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Biomedical subjects

S Stone

Publications and source records attributed to S Stone.

At least 235 records · Page 13Linked to original sources

Pharmacological modification of the light-induced responses of Müller (glial) cells in the amphibian retina.

The light-evoked responses of Müller (glial) cells were monitored by intracellular recording in the isolated, superfused retina of Xenopus laevis. Müller cells had dark resting potentials of -88.5 +/- 6.9 mV and small 1-2 mV light responses of variable waveform in normal Ringer's solution. Exposure to picrotoxin (0.5-1.0 mM) greatly enhanced the light response which then consisted of depolarizing transients (Vmax 5-15 mV) at stimulus onset and offset. GABA (5-10 mM) antagonized the picrotoxin effect and suppressed the light response, whereas 2-amino 4-phosphonobutyrate (0.10-0.15 mM) blocked selectively the 'on' transient. None of these agents appreciably modified the glial cells resting potential level. On the other hand, veratrine (6-9 micrograms/ml) depolarized the Müller cell by 4-13 mV and slowed and greatly reduced the light response. These effects were antagonized by tetrodotoxin (1-4 microM) which itself reduced the light response by 30-50% without altering its shape. On the basis of these findings, we suggest that alterations in the activity of the inner retinal neurons, i.e. amacrine and ganglion cells, are primarily responsible for the drug-induced changes in the membrane potential and light-evoked responses of the Müller cell.

Aminobutyrates↗

The effect of hypoglycaemia on visual function: a clinical and electrophysiological study.

Disturbance of vision commonly accompanies hypoglycaemia. This study was designed to investigate the nature of the visual disturbance, the blood glucose threshold at which the disturbance occurred and the physiological basis. Measurements were made of the corrected visual acuity, colour vision (100 Hue test), visual evoked potentials (VEP), electroencephalography (EEG) frequency analysis and psychometry (digit recall) during stepwise induction of controlled hypoglycaemia produced by an intravenous insulin infusion. Six male volunteers and five insulin-dependent diabetic subjects were studied. During hypoglycaemia corrected visual acuity was unchanged. Colour vision was significantly impaired. Baseline VEP were normal in both groups but significantly prolonged during hypoglycaemia (mean increment 10.8 ms) and increased by greater than 5 ms in nine out of 11 subjects. Quantitative EEG analysis demonstrated slowing with a power density spectral shift from fast alpha to slow alpha, theta and delta which correlated with VEP latency and amplitude changes. The findings have clinical implications. A deterioration in colour vision is likely to impair the ability to read reagent strips by eye. VEP measurements in diabetic patients are likely to be misleading if hypoglycaemia is present; EEG changes are a sensitive index of cortical dysfunction during hypoglycaemia and provide a theoretical basis for developing a portable device to detect early hypoglycaemia.

Adult↗

Maximal work capacity in prepubescent obese and nonobese females.

Measurements of cardiorespiratory function during an incremental treadmill test were compared in 15 obese (OB) prepubescent girls, 7 to 12 years old, and in 15 age-matched, nonobese (NOB) controls. Open circuit calorimetry was used for data collection during the progressive work test. Maximal oxygen consumption indexed for weight was significantly lower in the obese group of girls (23.0 +/- 3.9 ml/kg/min) than in the nonobese controls (36.7 +/- 0.9 ml/kg/min). In addition, exercise tolerance was longer in the nonobese group, albeit not statistically significant. In conclusion, diminished cardiopulmonary performance and attenuated exercise tolerance in prepubescent obese females in the current investigation seemed to be influenced by excess body weight.

Body Height↗

Radionuclide hysterosalpingography for evaluation of fallopian tube patency.

A prospective study was undertaken to evaluate the efficacy of radionuclide hysterosalpingography (RNHSG) using a technique with some modifications, that was described by Iturralde and Ventner (1). As these investigators demonstrated, technetium-labeled human albumin microspheres (HAM) will normally migrate spontaneously from the vagina to the ovaries. This study confirms that in the presence of fallopian tube obstruction, fibrosis and/or lack of motility, this migration does not take place, and that the presence or absence of migration of HAM can be imaged with a gamma camera. In the evaluation of 52 tubes we found that the efficiency of RNHSG for evaluation of fallopian tube patency when compared with contrast hysterosalpingography and/or direct observation of surgical pathology was over 94%. RNHSG is an essentially innocuous technique for assessing functional and mechanical fallopian tube obstruction that can be performed with conventional nuclear imaging equipment.

