Search PubMed⌕ Search

Biomedical subjects

G Duncan

Publications and source records attributed to G Duncan.

At least 109 records · Page 6Linked to original sources
PubMed1991

Diamide induces reversible changes in morphology, cytoskeleton and cell-cell coupling in lens epithelial cells.

The isolated frog lens epithelium can be maintained with its cell shape, cytoskeletal organization and membrane electrophysiological characteristics intact for more than 24 hr. Perifusion with the permeant oxidant diamide (1 mM) led to drastic, but reversible, changes in all the above parameters. After a 20 min exposure to diamide, the regular polygonal arrangement of the epithelial cells become increasingly disrupted as the cells reorganized and a 'rosette' pattern formed. The cells at the edges of the rosette pulled apart from one another while those in the centre maintained a relatively normal appearance. Blebs formed on the apical surface of all of the cells on prolonged exposure and the internal structure was also found to be severely disrupted. The cytoplasm became granular, vacuolated and the nucleus had a banded, non-homogeneous appearance. Phalloidin staining of F-actin microfilaments revealed that there was a general disruption of organization, with actin losing its association with the membrane. The microtubule array, organized around the centrosome, was also severely disrupted although microtubules were still discernible in most cells. During exposure to diamide the membrane potential depolarized and both electrical and dye coupling, which are normally extremely efficient in these cells, were disturbed. If the epithelium was exposed to 1 mM diamide for more than 45 min then all of the above changes were irreversible and cell death followed. If exposure was restricted to less than 30 min, then all of the above changes occurred and, in fact, progressed for over 1 hr; but if the epithelium was perifused for a further 20 hr in control medium, then most of the changes were reversible.

Actin Cytoskeleton↗
PubMed1991

Review of 18 years' experience of a diagnostic geriatric neurology referral service.

From 1971 to 1989, 1446 cases were referred from Glasgow and the West of Scotland to the University Department of Geriatric Medicine for neurological diagnosis. In that time, the number increased from one per week to more than two per week, and the proportion from outside Glasgow from 2% to 24%. Eighty-seven per cent had CT scans and 8% electrophysiological studies. One third of patients stayed three days or less, and one third over a week. Cerebrovascular disease was diagnosed in 637 cases (44%), subdural haematoma or hygroma in 59 (4%), and intracranial tumour in 228 (16%), of which 26 (11%) were benign. In 104 cases (7%) no definite diagnosis was made. Management was changed in 402 of the 1446 cases (28%). In the 635 (44%) in whom a referring diagnosis was documented, this was not confirmed in 63%; diagnosis and/or management was changed in 80%. The proportions of referring diagnoses of subdural haematoma and intracranial tumour that were confirmed rose with time. The value of the service lay in the speed and ease of access to it, and the opportunities for teaching and learning it provided. The problems it posed were those of the transfer of ill patients, the distances sometimes necessary, and the need for high standards of communication.

Aged↗
PubMed1990

Mammalian lens inter-fiber resistance is modulated by calcium and calmodulin.

The relationship between Ca2+ and lens fiber cell communication was investigated in the isolated intact rat lens by using radiotracer and electrophysiological techniques. The lens internal calcium was increased by adding the SH oxidant diamide (1 mM), by incubating in a sodium-free (n-methylglucamine) solution or by increasing external calcium from 1 to 10 mM. A 12 hours incubation in diamide produced a ten-fold increase in 45Ca uptake into the lens which was accompanied by a ten-fold increase in internal resistance. Incubation in Na-free solution or in 10 mM Ca2+ both produced a 5-fold increase in 45Ca content, while the increase in internal resistance was five and six fold respectively. This uncoupling was prevented in the diamide and Na-free treated lenses by omitting Ca2+ from the incubation medium. Fiber cell uncoupling was noticed in each of these experimental conditions after approximately 5 hours incubation, and good recovery was obtained in the high calcium solution if the stress was removed. The calmodulin antagonists calmidazolium (3 microM) and W7 (100 microM) both prevented uncoupling in the high calcium solution, provided there was a 2 hours preincubation period in calcium-free solution containing antagonist before the stress was applied. These data indicate that lens fiber cell communication is required by Ca2+ and calmodulin.

Animals↗
PubMed1990

Calcium-induced opacification and proteolysis in the intact rat lens.

When intact rat lenses were incubated in artificial aqueous humor in the presence of 1 mM calcium and a sulfhydryl reagent p-chloromercuriphenyl sulfonate (pCMPS) a visible annular opacity developed within 4 hours. Combined photographic and ion-sensitive microelectrode investigations of the lenses demonstrated that the subsequent linear increase in opacification was accompanied by an increase in internal free calcium. Opacities were not observed in lenses incubated in the absence of either pCMPS or calcium. Gel electrophoresis of the soluble and urea-soluble fractions from lenses exposed to 1 mM calcium for periods of up to 14 hours showed no evidence for crystallin degradation and only minor proteolysis of cytoskeletal proteins. When lenses were incubated under identical conditions, but with 5 mM calcium, the degree of opacification increased up to approximately 8 hours and then remained constant. A progressive loss in cytoskeletal proteins was observed which correlated with a further increase in free calcium such that by 14 hours of incubation, when the internal calcium approached 1 mM, most of the spectrin and vimentin present in the cortex of the lens had disappeared. An unidentified 110-kilodalton protein also disappeared from lenses incubated in 5 mM calcium. These results indicate that proteolysis by calcium-dependent enzymes such as calpain may play a significant role in cytoskeletal regulation and metabolism in the lens. A role for cytoskeleton/membrane/crystallin interaction in calcium-induced opacification is discussed.

