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Biomedical subjects

S G Ball

Publications and source records attributed to S G Ball.

At least 145 records · Page 8Linked to original sources
PubMed1990

The effect of unsaturated fatty acids on sodium nitroprusside stimulation of guanylate cyclase in the human astrocytoma clone, D384, and the human neuroblastoma clone, NB1-G.

Sodium nitroprusside (SNP) stimulates cGMP formation to a greater extent in 20,000 g supernatant fractions of the human neuroblastoma clones NB1-G and SH-SY5Y than in the human astrocytoma clone D384. This suggests that these cell lines contain the soluble form of guanylate cyclase. Arachidonic, 8,11,14- and 11,14,17-eicosatrienoic acids inhibit SNP (10(-4) M)-stimulated cGMP formation more potently than the C18 unsaturated fatty acids linolenic and linoleic acids in D384 and NB1-G. In contrast the C20 saturated fatty acid, arachidic acid had little effect even at 10(-4) M concentration. In addition arachidonic and 8,11,14-eicosatrienoic acids inhibited basal guanylate cyclase activity, in NB1-G, over the same concentration range as they inhibited SNP-stimulated cGMP formation. No evidence could be obtained for the stimulation of guanylate cyclase by arachidonic acid in either NB1-G or D384. These results provide further support for suggestions that arachidonic acid or its metabolites may be important regulators of cGMP formation in the nervous system.

8,11,14-Eicosatrienoic Acid↗
PubMed1990

Homologous desensitization of the D1 dopamine receptor.

Preincubation of D384 cells, derived from the human astrocytoma cell line G-CCM, with dopamine resulted in a time-dependent attenuation of cyclic AMP responsiveness to subsequent dopamine stimulation. This effect was agonist specific because the prostaglandin E1 (PGE1) stimulation of cyclic AMP of similarly treated cells remained unchanged. The attenuation by dopamine was concentration dependent with a maximum observed at 100 microM. A comparison of dopamine concentration-response curves of control and dopamine-preincubated cells revealed no change in the Ka apparent value, but a marked attenuation of the maximal response. Preincubation of cells with dopamine in the presence of D1 but not D2 selective antagonists partially prevented the observed attenuation. Attenuations in dopamine responsiveness were also obtained when D384 cells were preincubated with D1 but not D2 receptor agonists. The level of attenuation attained related to agonist efficiency in stimulating cyclic AMP: SKF38393 less than 3,4-dihydroxynomifensine less than fenoldopam less than 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene = dopamine. However, increasing the efficiency of 3,4-dihydroxynomifensine stimulation of cyclic AMP, using the synergistic effect of adding a low concentration of forskolin, produced no further change in the attenuation of the subsequent response to dopamine. Thus, the D1 dopamine receptors expressed by D384 cells undergo homologous desensitization. Uncoupling of the D1 dopamine receptor appears to be independent of cyclic AMP formation, analogous to a mechanism proposed for the beta-adrenergic receptor.

Alprostadil↗
PubMed1990

Experimental and clinical percutaneous angioscopy experience with dynamic angioplasty.

The authors have used ultrathin angioscopes with high optical resolution to assess the effects of dynamic angioplasty in vitro and in vivo. Experimentally, angioscopy was used to study the effects of the 5F "Kensey" catheter in "normal" porcine coronary arteries (NPCA) and postmortem human coronary arteries (PMHCA). In NPCA, the catheter keeps a coaxial position. Intimal flaps (IFs) were seen in 21/23 NPCAs. They occurred with all cam rotation speeds and were usually single and small (less than 25% of lumen). Perforations in patent arteries were rare (1/23). However, when the catheter was forced against the wall by passing through a narrowing of 5F diameter (made by a band ligature), perforations were more common at higher cam speeds. The epicardium remained intact in two thirds of perforations. Angioscopy visualized perforations in only 10% of cases (1/10), the common sign being that of large and multiple intimal flaps, which were often obstructive (5/10). In PMHCAs, angioscopy was more sensitive than angiography in detecting atheromatous lesions. The authors were able to give a better assessment of the effect of dynamic angioplasty on treated lesions, including the demonstration of intimal flaps that were not visible on angiography. In vivo, they have performed percutaneous angioscopy before and after dynamic angioplasty using 8 French Kensey catheters. Angioscopy revealed features that were not shown angiographically.

