Search PubMed⌕ Search

Biomedical subjects

D M Cooper

Publications and source records attributed to D M Cooper.

At least 19 recordsLinked to original sources
PubMed2006

Do circulating leucocytes and lymphocyte subtypes increase in response to brief exercise in children with and without asthma?

BACKGROUND: Exercise can alter health in children in both beneficial (eg reduced long-term risk of atherosclerosis) and adverse (eg exercise-induced asthma) ways. The mechanisms linking exercise and health are not known, but may rest, partly, on the ability of exercise to increase circulating immune cells. Little is known about the effect of brief exercise, more reflective of naturally occurring patterns of physical activity in children, on immune cell responses. OBJECTIVES: To determine whether (1) a 6-min bout of exercise can increase circulating inflammatory cells in healthy children and (2) the effect of brief exercise is greater in children with a history of asthma. METHODS: Children with mild-moderate persistent asthma and age-matched controls (n = 14 in each group, mean age 13.6 years) performed a 6-min bout of cycle-ergometer exercise. Spirometry was performed at baseline and after exercise. Blood was drawn before and after exercise, leucocytes were quantified and key lymphocyte cell surface markers were assessed by flow cytometry. RESULTS: Exercise decreased spirometry only in children with asthma, but increased (p<0.001) most types of leucocytes (eg lymphocytes (controls, mean (SD) 1210 (208) cells/microl; children with asthma, 1119 (147) cells/microl) and eosinophils (controls, 104 (22) cells/microl; children with asthma, 88 (20) cells/microl)) to the same degree in both groups. Similarly, exercise increased T helper cells (controls, 248 (60) cells/microl; children with asthma, 232 (53) cells/microl) and most other lymphocyte subtypes tested. By contrast, although basophils (16 (5) cells/microl) and CD4+ CD45RO+ RA+ lymphocytes (19 (4) cells/microl) increased in controls, no increase in these cell types was found in children with asthma. CONCLUSIONS: Exercise increased many circulating inflammatory cells in both children with asthma and controls. Circulating inflammatory cells did increase in children with asthma, but not to a greater degree than in controls. In fact, basophils and T helper lymphocyte memory transition cells did not increase in children with asthma, whereas they did increase in controls. Even brief exercise in children and adolescents robustly mobilizes circulating immune cells.

Adolescent↗
PubMed2006

Body fat and circulating leukocytes in children.

OBJECTIVE: To determine the effects of obesity on baseline levels of circulating granulocytes, monocytes, and lymphocyte subtypes in otherwise healthy children. DESIGN: Two group comparison of leukocytes in normal weight control and overweight children. SUBJECTS: In total, 38 boys and girls, ages 6-18 years, divided in two groups: normal weight, (NW, BMI<85th %tile, n=15) and overweight (OW, body mass index (BMI)>85th %tile, n=23). MEASUREMENTS: BMI obtained from direct measures of height and body mass. Body fat was assessed by DEXA. Complete blood counts (CBC) were obtained by standard clinical hematology methods and surface antigen staining by flow cytometry. RESULTS: The OW group compared to the NW group had increased total leukocytes counts (P=0.011), neutrophils (P=0.006), monocytes (P=0.008), total T (CD3) lymphocytes (P=0.022), and Helper T (CD4(+)) cells (P=0.003). Significant correlations were evident between leukocytes, and BMI percentile, BMI, or percent body fat. Neither lean body mass nor VO(2peak) per unit lean body mass were significantly related to any of the leukocytes. Percent body fat and BMI percentile were positively correlated (P<0.05) to total T cells (CD3) and/or helper T cells (CD4(+)). CONCLUSION: A group of 23 overweight children displayed elevated counts in most types of circulating immune cells, suggesting the presence of low-grade systemic inflammation, a known pathogenetic mechanism underlying most long-term complications of obesity. Our data provide an additional rationale for the importance of avoiding or correcting pediatric obesity.

Adipose Tissue↗
PubMed2006

Presence of diabetes risk factors in a large U.S. eighth-grade cohort.

