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Biomedical subjects

D M Cooper

Publications and source records attributed to D M Cooper.

At least 91 records · Page 5Linked to original sources
PubMed1996

Effect of exercise training on energy expenditure, muscle volume, and maximal oxygen uptake in female adolescents.

OBJECTIVES: American female adolescents are at high risk of a physically inactive lifestyle that likely leads to health problems later in life. We hypothesized that a brief program of endurance exercise training in female adolescents would result in increased energy expenditure and quantifiable structural and functional adaptations. STUDY DESIGN: Forty-four high school girls (aged 15 to 17 years, none were elite athletes) enrolled in a 5-day per week anatomy class for 5 weeks and were randomly assigned to control (n = 22) and training groups. All subjects participated in a 2-hour daily teaching program. During the remaining time (2 hours), the training group members underwent endurance-type training and control group subjects participated in a computer workshop. The intervention was assessed by (1) comparison of total energy expenditure between groups with the doubly labeled water technique, (2) determination of changes in thigh muscle volume by magnetic resonance imaging, and (3) determination of changes in maximal oxygen uptake by use of respiratory gas exchange responses. RESULTS: Total energy expenditure was significantly greater (15.3%) in the training group compared with the control subjects (p < 0.003). Five weeks of training led to a 4.3% +/- 1% increase in thigh muscle volume (p < 0.0002) and a 12.1% +/- 3.7% increase in maximal oxygen uptake (p < 0.004); there were no changes in the control group. The training effect was most pronounced in the least fit subjects. CONCLUSIONS: Exercise training programs for female adolescents can be successfully integrated into a high school summer curriculum. Quantifiable, substantial structural and functional responses occur with relatively short periods of training. Approximately 60% of the training response was related to factors independent of muscle size per se. These data may serve to better design physical activity programs for female adolescents.

Adolescent↗
PubMed1996

Genotype of the cystic fibrosis population of the Hunter Region of New South Wales.

OBJECTIVE: To determine the genotype of patients attending the cystic fibrosis clinic at John Hunter Hospital, Newcastle, Australia. METHODOLOGY: Seventy-five of the 76 patients attending the clinic over a 6 month period had blood collected for genetic analysis of 17 of the cystic fibrosis (CF) gene mutations. RESULTS: Sixty-one per cent of the patients were homozygous for the delta F508 mutation and all except one child had at least one delta F508 mutation. DISCUSSION: Nearly 80% of the CF genes were the delta F508 mutation. This prevalence suggests that the obligatory false negative rate of a newborn screening programme for CF based on a combination of immunoreactive trypsin and the delta F508 gene may be as low as 4-5%.

Adolescent↗
PubMed1996

Acute effect of brief low- and high-intensity exercise on circulating insulin-like growth factor (IGF) I, II, and IGF-binding protein-3 and its proteolysis in young healthy men.

We measured circulating levels of the GH insulin-like growth factor (IGF) system in response to brief exercise of different intensities. Ten males (mean age 28 +/- 5 yr) were studied on three separate occasions: once under resting conditions (control) and once each performing 10 min of low- or high-intensity exercise. Blood samples were assayed by RIA for GH, IGF-I and -II, IGF-binding protein-3 (IGFBP-3), and IGFBP-3 proteolytic activity. After 10 min of low-intensity exercise, IGF-I and IGFBP-3 had increased over preexercise baseline by 7.7 +/- 2.7% (P < 0.05) and 12.5 +/- 3.3% (P < 0.004), respectively. After 10 min of high-intensity exercise, all measured components of the IGF system were increased: IGF-I by 13.3 +/- 3.2% (P < 0.002), IGF-II by 15.7 +/- 3.1 (P < 0.01), and IGFBP-3 by 23 +/- 6% (P < 0.001). IGFBP-3 proteolytic activity also was increased (44 +/- 14% above baseline, P < 0.05). GH reached its peak 10 min after the cessation of high-intensity exercise, unlike the earlier peaks of IGF-I and II. In summary: 1) brief exercise leads to small but significant increases in circulating IGF-I, IGF-II, IGFBP-3, and IGFBP-3 proteolysis; and 2) these responses may be influenced by exercise intensity. The IGF responses seem to be unrelated to GH. Acute exercise-induced proteolysis of IGFBP-3 may contribute to anabolic effects of physical activity by increasing the bioavailability of IGF-I.

Adult↗
PubMed1996

Physical fitness, endurance training, and the growth hormone-insulin-like growth factor I system in adolescent females.

