Ethylenediaminetetraacetic acid tetracycline and toxicity of barium chloride and sodium fluoride.


Conduction velocity in myelinated nerve fibres of Xenopus laevis. 1. The relationship between conduction velocity and nerve diameter in single myelinated nerve fibres from Xenopus laevis was measured and was found to be linear.2. The relationship between conduction velocity and temperature in nerve fibres of various diameters was measured over the range 15-30 degrees C and was found to be linear for each fibre.3. The slope of the conduction velocity-temperature relationship was directly proportional to the diameter of the nerve fibre.4. The form of the conduction velocity-temperature relationship was determined by numerical solution of the Frankenhaeuser-Huxley equations for the case of a propagated action potential. The computation predicted that conduction velocity is a linear function of temperature over the range studied.


The response of some sympathetic neurones to volleys in various afferent nerves. 1. Responses of sympathetic neurones to various afferent inputs have been analysed both in anaesthetized cats with intact neuraxis and in spinal cats.2. In anaesthetized cats electrical stimulation of low threshold group III afferent fibres in skin and muscle nerves inhibited sympathetic neurones and gave depressor responses. The silent period following a sympathetic reflex discharge is most likely due to inhibition brought on by a particular subgroup within this afferent group.3. High threshold group III and group IV afferent fibres excited sympathetic neurones and elicited pressor responses.4. Sympathetic reflex arcs could be temporally facilitated during the somatic afferent induced inhibition, by group IV, and to a lesser extent by group III volleys.5. Section of the spinal cord shortened the time course and lessened the degree of group III inhibition suggesting that suprasegmental pathways are involved in the long-lasting depression following a reflex.6. Baroreceptor afferent stimulation inhibited group III- and group IV- evoked reflexes even with some temporal facilitation in the pathway.7. The special properties of the sympathetic reflex arcs and the relation of the results to other work on B.P. reflexes are discussed. It is suggested that the group III and IV muscle afferents have a chemoreceptor function and are responsible for mediation of the pressor reflex during muscle exercise.


The origin of human placental oxytocinase. 1. Placentas from normal women and from those with pre-eclamptic toxaemia, taken immediately after labour, were examined for oxytocinase activity and analysed morphometrically.2. Both enzyme activity and volume of syncytiotrophoblast were significantly reduced in placentas from patients with toxaemia.3. There was a positive correlation between the enzyme activity and the proportion of trophoblast in the placenta. When the activity was expressed per unit volume trophoblast, there was very little difference between placentas, whether from normal subjects or from patients with toxaemia.4. It is concluded that human placental oxytocinase is located in the syncytiotrophoblast.


The half-life of exogenous gastrin in the circulation. 1. A method of gastrin bio-assay is described which can be used on as little as 30 ng synthetic human gastrin I at a minimum concentration of 2.5 ng/ml.2. Pentagastrin or synthetic human gastrin I added to cat plasma can be stored on ice or at 4 degrees C, for periods up to 27 hr without apparent loss of gastrin activity.3. Between 1(1/2) and 13 min after the rapid I.V. injection of pentagastrin in the anaesthetized cat and between 1(1/2) and 15 min after the injection of synthetic human gastrin I, there is a rapid reduction of the gastrin concentration in the arterial plasma. The data relating log(10) gastrin concentration in arterial plasma with time can be fitted by a single term.4. Studies in vitro show that over the periods of time involved in the in vivo studies, both pentagastrin and synthetic human gastrin I are stable in cat plasma at 37 degrees C in concentrations which occurred in the circulating plasma.5. The half-life of pentagastrin in the circulating arterial plasma of the anaesthetized cat is 1.50 min (S.E. +/- 0.08) and the half-life of synthetic human gastrin I is 2.65 min (S.E. +/- 0.09).


Responses of unshorn and shorn sheep to thermal stress. 1. The effect of close shearing upon the respiratory frequency of ewes at ambient temperature of 20 degrees C and 55% relative humidity has been described.2. Removal of an adequate area of fleece (3000 cm(2) or more) on the thoraco-lumbar region resulted in a depression of respiratory responses and this was attributed to the exposure of cold receptors located beneath the fleece.3. The continued depression of respiratory frequency of partially shorn sheep (3000 cm(2)) during rising ambient temperature appears to be due to persistence of cold receptor drive originating from the shorn area.4. The absence of any rise in carotid blood temperature before the onset of polypnoea in unshorn sheep, during rising ambient temperature, suggests that the onset of panting in sheep can occur almost immediately upon a rise in ambient temperature even in the absence of any rise in the temperature of the blood supplying the brain.


