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Biomedical subjects

R E Olver

Publications and source records attributed to R E Olver.

At least 55 records · Page 3Linked to original sources
PubMed1989

Transport of sodium into apical membrane vesicles prepared from fetal sheep alveolar type II cells.

A method is described for isolating apical plasma membrane vesicles from fetal alveolar type II cells. The procedure yields purified apical membranes which are enriched 24-fold with the brush-border enzyme marker, alkaline phosphatase. Contamination of this fraction by basolateral membranes and organelles is minimal. Evidence for transport of Na+ into an intravesicular space is demonstrated by: (1) time-dependent uptake of Na+ with release of accumulated Na+ by treatment with detergent; (2) a linear inverse correlation between Na+ uptake and medium osmolarity. In addition, Na+ uptake is shown to be anion dependent (SCN- greater than Cl- greater than gluconate-) and sensitive to amiloride inhibition at a concentration of 1 mM.

Amiloride↗
PubMed1986

Sodium and chloride transport by the tracheal epithelium of fetal, new-born and adult sheep.

In vitro measurements were made of Na+ and Cl- isotopic fluxes across the tracheal epithelium of mature fetal lambs (130-143 days gestation), new-born lambs (up to 41 days of age) and adult sheep under conditions of continuous short circuiting. The effects of a variety of drugs were examined, but only in the case of amiloride and isoprenaline were observations made in all three groups. Experiments designed to elucidate the mechanism of basal Cl- secretion were performed in adult trachea only. Under resting conditions the net flux of Na+ from lumen to submucosa exceeds that of Cl- in the reverse direction in fetal and adult trachea. In the new-born the two fluxes are more or less equivalent in magnitude. In none of the three groups is the sum of ion fluxes significantly different from the short-circuit current (Isc). Removal of Na+ from, or addition of furosemide (10(-3) M) to, the solution bathing the submucosal surface of adult trachea has the effect of reducing Isc by an amount which approximates to the Cl- current (29%). At a concentration of 10(-4) M on the submucosal side of adult trachea, ouabain causes potential difference and Isc to fall to zero within 70 min of addition to the bathing solution. Nevertheless, there remains a significant net Na+ flux from submucosa to lumen. The addition of isoprenaline (10(-4) M) to the medium bathing the submucosal surface of both fetal and adult trachea causes an increase in the one-way flux of Cl- from submucosa to lumen with consequent increase in net Cl- flux towards the lumen. (The Na+ fluxes are unchanged.) However, in the adult the Cl- secretory response to isoprenaline is very much less and is not accompanied by an increase in electrical conductance. As judged by the change in Isc, all the post-natal fall in beta-agonist responsiveness takes place within the 3 week period following birth. Whereas, in the fetus, the effect of luminally applied amiloride on the Na+ fluxes is negligible, in the adult the one-way flux of Na+ from lumen to submucosa is reduced by 35% with a consequent 60% fall in net Na+ flux towards the submucosa.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗
PubMed1986

The role of amiloride-blockable sodium transport in adrenaline-induced lung liquid reabsorption in the fetal lamb.

Adrenaline was infused intravenously at rates of 0.1-1.0 microgram/min into chronically catheterized fetal lambs (125-141 days gestation) to induce slowing of secretion or reabsorption of lung liquid. There was an electrical potential difference (p.d.) of -0.3 to -9.5 mV (mean -3.4 mV) between lung liquid and plasma (lung liquid negative) during control lung liquid secretion. In response to adrenaline infusion, the p.d. increased (lung lumen more negative) and this change was greatest (1.8 +/- 0.3 mV) in experiments in which reabsorption occurred. Measurements were made of bidirectional fluxes of Na+ and Cl- across the pulmonary epithelium during control lung liquid secretion and during adrenaline infusion. Adrenaline-induced reabsorption of lung liquid was associated with an increase in Na+ flux from lung lumen to plasma. Similar but smaller changes occurred when the adrenaline response was slowing of secretion. The difference between measured flux ratios and those predicted from the forces determining passive flux provided evidence for active transport of Cl- from plasma to lung lumen, as previously demonstrated by Olver & Strang (1974). When adrenaline was infused, there was evidence of active Na+ transport in the direction lung lumen to plasma and an associated decrease in active Cl- transport in the opposite direction. These changes were greatest when the response to adrenaline was reabsorption. Amiloride, when mixed into the lung liquid to give a calculated concentration of 10(-4) M, abolished the changes in p.d. and ion flux induced by adrenaline. In experiments using amiloride concentrations between 10(-8) and 10(-4) M it was shown that 50% inhibition of the reabsorptive response to adrenaline (KI) was induced by 4 X 10(-6) M-amiloride in the lung lumen. Thus adrenaline-induced slowing of secretion or reabsorption of lung liquid is mediated by active Na+ transport from lung lumen to plasma and depends on amiloride-inhibitable Na+ channels on the luminal surface of the pulmonary epithelium.