We examined the relationship between physical fitness and circulating components of the GH-insulin-like growth factor I (IGF-I) system [i.e. GH, GH-binding protein (GHBP), IGF-I, and IGF-binding proteins 1-5 (IGFBP-1 through-5)] in adolescent females (age range, 15-17 yr). The study consisted of 1) a cross-sectional protocol (n = 23) in which GH-IGF-I components were correlated with fitness, as estimated by thigh muscle volume and maximal O2 uptake; and 2) a prospective study in which fitness, GH-IGF-I system components, and osteocalcin were examined before and after a 5-week period of endurance-type training (control, n = 6; trained, n = 10). The cross-sectional analysis revealed significant (P < 0.05) positive correlations between fitness and 1) mean 12-h overnight GH levels, 2) GHBP, and 3) IGF-I. Muscle volume was negatively correlated with both IGFBP-2 and -4. The prospective training study was associated with 1) increases in circulating osteocalcin (39 +/- 14%; P < 0.007), and 2) decreases in IGF-I (-14 +/- 5%; P < 0.05) and IGFBP-5 (-10 +/- 4%; P < 0.04). Unexpectedly, IGFBP-3 fell in both control (-8 +/- 2%; P < 0.01) and trained subjects (-5 +/- 3%; P < 0.05), and GHBP was reduced only among control subjects (-10 +/- 7%; P < 0.04). In summary, fitter adolescent girls tended to have increased mean serum GH, GHBP, and IGF-I. In contrast, brief endurance training led to increases in muscle mass and serum osteocalcin that were not accompanied by increases in GH or IGF-I. In fact, training may, in the short term, have led to a catabolic state hormonally expressed by reductions in IGF-I and IGFBP-5.

Adolescent↗
PubMed1995

Immunohistochemical localization of adenylyl cyclase in rat brain indicates a highly selective concentration at synapses.

Only three isoforms of adenylyl cyclase (EC 4.6.1.1) mRNAs (AC1, -2, and -5) are expressed at high levels in rat brain. AC1 occurs predominantly in hippocampus and cerebellum, AC5 is restricted to the basal ganglia, whereas AC2 is more widely expressed, but at much lower levels. The distribution and abundance of adenylyl cyclase protein were examined by immunohistochemistry with an antiserum that recognizes a peptide sequence shared by all known mammalian adenylyl cyclase isoforms. The immunoreactivity in striatum and hippocampus could be readily interpreted within the context of previous in situ hybridization studies. However, extending the information that could be gathered by comparisons with in situ hybridization analysis, it was apparent that staining was confined to the neuropil--corresponding to immunoreactive dendrites and axon terminals. Electron microscopy indicated a remarkably selective subcellular distribution of adenylyl cyclase protein. In the CA1 area of the hippocampus, the densest immunoreactivity was seen in postsynaptic densities in dendritic spine heads. Labeled presynaptic axon terminals were also observed, indicating the participation of adenylyl cyclase in the regulation of neurotransmitter release. The selective concentration of adenylyl cyclases at synaptic sites provides morphological data for understanding the pre- and postsynaptic roles of adenylyl cyclase in discrete neuronal circuits in rat brain. The apparent clustering of adenylyl cyclases, coupled with other data that suggest higher-order associations of regulatory elements including G proteins, N-methyl-D-aspartate receptors, and cAMP-dependent protein kinases, suggests not only that the primary structural information has been encoded to render the cAMP system responsive to the Ca(2+)-signaling system but also that higher-order strictures are in place to ensure that Ca2+ signals are economically delivered and propagated.

Adenylyl Cyclases↗
PubMed1995

The characterization of a novel human adenylyl cyclase which is present in brain and other tissues.

We characterized a human cDNA clone which encodes a novel adenylyl cyclase. Data from Southern and Northern blot analysis, and analysis of sequence similarity with a recently cloned mouse adenylyl cyclase (10), indicated that the human adenylyl cyclase was a species variant of type VII adenylyl cyclase. The sequence of the novel human adenylyl cyclase indicated it was a member of the type II adenylyl cyclase family, and we compared the regulatory characteristics of the novel human enzyme with those of type II adenylyl cyclase. The human type VII and rat type II adenylyl cyclases, expressed in human embryonic kidney 293 cells, were activated by prostaglandin E1 (PGE1), but only type VII was activated by isoproterenol. The stimulation of type VII adenylyl cyclase by PGE1 and isoproterenol was attenuated by pretreatment of the cells with staurosporine. Phorbol 12,13-dibutyrate synergistically enhanced the stimulation of both type VII and type II enzyme activity by PGE1 and by the constitutively active Gs mutant Gs (Q227L). The human type VII adenylyl cyclase activity was unresponsive to capacitatively induced changes in intracellular Ca2+. The functional characteristics of human type VII adenylyl cyclase resemble those of the rat type II enzyme, but the enzymes may respond differently to in vivo phosphorylation conditions. While the mRNA for adenylyl cyclase type II was found in several brain areas, the message for type VII adenylyl cyclase was localized primarily to the cerebellar granule cell layer.