Role of naso-buccal passages in thermoregulation in sheep. 1. Experiments with a face-mask in which the temperature of the air in the face-mask was raised to 40 degrees C while the ambient temperature in the chamber was maintained at 20 degrees C, resulted in a marked increase in respiratory frequency and a slight decline in carotid blood temperature of unshorn sheep. Partially shorn sheep showed only small respiratory responses.2. Localized infra-red irradiation of the naso-buccal area of unshorn sheep also resulted in an increased respiratory rate.3. It is suggested that the initiation of polypnoea during infra-red irradiation of the naso-buccal region and following rise in the temperature of the air in the face-mask is due to stimulation of warm receptors in the upper respiratory tract.4. Cooling the naso-buccal air in the face-mask to 10 degrees C after thermal polypnoea had been established at an ambient temperature of 40 degrees C resulted in a moderate decline of 30-40 respirations/min. This decline was attributed to the stimulation of cold receptors located in the upper respiratory tract.


Reflex onset of polypnoea in sheep.

Reflex onset of polypnoea in sheep. 1. Measurements have been made of the cardio-respiratory activities, ear and lumbar skin temperatures, and temperature of the blood in the carotid artery and jugular vein of partially shorn and unshorn sheep during mammary heating at ambient temperatures of 20/55, 15/55 and 10/55 (dry bulb temperature, degrees C/relative humidity,%).2. Heating the mammary region resulted in a marked rise in respiratory and heart rates of unshorn sheep, whereas, in partially shorn sheep, the heart rates increased without being accompanied by a similar rise in respiratory rates.3. With decrease in ambient temperature from 20 to 10 degrees C, there was a decrease in respiratory response of unshorn sheep during mammary heat treatment suggesting that the magnitude of respiratory response during mammary heat treatment depends on the environmental temperature to which the sheep is exposed.4. The carotid blood temperature declined following mammary heat treatment at all ambient temperatures studied, both in unshorn and partially shorn sheep, but the magnitude of decline was greater in unshorn than in partially shorn sheep.5. The rise in respiratory rates following mammary heating of unshorn sheep at all ambient temperatures, in spite of a decline in carotid blood temperature and the absence of similar responses during flank heating, is attributed to the stimulation of warm receptors in the mammary region.


Actions of noradrenaline and acetylcholine on sympathetic ganglion cells. 1. The responses of the post-synaptic membrane of sympathetic ganglion cells to noradrenaline (NA) and to acetylcholine (ACh) were studied in relation to the slow inhibitory post-synaptic potential (S-IPSP) and slow excitatory one (S-EPSP) respectively.2. NA produced an hyperpolarization of about 4 mV in cells of rabbit superior cervical ganglia.3. The hyperpolarizing response to NA was not accompanied by any detectable change in membrane resistance, and it was depressed by conditioning depolarization.4. NA also depressed all the post-synaptic potentials, presumably by an action on presynaptic function.5. ACh produced a large depolarization in ganglion cells of rabbit and of frog (paravertebral) ganglia, which was accompanied by a large decrease in membrane resistance.6. When ACh was applied during nicotinic blockade, achieved with high concentration of nicotine (frog ganglia) or D-tubocurarine (rabbit ganglia), it still produced a considerable depolarization. This response could be blocked by atropine, and is presumably a muscarinic type of action.7. The muscarinic-ACh response was not accompanied by a decrease in membrane resistance. Instead, the frog ganglion cells exhibited increased resistances of up to more than twice the resting value during both the muscarinic-ACh depolarization and the S-EPSP.8. The muscarinic-ACh depolarization and the S-EPSP were both depressed by conditioning hyperpolarization (in nicotinized frog cells). An initial hyperpolarizing phase now appeared in both of these responses.9. It is concluded that the hyperpolarizing response to NA and the depolarizing response to muscarinic-ACh action are not generated by increases in ionic mobilities in the post-synaptic membrane; and that these two responses are produced by the same electrogenic mechanisms which underlie the S-IPSP and the S-EPSP respectively.


