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Biomedical subjects

D M Cooper

Publications and source records attributed to D M Cooper.

At least 163 records · Page 9Linked to original sources
PubMed1990

Are obese children truly unfit? Minimizing the confounding effect of body size on the exercise response.

To test the hypothesis that obese children are unfit (i.e., have abnormal responses to exercise testing consistent with reduced levels of habitual physical activity), we used new analytic strategies in studies of 18 obese children performing cycle ergometry. The subject's weight (mean +/- SD) was 168 +/- 24% that predicted by height, and the age range was 9 to 17 years. Size-independent measures of exercise (e.g., the ratio of oxygen uptake (VO2) to work rate during progressive exercise and the temporal response of VO2, carbon dioxide output (VCO2), and minute ventilation (VE) at the onset of exercise) were used. The ability to perform external mechanical work was corrected for VO2 at unloaded pedaling (change in maximum oxygen uptake (delta VO2max) and in anaerobic threshold (delta AT). On average, obese children's responses were in the normal range: delta VO2max, 104 +/- 41% (+/- SD) predicted (by age); delta AT, 85 +/- 51%; ratio of change in VE to change in VCO2, 111 +/- 21% and ratio of change in VO2 to change in work rate, 100 +/- 24%, but six of the obese children had values of delta VO2max or delta AT that were more than 2 SD below normal. In addition, obese children did not have increased delta VO2max or delta AT with age as observed in nonobese children. Although the response time of VO2 was normal (99 +/- 32% of predicted), those for both VCO2 and VE were prolonged. We conclude that the finding of obesity in a child is not a reliable indicator of poor fitness but that testing cardiorespiratory responses to exercise can be used to identify subjects with serious impairment and to individualize therapy.

Adolescent↗
PubMed1990

Influence of increased metabolic rate on [13C]bicarbonate washout kinetics.

The effect of changes in metabolic rate on the dynamics of CO2 exchange among its various compartments in the human body is not well understood. We examined CO2 dynamics in six healthy male subjects using an intravenous bolus of [13C]bicarbonate. Subjects were studied while resting, during light exercise [50% of the lactate threshold (LT), 3-4 times resting O2 uptake (VO2)], and during moderate exercise (95% of the LT, 6 times resting VO2). The sum of three exponential terms well described the washout of 13CO2 in exhaled breath both at rest and during each exercise level despite substantial increases in metabolic rate accompanying the exercise studies. Average recovery of 13C label rose from 67% during rest to 80% during light and moderate exercise (P less than 0.01). The estimate of CO2 elimination (VCO2) calculated from the washout parameters and corrected for recovery was in very good agreement with the VCO2 directly measured simultaneously breath by breath (r = 0.993, SE for VCO2 = 0.079 l/min). By use of a three-compartment mammillary model, the quantity of CO2 in the central pool (Q1) doubled from rest to light exercise (233 +/- 60 to 479 +/- 76 mmol, P less than 0.01) but did not change further with moderate exercise (458 +/- 74 mmol). Rate constants for exchange between pools and for irreversible loss from the system tended to increase with metabolic rate, but there was large variation in the responses. We conclude that the compartmental dynamics of CO2 transport and storage are very sensitive to changes in metabolic rate induced by exercise.

Adult↗
PubMed1990

Oral [13C]bicarbonate measurement of CO2 stores and dynamics in children and adults.

During exercise, less additional CO2 is stored per kilogram body weight in children than in adults, suggesting that children have a smaller capacity to store metabolically produced CO2. To examine this, tracer doses of [13C]bicarbonate were administered orally to 10 children (8-12 yr) and 12 adults (25-40 yr) at rest. Washout of 13CO2 in breath was analyzed to estimate recovery of tracer, mean residence time (MRT), and size of CO2 stores. CO2 production (VCO2) was also measured breath by breath using gas exchange techniques. Recovery did not differ significantly between children [73 +/- 13% (SD)] and adults (71 +/- 9%). MRT was shorter in children (42 +/- 7 min) compared with adults (66 +/- 15 min, P less than 0.001). VCO2 per kilogram was higher in the children (5.4 +/- 0.9 ml.min-1.kg-1) compared with adults (3.1 +/- 0.5, P less than 0.0001). Tracer estimate of CO2 production was correlated to VCO2 (r = 0.86, P less than 0.0001) and when corrected for mean recovery accurately predicted the VCO2 to within 3 +/- 14%. There was no difference in the estimate of resting CO2 stores between children (222 +/- 52 ml CO2/kg) and adults (203 +/- 42 ml CO2/kg). We conclude that orally administered [13C]bicarbonate can be used to assess CO2 transport dynamics. The data do not support the hypothesis of lower CO2 stores under resting conditions in children.

