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Biomedical subjects

G Duncan

Publications and source records attributed to G Duncan.

At least 127 records · Page 7Linked to original sources
PubMed1988

Efflux of chloride from the rat lens: influence of membrane potential and intracellular acidification.

The efflux of 36C1 from perifused rat lenses consisted of two components: a fast (extracellular) component and a slow (cellular) component. The 36C1 efflux rate constant of the cellular component was 5.7 X 10(-3) min-1. The 36C1- efflux was sensitive to changes in lens potential induced by treatment with high-K+ solutions. The decrease in the 36C1- efflux rate constant caused by high-K+ solutions was consistent with the Goldman model, indicating that, under normal conditions, the majority of the 36C1 efflux is by diffusion. The 36C1- efflux rate constant corresponds to a C1 permeability of 1.3 X 10(8) ms 1. The C1- channel inhibitor anthracene-9-carboxylate (A-9-C), however, caused a relatively small reduction in the efflux rate constant. The anion-exchange inhibitor 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulphonate (SITS) has little effect on the 36C1 efflux under control conditions. Intracellular acidification, induced by pre-treatment with NH1+, leads to a rapid stimulation of 36C1- efflux. This increased 36C1- efflux is blocked by SITS. Thus, it appears that at low intracellular pH (pH), a normally quiescent, SITS-sensitive, anion-exchange mechanism is activated. The possible role of this exchange mechanism in regulating pH, is discussed.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗
PubMed1988

The influence of pH on membrane conductance and intercellular resistance in the rat lens.

1. The conductance of the rat lens was measured using a two-internal-microelectrode technique. The voltage response to a step of current consisted of two components arising from bulk and membrane resistance respectively. 2. The potassium permeability was calculated by applying Goldman theory to 86Rb+ efflux data. 3. The internal pH (pHi) and internal free calcium (pCai) were measured directly using single- and double-barrelled ion-sensitive microelectrodes. 4. Lens pHi was 6.9 in control solution (external pH, pHo = 7.3) and was reduced on lowering pHo. The presence of propionate or 100% CO2 in the external solution accentuated this effect. 5. Internal acidification was accompanied by a depolarization of membrane potential, an increase in membrane and cell-to-cell resistance and a decrease in potassium permeability. The acidification had no effect on pCai. 6. The intracellular pH was increased by perifusing with trimethylamine or NH4Cl. Both treatments induced a membrane depolarization with little change in potassium permeability. Subsequent removal of NH4Cl led to a sustained decrease in pHi. 7. In every case where pHi decreased, the changes in membrane potential and conductance could be explained largely on the basis of a decrease in potassium permeability. The concomitant increase in cell-to-cell resistance was less pronounced and probably insufficient to uncouple the lens system.

Animals↗
PubMed1988

p-chloro-mercuriphenyl sulphonate activates a quinine-sensitive potassium conductance in frog lens.

1. The effects of the sulphydryl-complexing reagent p-chloro-mercuriphenyl sulphonate (pCMPS) on membrane voltage and electrical conductance were studied on the isolated frog lens. 2. At low concentrations (0.1-50 microM) pCMPS induced a rapid and graded hyperpolarization of the lens membrane potential which saturated at -97 mV. 3. The lens conductance also showed a graded increase, but the initial changes were apparent only at concentrations above 1 microM. 4. Decreasing the external potassium concentration from 2.5 to 0.5 mM had little effect on the membrane potential in the absence of pCMPS, but increased the voltage from -97 to -110 mV when pCMPS was present. 5. Quinine (300 microM) had no effect when added in control solution, but depolarized the membrane potential and decreased the conductance when added to a pCMPS-treated preparation. 6. These data suggest that pCMPS activates voltage-sensitive potassium channels that are quiescent at the frog resting potential in control solution. 7. At pCMPS concentrations greater than or equal to 100 microM, the initial hyperpolarization is followed by a marked but slow depolarization of the membrane potential and a further increase in lens conductance. These data suggest that non-specific cation channels are activated in this case. 8. Cysteine (5 mM) added to a pCMPS-treated lens leads to a rapid recovery of membrane potential and conductance to near their resting values whether the lens had previously been exposed to low or high concentrations of pCMPS. 9. All of these changes in lens voltage and conductance occurred without apparent alteration in the lens internal sulphydryl content.