Activity patterns in respiratory muscles and in respiratory neurones of the rostral medulla of the cat. 1. In the rostral medulla the activity patterns of respiratory neurones are of two main types: inspiratory and expiratory (Fig. 1). Some expiratory neurones begin activity early enough to fit Cohen & Wang's (1959) category of ;inspiratory-expiratory'. However, in the rostral medulla, ;inspiratory-expiratory' neurones do not constitute a distinct category within the expiratory group, since all intermediate activity patterns are observed. Similarly, no distinct categories of activity patterns can be distinguished within the inspiratory group.2. Expiratory neurones are rare in the extreme medial and lateral portions of the respiratory regions on each side of the rostral medulla (Fig. 3). Respiratory neurones are not bunched in anatomical clusters within each region, though a medio-dorsal group of neurones on each side is somewhat anatomically separated from the rest.3. At any one time there are at the very least 1000 respiratory neurones on each side of the rostral medulla.4. Many of the patterns of single unit activity recorded in respiratory muscles of the nose, throat and pharynx are different from the patterns of activity typical of respiratory neurones in the medulla near the cranial motor nuclei (Figs. 1 and 4). This suggests that many of the medullary recordings are from cells other than the motor neurones innervating these muscles.


Evoked potentials from the human scalp to visual half-field stimulation.


Membrane properties of a barnacle photoreceptor examined by the voltage clamp technique. 1. Electrical properties of the membrane of photoreceptor cells in the lateral ocelli of barnacles, Balanus amphitrite and B. eburneus were investigated by intracellular recording, polarization and voltage-clamp techniques.2. The resting potential of a dark adapted cell was 36.3 +/- 6.6 mV (S.D.) and depended mainly on the external K(+) concentration.3. Current-voltage relations obtained from voltage-clamp experiments in the absence of light were non-linear and varied with time after the onset of a step change in membrane potential; the steady state was reached after about 0.5 sec.4. Illumination resulted in a membrane potential change under current clamp and in a change of membrane current (light-initiated membrane current (L.I.C.): total membrane current with illumination minus current without illumination) under voltage-clamp conditions. Amplitudes and time course of L.I.C. depended on the light intensity as well as membrane potential.5. The L.I.C.-voltage relation was non-linear and corresponded with a slope conductance increase with increasing positive membrane potential.6. The reversal potential of L.I.C. was independent of the light intensity and the time after onset of illumination; the average value obtained in normal saline was +26.9 +/- 5.0 mV.7. The membrane conductance estimated from instantaneous L.I.C.-voltage relations agreed with the chord conductance of the non-linear L.I.C.-voltage relation.8. Decreasing external Na(+) concentration decreased the inward component of L.I.C. but not the outward component.9. Decreasing external Ca(2+) concentration increased the inward as well as the outward component of L.I.C.10. The reversal potential shifted in the negative direction with decreasing external Na(+) concentration (the rate was 10-15 mV for a tenfold change in concentration) and the rate was augmented in the absence of Ca(2+) but did not exceed 21 mV.11. The change of reversal potential with changes of external Ca(2+) concentration was negligible in normal Na(+) media but was significant in the absence of Na(+) (rate as high as 20 mV).12. Alteration of the external K(+) or Cl(-) concentrations did not affect the amplitude or reversal potential of L.I.C.13. The results indicate that illumination increases the membrane permeability mainly to Na(+) ions and that the primary effect of Ca(2+) ions is suppression of the permeability increase; Ca(2+) permeability may increase slightly during illumination.


Efflux mechanism contributing to the stability of the potassium concentration in cerebrospinal fluid. 1. The clearance of (42)K from c.s.f. has been separated into two components by means of ventriculo-cisternal perfusion in the rabbit. At 2 hr the largest fraction of radioactivity is recoverable from brain. A smaller fraction passes into the bloodstream and this loss can be expressed as a barrier clearance.2. The clearance into brain was largely independent of potassium concentrations in the perfusion fluid of 15 m-equiv/l. and below. It was depressed by ouabain, 10(-2) mM.3. The barrier clearance was small, about 9% of the total, when the perfusion fluid contained potassium (1.5 m-equiv/l. or below). Above this concentration it increased steeply reaching 32 mul./min or 37% of the total at 10 m-equiv/l. A similar high barrier clearance was caused by replacing 84% of the sodium in the perfusion fluid with choline. Ouabain, 10(-2) mM, abolished the increased barrier clearance due to potassium (10 m-equiv/l.).4. The clearance of [(14)C]urea into both brain and blood was unaffected by the potassium concentration in c.s.f. The barrier clearance of [(14)C]urea was, if anything, increased by 10(-2) mM ouabain.5. Perfusion of the low sodium fluid caused a net loss of potassium from c.s.f.6. The influx of (42)K into c.s.f. from blood was the same, when the perfusion fluid contained potassium (2.9 or 10 m-equiv/l.).7. The potential between c.s.f. and blood of about 4 mV (c.s.f. positive) was little affected by the potassium or sodium concentration in the perfusion fluid.8. These observations indicate that the net flux of potassium ions from c.s.f. to blood begins to increase very steeply with the potassium concentration in c.s.f., when the latter is between 2 and 3 m-equiv/l. This relation, taken together with the variation of influx with the potassium concentration in blood plasma, can largely explain the known stability of the potassium concentration in the c.s.f. of the rabbit at 2.8-2.9 m-equiv/l.9. The increased flux of potassium from c.s.f. at raised concentrations of potassium in this fluid appears to depend on a sodium-potassium pump inhibitable by ouabain.