Adenylyl Cyclases↗
PubMed1995

Adenylyl cyclases and the interaction between calcium and cAMP signalling.

Adenylyl cyclase is the prototypical second messenger generator. Nearly all of the eight cloned adenylyl cyclases are regulated by one or other arm of the phospholipase C pathway. Functional and ultrastructural investigations have shown that adenylyl cyclases are intimately associated with sites of calcium ion entry into the cell. Oscillations in cellular cyclic AMP levels are predicted to arise because of feedback inhibition of adenylyl cyclase by Ca2+. Such findings inextricably intertwine cellular signalling by cAMP and internal Ca2+ and extend the known regulatory modes available to cAMP.

Adenylyl Cyclases↗
PubMed1995

Ca(2+)-inhibitable adenylyl cyclase modulates pulmonary artery endothelial cell cAMP content and barrier function.

Maintenance by the endothelium of a semi-permeable barrier is critically important in the exchange of oxygen and carbon dioxide in the lung. Intracellular free Ca2+ ([Ca2+]i) and cAMP are principal determinants of endothelial cell barrier function through their mutually opposing actions on endothelial retraction. However, details of the mechanisms of this antagonism are lacking. The recent discovery that certain adenylyl cyclases (EC 4.6.1.1) could be acutely inhibited by Ca2+ in the intracellular concentration range provided one possible mechanism whereby elevated [Ca2+]i could decrease cAMP content. This possibility was explored in pulmonary artery endothelial cells. The results indicate that a type VI Ca(2+)-inhibitable adenylyl cyclase exists in pulmonary artery endothelial cells and is modulated by physiological changes in [Ca2+]i. Furthermore, the results suggest the inverse relationship between [Ca2+]i and cAMP that is established by Ca(2+)-inhibitable adenylyl cyclase plays a critical role in modulating pulmonary artery endothelial cell permeability. These data provide evidence that susceptibility to inhibition of adenylyl cyclase by Ca2+ can be exploited in modulating a central physiological process.

Adenylyl Cyclases↗
PubMed1995

Capacitative Ca2+ entry exclusively inhibits cAMP synthesis in C6-2B glioma cells. Evidence that physiologically evoked Ca2+ entry regulates Ca(2+)-inhibitable adenylyl cyclase in non-excitable cells.

Elevation of cytosolic free Ca2+ inhibits the type VI adenylyl cyclase that predominates in C6-2B cells. However, it is not known whether there is any selective requirement for Ca2+ entry or release for inhibition of cAMP accumulation to occur. In the present study, the effectiveness of intracellular Ca2+ release evoked by three independent methods (thapsigargin, ionomycin, and UTP) was compared with the capacitative Ca2+ entry that was triggered by these treatments. In each situation, only Ca2+ entry could inhibit cAMP accumulation (La3+ ions blocked the effect); Ca2+ release, which was substantial in some cases, was without effect. A moderate inhibition, as was elicited by a modest degree of Ca2+ entry, could be rendered substantial in the absence of phosphodiesterase inhibitors. Such conditions more closely mimic the physiological situation of normal cells. These results are particularly significant, in demonstrating not only that Ca2+ entry mediates the inhibitory effects of Ca2+ on cAMP accumulation, but also that diffuse elevations in [Ca2+]i are ineffective in modulating cAMP synthesis. This property suggests that, as with certain Ca(2+)-sensitive ion channels, Ca(2+)-sensitive adenylyl cyclases may be functionally colocalized with Ca2+ entry channels.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1995

Adenylate cyclases: critical foci in neuronal signaling.

Current findings show that adenylate cyclases comprise a heterogeneous multigene family, members of which are variously regulated by the alpha and beta gamma subunits of G proteins, by Ca2+ and by protein kinases. In the CNS, individual isoforms of adenylate cyclase are expressed discretely in select regions of the brain. At the subcellular level, adenylate cyclases can be concentrated into dendritic spines, thereby increasing their susceptibility to multiple regulatory influences. Altogether, such findings greatly expand knowledge of the potential role of this archetypical signaling system in the modulation of neuronal function.

Adenylyl Cyclases↗
PubMed1995

Parental asthma knowledge: its association with readmission of children to hospital.

OBJECTIVE: To assess whether poor parental knowledge about asthma was a risk factor for readmission of their children to hospital. METHODOLOGY: Parents of children who were admitted to the paediatric facility at Newcastle Mater and John Hunter Hospitals were administered a previously validated asthma knowledge questionnaire with a maximum possible score of 31. RESULTS: The mean parental knowledge scores for three groups of children were determined: those with a previous diagnosis of asthma being readmitted to hospital (170 children, mean score 18.3); those with a previous diagnosis of asthma being admitted for the first time (114 children, mean score 17.2); and children being admitted with their first attack of asthma (65 children, mean score 15.6). There was a significant difference in parental asthma knowledge between the first and third group (P < 0.001) but not between the first and second group. A linear regression model with knowledge score as an outcome found that increased knowledge was associated with previously diagnosed asthma, higher parental occupation and no smoker in the home. CONCLUSIONS: Knowledge was poor in all groups. Readmission rate was related to the severity of the child's asthma.