Adult↗
PubMed1990

Human wound assessment: status report and implications for clinicians.

Wound care has long been carried out by professional nurses. Yet, as a result of their increasing qualifications and changes in health care practices, the nurse's role in and responsibility for wound care has expanded. Despite this, there is a paucity of valid and reliable methods by which nurses and physicians alike can evaluate healing status. This chapter provides an overview of the instruments designed to evaluate healing in humans, focusing particular attention on those intended to measure healing noninvasively. Implications for clinical practice and suggestions for research also are offered. Additionally, this article is written to raise clinicians' awareness to the need for concentrated efforts in devising clinically usable, valid, and reliable instruments to evaluate human tissue repair.

Humans↗
PubMed1990

Optimizing wound healing. A practice within nursing's domain.

Clinicians could be overwhelmed with all that needs to be done to advance the clinical care of tissue wounds. This is not the time to be discouraged, however. Perhaps there has been no period in the history of health care when the possibility of influencing future trends in wound care was greater. Generally speaking, nurses are increasing their understanding of their place in healing activities and are involved in tending wounds that demand greater direct care. Simultaneously, some manufacturers of wound care products seek the input of clinicians as they attempt to produce sound and usable products. Articles appear that delimit scientifically based approaches to wound care and debunk those based solely on tradition. Levine reminded us that "perhaps no worker can influence the success of the healing process more than the nurse." I encourage the readers of this article to take Levine's statement to heart, to latch onto the current momentum, and to force the next decade in health care to be referred to not as the "era of the wound" but rather as the "era of healing."

Cell Division↗
PubMed1989

Pertussis toxin lesioning of the nucleus caudate-putamen attenuates adenylate cyclase inhibition and alters neuronal electrophysiological activity.

Receptor-mediated inhibition of brain adenylate cyclase activity has been well characterized at the biochemical level. However, less understood is how these, typically modest, inhibitory effects on cyclase activity correlate with the electrophysiological activity of brain preparations. In addressing this question, we injected pertussis toxin (PT) into the nucleus caudate-putamen of intact rats, and observed a subsequent attenuated inhibition of adenylate cyclase activity in caudate membranes, which correlated with altered electrophysiological activity in this nucleus. PT completely abolished and electrophysiological activity in this nucleus. PT completely abolished and significantly reduced, respectively, dopamine D2 and opioid receptor-mediated inhibition of adenylate cyclase. In addition, pretreatment of rat caudate nuclei with PT attenuated the amount of in vitro ADP-ribosylation of 41,000 and 39,000 Da PT substrates measured in caudate membranes. Extracellular recording of the spontaneous activity of caudate neurons revealed that PT pretreatment significantly increased firing rates above those of cells recorded from sham-operated and unoperated controls. Furthermore, a significantly greater number of cells pretreated with PT displayed interspike intervals less than 50 ms, reflecting 'burst-like' activity. In short, the inactivation of G-proteins serving as PT substrates in rat caudate-putamen renders caudate cells more likely to fire spontaneously, and to fire in bursting, rather than uniform, patterns of activity. These observations suggest that PT substrates identical or similar to those which regulate adenylate cyclase, play a significant role in governing the electrophysiological behavior of intact caudate neurons.

Action Potentials↗
PubMed1989

Solubilization of stable adenosine A1 receptors from rat brain.

Despite numerous reports of solubilization of adenosine A1 receptors, little progress has been made in isolating or purifying the receptor, owing to the extreme lability of the preparations. The present solubilization strategies recognized the possible role of endogenous adenosine to produce adenosine-receptor-N-protein complexes, which are intrinsically unstable, and instead attempted to use caffeine to solubilize free adenosine receptors, which might be more stable. Endogenous adenosine was removed from membranes by using adenosine deaminase along with GTP to accelerate the release of receptor-bound adenosine. The receptors were then occupied with caffeine and solubilized with 3-[(3-cholamidopropyl)-dimethylammonio]-1-propanesulphonate (CHAPS) in the presence of glycerol. These soluble preparations exhibited the characteristics of free adenosine receptors. They bound the A1-selective antagonist 8-cyclopentyl-1,3-dipropylxanthine (CPDPX) with high affinity to a single class of binding sites, which were insensitive to GTP. The binding activity was extremely stable, with a half-life of about 5 days at 4 degrees C; there was little change in either receptor number or affinity during 3 days at 4 degrees C. This methodology should greatly facilitate the characterization, isolation and purification of the adenosine A1 receptor.