4-Chloromercuribenzenesulfonate↗
PubMed1988

Oxidative cross-linking of fodrin parallels a membrane conductance increase in the mammalian lens.

An oxidative cross-linking of the lens spectrin-like protein fodrin was induced by incubating WKY-rat lenses in the presence of the SH-reagent diamide. The oxidation of fodrin was paralleled by an increase in lens membrane conductance. The time relationship between these two events as well as the reversibility of both, achieved by incubating the lens in the presence of dithiothreitol, indicate that normal permeability characteristics of the lens membranes require the integrity of the membrane attached cytoskeleton.

Animals↗
PubMed1988

Membrane and communication properties of tissue cultured human lens epithelial cells.

Explant cultures were established from capsule/epithelium preparations from both normal and cataractous lenses to investigate properties of human lens epithelial cells. The cultured cells were found to have similar membrane potentials to whole human lenses and isolated epithelia, and similar free ionic concentrations of potassium, sodium, and calcium (131 mM, 17 mM and 0.8 microM respectively) to whole human lenses. The free ionic concentrations were measured in both cases using neutral resin-filled electrodes. Cellular communication was investigated using electrical (two internal microelectrodes) and dye injection techniques. The electrical resistance of a confluent cell monolayer was approximately 4 M omega when the voltage measuring and current passing microelectrodes were in neighbouring cells or several cell diameters apart. Additionally, Lucifer Yellow dye injected into one cell spread rapidly over a wide area of cells. The cells thus appear to be extremely well coupled. Electrical communication could be disrupted by internal acidification (following exposure to 100% CO2), exposure to 1 mM octanol and by membrane depolarization. In the latter case the blockade was only partial. All uncoupling methods proved to be reversible. The diffusion of Lucifer Yellow dye was also inhibited by internal acidification and exposure to octanol. The sensitivity of both dye and electrical coupling to internal acidification and exposure to octanol is similar to that observed in hepatocytes and other tissues, whereas the effect on cell communication induced by changing the resting potential appears to occur only in a few cell types such as those of embryonic origin.

Carbon Dioxide↗
PubMed1987

Colchicine myopathy and neuropathy.

Although colchicine has been used for centuries, its neuromuscular toxicity in humans is largely unrecognized. In this report we describe a characteristic syndrome of myopathy and neuropathy and present 12 new cases of the condition. Colchicine myopathy may occur in patients with gout who take customary doses of the drug but who have elevated plasma drug levels because of altered renal function. It usually presents with proximal weakness and always presents with elevation of serum creatine kinase; both features remit within three to four weeks after the drug is discontinued. The accompanying axonal polyneuropathy is mild and resolves slowly. Electromyography of proximal muscles shows a myopathy that is marked by abnormal spontaneous activity. Because of these features, colchicine myoneuropathy is usually misdiagnosed initially, either as probable polymyositis or as uremic neuropathy. The myopathy is vacuolar, marked by accumulation of lysosomes and autophagic vacuoles unrelated to necrosis or to the mild denervation in distal muscles. The morphologic changes in muscle suggest that the pathogenesis involves disruption of a microtubule-dependent cytoskeletal network that interacts with lysosomes. Correct diagnosis may save patients with this disorder from inappropriate therapy.

Action Potentials↗
PubMed1987

Membrane conductance and potassium permeability of the rat lens.