Absorption↗
PubMed1984

Domestic metallic mercury poisoning.

In a family exposed to metallic mercury vapour two patients had acrodynia, one had the nephrotic syndrome, and one person remained well. Recognition of the variable manifestations of the disease and prevention of further exposure were the most important aspects of management. Recovery appeared to be complete as blood mercury levels fell to normal. Urinary mercury levels were too variable to be reliable as indications of progress.

Accidents, Home↗
PubMed1983

Effects of adrenaline and of spontaneous labour on the secretion and absorption of lung liquid in the fetal lamb.

In the chronically catheterized fetal lamb, intravenous infusion of adrenaline at 0.5 microgram/min produced slowing of the secretion of lung liquid or its absorption, an effect which increased exponentially with advancing gestation. Between 120 and 130 days, the characteristic response was slowing of secretion, whereas after 130 days it was absorption. Stimulus-response curves, relating secretion or absorption rate to plasma adrenaline concentration, were obtained by infusing adrenaline into the fetus intravenously at rates between 0.1 and 1.0 microgram/min (0.55-5.5 nmol/min). These curves allowed estimation of the minimum concentration of adrenaline required to inhibit secretion [( Ai]) and this was found to decrease from 0.43 ng/ml. (2.35 nM) at 132-4 days' gestation to 0.029 ng/ml. (0.16 nM) at gestations above 140 days. During spontaneous labour there was a slowing of lung liquid secretion in the early stages followed by absorption during the last 50-150 min. The mean concentration of adrenaline in plasma increased from 0.087 ng/ml. (0.48 nM) in early labour to 6.86 ng/ml. (37.5 nM) in the last 50 min and to 7.17 ng/ml. (39.2 nM) in the early post-natal period. Mean noradrenaline levels at the same times were 1.71 ng/ml. (10.1 nM), 12.14 ng/ml. (71.8 nM) and 9.10 ng/ml. (53.9 nM). The relationship between the plasma adrenaline concentration and the rate of absorption during labour was similar to that found when adrenaline was infused at various rates into the non-labouring fetus of comparable gestational age. The upper airway of the fetus was shown to be capable of acting as a one-way valve allowing outflow but not inflow of liquid. Thus withdrawal of liquid at 5-20 ml./hr from the fetal trachea below the larynx caused closure of the upper airway and this result was obtained both when the recurrent laryngeal nerves were intact and when they were divided.

Absorption↗
PubMed1981

Epithelial solute permeability, ion transport and tight junction morphology in the developing lung of the fetal lamb.

1. Experiments were performed on exteriorized fetal lambs of between 69 days' gestation and term (147 days) in order to observe changes in lung volume and lung liquid secretion rate, and to delineate any alterations in solute permeability, ion transport and tight junction morphology in the maturing lung epithelium. Whilst it was technically possible to measure solute permeability as early as 69 days it was not feasible to apply the Ussing flux ratio technique before 84 days.2. Fetal lung liquid volume and secretion rate, when normalized for body weight, increase linearly with gestation, whereas tracheal volume expressed in the same manner remains constant.3. When expressed in terms of pore theory, epithelial permeability to small polar non-electrolytes does not change between 69 days and term (equivalent pore radius 0.66 nm and 0.64 nm respectively).4. In the immature fetus of 69-76 days, mean epithelial tight junction strand number is 8.3, whereas by the end of gestation it has fallen to 4.6.5. The transfer constants (min(-1)) for sodium and chloride movement in the direction lung liquid to plasma are, respectively, some 6 and 4 times greater at 84-87 days than at term.6. As in the mature fetus, the lung epithelium at 84-87 days actively transports chloride from plasma to lung lumen, albeit with a slightly reduced transport e.m.f. Sodium movement does not, at any gestational age, differ from the predictions for passive transfer.7. In lung liquid the concentrations of chloride and potassium increase and that of bicarbonate decreases during gestation, whilst that of sodium does not change. The rises in lung liquid chloride and potassium concentrations follow those in plasma, maintaining plasma/lung liquid ratios of 0.7 and 0.95 respectively. However, plasma bicarbonate remains constant and the plasma/lung liquid ratio for bicarbonate rises from 3 at 69-76 days to 20 near term as the lung liquid bicarbonate falls from 9.8 to under 2 m-mole kg(-1) H(2)O.8. Whereas lung liquid protein concentration remains constant and low at about 0.35 g l.(-1), plasma protein concentration rises from 23 g l.(-1) at 69-76 days to 43 g l.(-1) near term. During the same period arterial blood pressure doubles.

Animals↗
PubMed1978

The role of catecholamines in lung liquid absorption at birth.