Animals↗
PubMed1989

Adenosine A1 receptors inhibit both adenylate cyclase activity and TRH-activated Ca2+ channels by a pertussis toxin-sensitive mechanism in GH3 cells.

The present study has examined the effects of adenosine A1 receptors on second messenger processes in GH3 cells. A1 receptors are present which are shown to inhibit adenylate cyclase in a GTP-requiring manner. Hormone (VIP) stimulation is also absolutely required for the observation of inhibition. Adenosine A1 receptor analogues also inhibit TRH-stimulated [Ca2+]i-mobilization in GH3 cells. Both effects of the adenosine receptor agonists are apparently mediated by pertussis toxin substrates, of which there are two--41,000 and 40,000 daltons respectively--in these cells. Somatostatin exerts analogous effects to the adenosine agonists in GH3 cells. Thus it may turn out that a general property of 'cyclase inhibitory receptors' is also to inhibit [Ca2+]i-mobilization in the same cells, when such mechanisms are present.

Adenylate Cyclase Toxin↗
PubMed1989

Blood glucose turnover during high- and low-intensity exercise.

We hypothesized that whole body glucose uptake (Rd) during exercise is not related in a simple, linear manner to O2 uptake (VO2). To test this, seven healthy male subjects (age range 23-34 yr) were studied in the postabsorptive but not glycogen-depleted state. Three conditions were examined: 1) rest, 2) 40 min of constant exercise in which the work rates were carefully chosen to consist of low-intensity exercise (no elevated blood lactate, a mean of 40% maximal VO2), and 3) 40 min of high-intensity exercise (markedly elevated blood lactate, 79% maximal VO2). Gas exchange was measured breath by breath, and glucose uptake and production were measured using [6,6-2H2]glucose. Low-intensity exercise (n = 7) resulted in a small but not statistically significant increase in mean Rd [3.06 +/- 0.37 (SE) mg.min-1.kg-1] compared with resting values (2.87 +/- 0.39 mg.min-1.kg-1) despite a fourfold increase in the production of CO2 and VO2. By contrast, the high-intensity exercise Rd (n = 5, 6.98 +/- 0.67 mg.min-1.kg-1) was significantly greater than the resting value (3.03 +/- 0.56 mg.min-1.kg-1). Results of glucose production were virtually the same. Similarly, mean levels of epinephrine and norepinephrine increased significantly above resting values during high- but not low-intensity exercise. Our data demonstrate that whole body glucose dynamics and regulation during 40 min of exercise do not change in a simple linear manner with respect to metabolic rate.

Adult↗
PubMed1989

Changes in breath 13CO2/12CO2 consequent to exercise and hypoxia.

Because the natural enrichment of carbohydrate with 13C is greater than that of lipid, we hypothesized that the natural enrichment of exhaled CO2 with 13C (EN) could be used to gauge endogenous substrate utilization in exercising human subjects. To test this, EN and the respiratory exchange ratio (R) which equals the respiratory quotient (RQ) in the steady state, were measured simultaneously in seven subjects. Rest and exercise protocols, performed under conditions of room air (sea level) and hypoxic (inspired O2 fraction = 0.15) breathing, were chosen to cause a variety of patterns of oxidative substrate utilization. Work rates were performed both below and above the subject's lactate threshold (LT). Work above the LT was expected to cause the greatest increase in EN reflecting greater utilization of glucose. There was significant intersubject (P less than 0.05) but not intrasubject variability in resting EN. By 40 min of exercise, EN increased significantly (P less than 0.05) over resting values in all exercise protocols during both room air and hypoxia conditions. In the room air studies, we found no difference in EN during the below-LT work, even though there were significant increases in O2 uptake (VO2). In contrast, above-LT work resulted in significantly greater increases in EN by 20 and 40 min of exercise (P less than 0.05). Contrary to our expectations, we observed no separate effect by hypoxia on the EN during exercise. Both EN and R tended to increase from rest to exercise, but during exercise there was no overall correlation between R and the EN. EN reflects changes in endogenous substrate utilization over relatively long periods of time such as at rest, but delays in the appearance of 13CO2 at the mouth due to dilution in body CO2 pools, and possibly isotopic fractionation, preclude the usefulness of EN as an indicator of endogenous fuel mix during short-term exercise.