OBJECTIVE: The study was conducted in 12 middle schools to determine the prevalence of diabetes, pre-diabetes, and diabetes risk factors in eighth-grade students who were predominantly minority and evaluate the feasibility of collecting physical and laboratory data in schools. RESEARCH DESIGN AND METHODS: Anthropometric measurements and fasting and 2-h post-glucose load blood draws were obtained from approximately 1,740 eighth-grade students. RESULTS: Mean recruitment rate was 50% per school, 49% had BMI > or = 85th percentile, 40.5% had fasting glucose > or = 100 mg/dl, 0.4% had fasting glucose > or = 126 mg/dl, and 2.0% had 2-h glucose > or = 140 mg/dl and 0.1% > or = 200 mg/dl. Mean fasting insulin value was 30.1 microU/ml, 36.2% had fasting insulin > or = 30 microU/ml, and 2-h mean insulin was 102.1 microU/ml. Fasting and 2-h glucose and insulin values increased across BMI percentiles, and fasting glucose was highest in Hispanic and Native American students. CONCLUSIONS: There was a high prevalence of risk factors for diabetes, including impaired fasting glucose (> or =100 mg/dl), hyperinsulinism suggestive of insulin resistance (fasting insulin > or = 30 microU/ml), and BMI > or = 85th percentile. These data suggest that middle schools are appropriate targets for population-based efforts to decrease overweight and diabetes risk.

Adolescent↗
PubMed2005

Breath sulfides and pulmonary function in cystic fibrosis.

We have determined the concentrations of carbonyl sulfide (OCS), dimethylsulfide, and carbon disulfide (CS(2)) in the breath of a group of cystic fibrosis (CF) patients and one of healthy controls. At the detection sensitivity in these experiments, room air always contained measurable quantities of these three gases. For each subject the inhaled room concentrations were subtracted from the time-coincident concentrations in exhaled breath air. The most significant differences between the CF and control cohorts in these breath-minus-room values were found for OCS. The control group demonstrated a net uptake of 250 +/- 20 parts-per-trillion-by-volume (pptv), whereas the CF cohort had a net uptake of 110 +/- 60 pptv (P = 0.00003). Three CF patients exhaled more OCS than they inhaled from the room. The OCS concentrations in the CF cohort were strongly correlated with pulmonary function. The dimethylsulfide concentrations in breath were greatly enhanced over ambient, but no significant difference was observed between the CF and healthy control groups. The net (breath minus room) CS(2) concentrations for individuals ranged between +180 and -100 pptv. They were slightly greater in the CF cohort (+26 +/- 38 pptv) vs. the control group (-17 +/- 15 pptv; P = 0.04). Lung disease in CF is accompanied by the subsistence of chronic bacterial infections. Sulfides are known to be produced by bacteria in various systems and were therefore the special target for this investigation. Our results suggest that breath sulfide content deserves attention as a noninvasive marker of respiratory colonization.

Adolescent↗
PubMed2005

Trends in surface water chemistry of acidified UK freshwaters, 1988-2002.

Analysis of water chemistry data from 15 years of monitoring at 22 acid-sensitive lakes and streams in the UK reveals coherent national chemical trends indicative of recovery from acidification. Excess sulphate and base cations exhibit significant decline, often accompanied by an increase in an alkalinity-based determination of acid neutralising capacity (AB-ANC) and, at fewer sites, a decline in hydrogen and labile aluminium. Acid neutralising capacity determined by "charge-balance" (CB-ANC) exhibits few trends, possibly due to compound errors associated with its determination. Trend slopes in excess sulphate correlate with those for base cations, hydrogen ion and AB-ANC, with between-site variability linked to catchment hydrology, sea-salt inputs and forestry. Nitrate concentrations have not changed significantly but show high sensitivity to varying climate. Trends in AB-ANC are influenced by significant increases in dissolved organic carbon, the cause of which it is vital to establish before trends in the former can definitively be attributed to decreasing acidic deposition.

Aluminum↗
PubMed2005

Evidence of sulphur and nitrogen deposition signals at the United Kingdom Acid Waters Monitoring Network sites.

Some recent studies of trends in sulphate in surface waters have alluded to possible lag effects imposed by catchment soils, resulting in discrepancies between trends in deposition and run-off. To assess the extent of these possible effects in the UK, sulphate concentration data from the United Kingdom Acid Waters Monitoring Network (AWMN) sites are compared with estimates of sulphur deposition at each site. From these data, input-output budgets are computed at an annual time scale. The estimated budgets suggest a close association between catchment sulphur inputs and outputs at an annual scale, with well-balanced annual budgets at most sites, indicative of only minor lag effects. A similar analysis of the AWMN site nitrogen budget shows little evidence of an association between nitrogen inputs and outputs at this time scale.

Acid Rain↗
PubMed2005

Long-term increases in surface water dissolved organic carbon: observations, possible causes and environmental impacts.

