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J A Strong

Publications and source records attributed to J A Strong.

18 recordsLinked to original sources

Divalent-selective voltage-independent calcium channels in Lymnaea neurons: permeation properties and inhibition by intracellular magnesium.

Calcium channels are tightly regulated. Voltage-gated calcium channels open only in response to depolarization, while voltage-independent calcium channels usually open only in response to specific intracellular or extracellular ligands. Voltage-independent calcium channels have been described in several invertebrate neurons. One difficulty in understanding the function of the neuronal channels is that their regulators are unknown. They open rarely in intact cells but are activated by formation of a cell-free patch, suggesting that some intracellular inhibitor usually keeps them closed. This article provides evidence that intracellular Mg2+ is one important regulator of the voltage-independent calcium channel (HP channel) in neurons of the pond snail Lymnaea stagnalis. Mg2+ (1 mM) rapidly and reversibly inhibited activity of this calcium channel when applied to the intracellular side of cell-free membrane patches. The primary effect of the Mg2+ was to promote long closings of the channel. The mechanism of the intracellular Mg2+ inhibition is distinct from open channel block, a phenomenon seen in a variety of cation channels. Open channel block can also be seen in the HP channels, but only at very positive membrane potentials. Some of the permeability and selectivity characteristics of these channels were also examined. The channels are permeable to Mg2+ and Ca2+ as well as Ba2+. Outward currents carried by monovalent cations can be observed only at very positive membrane potentials, indicating high selectivity for divalent over monovalent cations. The single channel current-voltage relationship is markedly nonlinear, becoming quite shallow near the reversal potential, and hence is qualitatively similar to that seen in many voltage-activated calcium channels.

Animals

Familial pseudohyperkalaemia. A new syndrome.

Inherited pseudohyperkalaemia due to an abnormal red-blood-cell potassium leak was discovered in 16 of 28 relatives of a woman with pseudohyperkalaemia. Autosomal dominance seemed to account for inheritance of this abnormality. Affected subjects were not anaemic and had normal in-vivo plasma-potassium concentrations.

Adult

The initiation of excitation and light adaptation in Limulus ventral photoreceptors.

Two types of experiments indicate that light adaptation and excitation are initiated by the same, rather than different, populations of visual pigment. (a) The criterion action spectra of light adaptation and excitation are the same. (b) Increment-threshold curves were measured with a voltage-clamp technique under conditions of high and low concentration of plasma membrane rhodopsin (Rhpm). SD, the dark-adapted sensitivity, and 1/I2, the inverse of the background irradiance that desensitized by 0.3 log units, underwent the same fractional change when the rhodopsin concentration was changed. Both quantities appear to be linearly related to Rhpm. Reversible reductions in Rhpm were achieved by orange irradiation during a brief increase of extracellular pH from 7.8 to 10. This procedure would be unlikely to produce similar concentration changes in a hypothetical intracellular pigment because the concurrent change in intracellular pH, measured using the dye, phenol red, was only 0.45 pH units. It is thus unlikely that an intracellular pigment initiates light adaptation. On the assumption that light adaptation is mediated by a light-induced release of Ca++ from an intracellular store. the results reported here imply that an intracellular transmitter is needed to couple Rhpm to the intracellular store.

Adaptation, Physiological

Hypothalmic-pituitary adrenal responsiveness to dexamethasone-insulin tolerance test in acromegalic patients before and during treatment with bromocriptine.

Insulin tolerance tests were carried out in 10 acromegalic patients after 1 mg dexamethasone had been given the previous evening (DEX-ITT). Nine patients showed a rise in plasma 11-OHCS and four patients showed a rise in plasma growth hormone (GH) levels. These responses were unaltered after treatment with bromocriptine 10 mg daily for two months. Basal plasma GH levels fell in 6 of the patients and the mean plasma GH levels of the 10 patients during an oral glucose tolerance test (OGTT) fell from 63.2 +/- 25.5 ng/ml before treatment to 53.0 +/- 27.1 ng/ml (mean +/- sem; p less than 0.05). These data fail to confirm a previous report of abnormal hypothalmic-pituitary-adrenal suppressibility during a DEX-ITT in acromegalic patients. They also indicate that bromcriptine does not alter the responses of plasma 11-OHCS and plasma GH to the DEX-ITT despite lowering plasma GH levels.

11-Hydroxycorticosteroids

Growth hormone, insulin, and prolactin secretion in anorexia nervosa and obesity during bromocriptine treatment.

We studied secretion of growth hormone (GH), insulin, and prolactin in eight women with anorexia nervosa and nine women with refractory obesity before and during treatment with bromocriptine, 10 mg/day. In the anorexic patients the raised plasma GH concentrations occurring during an oral glucose tolerance test fell significantly while on bromocriptine treatment, but there was no change in plasma insulin or blood glucose concentrations. In the obese patients, however, plasma GH concentrations remained low during the oral glucose tolerance test, and were not modified by bromocriptine. Blood glucose and plasma insulin concentrations were also unchanged. Plasma GH and plasma 11-hydroxycorticosteroid responses to insulin-induced hypoglycaemia were unaffected. Serum prolactin concentrations which were raised in five anorexic patients and marginally raised in two obese subjects, fell significantly in both groups during treatment. We observed no consistent weight changes in either groups.

Adolescent

The relationship between thyroid function and the renal response to parathyroid hormone.