The membrane potential, electrical impedance and 86Rb+ efflux rate constants were measured in the rat lens perifused at 35 degrees C. The membrane conductance was obtained from the difference between the magnitude of the impedance at low (less than 0.1 Hz) and high (greater than 100 Hz) frequencies. Values of the rubidium permeability coefficients (PRb) were obtained from the rate constant and potential data. The values for the membrane potential and conductance in control solution (5 mM potassium) were -69.6 mV and 5.5 X 10(-4) S respectively, while the computed permeability was 2.9 X 10(-8) m.s-1. On perifusing with 35 mM potassium, the membrane depolarized by 25 mV and the conductance and rubidium permeability increased considerably. These increases could be blocked by quinine (0.3 mM), tetraethylammonium (30 mM) and 4-aminopyridine (10 mM). The latter agent was more effective at alkaline pH (8.3). It is suggested that there are voltage-gated potassium channels that are inhibited by these three agents. After the initial depolarization in high potassium, there was little further change in membrane potential with any of the inhibitors. All three agents, however, produced a marked depolarization when applied in control solution. This was accompanied by a decrease in conductance and rubidium permeability, suggesting that, in the rat lens, some voltage-gated potassium channels are activated at the resting potential.

4-Aminopyridine↗
PubMed1987

Amino acid transport and protein synthesis in human normal and cataractous lenses.

The ability of normal and cataractous human lenses to accumulate amino acids and synthesize proteins was studied under organ culture conditions. As expected, normal lenses regulate their internal ion levels, accumulate amino acids against a concentration gradient, and continue to synthesize proteins even in advanced age (greater than 60 yrs). The cataractous lenses fell basically into two groups. Those with a low internal sodium and calcium content behaved in a similar manner to normal lenses, but cataractous lenses with high sodium and calcium contents showed a markedly reduced ability to accumulate amino acid and synthesized less low molecular weight protein. They incorporated, however, a much higher proportion of labelled amino acid into high molecular weight protein. While sodium appears to be the ion involved in changes in amino acid accumulation, calcium seems to play a critical role in the disturbance of lens protein synthesis and also protein-protein interaction. Both loss of protein and accumulation of high molecular weight aggregates may be due to modifications induced by the calcium-activated protease, calpain. None of the changes appeared to be correlated with increasing nuclear brunescence.

Amino Acids↗
PubMed1986

Dorsal horn opiate administration attenuates the perceived intensity of noxious heat stimulation in behaving monkey.

In monkeys trained to detect and discriminate noxious heat stimuli, morphine microinjected into the medullary dorsal horn attenuated the perceived intensity of noxious heat in a dose- and stimulus-dependent fashion. These data demonstrate a pharmacologically specific effect of opiates on the sensory intensity component of pain at the earliest central relay pathway transmitting noxious information.

Animals↗
PubMed1986

Evaluation of fetal thigh circumference measurements: a comparative ultrasound and anatomical study.

This investigation is concerned with establishing the anatomical location of the site proposed for making fetal thigh circumference (ThC) measurements with ultrasound. An evaluation of the accuracy of ultrasonic ThC measurements has also been made. The results of these studies indicate that the change in femur profile (polygonal to oval) used to identify the site of measurement (transition plane) occurs at the junction of the upper and middle thirds of the thigh, at the level of the proximal nutrient foramen of the femur. Ultrasonic ThC measurements are systematically larger (mean: 4.3%; range: 1.3-10.3%) than comparable anatomical measurements. Measurements made within 1-2 cm of the transition plane are quite similar, demonstrating that exact positioning of the plane is not necessary. These results indicate that ThC measurements can be made in a reliable manner and thus could be used to detect changes in soft tissue mass and improve weight estimation procedures.

Female↗
PubMed1986

Fetal thigh circumference: a critical evaluation of its relationship to menstrual age.

To provide standards for evaluating fetal thigh circumference measurements obtained with ultrasound, a study of the growth of this parameter during pregnancy was made. Because of possible sampling problems before 22 weeks (menstrual age), this investigation was limited to the 22-40 week time period. Regression analysis indicated that the optimal model (R2 = 88.9%) for describing thigh circumference (ThC) growth was a power function. ThC variability increased with menstrual age, from 1.3 cm at 22 weeks to 3.1 cm at 40 weeks. These data were used to construct a standard growth curve for the ThC.

