri receptor.

The adenosine receptor of rat cerebral-cortical membranes was examined by radiation inactivation. In control membranes the receptor is distributed between high- and low-affinity states, that can be preferentially expressed by Mg2+ ions and guanine nucleotides respectively. Upon exposure to increasing doses of radiation, the high-affinity receptor decayed linearly as a function of radiation dose. This decay rate corresponded to a target size of 63,000 Da, when compared with the decay of the muscarinic cholinergic receptor that was also measured in these membranes.

Animals↗
PubMed1986

Pituitary apoplexy: a complication of cardiac surgery.

Pituitary apoplexy occurred in 3 patients in the immediate postoperative period following cardiac operation with cardiopulmonary bypass. In this setting, this complication is extremely rare and not widely recognized. Precipitating factors may be related to the extracorporeal bypass apparatus, anticoagulation, low cerebral blood flow, and even anesthetic agents. Neurosurgical decompression can be safely performed in the early postoperative period following open-heart operations.

Cardiopulmonary Bypass↗
PubMed1986

Interaction of the inhibitory GTP regulatory component with soluble cerebral cortical adenylate cyclase.

Functional interaction of the inhibitory GTP regulatory component (Ni) with the adenylate cyclase catalytic subunit has not previously been demonstrated after detergent solubilization. The present report describes a sodium cholate-solubilized preparation of rat cerebral cortical membrane adenylate cyclase that retains guanine nucleotide-mediated inhibition of activity. Methods of membrane preparation, cholate extraction, and assay conditions were manipulated such that guanosine-5'-(beta-gamma-imido)triphosphate [Gpp(NH)p] inhibited basal activity 40-60%. The rank order of potency among various GTP analogs was similar in cholate extracts and in membranes: guanosine-5'-0-(3-thiotriphosphate) greater than Gpp(NH)p greater than GTP. Inclusion of 0.1 mM EGTA reduced basal activity 70-90% and abolished Gpp(NH)p inhibition of basal activity in both membranes and cholate extracts. Forskolin-stimulated activity was also inhibited by Gpp(NH)p. Treatment of either membranes or cholate extracts with N-ethylmaleimide abolished Gpp(NH)p inhibition. Gel filtration of the cholate extract over a Sepharose 6B column in 0.1% Lubrol PX partially resolved the adenylate cyclase components. However, Gpp(NH)p inhibition of basal activity (60% of the control) was maintained in select column fractions. Sucrose gradient centrifugation totally resolved the catalytic subunit from both functional Ni and stimulatory GTP regulatory component (Ns) activities. The sedimentation of functional Ni activity was detected by assaying the ability of sucrose gradient fractions to confer Gpp(NH)p inhibition of the resolved catalytic activity. Labeling of gradient or column fractions with pertussis toxin and [32P]NAD revealed that both the 39,000- and 41,000-dalton substrates comigrated with the functional Ni activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclase Inhibitors↗