We have examined the effect on lung liquid secretion of catecholamines infused in chronically catheterized fetal lambs in utero. Isoproterenol and epinephrine inhibited secretion, an effect which increased with gestation and, in fetuses near delivery, caused absorption of lung liquid. In 7 out of 8 experiments nor-epinephrine had no effect on secretion. This pattern of response and the fact that the inhibitory effect could be blocked by propranolol indicate a mode of action involving beta-adrenergic receptors.

Animals↗
PubMed1978

Development of intercellular junctions in the pulmonary epithelium of the foetal lamb.

The integrity of epithelial tight junctions in foetal mammalian lungs is essential to maintain the unique ionic composition of lung liquid, and to prevent leakage of serum proteins into peripheral air spaces. In the present study the development of intercellular junctions of the lining epithelium of foetal lamb lungs during gestation was examined by light and electron microscopy. Both thin sections and freeze-fracture replicas were examined by electron microscopy. By 39 days of gestation, epithelial tight junctions consist of a minimum of 3.1 +/- 1.6 (s.D.) and a maximum of 5.8 +/- 2.0 discontinuous rows of particles and short segments of strands on P face ridges and in complementary E face grooves, while from 58 to 76 days they are composed of a network of 4.3 +/- 1.6 to 7.7 +/- 1.9 focally interrupted P face strands. Complementary replicas show that many of the discontinuities on the P face are due to separation of junctional particles on to the E face during fracturing, and not to an absence of junctional particles. From 76 days to term, epithelial tight junctions (exclusive of upper airway epithelium which was not examined) resemble those of adult lungs, and consist of a continuous network of 4.5 +/- 2.0 to 7.5 +/- 2.5 P face strands and complementary particle-free grooves. Permeability measurements, published elsewhere, indicate that the epithelium is functionally 'tight' from 69 days onwards. Tight junctions in peripheral air-space epithelium, therefore, are structurally continuous and functionally 'tight' early in foetal lung development, and form seals at one end of long, narrow intercellular spaces; these features may be important for coupled ion and water transport. When the bounding epithelial cells become flattened, these narrow intercellular spaces remain intact as a result of complex interdigitations of adjacent cell membranes. Desmosomes were present throughout gestation near the abluminal side of the tight junctions and occasionally near the base of the intercellular space. These junctions may serve to connect cells to each other at a time when tight junctions may be mechanically weak. In addition, gap junctions are associated with tight junctions from the glandular through the canalicular stages of lung development. They disappear by 120 days when the epithelial cells are differentiated.

Animals↗
PubMed1976

Ion transport and water flow in the mammalian lung.

The coupling of bulk water flow to active ion transport has been described in various epithelia; evidence presented here suggests that this is also a feature of the mammalian lung. Measurements of the ionic composition of lung liquid and its rate of formation in the fetal lamb in vivo have made it possible to estimate the net flux of each ion and, with water tracer measurements of ion one-way fluxes, to calculate flux ratios. When these are compared with the ratios predicted by the Ussing flux ratio equation it is clear that the secretion of lung liquid is linked to active transport of Cl- from plasma; sodium moves passively. In addition there is an apparent uphill transfer of HCO2- out of lung liquid. In an in vitro preparation of adult canine trachea Cl- is actively transported towards the lumen and is associated with a small net flux of Na+ in the opposite direction. Addition of acetylcholine increases the net Cl- flux towards the lumen but reverses the orientation of the net Na+ flux. Changes such as these may be important determinants of bulk liquid flow in vivo as well as in vitro.

Animals↗
PubMed1976

Lung inflation and alveolar permeability to non-electrolytes in the adult sheep in vivo.

1. Experiments were performed on adult sheep to determine the effect of lung distension on the passive permeability of alveoli to water soluble non-electrolytes. With the animal breathing oxygen spontaneously, a segment of one lung was isolated by passing a balloon-tipped catheter through a tracheostomy into a distal bronchus. This isolated atelectatic segment was filled with an isosomotic saline solution containing radio-labelled solutes of known molecular size: [125I]albumin, [14C]inulin, [14C]-sucrose, [3H]mannitol, and [14C]urea. The segment was inflated with oxygen either to a preselected pressure, or to a predetermined fraction of its capacity. Inflation was then maintained for several 10-15 min periods between which the oxygen supply was disconnected and the saline sampled, allowing the tracer concentrations to be measured. 2. At low inflating pressures (20-32 cmH2O) and at low volumes (24-54% of capacity), alveolar permeability to water soluble solutes was slight and could be characterized in terms of a membrane penetrated by cylindrical water filled pores of 0-5-1-6 nm radius. In all experiments showing restricted diffusion, absorption of saline occurred. 3. There was a positive correlation between the degree of lung inflation and pore radius in both the pressure controlled and volume controlled experiments. At high inflating pressures and at inflation volumes which were close to the total capacity of the isolated segment, restriction of solute diffusion was lost; in five out of six such experiments there was a net movement of liquid into the alveoli. 4. These results can be explained by postulating that as the lung epithelium is progressively stretched there is an opening up of water filled channels between alveolar cells. At peak inflation, restriction of diffusion of water soluble solutes is lost, and the alveolar epithelium ceases to function as a barrier between the circulation and air spaces.