Dissolved organic carbon (DOC) concentrations in 22 UK upland waters have increased by an average of 91% during the last 15 years. Increases have also occurred elsewhere in the UK, northern Europe and North America. A range of potential drivers of these trends are considered, including temperature, rainfall, acid deposition, land-use, nitrogen and CO2 enrichment. From examination of recent environmental changes, spatial patterns in observed trends, and analysis of time series, it is suggested that DOC may be increasing in response to a combination of declining acid deposition and rising temperatures; however it is difficult to isolate mechanisms based on monitoring data alone. Long-term DOC increases may have wide-ranging impacts on freshwater biota, drinking water quality, coastal marine ecosystems and upland carbon balances. Full understanding of the significance of these increases requires further knowledge of the extent of natural long-term variability, and of the natural "reference" state of these systems.

Agriculture↗
PubMed2004

IL-6-induced skeletal muscle atrophy.

Chronic, low-level elevation of circulating interleukin (IL)-6 is observed in disease states as well as in many outwardly healthy elderly individuals. Increased plasma IL-6 is also observed after intense, prolonged exercise. In the context of skeletal muscle, IL-6 has variously been reported to regulate carbohydrate and lipid metabolism, increase satellite cell proliferation, or cause muscle wasting. In the present study, we used a rodent local infusion model to deliver modest levels of IL-6, comparable to that present after exercise or with chronic low-level inflammation in the elderly, directly into a single target muscle in vivo. The aim of this study was to examine the direct effects of IL-6 on skeletal muscle in the absence of systemic changes in this cytokine. Data included cellular and molecular markers of cytokine and growth factor signaling (phosphorylation and mRNA content) as well as measurements to detect muscle atrophy. IL-6 infusion resulted in muscle atrophy characterized by a preferential loss of myofibrillar protein (-17%). IL-6 induced a decrease in the phosphorylation of ribosomal S6 kinase (-60%) and STAT5 (-33%), whereas that of STAT3 was increased approximately twofold. The changes seen in the IL-6-infused muscles suggest alterations in the balance of growth factor-related signaling in favor of a more catabolic profile. This suggests that downregulation of growth factor-mediated intracellular signaling may be a mechanism contributing to the development of muscle atrophy induced by elevated IL-6.

Animals↗
PubMed2004

Motion artefact reduction of the photoplethysmographic signal in pulse transit time measurement.

Motion artefact is a common occurrence that contaminates photoplethysmographic (PPG) measurements. To extract timing information from signals during artefact is challenging. PPG signal is very sensitive to artefacts and can be used in applications like, pulse transit time (PTT) as part of the polysomnographic studies. A correlation cancellation or signal processing approach is implemented with the adaptive cancelling filter concept and a triaxial accelerometry. PPG signals obtained from a Masimo (Reference) pulse oximeter is used as reference to compare with the reconstructed PPG signals. Different hands are used for each PPG source, one stationary while the other involves typical movements during sleep. A second Masimo pulse oximeter is used to register intensity of timing errors on commercial PPG signals. 108 PTT measurements are recorded in three different movements with PTT estimates from unprocessed PPG signals showing 35.51+/-27.42%, Masimo 50.02+/-29.40% and reconstructed 4.32+/-3.59% difference against those from the Reference PPG. The triaxial accelerometry can be used to detect the presence of artefact on PPG signals. This is useful in PTT measurements when signal contaminated with artefacts are required for further analysis, especially after and during arousals in sleep. The suggested filtering model can then reconstruct these corrupted PPG signals.

Acceleration↗
PubMed2004

Effect of intense wrestling exercise on leucocytes and adhesion molecules in adolescent boys.

BACKGROUND: In adults, exercise is a powerful and natural stimulator of immune cells and adhesion molecules. Far less is known about exercise responses during childhood and adolescence and whether or not exercise in "real life" activities of healthy adolescents influences immune responses. OBJECTIVE: To determine if strenuous exercise leads to significant changes in leucocyte number and adhesion molecule expression in adolescent boys. METHODS: Eleven healthy, high school boys, aged 14-18.5 years, performed a single, typical, 1.5 hour wrestling practice session. Blood was sampled before and after the session. Flow cytometry was used to evaluate changes in immune responses. RESULTS: The exercise led to significant (p<0.05) and robust increases in granulocytes, monocytes, and all lymphocyte subpopulations. The most significant changes were observed for natural killer cells (p<0.0005). The number of T cytotoxic and T helper cells expressing CD62L increased significantly (p<0.002 and p<0.0005 respectively), as did the number of T cytotoxic and T helper cells not expressing CD62L (p<0.003 and p<0.009 respectively). The density of CD62L on lymphocytes decreased significantly with exercise (p<0.0005), whereas CD11a (p<0.01) and CD54 (p<0.01) increased. CONCLUSIONS: The data show that an intense wrestling bout in adolescent boys leads to profound stimulation of the immune system. The role of these common changes in overall immune status and the development of the immune and haemopoietic systems has yet to be determined.