The effect of thyroid status on renal adenosine 3', 5'-cyclic monophosphate (cyclic AMP) metabolism was assessed by measuring the increase in plasma cyclic AMP concentration following the intravenous administration of parathyroid hormone (PTH) to five hypothyroid and six hyperthyroid patients and seven euthyroid control subjects. PTH caused a rapid, transient increase in the concentration of plasma cyclic AMP which was similar in magnitude and time course in the euthyroid and hyperthyroid groups, but reduced in magnitude in the hypothyroid patients. The magnitude of the plasma cyclic AMP response to PTH was positively related to the free thyroxine index. The results suggest that the development of hypothyroidism may impair the renal response to PTH by affecting the turnover of cyclic AMP in the renal cortex.

Cyclic AMP

Thyroxine and triiodothyronine levels in hyperthyroid patients during treatment with propranolol.

Serum triiodothyronine (T3) and thyroxine (T4) levels were measured in twelve hyperthyroid patients before and after treatment with propranolol, 40 mg four times daily, for 2 weeks. There was a significant fall in serum T3 and a significant rise in serum T4 concentrations in the group as a whole and it was concluded that the clinical effectiveness of propranolol in hyperthyroidism may be mediated in part by its action on the peripheral metabolism of thyroid hormones. Propranolol treatment should be withdrawn gradually as removal of the suppressive action of the drug on thyroid hormone metabolism is potentially hazardous, particularly in patients with ischaemic heart disease.

Adult

The effect of dialysate calcium concentration on 1alpha-hydroxyvitamin D3 on skeletal calcium loss and hyperparathyroidism in haemodialysis patients.

The response of hyperparathyroidism and skeletal calcium loss in haemodialysis patients to treatment with 1alpha-hydroxyvitamin D3 and a dialysate calcium concentration of 1.375 mmol/l was compared with the response to treatment with a dialysate calcium concentration of 1.375 or 1.75 mmol/l alone over a 6 month period. In patients treated with 1alpha-hydroxyvitamin D3 there was a significant rise in plasma calcium associated with a significant fall in plasma alkaline phosphatase and plasma parathyroid hormone as well as resolution of sub-periosteal erosions. In these patients there was a significant rise in the calcium content of the forearm assessed by neutron activation analysis in comparison to patients treated with a dialysate calcium concentration of 1.75 or 1.375 mmol/l alone. In patients treated with a dialysate calcium concentration of 1.375 or 1.75 mmol/l alone there was no significant change in the plasma calcium, alkaline phosphatase or parathyroid hormone after 6 months and in these patients subperiosteal erosions either did not change or became worse. No significant difference in the response in these two groups was observed. This study indicates that treatment of haemodialysis patients with 1alpha-hydroxyvitamin D3 is significantly more effective than treatment with a dialysate calcium concentration of 1.375 or 1.75 mmol/l alone in preventing progression of hyperparathyroidism and skeletal calcium loss.

Adult

Effect of propranolol on glucose tolerance in hyperthyroidism.

Glucose tolerance tests were performed on six hyperthyroid patients in the morning and afternoon before, and at the end of treatment with propranolol for 2 weeks. All six subjects showed normal glucose tolerance with a normal diurnal rhythm before treatment and this remained normal in five during treatment with propranolol, while one patient developed abnormal glucose tolerance and the diurnal variation was abolished. No change in insulin levels was noted in any of the patients either before or during treatment. Propranolol may cause deterioration in glucose tolerance in some subjects with hyperthyroidism and this possibility should not be overlooked.

Adult

Paget's disease.

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Calcitonin

The problem of obesity.

In countries with unrestricted access to food, obesity is common and is associated with enhanced mortality. Morbidity is difficult to assess, but must be a cause for much concern. The mechanisms concerened in the development of obesity have been studied intensively, but any single factor which might distinguish the obese from the lean remains elusive. The management of obesity must be based on altering the eating habits of the patient, and this, in turn is still an exercise in persuasion rather than a pharmacological operation.

Adult

Treatment of Paget's disease of bone with porcine calcitonin: clinical and metabolic responses.

The clinical and metabolic responses of 12 patients with painful Paget's disease have been assessed before, during and after an 18-day course of treatment with purified porcine calcitonin, 160 MRC units i.m. daily. The indices of response included relief from pain, changes in concentration of serum alkaline phosphatase, calcium, magnesium, electrolytes and plasma inorganic phosphate; balance studies of calcium, phosphate, magnesium and in some cases sodium and potassium were undertaken. Urinary excretion of hydroxyproline was also measured. Remission of pain was complete in 11 of 15 courses of treatment. Coexistent osteoarthrosis was considered to be responsible where remission was incomplete. The mean duration of remission of pain was 12 months. Three patients who received a second course of treatment achieved further remission of pain. Side effects were not troublesome. Serum levels of alkaline phosphatase decreased to 67 per cent of the initial reading and the degree of suppression depended on the initial alkaline phosphatase activity. Urinary hydroxyproline correlated closely with the activity of serum alkaline phosphatase before, during and after treatment. The ratio of serum alkaline phosphatase:hydroxyproline excretion rose at the start and at the termination of treatment. Retention of calcium and inorganic phosphate occurred during the early phase of treatment only. Withdrawal of treatment resulted in a rebound retention of calcium and inorganic phosphate. The degree of calcium retention after treatment correlated with the level of plasma inorganic phosphate prevailing before treatment. The efficacy of these short courses of calcitonin are discussed and the metabolic observations related to theories of bone remodelling at a cellular and hormonal level.

Aged