Albumins↗
PubMed1975

Changes in non-electrolyte permeability of alveoli and the absorption of lung liquid at the start of breathing in the lamb.

1. Experiments were done on mature foetal lambs, 135-145 days in gestation, exteriorized at Caesarean section, and on new-born lambs aged 12-60 hr. In the foetal lambs, test substances were added to lung liquid and then spontaneous ventilation was induced or the lungs were statically inflated with gas or saline. In the new-born lambs, the left lung was ventilated in order to maintain respiratory gas-exchange, while foetal lung liquid, taken from previous experiments and containing test substances, was introduced into the right lung, which was then inflated with gas and used for permeability measurements. In both foetuses and new-borns, the gas used was O2 or N2O and, at 20 min intervals, ventilation or static inflation was interrupted, the gas in the lungs absorbed into the circulation and the remaining liquid sampled through the trachea. The following test substances were used in various combinations: [14C]-erythritol, [3H]sucrose, [14C]inulin, [131I]albumin, and the polymer [131I]-PVP. The last of these was separated, after the experiments, by gel filtration with Sephadex G200 or G50, into fractions of defined molecular radius. [131I]albumin, or a large molecule fraction of [131I]PVP, was used as a volume marker. 2. Spontaneous ventilation was associated with the absorption of liquid and with an alteration in the foetal pattern of non-electrolyte permeability that could be characterized by postulating an opening up of water-filled cylindrical pores to 34-56 A in radium. In the new-born lambs, the results suggested pores 7-14 A in radius. 3. Static inflation of the foetal lungs with gas, to pressures of 25-35 cmH2O, gave permeabilities appropriate for pores 5-5-12 A in radius. Static inflation with gas, to pressures of 41-49 cmH2O, produced changes appropriate for much larger channels, more than 125 A in radius and possibly much larger. With one exception, expansion with saline produced changes similar to those obtained by gas inflation to 25-35 cmH20. 4. It was concluded that in the initial stages of pulmonary ventilation a change takes place in alveolar epithelial cells. The increase in size would be sufficient to allow for rapid liquid absorption, but is not so great as to permit significant penetration by plasma albumin. The results obtained in the lung of the new-born lamb statically inflated to 25-32 cmH2O suggest that, following the initial adaptation, alveolar permeability returns towards the foetal pattern, although the pores remain larger than in the foetus. The change in permeability pattern at birth appears to depend on the degree of lung expansion with gas.

Absorption↗
PubMed1975

Active transport of Na+ and Cl- across the canine tracheal epithelium in vitro.

The flow of water across the tracheobronchial epithelium is likely to be an important determinant of the efficiency of mucociliary clearance. Because bulk water flow has been shown to be coupled to net ion flux in several epithelia, experiments were performed to determine whether ions are transported actively by the canine tracheal epithelium. Electrical potential difference, short circuit current, and the unidirectional fluxes of positive sodium ions (Na+) and negative chloride ions (Cl-) were measured using an in vitro preparation of the posterior membranous portion of canine trachea. The values of the electrical parameters were potential difference, 30.7 +/- 2.7 mV (SE; n = 30), lumen negative to submucosa; short circuit current, 108 +/- 8 muA per cm2 (SE; n = 30). Bidirectional fluxes of Na+ and Cl- were measured both with and without continuous short circuiting of the epithelium. Under short circuit conditions there was a unidirectional flux of Cl- toward the lumen of 7.4 +/- 1.2 muEq per cm2 per hour (SE; n = 6) and toward the submucosa of 4.7 +/- 1.1 muEq per cm2 per hour (SE; n = 6), resulting in a calculated net flux of Cl- of 2.7 +/- 0.6 muEq per cm2 per hour toward the lumen. The unidirectional flux of Na+ toward the lumen was 1.3 +/- 0.5 muEq per cm2 per hour (SE; n = 8) and toward the submucosa was 2.1 +/- 0.7 muEq per cm2 per hour (SE; n = 8). This resulted in a calculated net flux of Na+ of 0.8 +/- 0.2 muEq per cm2 per hour toward the submucosa. These fluxes are consistent with active transport and together they account for the entire short circuit current. Under open circuit conditions, the calculated net fluxes of Cl- and Na+ were not significantly different from zero.

Animals↗