Adolescent↗
PubMed1995

The level and tempo of children's physical activities: an observational study.

We develop an observation system that quantifies the duration, intensity, and frequency of children's physical activities. We use this system to assess the level and tempo of energy expenditure under free-ranging, natural conditions experienced by 15 children aged 6-10 yr in southern California. Observations were recorded every 3 s during 4-h time blocks from 8:00 a.m.-8:00 p.m. Agreement among observers using the coding system was 91%. Using indirect calorimetry, calibration studies in the laboratory determined VO2 (ml.min-1.min-1) during each coded activity, and activities were categorized by intensity (low, medium, or high). Subjects were found to engage in activities of low intensity 77.1% of time and activities of high intensity 3.1% of time. The median duration of low and medium intensity activities was 6 s, of high intensity activities only 3 s with 95% lasting less than 15 s. Children engaged in very short bursts of intense physical activity interspersed with varying intervals of low and moderate intensity. These findings may be important for discovering how children's activity patterns under natural conditions influence physiological processes leading to growth and development. This study demonstrates the advantages of using an observational system that captures more than the intensity and frequency of children's activities to include duration and the length of intervals between activities of varying intensity.

Child↗
PubMed1995

Treatment of idiopathic clubfoot. A thirty-year follow-up note.

We evaluated forty-five patients who had seventy-one congenital clubfeet. The average age was thirty-four years (range, twenty-five to forty-two years). Twenty-nine of these patients had been evaluated and reported on in 1980. We performed pedobarographic and electrogoniometric analyses in addition to the clinical and radiographic studies performed previously. With the use of pain and functional limitation as the outcome criteria, thirty-five (78 per cent) of the forty-five patients had an excellent or good outcome compared with eighty-two (85 per cent) of ninety-seven individuals who did not have congenital deformity of the foot. The patient's occupation, passive dorsiflexion as measured with a hand-held goniometer, the antero-posterior calcaneus-fifth metatarsal angle, the total foot pressure time integral, and the number of rapid single-limb toe-ups that could be performed were the only variables that differed significantly between the feet that had an excellent or good result and those that had a poor result (p < 0.05). A comparison of the feet that had an excellent or good outcome with those that had a poor outcome with regard to body-mass index, peak pressure under the heel, and force time integral under the metatarsal heads revealed a p value that was between 0.05 and 0.08 for each variable. The technique of treatment led to good long-term results in our patients who had clubfoot. The data suggest that a sedentary occupation and avoidance of excessive weight gain may improve the over-all long-term result. Excessive weakening of the triceps surae may predispose patients to a poor result; therefore, it is prudent to avoid overlengthening of this muscle. The outcome could not be predicted from the radiographic result.

Adult↗
PubMed1994

Type VIII adenylyl cyclase. A Ca2+/calmodulin-stimulated enzyme expressed in discrete regions of rat brain.

A cDNA that encodes type VIII adenylyl cyclase has been isolated from two rat brain libraries. The open reading frame encodes a 1248-amino acid protein predicted to have two sets of six transmembrane spans and two putative nucleotide binding domains as is characteristic of other mammalian adenylyl cyclases. Two type VIII messages are detected in rat brain with estimated sizes of 5.5 and 4.4 kilobases. In situ hybridization indicates that the type VIII messages are most abundantly expressed in the granule cells of the dentate gyrus, the pyramidal cells of hippocampal fields CA1-CA3, the entorhinal cortex, and the piriform cortex. Hybridization is also detected in the neocortex, the amygdaloid complex, and regions of the thalamus and hypothalamus. Stable expression of the type VIII cDNA in human embryonal kidney cells leads to the appearance of a novel 165-kDa glycoprotein in the membrane fraction. Stimulation of these cells with agents that increase intracellular Ca2+ results in up to 43-fold increases in cAMP accumulation over that of control cells transfected with the expression vector. Addition of isoproterenol alone does not lead to type VIII-specific effects in intact cells. Adenylyl cyclase activity in membranes prepared from type VIII-transformed cells is stimulated up to 40-fold by the addition of Ca2+/calmodulin (EC50 = 53 nM calmodulin). The addition of activated recombinant alpha subunit of Gs synergistically increases the Ca2+/calmodulin-stimulated activity. A possible role for type VIII adenylyl cyclase in long-term potentiation is discussed.

Adenylyl Cyclases↗