Adult↗
PubMed1989

Effect of hypoxia on ventilatory control during exercise in children and adults.

Little is known about maturation of peripheral chemoreceptor tone (PCT) during growth. We recently demonstrated that the increase in PCT was 49% greater during hypoxic (15% O2) exercise in children compared to adults. As the PCT is a major determinant of ventilatory (VE) response at the onset of exercise (measured by the time constant tau), we hypothesized that hypoxia would affect tau VE (and tau VCO2) to a greater extent in children. Nine healthy children (6-10 y old) and nine healthy adults (18-40 y old) performed multiple transitions from rest to constant work rate on the cycle ergometer. Studies were done breathing 21% O2 and 15% O2. Hypoxic breathing quickened the VE responses in all of the adults and children, but the magnitude of the hypoxic effect did not differ between the two groups (in children, tau VE was 50.9 +/- 9.9 s during 21% O2 breathing and 32.6 +/- 6.9 s during hypoxia; in adults, tau VE was 69.4 +/- 17.6 s, which fell to 50.9 +/- 18.4 s during hypoxia). The hypothesized greater ventilatory response to hypoxia in children compared to adults during exercise was not observed. During 21% O2 breathing, the data demonstrated that children stored relatively less CO2 (by 49%) than did adults in the transition between rest and exercise, possibly explaining the faster ventilatory kinetics. We speculate that there must be additional respiratory control differences between adults and children such that for a given increase in PCT-induced by hypoxia, the VE response at the onset of exercise is less in children than in adults.

Adolescent↗
PubMed1988

Evaluation of methods for the isolation of plasma membranes displaying guanosine 5'-triphosphate-dependence for the regulation of adenylate cyclase activity: potential application to the study of other guanosine 5'-triphosphate-dependent transduction systems.

The GTP-dependence for stimulatory and inhibitory regulation of plasma membrane adenylate cyclase activity was measured in plasma membrane fractions isolated from a variety of cell types (platelets, lymphocytes, PC12 cells, GH3 cells, NBP2 cells, and hepatocytes). This report shows that the isolation of plasma membranes for the study of GTP-dependent adenylate cyclase activity was, for some cells, enhanced by the exposure of the cells to glycerol prior to cell lysis. The isolation of plasma membranes from other cells, which did not appear to be sensitive to glycerol pretreatment, was enhanced by the removal of heavy particulate matter prior to fractionation of the cell lysate. The regulation of enzyme activity by various agents was found to be dependent upon the presence of (exogenous) GTP to varying degrees, indicating variable contamination of membrane preparations with GTP. It is concluded that (i) exposure of platelets and lymphocytes to glycerol prior to cell lysis decreases subsequent contamination of the plasma membrane preparation with GTP, and (ii) although glycerol pretreatment of other cells does not ensure the subsequent isolation of plasma membrane adenylate cyclase activity displaying high requirements for (exogenous) GTP, it is a reasonable first approach to be used during the development of procedures for the isolation of plasma membranes.

Adenylyl Cyclases↗
PubMed1988

Calmodulin plays a dominant role in determining neurotransmitter regulation of neuronal adenylate cyclase.