Evaluation Studies as Topic↗

The actions of gamma-aminobutyric acid, glycine and their antagonists upon horizontal cells of the Xenopus retina.

We examined the effects of gamma-aminobutyric acid (GABA) and glycine and their respective antagonists, picrotoxin and strychnine, upon the membrane potential and light-evoked responses of the type H1 horizontal cell of the Xenopus retina. This horizontal cell receives mixed input from rod and cone receptors. Under control conditions the mean membrane potential was -37.8 +/- 9.7 mV. Addition of 5 mM-GABA to the superfusate hyperpolarized the cell by 4.0 +/- 2.6 mV within 3-5 min; addition of 0.5 mM-picrotoxin depolarized the cell by 4.3 +/- 2.1 mV. Prolonged (greater than 15 min) exposures to the drugs elicited more pronounced changes in membrane potential. GABA and picrotoxin affected primarily the cone-dependent input to the H1 horizontal cell. Under dark-adapted conditions, response wave forms were essentially unaltered by the drugs, but when the horizontal cell was moderately or fully light adapted, GABA reduced and picrotoxin enhanced the cone-dependent component of its response to light. Long-term (greater than 15 min) exposures to GABA and picrotoxin elicited changes in response kinetics usually associated with dark and light adaptation, respectively. Glycine, at bath concentrations of 0.6 mM or greater, depolarized horizontal cells by 21 mV on average and reduced or abolished their light response. This action did not occur in the presence of 0.1 mM-strychnine. When all light-evoked activity was blocked by 20-40 mM-magnesium, the depolarizing action of glycine still occurred. Thus, glycine appears to act directly upon the horizontal cell membrane. Neither GABA nor glycine, nor their respective antagonists, affected the spatial extent of the horizontal cell receptive field.

Action Potentials↗

Gaba-ergic and dopaminergic regulation of thyroid stimulating hormone. Effects of baclofen and metoclopramide.

The effects of the GABA analogue, baclofen, and the dopamine antagonist, metoclopramide, on basal and TRH-stimulated TSH release were studied in 6 normal male volunteers. Basal TSH secretion was not influenced by baclofen (10 mg orally three times daily for 3 days) or metoclopramide (10 mg i.v.), given alone or together. Baclofen produced a blunting of the TRH-stimulated TSH release (p less than 0.05), which persisted after metoclopramide administration. It is speculated that GABA and its analogues exert an inhibitory effect on TSH secretion, presumably at the level of the pituitary, and this effect is not mediated by dopamine.

Adult↗

Rod and cone inputs to bipolar and horizontal cells of the Xenopus retina.

This report summarizes some recent studies of the Xenopus retina in which intracellular recordings were made from photoreceptors, horizontal and bipolar cells. The studied cells were identified by injection of Lucifer yellow. Rod spectral sensitivity functions conformed to the density spectrum of a 524 nm pigment, those of cones to that of a 612 nm pigment. Horizontal cell responses reflected both these classes of photoreceptor input. Rod input evoked a slow waveform, with Vmax less than or equal to 18 mV, cone input a faster waveform with Vmax = 30-40 mV. In the mesopic state the horizontal response reflected both waveforms. Rod and cone inputs to the horizontal cells appeared not to act independently, in that a steady weak green background greatly enhanced the response to a superimposed red flash, but not the reverse. A third photoreceptor type (blue-sensitive rod, Y lambda max = 445 nm) provided input to a chromatic bipolar cell which was hyperpolarized by blue light and depolarized by red light. Such chromatic bipolars had broad areas of spatial integration and lacked center-surround organization.

Adaptation, Ocular↗

GABA-ergic and dopaminergic mechanisms in gonadotrophin secretion in males--effects of baclofen and metoclopramide.