Particle transport within the human micro-environment.


Intracellular hydrolysis of short chain glycerides by rat small intestine in vitro and transfer of glycerol. 1. When triacetin, tripropionin and tributyrin are incubated with sacs of rat everted intestine, they enter the epithelial cells and are completely hydrolysed to free fatty acids and glycerol.2. The distribution between the mucosal and serosal fluids of the glycerol released is very different from that of the fatty acid. Although both hydrolytic products are accumulated in the serosal fluid, a much higher fraction of the fatty acid appears in this compartment.3. When glycerol is initially present in the mucosal fluid there is no evidence of its movement against a concentration gradient.4. The results confirm the existence of a transport mechanism for fatty acids released intracellularly but do not require the hypothesis of a special mechanism for glycerol transfer.


Stimulation and desensitization of the hypothalamic heat-sensitive structures by capsaicin in rats. 1. In rats the injection of capsaicin into the pre-optic area of the anterior hypothalamus produces a prompt fall in body temperature and abolishes shivering. With repeated injections of capsaicin the hypothermic effect gradually diminishes and finally vanishes (local desensitization).2. Rats desensitized by hypothalamic injections exhibit a behaviour similar to rats pre-treated parenterally with capsaicin: put in a heat box at 37-39 degrees C they lose their ability to regulate against overheating of their bodies and respond with an enhanced hyperthermia to strong sensory stimuli such as repeated pinching of the tail.3. Parenteral desensitization strongly inhibits the effect of capsaicin given into the hypothalamus. On the other hand in intrahypothalamically desensitized rats the hypothermic response to subcutaneously given capsaicin is also reduced.4. The hypothermic response to local heating of the anterior hypothalamus by diathermy (from 1 to 4 degrees C above the initial temperature) was markedly reduced or even abolished in rats pre-treated parenterally with large doses of capsaicin.5. It is concluded that the hypothalamic warmth detectors are stimulated and subsequently desensitized by capsaicin. Thus, in the thermoregulatory disturbances caused by capsaicin the impairment of the hypothalamic warmth detectors plays an important role.6. Capsaicin is proposed as a tool in studying the function of the hypothalamic warmth detectors.


A simple method for demonstrating the mechanical properties of frog slow muscle fibres.


The rates of release and binding of thyroxine by bovine serum. 1. Estimates have been made of the rates of release and binding of thyroxine by bovine serum proteins. The method involves measuring the rates at which columns of Amberlite resin take up thyroxine from serum.2. At 37 degrees C the dissociation rate (the rate of release of bound thyroxine into free solution) is about 2.2% sec(-1).3. The binding of thyroxine by serum is a complex process, the majority of the hormone being ;loosely' bound within 0.1 sec but the over-all process taking some 20 sec to completion.4. A mechanism is proposed for the uptake of thyroxine by the liver. It involves a simple competition between the plasma and the liver binding sites for the free thyroxine released into solution by the dissociation reaction.


Measurement of left ventricular pressure and its first time derivative.


