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J M Wakefield

Publications and source records attributed to J M Wakefield.

8 recordsLinked to original sources
PubMed2001

Regulation of glucose transport in aortic smooth muscle cells by cAMP and cGMP.

We have studied the ability of cGMP and cAMP to modulate platelet-derived growth factor (PDGF)-stimulated 2-deoxy-D-glucose (deGlc) transport in primary cultures of vascular smooth muscle cells (VMSC) from rat aorta. PDGF stimulated deGlc transport in a time- and concentration-dependent manner. 8-Bromo-cGMP and atrial natriuretic peptide(1-28) [ANP(1-28)] were found to reduce PDGF-stimulated deGlc transport without affecting basal (unstimulated) transport activity. In contrast, 8-bromo-cAMP and dibutyryl-cAMP stimulated basal deGlc transport 2-fold and were without effect on PDGF-stimulated deGlc transport. 8-Bromo-cGMP also inhibited 8-bromo-cAMP-stimulated deGlc transport. The stimulation of deGlc transport by PDGF was sensitive to the mitogen-activated protein kinase (MAPK)/extracellular-signal-regulated kinase (ERK) kinase (MEK) inhibitor PD98059, and we show that ERK1/2 was activated by PDGF. Neither 8-bromo-cGMP nor ANP(1-28) inhibited PDGF-stimulated ERK activation, suggesting that the effects of cGMP and ANP(1-28) were not mediated by inhibition of this kinase. Our data also argue against a role for cGMP-dependent protein kinase in mediating the effects of cGMP or ANP(1-28). Collectively, our data suggest that in VSMC: (i) cGMP and cAMP have opposing effects on deGlc transport; (ii) PDGF and cAMP have common elements in the pathways by which they activate deGlc transport; and (iii) a common element may be the target of the cGMP-mediated inhibition of deGlc transport.

Animals↗
PubMed1988

Evidence of prednisolone induced mood change ('steroid euphoria') in patients with chronic obstructive airways disease.

1. It is a clinical impression that some patients given oral corticosteroids develop a sense of wellbeing that is 'inappropriate' to improvements in physical health. This has been termed steroid 'euphoria', but unlike steroid-induced psychosis it has not been documented. 2. To test for the size and frequency of this phenomenon, 20 patients with severe chronic obstructive airways disease (mean FEV1 0.86 l) were given 30 mg of prednisolone for 14 days, after a period of placebo administration in a single-blind study. 3. Lung spirometry and arterial saturation during exercise were measured serially, together with established measures of mood state. 4. No changes in spirometry or arterial saturation during exercise were detected until 7 days of active therapy. 5. Mood state did not change during the placebo period, but small significant reductions in anxiety and depression were measured after 3 days of prednisolone and before any measurable improvement in lung function. Mood state did not then further improve, despite measurable improvements in lung spirometry. 6. This is evidence that prednisolone may produce a mild 'inappropriate' sense of wellbeing within a population receiving the drug, rather than as an occasional idiosyncratic response.

Aged↗
PubMed1987

A simple and portable paced step test for reproducible measurements of ventilation and oxygen consumption during exercise.

A single work rate paced step test is described. It was designed to allow the measurement of minute ventilation (VI) and oxygen consumption (VO2), under standardised conditions, during exercise in the clinic and lung function laboratory and in field work. The subjects and the operator found the test simple to perform. The values for ventilation at a given oxygen consumption were similar to those from more complex and stressful tests and had a high degree of reproducibility. The ergometer was a 12 inch (30 cm) step with hand rails. The subjects stepped down, once every four seconds in response to a buzzer for 10 minutes. VI and VO2 were measured with a small portable device. In 53 normal subjects of mean weight 69 (range 49-107) kg, mean VO2 measured during the last 5 minutes of the test was 0.89 (range 0.53-1.52) 1/min. Weight and height were independent contributors to the oxygen cost of stepping. The ventilatory equivalent for oxygen (VIO2, which equals VI divided by VO2) increased with age, and was similar to normal values for ventilation at 1.01/min VO2 obtained by workers who used multiple work rate tests on more complex equipment. The within subject variation in VIO2, expressed as the coefficient of variation (cv) and calculated for each age decade, was 14%. This again compared very favourably with the cv for values of ventilation at 1.01/min VO2 from other studies. In 20 normal subjects daily testing showed significant falls in VO2 and V1 over three days of 4% and 5.9% respectively; VIO2 fell by 2%. Testing over four consecutive weeks showed small significant differences between weeks but no clear trend; the within subject weekly variation accounted for less than 3.5% of the total variance for each of the variables. Testing at least four months apart showed a 3.3% fall in the oxygen cost of stepping. No significant diurnal effects on the exercise responses were found.