Ca2+, through the mediation of calmodulin, stimulates the activity of brain adenylate cyclase. The growing awareness that fluctuating Ca2+ concentrations play a major role in intracellular signalling prompted the present study, which aimed to investigate the implications for neurotransmitter (receptor) regulation of enzymatic activity of this calmodulin regulation. The role of Ca2+/calmodulin in regulating neurotransmitter-mediated inhibition and stimulation was assessed in a number of rat brain areas. Ca2+/calmodulin stimulated adenylate cyclase activity in EGTA-washed plasma preparations from each region studied--from 1.3-fold (in striatum) to 3.4-fold (in cerebral cortex). The fold-stimulation produced by Ca2+/calmodulin was decreased in the presence of GTP, forskolin, or Mn2+. In EGTA-washed membranes, receptor-mediated inhibition of adenylate cyclase was strictly dependent upon Ca2+/calmodulin stimulation in all regions, except striatum. A requirement for Mg2+ in combination with Ca2+/calmodulin to observe neurotransmitter-mediated inhibition was also observed. In contrast, receptor-mediated stimulation of activity was much greater in the absence of Ca2+/calmodulin. The findings demonstrate that ambient Ca2+ concentrations, in concert with endogenous calmodulin, may play a central role in dictating whether inhibition or stimulation of adenylate cyclase by neurotransmitters may proceed.

Adenylyl Cyclases↗
PubMed1988

Oxygen uptake as related to work rate increment during cycle ergometer exercise.

We postulated that the commonly observed constant linear relationship between VO2 and work rate during cycle ergometry to exhaustion is fortuitous and not due to an unchanging cost of external work. Therefore we measured VO2 continuously in 10 healthy men during such exercise while varying the rate of work incrementation and analyzed by linear regression techniques the relationship between VO2 and work rate (delta VO2/delta wr). After excluding the first and last portions of each test we found the mean +/- SD of the delta VO2/delta wr in ml.min-1.W-1 to be 11.2 +/- 0.15, 10.2 +/- 0.16, and 8.8 +/- 0.15 for the 15, 30, and 60 W.min-1 tests, respectively, expressed as ml.J-1 the values were 0.187 +/- 0.0025, 0.170 +/- 0.0027 and 0.147 +/- 0.0025. The slopes of the lower halves of the 15 and 30 W.min-1 tests were 9.9 +/- 0.2 ml.min-1.W-1 similar to the values for aerobic work reported by others. However the upper halves of the 15, 30, and 60 W.min-1 tests demonstrated significant differences: 12.4 +/- 0.36 vs 10.5 +/- 0.31 vs 8.7 +/- 0.23 ml.min-1.W-1 respectively. We postulate that these systematic differences are due to two opposing influences: 1) the fraction of energy from anaerobic sources is larger in the brief 60 W.min-1 tests and 2) the increased energy requirement per W of heavy work is evident especially in the long 15 W.min-1 tests.

Adult↗
PubMed1988

Distinct interactions between Ca2+/calmodulin and neurotransmitter stimulation of adenylate cyclase in striatum and hippocampus.

1. Ca2+ and cAMP both act as intracellular second messengers of receptor activation. In neuronal tissue, Ca2+ acting via calmodulin can elevate cAMP levels. This regulation by Ca2+ provides a means whereby the elevation of intracellular [Ca2+] might modulate cAMP generation. 2. In the present studies, the impact of the Ca2+/calmodulin regulation on receptor-mediated stimulation of activity is compared in striatum and hippocampus--regions of differing sensitivity to Ca2+/camodulin. Ca2+/calmodulin stimulated striatal and hippocampal adenylate cyclase activity by 1.4- and 2.7-fold respectively, while dopamine and vasoactive intestinal peptide (VIP) stimulated the enzyme activity of these respective regions by 1.3- and 2-fold. 3. In the presence of Ca2+/calmodulin, the dopamine dose-response curve in the striatum was shifted upward, without alteration of the slope of the curve or of the maximal stimulation of activity elicited by dopamine. In the hippocampus, the ability of VIP to stimulate adenylate cyclase activity was reduced by the presence of calmodulin. 4. The dose dependence of these actions of calmodulin was examined. In the striatum, the stimulation of adenylate cyclase activity by 0.1 to 0.3 microM calmodulin obscured dopamine stimulation, while 1 to 10 microM was additive with the dopamine stimulation. In the hippocampus, all concentrations of calmodulin (0.1 to 10 microM) reduced VIP-mediated stimulation of enzyme activity. 5. These data suggest that the ratio of calmodulin-sensitive to calmodulin-insensitive adenylate cyclase activity varies in different rat brain regions and that, in those regions in which this ratio is low (e.g., rat striatum and most peripheral systems), calmodulin- and receptor-mediated activation of adenylate cyclase activity will be additive, while in those systems in which this ratio is high (e.g., most of the central nervous system), calmodulin will reduce receptor-mediated stimulation of enzyme activity.

Adenylyl Cyclases↗