Changes in the blood volume of the rabbit with age. 1. The changes in blood haemoglobin concentration, great vessel haematocrit value, red cell volume, plasma volume and total blood volume have been studied in rabbits from birth to 4 months of life.2. The plasma volumes were measured with [(131)I]human serum albumin and/or rabbit serum [(14)C]albumin. Red cell volumes were measured with [(51)Cr]-rabbit red blood cells. Blood volumes were also calculated from carbon clearance curves.3. The haemoglobin concentration and the great vessel haematocrit value fell during the first 11 days of life. The great vessel haematocrit value was then not significantly different from the value at 4 months; whereas the haemoglobin concentration fell further until 22 days, when it started to rise towards the concentration at 4 months.4. The true plasma volume could not be accurately measured during the first 48 hr of life by the injection of labelled albumin since it rapidly equilibrated with an extravascular albumin space. As the ratio of the whole body haematocrit to the great vessel haematocrit (F(cells)) did not appear to change with age the plasma volume at this time was best obtained by calculation from the red volume and corrected great vessel haematocrit.5. The blood volume fell significantly during the first 4 months of life due to significant falls in the red cell and plasma volumes.


A quick phase in the series-elastic component of striated muscle, demonstrated in isolated fibres from the frog.


Threshold activation of slow crayfish muscle fibres.


Changes in optic nerve activity on awakening.


Autoradiography of labelled amino acids injected iontophoretically into the giant squid synapse.


A portable system for tremor and e.e.g. recording.


The response of arteries to nerve stimulation and to noradrenaline and the relationship of this to innervation density and wall thickness.


The effect of distending the junction between the superior vena cava and the right atrium in the dog.


Projections of the orbital cortex on the anterior lobe of the cerebellum.


A comparison between adult and neonate porcine neurophysin.


The forms of vitamin B 12 in the ileal enterocyte of the guinea-pig during fasting and absorption of cyanocobalamin.


The acute physiological, pharmacological and immunological effects of inhaled cotton dust in normal subjects.


Effects of lysine-vasopressin dosage on renal tissue and urinary composition in the conscious, water diuretic rat.


Heat production in twitches of stretched muscle.


Rapid transport of neurohypophysial hormones in the hypothalamoneurohypophysial tract.


On the 'filters' in the photophores of mesopelagic fish and on a fish emitting red light and especially sensitive to red light.


Narrow 'tuning' of the responses of cochlear nerve fibres emanating from the exposed basilar membrane.


The resistance of a lymph node to lymph flow.


Stimulation of enzyme secretion from the perfused cat pancreas by potassium.


Two phases of calcium entry during the action potential in giant axons of Loligo.


Effect of anticholinesterases on the response to stimulation of adrenergic fibres.


The effect of intraventricular noradrenaline on plasma unesterified fatty acids in the ox.


Changes in thyroxine utilization by the young growing lamb.


Electron microscopy of frog muscle fibres in extreme passive shortening.


Morphological changes associated with inhibition of fluid transport in the rabbit choroid plexus.


Analysis of horizontal eye movements during visual pursuit.


Input-output relations of the inferior olive.


A comparison of protein synthesis in the brains of mice before and after puberty.


The mechanism of the cardio-acceleration elicited by electrical stimulation of the parahypoglossal area in the cat. 1. In chloralosed and in decerebrated cats localized electrical stimulation of a discrete parahypoglossal area (including the nucleus intercalatus and a discrete neighbouring region ventrolateral to the hypoglossal nucleus) elicited cardio-acceleration and arterial hypertension, either singly or together.2. The cardio-acceleratory response was decreased by intravenous administration of propranolol (2 mg/kg). In another group of experiments the response was abolished by acute bilateral cervical vagotomy but it was observed to return partially when stimulation was applied one or more hours after vagotomy. The hypertensive response was not affected by propranolol or by vagotomy.3. Evoked electrical activity with a latency of 3-10 msec was recorded from pre- and post-ganglionic sympathetic cardio-acceleratory nerves during stimulation of this region.4. These findings demonstrate the existence of a discrete medullary area which controls heart rate by activation of a sympathetic pathway and inhibition of a parasympathetic pathway.


An efferent synapse from a small granule-containing cell to a principal neurone in the superior cervical ganglion.