Adolescent↗
PubMed2002

Phosphorus in soils and field drainage water in the Thame catchment, UK.

Field drains were sampled at five farms in a catchment in south-central England. The farms were selected to include the main soil types present in the catchment, stagnogleys and pelosols. The phosphorus content of field drainage water was measured on several occasions from 1999 to 2000, under varying flow conditions. The components measured were soluble reactive phosphorus (SRP), total dissolved phosphorus (TDP) and total phosphorus (TP). SRP concentrations in drainage water were lower than in streams in the catchment which had no apparent point source. This indicated that many streams were receiving unidentified point sources of SRP. Measurements of P in field drainage water samples under high flow conditions showed concentrations of particulate phosphorus and SRP up to 1300 and 300 microg l(-1), respectively, these being associated with high suspended sediment concentrations. Comparison of field drain and soil phosphorus contents at the locations sampled did not provide evidence of an inter-relationship. The equilibrium phosphorus content (EPC0) of surface soil was generally higher than the SRP content of drainage water, at one farm by 1 order of magnitude. The variability in measurements suggested a larger-scale and more focussed survey would be required to characterise catchment-scale phosphorus losses from commercial farms by land use and soil type.

Journal Article↗
PubMed2002

The phosphorus budget of the Thame catchment, Oxfordshire: 2. Modelling.

The phosphorus budget of the River Thame was modelled at a daily time scale, using estimates of diffuse and point source contributions of discharge. The model simulated suspended sediment (SS), soluble unreactive phosphorus (SUP), soluble reactive phosphorus (SRP) and particulate phosphorus (PP) concentrations within the main river and major tributaries. Diffuse source estimates of phosphorus loads were based on characteristic losses from identified main landscape classes, with hydrology described by a simple conceptual storage model. In-stream flow was modelled using a kinematic wave equation. Transfer of suspended sediment and phosphorus components was approximated by advection. In-stream sources and sinks included uptake and release of soluble reactive phosphorus by bed sediment, instant equilibration between SRP and the PP concentration on suspended sediment, and flow-related entrainment and deposition of suspended sediment. Simulations at sites within the catchment were compared with measurements made in 1998-1999. Results showed the P budget is dominated by mixing of diffuse and point source water, but some within-river processes have been shown to be capable of significantly influencing SRP concentrations. The development of a sediment entrainment and deposition component of the model has proved particularly valuable in emulating the hysteretic relationship between discharge and suspended sediment concentration in the river. It also provides a measure of available bed sediment.

England↗
PubMed2002

The phosphorus budget of the Thame catchment, Oxfordshire, UK: 1. Mass balance.

The relative magnitudes of annual diffuse and point source loads of phosphorus (P) to the River Thame were estimated from daily and monthly measurements of discharge and concentration. Existing data from gauging and monitoring sites on the river network and at point sources were supplemented by survey data at a range of spatial scales. Results showed that during low flow periods most of the P could be attributed to point sources, while at high flows the figure was less than 10%. The introduction of P stripping at Aylesbury, a major sewage treatment works in the catchment, was estimated to have reduced the annual load of P from the sewage treatment works by approximately 45 t, with a similar reduction in loss from the catchment. This gave a reduction in low flow concentrations of soluble reactive phosphorus (SRP) from 2.5 to 1.7 mg l(-1). Concentrations of SRP in river water remain above eutrophication thresholds because of the influence of other STWs in the catchment and insufficient natural discharge to dilute this.

Environmental Monitoring↗
PubMed2001

A uniform extracellular stimulus triggers distinct cAMP signals in different compartments of a simple cell.

cAMP, the classical second messenger, regulates many diverse cellular functions. The primary effector of cAMP signals, protein kinase A, differentially phosphorylates hundreds of cellular targets. Little is known, however, about the spatial and temporal nature of cAMP signals and their information content. Thus, it is largely unclear how cAMP, in response to different stimuli, orchestrates such a wide variety of cellular responses. Previously, we presented evidence that cAMP is produced in subcellular compartments near the plasma membrane, and that diffusion of cAMP from these compartments to the bulk cytosol is hindered. Here we report that a uniform extracellular stimulus initiates distinct cAMP signals within different cellular compartments. By using cyclic nucleotide-gated ion channels engineered as cAMP biosensors, we found that prostaglandin E(1) stimulation of human embryonic kidney cells caused a transient increase in cAMP concentration near the membrane. Interestingly, in the same time frame, the total cellular cAMP rose to a steady level. The decline in cAMP levels near the membrane was prevented by pretreatment with phosphodiesterase inhibitors. These data demonstrate that spatially and temporally distinct cAMP signals can coexist within simple cells.