Female↗
PubMed1986

Membrane permeability characteristics of perfused human senile cataractous lenses.

Human cataractous lenses were removed by the cryoprobe technique and were maintained for up to 24 hr in a solution of similar ionic composition to human aqueous humour. The bimodal distribution of internal sodium concentrations was similar to that previously reported for unincubated human lenses. Lenses with lower total and free sodium contents had relatively higher membrane potentials and they lost 86Rb at a slower rate than lenses with high internal sodium. The 86Rb efflux in these lenses was stimulated four-fold by removing external calcium. The efflux was reduced by increasing external calcium, but was increased during a small (60 mosmol) hyperosmotic shock. A similar hyperosmotic shock also surprisingly increased 86Rb efflux. Lenses with increasing internal sodium (and calcium) levels showed an increasing rate of loss of 86Rb and the stimulation by calcium removal was progressively diminished. The efflux from lenses with disturbed ion levels was also relatively insensitive to changes in external osmolarity and to increasing external potassium. Lenses with raised sodium concentrations also had an increased inulin space. Frog, rat and rabbit lenses were also exposed to the same range of stimuli and only frog lenses responded to the low calcium solution with more than a four-fold increase in efflux rate. Although only a two- to four-fold increase in efflux rate was obtained from rabbit lenses exposed to Ca-free conditions, this was the only type of animal lens so far tested that, like the human lens, responded to both hyperosmotic and isosmotic shocks with an increase in efflux rate. All three species of mammalian lenses responded with an increase in efflux rate when exposed to a hyperosmotic test solution while in the frog, the efflux rate from the lens decreased. The glucose efflux from human cataractous lenses was inhibited by cytochalasin B in a similar manner to the efflux from rat and frog lenses. It was concluded, therefore, that the cryoprobed human lens can be kept for a limited period in a relative simple artificial aqueous humour solution. The potassium permeability characteristics of low sodium cataracts remained relatively intact and showed a unique response (relative to lenses from other animals) when exposed to various stimuli that are known to be potentially cataractogenic.

Animals↗
PubMed1986

Calcium-induced opacification and loss of protein in the organ-cultured bovine lens.

A long-term system of organ culture for bovine lenses was used to investigate the effect of osmotic stress on lens opacification and crystallin loss. Lenses were pre-incubated in control medium containing L-[U-14C]tyrosine so that labelled crystallins were produced. The fate of these crystallins was studied in relation to two forms of osmotic stress. The addition of either ouabain or EGTA to the medium induced severe osmotic swelling and disturbance of the lens monovalent cation balance, but only the former treatment was followed by an increase in lens calcium. The changes due to osmotic stress were accompanied by loss of transparency and protein only in the lenses with increased calcium. Both opacification and increased calcium were found largely to be confined to the outer cortical fibres. Protein loss increased with time as lens calcium continued to increase. The protein recovered from the incubation medium was characterized by gel filtration and immunological techniques. The first protein detected was beta L-crystallin, and this formed the major part of the lost protein throughout, although alpha- and gamma-crystallins were detected at a later stage. Increased calcium also resulted in a change in the susceptibility of the crystallins to aggregation, since there was an increase in [14C]tyrosine incorporated into the lens high-molecular-weight (HM) fraction after exposure to ouabain, but not after exposure to EGTA. The relevance of these findings to human cataract is discussed.

Animals↗
PubMed1985

Direct measurement of pH in the rat lens by ion-sensitive microelectrodes.