The relationship of blood flow to myoglobin, capillary density, and twitch characteristics in red and white skeletal muscle in cat. 1. The fractional distribution of blood flow was measured by the isotope dilution method and absolute blood flow estimated in twenty-four muscles of chronically prepared, unanaesthetized cats.2. In the quiet, alert cat the estimated mean muscle blood flow ranged from 5.9 to 39.3 ml./min 100 g muscle. Flow was three times greater in grouped red than white limb muscles.3. The myoglobin concentration ranged from 0.88 to 3.91 mg/g muscle. The myoglobin concentration of grouped red exceeded that of white muscle and varied in each muscle directly and linearly with blood flow with a high correlation (P < 0.001).4. Capillary density was estimated by determination of alkaline phosphatase activity. Alkaline phosphatase activity was significantly greater in red than white muscles and varied directly with fractional blood flow in these same muscles with a high correlation (P < 0.001).5. Contraction time was generally two to three times longer in red than white muscle. There was a direct and highly correlated relationship (P < 0.001) between blood flow and contraction time.6. The direct linear relationship between muscle blood flow and myoglobin concentration, capillary density, and contraction time characteristic of quiet wakefulness was lost during rapid eye movement sleep or excitement produced by electrical stimulation of the hypothalamus as a consequence of selective changes in flow in red and white skeletal muscle.7. The type of metabolism of any skeletal muscle is adapted to its activity during quiet, alert behaviour, rather than during sleep or excitement.


Synaptic connexions in the glomerular layer of the olfactory bulb.


Effect of neurohypophysial hormones on fluid movement across isolated bladder of Rana cancrivora, Rana temporaria and Bufo melanostictus. 1. The rate of fluid movement across the wall of isolated amphibian urinary bladder was estimated using hemi-bladders of the tropical euryhaline Rana cancrivora, the temperate R. temporaria and the tropical Bufo melanostictus.2. The rate of water outflow across the bladder walls was: Rana cancrivora, 4.8 mul./cm(2).hr; R. temporaria, 7.2 mul./cm(2).hr; Bufo melanostictus, 3.7 mul./cm(2).hr.3. When neurohypophysial peptides were added to the serosal solution the rates of water outflow were increased; dose-response curves were prepared relating the augmented rate of fluid movement to the concentration in the bathing fluid of vasopressin, oxytocin or vasotocin.4. The potencies of the peptides in respect of bladders of each species were:Vasopressin, B. melanostictus:Rana temporaria:R. cancrivora, 500:20:1.Oxytocin, R. temporaria:B. melanostictus:Rana cancrivora, 100:5:1.5. The ratio of sensitivity of the bladder of each species to the presence of the different peptides was:R. cancrivora, vasotocin:oxytocin:vasopressin, 1000:5:1.R. temporaria, oxytocin:vasopressin, 15:1. Bufo melanostictus, oxytocin:vasopressin, 1:30.6. The effect of extract of the pituitary gland of Rana cancrivora was examined on R. cancrivora bladder. It had a dose-response curve similar to the dose-response curve of vasotocin.7. The vasotocin content of the pituitary gland of R. cancrivora was estimated(a) from the dose-response curves using R. cancrivora bladder,(b) by a three-point assay using R. cancrivora bladder and(c) by its effect on water uptake across the skin of Bufo melanostictus. One pituitary gland of Rana cancrivora was found to contain about 0.1 mug vasotocin.8. The urinary bladder of R. cancrivora was less responsive to neurohypophysial peptides than the bladder of R. temporaria or Bufo melanostictus.9. The hormonal content of the pituitary gland of Rana cancrivora was smaller than that found in other amphibians.