Angioplasty, Balloon↗
PubMed1989

The sympathetic nervous system and converting enzyme inhibition.

Angiotensin II appears to have important actions in modulating sympathetic nerve activity; conversely, sympathetic stimulation alters renin release. Drugs that inhibit angiotensin II formation would be expected then not only to offset the direct vasoconstricting and aldosterone releasing actions of this peptide but also to reduce sympathetic nerve activity. Hypertension and cardiac failure are two major conditions in which converting enzyme inhibitors have found important therapeutic roles; both are considered to be associated with increased activity of the renin-angiotensin-aldosterone and sympathetic nervous systems. However, in spite of considerable experimental evidence for a sympatholytic action of converting enzyme inhibitors, direct proof has been difficult to obtain in humans. In part, this results from the lack of any satisfactory way of assessing sympathetic activity in the clinical situation. Nevertheless, our failure to understand the pathophysiology of disease and the precise mechanism of action of drugs has not precluded exploiting the salutatory effects of inhibition of converting enzyme.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1989

Glucocorticoids modify differentially dopamine- and prostaglandin E1-mediated cyclic AMP formation by the cultured human astrocytoma clone D384.

The effects of steroid hormones on the cyclic AMP responses to stimulation of human astrocytoma cells (D384) by dopamine, prostaglandin E1 (PGE1), and isoprenaline were investigated. Incubation of D384 cells with dexamethasone resulted in a potentiation of the PGE1 and isoprenaline responses and a marked attenuation of the dopamine response. The time courses of the effects of dexamethasone on dopamine and PGE1 responses were similar, requiring long-term (at least 18 h) incubation of cells with the steroid. Concentration-response curves of dexamethasone effects on dopamine and PGE1 responses yielded similar Ka apparent values, suggesting a common mechanism. Cycloheximide, a protein synthesis inhibitor, prevented the effects of dexamethasone. Only steroids with glucocorticoid activity reproduced the dexamethasone effects. Direct stimulation of Gs with 5-guanylylimidodiphosphate and adenylate cyclase with forskolin revealed no significant differences in their activities in dexamethasone-treated and untreated cells. Furthermore, a comparison of the dopamine and PGE1 concentration-response curves obtained from dexamethasone-treated and untreated cells suggested that the affinity of the receptors for their agonists remained unchanged. These results suggest that glucocorticoids may alter protein synthesis and thereby the number of receptors expressed by D384 cells.

Adenylyl Cyclases↗
PubMed1989

Regulation of cyclic AMP formation in cultures of human foetal astrocytes by beta 2-adrenergic and adenosine receptors.

Two cell cultures, NEP2 and NEM2, isolated from human foetal brain have been maintained through several passages and found to express some properties of astrocytes. Both cell cultures contain adenylate cyclase stimulated by catecholamines with a potency order of isoprenaline greater than adrenaline greater than salbutamol much greater than noradrenaline, which is consistent with the presence of beta 2-adrenergic receptors. This study reports that the beta 2-adrenergic-selective antagonist ICI 118,551 is approximately 1,000 times more potent at inhibiting isoprenaline stimulation of cyclic AMP (cAMP) formation in both NEP2 and NEM2 than the beta 1-adrenergic-selective antagonist practolol. This observation confirms the presence of beta 2-adrenergic receptors in these cell cultures. The formation of cAMP in NEP2 is also stimulated by 5'-(N-ethylcarboxamido)adenosine (NECA) more potently than by either adenosine or N6-(L-phenylisopropyl)adenosine (L-PIA), which suggests that this foetal astrocyte expresses adenosine A2 receptors. Furthermore, L-PIA and NECA inhibit isoprenaline stimulation of cAMP formation, a result suggesting the presence of adenosine A1 receptors on NEP2. The presence of A1 receptors is confirmed by the observation that the A1-selective antagonist 8-cyclopentyl-1,3-dipropylxanthine reverses the inhibition of isoprenaline stimulation of cAMP formation by L-PIA and NECA. Additional evidence that NEP2 expresses adenosine receptors linked to the adenylate cyclase-inhibitory GTP-binding protein is provided by the finding that pretreatment of these cells with pertussis toxin reverses the adenosine inhibition of cAMP formation stimulated by either isoprenaline or forskolin.