4-Chloromercuribenzenesulfonate↗
PubMed1989

Calcium-induced cleavage and breakdown of spectrin in the rat lens.

Incubation of intact rat lenses under conditions that stimulated a net influx of calcium resulted in a pronounced loss of transparency and a major decrease in the levels of spectrin. The progressive loss of this cytoskeletal component coincided with the appearance of polypeptides of approximately 150 kDa which showed immunoreactivity with an antibody raised to spectrin. These bands disappeared on further incubation. It is, therefore, suggested that a calcium-activated protease is present in the lens which is capable of degrading spectrin by the initial removal of approximately 90 kDa fragments. This process calcium-induced proteolysis may be the basis for the cytoskeletal reorganisation observed during the differentiation of lens fibre cells and may be involved in cataract development.

Animals↗
PubMed1989

Electrodiagnosis of human colchicine myoneuropathy.

Colchicine may produce a neuromuscular disorder even when given in customary doses. We report the electrodiagnostic features in eight pathologically proven cases of colchicine-induced myoneuropathy. Myopathic motor unit potentials and early recruitment were found in proximal limb and truncal muscles, frequently with fibrillations, positive sharp waves, or complex repetitive discharges. These electromyographic findings correlated with the course of the weakness, which rapidly resolved within weeks of drug discontinuation, indicating that the major functional disturbance in the patients was myopathy. The accompanying signs of axonal neuropathy persisted longer, with little functional consequence. Although often misrecognized as polymyositis, colchicine myoneuropathy was identifiable by the rapid clinical and electrophysiologic improvement following drug withdrawal as well as by its distinctive morphology.

Aged↗
PubMed1989

Human lens membrane cation permeability increases with age.

Parallel studies of the ionic balance and membrane permeability characteristics of normal human lenses were carried out in three countries (USA, England and Italy). Similar age-related changes were found in each laboratory. The lens membrane potential and resistance declined markedly with age while internal Na+ and free Ca2+ increased. There was a concomitant stimulation of Na+ and K+ transmembrane fluxes. These data indicate that in the ageing process there is an increasing contribution to membrane ion traffic from a channel, or channels, that permit Na+, K+ and Ca2+ to pass. The increase in permeability coincides exactly with the increase in optical density that occurs in the ageing human lens.

Adult↗
PubMed1988

Membrane and junctional properties of the isolated frog lens epithelium.

The isolated frog lens epithelium can be maintained intact in both appearance and electrical properties for more than 24 hours. The mean resting membrane potential was -80 mV and the cells were depolarized by both high potassium and low calcium Ringer's solution in a manner very similar to that of the whole lens. The epithelial cells were found to be well coupled using both electrical and dye-injection techniques. Electrical coupling was measured using separate current-injection and voltage-measuring electrodes and the relationship between the induced voltage and distance from the current-passing electrode could be well fitted by a Bessel Function solution to the cable equation. The values obtained from the fit for the membrane and internal resistances were 1.95 omega m2 and 25 omega m, respectively. Exposure to octanol (500 microM) or low external Ca2+ (less than 1 microM) failed to disrupt significantly the intercellular flow of current. There was evidence to suggest that raised intracellular calcium does, however, uncouple the cells. Dye coupling was investigated by microinjecting Lucifer Yellow CH into single epithelial cells. Diffusion into surrounding cells was rapid and, in control medium, occurred in a radially symmetrical manner. In contrast to the electrical coupling data, dye transfer appeared to be blocked by exposure to 500 microM octanol and was severely restricted on perfusing with low external calcium. Differences between the electrical and dye-coupling experiments indicate either that there are two types of junction within the cell and only the larger type, permeable to Lucifer Yellow, is capable of being uncoupled or that there is only one large type of junction which can be partially closed by uncoupling agents.

Animals↗
PubMed1988

Diamide alters membrane Na+ and K+ conductances and increases internal resistance in the isolated rat lens.

The voltage and conductance of the isolated rat lens were measured using a two-internal-microelectrode technique and the potassium permeability was calculated by applying Goldman theory to 86Rb efflux data. The SH oxidizing agent diamide induces a multiphasic response in lens voltage, conductance and potassium permeability. The initial response (less than or equal to 30 min) to 1 mM diamide consists of a small depolarization (approximately 10 mV) of membrane potential accompanied by a significant decrease in conductance. The 86Rb efflux and permeability data also show an initial decrease. As this initial response is abolished by TEA (20 mM) it is probably due to an inactivation of voltage-sensitive potassium channels. After 30 min exposure to 1 mM diamide both the electrical conductance and the rate of depolarization increase. The 86Rb permeability also increases. Since the conductance increase is abolished by replacing Na+ by methyl glucamine and as it is reduced by amiloride (10(-4) M) the second phase is probably due to the activation of nonspecific cation channels. The third phase is only apparent after prolonged (approximately 12 hr) incubation in 1 mM diamide and consists of a marked increase in the bulk resistance component of the lens impedance. It is suggested that this component arises from an increase in the resistance of the fibre cell gap junctions. This cellular uncoupling may be due to calcium entering the lens through the nonspecific cation channels.

Amiloride↗