Adult↗
PubMed1985

Performance, ventilation, and oxygen consumption in three different types of exercise test in patients with chronic obstructive lung disease.

Seventeen patients (six men and 11 women, mean age 66 years) with severe chronic obstructive lung disease (mean FEV1 0.8 (SD 0.3)1) performed three different types of exercise test on four occasions within one week. Three daily doses of placebo tablets were given between the third and fourth attempt at each test. The tests were the 12 minute walking test, a fixed rate and height paced step test, and a cycle ergometer test in which the work rate was increased by 10 watts each minute. Performance increased significantly (p less than 0.01) between the first and fourth attempts in each type of test (12 min walking distance 16% (SD 20%); steps climbed 96% (74%); duration of cycling 29% (41%]. There was a trend for the increase in performance between successive attempts to become progressively smaller but this was not significant. No effect of placebo on exercise performance was detected. The greatest intersubject range of performance was seen in the step test (14-126 steps) and the least in the walking test (438-1014 m). Significant correlations (p less than 0.01) were observed between performance in all three types of exercise test, but the correlations found between the results of the various tests of exercise performance and the FEV1 and the FVC were either weak (p less than 0.05) or non-significant. Ventilation (VE) and oxygen consumption (VO2) were subsequently measured and compared in eight patients during all three types of exercise test. Both the VE and the VO2 that were achieved in the step test were significantly greater than in either the cycle or the walking test. No patient was able to reach and sustain steady state values of VE and VO2 in the step test, whereas a steady state for both VE and VO2 was reached and sustained by all eight patients in the walking test. It is suggested that at least three practice attempts at any exercise test should be made before the introduction of either placebo or specific pharmacological treatment and that even then it may be necessary to allow for the effects of further repeated testing in the assessment of the results of treatment.

Aged↗
PubMed1984

Differences in the effect of mediastinal radiotherapy on lung function and the ventilatory response to exercise.

To examine the effect of lung inflammation on lung volumes and carbon monoxide transfer and their relationship to the ventilatory and gas exchange responses to exercise, a prospective study was performed in patients having Hodgkin's disease, with no evidence of intrathoracic involvement, who received prophylactic mantle-field radiotherapy to the chest. From 6 weeks to 6 months from the start of therapy, vital capacity (FVC) was on average 10.4% lower than during the baseline period and the total transfer of carbon monoxide (TLCO) was 10.5% lower. Minute ventilation (VE) at any given work load during an incremental exercise test was on average 10.5% higher than baseline. The stimulation of ventilation after radiotherapy was present at all work rates, but greater at high work rates. A number of other changes in the ventilatory and gas exchange responses to exercise were also seen. Most of these lay outside the range of variability observed in a group of normal subjects tested concurrently with the patients. There was a poor, but statistically significant, positive correlation between reduction in FVC and increase in VE after radiotherapy and between reduction in carbon monoxide transfer and increase in VE. A significant correlation between reduction in FVC and change in respiratory rate was also seen after radiotherapy, together with a significant inverse correlation between increase in respiratory rate and fall in tidal volume. The ratio of VE to oxygen consumption, the ventilatory equivalent for oxygen, was calculated at each work rate. There was a negative correlation between the mean increase in this parameter, averaged over all work rates, and the reduction in FVC and TLCO, i.e. the greatest stimulation of breathing relative to metabolic demand occurred in those patients with the least change in lung volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Relationship between ventilation and breathlessness during exercise in chronic obstructive airways disease is not altered by prevention of hypoxaemia.

We have examined the hypothesis that hypoxaemia contributes to breathlessness by a mechanism distinct from its action as a ventilatory stimulant. Five patients who developed arterial oxygen desaturation during incremental exercise were studied. Exercise tests were performed on a cycle-ergometer. Breathlessness was measured by using a visual analogue scale technique. All five patients had considerable previous experience of these procedures. Two identical exercise tests were performed by each patient, breathing either room air or 60% oxygen in a blind randomized study. Breathing air, arterial saturation at rest was 93% and fell by 7% during exercise. Breathing 60% oxygen, resting saturation was 98% and there was no fall during exercise. Breathing oxygen, ventilation for a given work load was reduced and exercise duration was increased when compared with air breathing. In each of the five patients the relationship between breathlessness and minute ventilation was the same whether breathing air or 60% oxygen, despite the reduction in ventilation for a given work rate.

Aged↗