Adenosine↗
PubMed1989

Effects of short-term ketanserin treatment on the QT interval and vagal function in healthy subjects.

1. The serotonergic type-2 (5HT2) antagonist ketanserin was given in a dose of 40 mg twice daily for 3 days to eight healthy subjects in a double-blind placebo controlled randomized crossover study. 2. The QTc interval was prolonged slightly but significantly (P less than 0.01) by a mean of 29 +/- 7 milliseconds after ketanserin compared to placebo. 3. Ketanserin reduced both mean arterial pressure and heart rate (P less than 0.05), by 5.7 +/- 1.8 mmHg and 3.5 +/- 1.5 beats minute-1 respectively, when compared to placebo. 4. There was a tendency (not statistically significant) for cardiac vagal outflow to be reduced after ketanserin (assessed by the heart rate responses to standing, deep breathing and the Valsalva manoeuvre). 5. In healthy man, ketanserin causes prolongation of the QTc interval and a reduction in heart rate. These changes do not appear to be due to enhanced cardiac parasympathetic activity.

Adult↗
PubMed1989

Kinetic analysis of the uptake of thyroid hormones by the human erythrocyte.

The uptake of 3,5,3'-tri-iodothyronine (T3) by human erythrocytes was shown to occur by two saturable processes. System I (Michaelis constant (Km) = 109 +/- 40 (mean +/- S.D.) nmol/l; maximal velocity (Vmax) = 43 +/- 16 pmol/min per 10(9) cells) was observed over the range 1-50 nmol T3/l whilst system II (Km = 8.8 +/- 8.0 pmol/l; Vmax = 29 +/- 6 fmol/min per 10(9) cells) was observed over the range 1-500 pmol T3/l. At low concentrations (1-500 pmol/l) uptake processes equivalent to system II could be demonstrated for thyroxine and 3,3',5'-tri-iodothyronine also. System II had the properties of a carrier-mediated process.

Erythrocytes↗
PubMed1988

Cultured mesenteric vascular smooth muscle cells express dopamine DA1-receptors.

Incubation of cultured mesenteric vascular smooth muscle cells with dopamine, in the presence of propranolol, caused an increase in cyclic AMP formation in a concentration-dependent manner (Ka apparent 6.8 +/- 0.5 microM). This effect of dopamine was inhibited by the DA1-receptor antagonist SCH 23390 (Ki = 1 nM). These results suggest that cultured mesenteric vascular smooth muscle cells express DA1-receptors linked to adenylate cyclase.

Adenylyl Cyclases↗
PubMed1988

The effects of the 5 HT2 antagonist ritanserin on blood pressure and serotonin-induced platelet aggregation in patients with untreated essential hypertension.

We have given the selective 5 HT2 antagonist ritanserin in a dose of 10 mg twice daily for 4 weeks in a double-blind, randomized, placebo-controlled, parallel group study of 18 patients with untreated essential hypertension. The fall in single platelet count due to 5 HT-induced platelet aggregation was significantly reduced by ritanserin compared with placebo (p less than 0.05). There were no significant changes in supine or erect blood pressure or heart rate after ritanserin compared to placebo. Forearm blood flow, measured by mercury-in-strain gauge venous occlusion plethysmography, was not significantly altered by ritanserin. Ritanserin caused prolongation of the QTc interval by 41 (SEM 11) ms (p less than 0.05 compared to placebo) but had no detectable effect on QRS duration, features suggestive of Class III antiarrhythmic activity. These findings do not support an independent role of the 5 HT2 receptor in maintaining raised arterial pressure in essential hypertension.

Aged↗
PubMed1988

The effects of the 5 HT2 antagonist ketanserin in adult atopic asthma.

We have studied eight adult atopic asthmatic patients in a randomized double-blind, placebo-controlled, cross-over trial in order to examine the effects of the 5 HT2 antagonist ketanserin on airways function (FEV1, FVC, V50(chi), and V25(pi]. Ketanserin did not significantly change resting bronchomotor tone. Treadmill exercise caused a similar maximal percentage fall in FEV1 after both drug [16.8 (3.7)%] and placebo [19.2 (4.2)%]; ketanserin did not significantly attenuate bronchoconstriction, measured over a 20-min period after exercise. These results suggest that 5 HT2 receptors do not play a major role in the control of resting bronchomotor tone or in exercise-induced bronchoconstriction in adult atopic asthmatic patients.