The GABA analogue, baclofen, and the dopamine antagonist, metoclopramide, were studied with respect to their effects on basal and LRH-induced LH and FSH release in 6 normal male volunteers. Basal gonadotrophin secretion was unchanged following the administration of baclofen or metoclopramide given alone or in combination. LRH-stimulated LH release was significantly blunted after metoclopramide administration in the baclofen pre-treated volunteers. Serum LH concentration (mean +/- SD) in the control phase was 30.1 +/- 17.2 mIU/ml and was 19.4 +/- 9.6 mIU/ml after baclofen plus metoclopramide (P less than 0.02). LRH-stimulated values, however, were unaffected by baclofen or metoclopramide when the drugs were given alone. LRH-stimulated FSH release was not significantly influenced by baclofen or metoclopramide given alone or in combination. Basal Prl secretion increased significantly when baclofen and metoclopramide were given separately and in combination. Basal Prl concentration (mean +/- SD) increased from 14 +/- 2 ng/ml to 18.7 +/- 4.8 ng/ml after baclofen and to 111.5 +/- 31.9 ng/ml after metoclopramide (P less than 0.01). The rise in serum Prl concentration, however, was not significantly different when measured after metoclopramide alone (111 +/- 31.9 ng/ml) or after metoclopramide and baclofen (112 +/- 33.3 ng/ml). It is proposed that GABA and dopamine exert opposing effects on LH secretion in normal men.

Adult↗

A presumptive role for gamma-aminobutyric acid in the regulation of gonadotropin secretion in man.

The effect of di-n-propylacetic acid (valproic acid), a gamma-aminobutyric acid transaminase inhibitor, on the luteinizing hormone (LH) and follicle-stimulating hormone (FSH) response to gonadotropin-releasing hormone (LHRH) was studied in five normal women during the proliferative and luteal phases of the menstrual cycle. Valproic acid produced no significant change in the basal serum concentrations of LH, FSH, estradiol, and progesterone in either the proliferative or the luteal phase of the study. In the proliferative phase the delta LH (maximum increment above baseline) following LHRH stimulation rose from 32.8 +/- 21.2 (mean +/- SD) to 52.2 +/- 28.7 mlU/ml (not significant) after valproic acid, while the delta FSH rose from 2.2 +/- 1.1 to 5.0 +/- 3.6 mlU/ml (not significant). Four of the five volunteers showed an augmentation of the delta LH response to LHRH after valproic acid while the fifth subject showed no change. In three subjects the augmented delta LH response after valproic acid was highly significant. By contrast, the delta LH in the luteal phase following LHRH stimulation fell from 65.3 +/- 20.1 to 43.1 +/- 12.9 mlU/ml after valproic acid (p less than 0.03). Corresponding delta FSH values were 2.5 +/- 1.1 and 2.1 +/- 0.8 mlU/ml (not significant). It is speculated that gamma-aminobutyric acid may exert a modulatory role on gonadotropin secretion following LHRH stimulation and that this effect is influenced by the phase of the menstrual cycle.

Adult↗

Modulatory role of gamma-aminobutyric acid (GABA) in the regulation of gonadotropin secretion in patients with chronic renal failure.

The role of gamma-aminobutyric acid (GABA) in the regulation of gonadotropin secretion in renal failure, was studied in 5 patients with chronic renal failure who were on maintenance dialysis. Di-n-propylacetic acid (valproic acid-VA), a GABA-transaminase inhibitor which has been shown to increase brain GABA levels, was used in the study. VA produced no significant change in the basal serum LH and FSH concentrations, or in E2 or T concentrations in the renal failure patients, or the E2 and P concentrations in normal controls, but augmented the delta LH (maximum increment above baseline) and delta FSH response to LH-RH. delta LH rose from 30.4 +/- 12.7 mIU/ml (mean +/- SD) to 41.1 +/- 16.8 mIU/ml (p less than 0.01) after VA, while delta FSH rose from 2.8 +/- 1.8 mIU/ml to 3.8 +/- 1.6 mIU/ml (p less than 0.05). The findings support a modulatory role for GABA in gonadotropin secretion in chronic renal failure.

Adult↗