1-Methyl-3-isobutylxanthine↗
PubMed2001

Fitness, acute exercise, and anabolic and catabolic mediators in cystic fibrosis.

Exercise can stimulate catabolic inflammatory cytokines even in healthy children. For patients with cystic fibrosis (CF), this may be problematic because CF is characterized by increased inflammation and suppressed growth. We examined fitness and the response to brief exercise of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), insulinlike growth factor-I (IGF-I), and IGF binding protein-1 (IGFBP-1) in 14 subjects with CF (10.5 +/- 0.8 yr of age), 9 of whom were treated with ibuprofen, and 14 healthy control subjects (11.6 +/- 0.5 yr of age, NS). Subjects performed brief intermittent, constant work rate protocol (scaled to each individual's exercise capacity) with blood and urine sampling. Peak V O(2) was correlated with IGF-I (r = 0.68, p < 0.01) in control subjects but not in subjects with CF. In subjects with CF, baseline IL-6 was 79% greater (p < 0.05) and IGF-I was 47% lower than in control subjects (p < 0.05). Post hoc analysis revealed a progressive increase in the IL-6 response to exercise, with the lowest increase observed in control subjects (11.8 +/- 4.6 pg/L/kJ), higher increases in patients with CF treated with ibuprofen (23.4 +/- 7.7 pg/L/kJ), and highest in subjects with CF not receiving ibuprofen (29.2 +/- 7.5 pg/L/kJ). Qualitatively similar results were observed for TNF-alpha. Exercise also significantly increased IGFBP-1 in both control subjects and subjects with CF. Brief exercise can increase even chronically elevated inflammatory mediators in CF, and this response may be attenuated by ibuprofen.

Adolescent↗
PubMed2001

Adenovirus encoded cyclic nucleotide-gated channels: a new methodology for monitoring cAMP in living cells.

The current, static methodologies for measuring cyclic AMP (cAMP) may underestimate its regulatory properties. Here, we have exploited the Ca2+-conducting properties of cyclic nucleotide-gated (CNG) channels to measure cAMP in live cells, in response to various stimuli. We placed a mutated CNG channel with high sensitivity to cAMP in adenovirus to maximize and render facile its expression in numerous cell types. The ready, continuous nature of the readout contrasted with the traditional approach, which yielded similar static information, but lacked any continuous or interactive qualities. It seems fair to predict that this readily adopted approach will broaden the perception of cAMP signaling.

Adenoviridae↗
PubMed2001

Persistent interactions between the two transmembrane clusters dictate the targeting and functional assembly of adenylyl cyclase.

Adenylyl cyclases possess complex structures like those of the ATP binding cassette (ABC) transporter family, which includes the cystic fibrosis transmembrane regulator, the P-glycoprotein, and ATP-sensitive K(+) channels [1-4]. These structures comprise a cytosolic N terminus followed by two tandem six-transmembrane cassettes, each associated with a highly homologous (ATP binding) cytosolic loop [5-8]. The catalytic domains, which are located in the two large cytoplasmic loops, are highly conserved and well studied. The crystal structure of these domains has even been described recently [9, 10]. However, nothing is known of the function or organization of the 12 transmembrane segments. In the present study we adopted a range of strategies including live-cell fluorescence resonance energy transfer (FRET) microscopy, coimmunoprecipitation, and functional assays of various truncated and substituted, fluorescently-tagged molecules to analyze the trafficking and activity of this molecule. When expressed as individual peptides, the two transmembrane domains - largely independently of any cytosolic region - formed a tight complex that was delivered to the plasma membrane. This cooperation between the two intact transmembrane domains was essential and sufficient to target the enzyme to the plasma membrane of the cell. The extracellular loop between the ninth and tenth transmembrane segments, which contains an N-glycosylation site, was also necessary. Furthermore, the interaction between the two transmembrane clusters played a critical role in bringing together the cytosolic catalytic domains to express functional adenylyl cyclase activity in the intact cell.

Adenylyl Cyclases↗