Adolescent↗
PubMed1988

Overnight clonidine suppression test in the diagnosis and exclusion of pheochromocytoma.

In a prospective study designed to differentiate pheochromocytoma from other forms of hypertension, urinary catecholamines were measured after sleep and clonidine administration in 12 patients with pheochromocytoma, 19 hypertensive patients in whom pheochromocytoma was suspected but later excluded, and 31 hypertensive patients in whom pheochromocytoma was never suspected. The test correctly identified all 12 patients in whom pheochromocytoma was present. Four of these had equivocal plasma levels of both norepinephrine and epinephrine, suggesting that overnight clonidine suppression may be of particular value when tumor secretion is intermittent or low. When pheochromocytoma was not present, urinary norepinephrine and epinephrine levels were suppressed below 60 and 20 nmol/mmol creatinine, respectively, after sleep and clonidine, the two in combination giving better suppression than sleep alone. Since urinary catecholamines can be determined relatively easily by high-pressure liquid chromatography with electrochemical detection, this test may be more widely applicable than suppression tests based on plasma measurements.

Adrenal Gland Neoplasms↗
PubMed1988

Characterization of dopamine and beta-adrenergic receptors linked to cyclic AMP formation in intact cells of the clone D384 derived from a human astrocytoma.

3,4-Dihydroxyphenylethylamine (dopamine) and beta-adrenergic receptor agonists and antagonists were assessed for their effects on cyclic AMP accumulation in human astrocytoma derived clone D384 cells. Dopamine, SKF 38393, and 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene increased cyclic AMP content with Ka values of 2.0, 0.2, and 1.6 microM. The D1-selective antagonists SCH 23390 (Ki, 1.2 nM) and SKF 83566 (Ki, 0.8 nM) were over 5,000-fold more potent than the D2-selective antagonist domperidone (Ki, 6.7 microM) at inhibiting dopamine stimulation of cyclic AMP formation. SCH 23388 (Ki, 560 nM; the S-enantiomer of SCH 23390) was 400-fold less potent than SCH 23390. Isoprenaline, adrenaline, salbutamol, and noradrenaline increased cyclic AMP content with Ka values of 0.13, 0.12, 0.22, and 7.60 microM. The beta 2-selective antagonist ICI 118,551 (Ki,0.8 nM) was almost 8,000-fold more potent than the beta 1-selective antagonist practolol (Ki, 5.9 microM) at inhibiting isoprenaline stimulated cyclic AMP accumulation. These results demonstrate that D384 cells express D1-dopamine and beta 2-adrenergic receptors linked to adenylate cyclase. Furthermore, the dopamine receptor expressed by D384 cells exhibits a pharmacological profile typical of a mammalian striatal D1-receptor and therefore the use of this clone represents another approach to studying central D1-receptors.

1-Methyl-3-isobutylxanthine↗
PubMed1988

Circulating adrenaline and noradrenaline concentrations during exercise in patients with exercise induced asthma and normal subjects.

A failure of the usual increase in plasma adrenaline and noradrenaline concentrations during submaximal exercise has been suggested as a contributory cause of exercise induced asthma. Six normal subjects and six asthmatic patients underwent a standard graded maximal exercise test. Measurements of oxygen consumption, minute ventilation, exercise time, blood lactate concentration, and heart rate indicated that the two groups achieved similarly high work loads during exercise. Mean FEV1 fell by 20% in asthmatic patients after exercise. Basal plasma adrenaline concentrations (nmol/l) increased in normal subjects from 0.05 to 2.7 and in asthmatic patients from 0.12 to 1.6 at peak exercise. Noradrenaline concentrations (nmol/l) increased in normal subjects from 2.0 to 14.3 and in asthmatic patients from 1.9 to 13.7 at peak exercise. The increases in adrenaline and noradrenaline in the asthmatic patients did not differ significantly from the increases in normal subjects. Thus a reduced sympathoadrenal response to exercise seems unlikely to be an important mechanism in the pathogenesis of exercise induced asthma.

Adolescent↗