The resting pH of the rat lens was determined using H+-sensitive liquid membrane microelectrodes and found to be 6.89 when measured in a perifusing solution of pH 7.20. The pH of the rat vitreous humour was also measured and was found to be 7.25. Attempts were made to perturb the lens pH by varying the pH of the perifusate. In the presence of alkaline solutions, the lens was able to maintain its resting pH and membrane potential but, upon perfusion with a more acidic solution, the lenticular pH equilibrated with the pH of the bathing solution and the potential depolarized. The internal pH could be manipulated independently of the external pH by perfusing the lens with Ringer solution containing 20 mM ammonium chloride. The ammonium chloride induced a rapid alkalinization and the return to control solution caused a fall in pH to below the normal resting level. The biphasic pH response to ammonium chloride was accompanied by changes in lens transparency and membrane potential.

Ammonium Chloride↗
PubMed1985

Operantly conditioned running: effects on brain catecholamine concentrations and receptor densities in the rat.

It was hypothesized that endurance exercise results in an alteration in the brain monoamine systems. Rats were trained to run for food reinforcement on a variable ratio schedule in running wheels. Yoked control rats were also allowed to run but were not specifically reinforced for running. The animals ran 5 days per week for 8 weeks and were sacrificed 48 hours after the last endurance training session. The brains were assayed for norepinephrine and dopamine concentrations and beta-adrenergic (3H-dihydroalprenolol binding) and dopaminergic (3H-spiroperidol binding) receptor densities. Changes in norepinephrine concentration and beta-adrenergic receptor densities were not significantly different between reinforced running and yoked control groups. Dopamine concentrations were significantly higher while dopamine receptor densities were significantly lower in the reinforced running group. These results suggest that chronic running elevates dopamine secretion and consequently produces a compensatory down-regulation of dopaminergic receptor sites. The relationship of these changes to motor activity and to the antidepressant effects of exercise are discussed.

Animals↗
PubMed1985

Amiodarone: risk factors for recurrence of symptomatic ventricular tachycardia identified at electrophysiologic study.

Ventricular tachycardia induced by programmed electrical stimulation during amiodarone therapy often does not preclude a good clinical response. The purpose of this study was to determine whether use of discriminant analysis could distinguish patients who remained asymptomatic from those who subsequently developed symptomatic ventricular tachycardia or cardiac arrest. Studies were performed in 37 patients with sustained ventricular tachycardia who still had ventricular tachycardia induced during programmed electrical stimulation during amiodarone therapy. The mean follow-up time was 14.1 +/- 1.3 months (+/- SEM). Twenty-three patients remained asymptomatic, whereas 14 patients had symptomatic recurrence of their ventricular tachycardia. In patients with recurrence of arrhythmia compared with asymptomatic patients, administration of amiodarone caused a longer ventricular effective refractory period (296 +/- 8 versus 271 +/- 7 ms, p less than 0.05) and a greater change in corrected QT [QTc] interval (90 +/- 18 versus 44 +/- 9 ms, p less than 0.02), but no difference in the decrease in premature ventricular complexes after treatment with amiodarone. During amiodarone therapy, nonbundle branch reentrant repetitive ventricular responses were induced by a single ventricular extrastimulus during sinus rhythm in 9 of 14 patients with recurrent arrhythmias compared with 2 of 21 asymptomatic patients (p = 0.001). Also, less aggressive pacing techniques were required to induce ventricular tachycardia in 9 of 14 symptomatic patients compared with 4 of 23 asymptomatic patients (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Amiodarone↗
PubMed1985

Adverse effect of smoking on the hyperaemic response in diabetic patients and control subjects.

In order to determine whether smoking had an adverse effect on the hyperaemic response, as measured by transcutaneous oximetry, matched groups of insulin-dependent diabetic smokers and non-smokers were compared both with each other and with similar matched groups of non-diabetic control subjects. The hyperaemic response was also measured immediately, 1 hour and 24 hours after smoking a cigarette in five control subjects who smoked. The hyperaemic response was significantly lower in the diabetic smokers compared with the diabetic non-smokers (p = 0.008) and in the control smokers compared with the control non-smokers (p = 0.011). No other significant differences were found. In the five subjects studied at intervals after smoking the responses were variable and inconsistent. Smoking modifies the hyperaemic response and this must be taken into account in any investigation using such measurements.

Adult↗