Passage of macromolecules between alveolar and interstitial spaces in foetal and newly ventilated lungs of the lamb. 1. Experiments were performed on exteriorized foetal lambs to measure transfer of macromolecules (proteins and [(125)I]PVP) between lung alveolar liquid (A(l)) and lung interstitial liquid as represented by lung lymph (L(ly)). Transfer was measured in the foetus and during a 2 hr period of positive pressure ventilation.2. In thirteen experiments [(125)I]PVP was introduced into A(l) and, after a control period, the lungs were ventilated for 2 hr. In six other experiments the [(125)I]PVP was injected intravenously; and in two of these the lungs were ventilated for 2 hr. Measurements were made of protein and of [(125)I]PVP concentration in plasma and L(ly) collected at intervals throughout the experiment, as well as in A(l) obtained before ventilation and at the end of ventilation after degassing the lung. [(125)I]PVP in the samples was separated into fractions of different Stokes-Einstein radius by gel filtration using Sephadex G-200.3. Before ventilation there was evidence of a negligible transfer of protein from L(ly) to A(l) (mean protein A(l)/L(ly) = 0.014) or of [(125)I]PVP from A(l) to L(ly) (mean [(125)I]PVP L(ly)/A(l) = 0.00017). The effect of ventilation for 2 hr was to produce an increase in both ratios, but by a variable amount (after 2 hr ventilation mean protein A(l)/L(ly) = 0.70 +/- 0.08 (S.E. of mean) and mean [(125)I]PVP L(ly)/A(l) = 0.48 +/- 0.09). By calculating L(ly)/A(l) ratios for [(125)I]PVP fractions obtained by gel filtration it was shown that in transfer from A(l) to L(ly) during ventilation molecular sieving could be detected, the degree of which was expressed by means of a Relative Sieving Index (RSI). Significant correlations were found between the minimum surface tension of lung extracts, and two other indicators of lung maturity on the one hand, and the protein and [(125)I]PVP ratios and RSI on the other; so that the more mature the lamb the less the transfer of macromolecules during ventilation and the greater the degree of molecular sieving.4. By comparing concentrations of [(125)I]PVP gel filtration fractions in lymph and plasma, when the [(125)I]PVP had been placed in A(l), we demonstrated some sieving of molecules (in the range 34-15 A) in their absorption from interstitial space to plasma.5. It was concluded that in the lungs of the foetal lamb there is an almost complete barrier to the transfer of macromolecules between alveolar and interstitial spaces; that positive pressure ventilation for 2 hr causes a very variable degree of break-down in this barrier, and that the degree of break-down is usually greater in immature than in mature lungs.


The termination of thalamo-cortical fibres in the visual cortex of the cat and monkey.


The visibility of transient changes of luminance. 1. The threshold intensities of various transient changes from a base line luminance in the mid-photopic range have been measured.2. Rectangular changes in luminance show no difference between increments and decrements, a threshold intensity decreasing inversely with durations up to 16 msec, a lesser reduction in threshold up to 64 msec and for longer durations a slight increase in threshold.3. Two brief flashes separated by an interval show incomplete summation at 10 msec, almost no summation at 65 msec and a second reduction in threshold at 100 msec.4. Two brief flashes in opposite directions negate each other at very small intervals but complement each other at longer intervals, maximally at 65 msec.5. A model of the detector system is proposed that passes the stimulus wave form through a band-pass filter and takes a running average of the variance of the filter output. Threshold is reached if this average attains a certain level.6. The model satisfactorily accounts for the observations that any two wave forms occurring together and not exceeding a total of 100 msec in duration will interact so that the relationship between them at the combined threshold will be an ellipse; and that this ellipse will have no obliquity if one wave form is the differential of the other.7. Measurements of the thresholds of two brief flashes separated by various intervals define the attenuation characteristics of the band-pass filter invoked to explain the thresholds of repetitive stimuli.8. The model reconciles the apparent disparity between the thresholds of single flashes of varying duration and pairs of flashes of varying interval.9. The statistical efficiency of such a system is discussed.


The site of termination of afferent fibres on the neurones of the caudate nucleus.


Electrical interaction between antidromically stimulated frog motoneurones and dorsal root afferents: enhancement by gallamine and TEA. 1. Electrical interactions have been studied in the isolated frog spinal cord preparation. It is found that gallamine and tetraethylammonium chloride (TEA) markedly enhance all non-cholinergic synaptic interactions, including the electrical interaction between motoneurones (VR-VRP). In addition, in the presence of either of these drugs, a short-latency interaction is seen to exist between antidromically stimulated motoneurones and dorsal root afferents (early VR-DRP). The early VR-DRP is rarely seen in the absence of gallamine or TEA.2. The early VR-DRP is of the same short latency as the VR-VRP and fulfils the same criteria for electrical interaction: it increases in amplitude with cooling from 17-10 degrees C, it is not blocked by a wide variety of pharmacological blocking agents, and it is suppressed by both Mg(2+) and Ca(2+), with no antagonism of action between the two.3. The early VR-DRP appears as a cluster of unitary events: all-or-none spikes conducted out the dorsal root fibres. No initial graded slow potentials are seen. Often there are two peaks in the response.4. The early VR-DRP is facilitated by a dorsal root volley, with a time course normally intermediate between that of the orthodromic ventral root potential (DR-VRP) and the dorsal root potential (DR-DRP). This orthodromic facilitation apparently is achieved by increasing invasion of motoneurone dendritic trees and depolarization of dorsal root afferents toward threshold.5. If the same ventral root is stimulated twice, or adjacent roots stimulated at different intervals, the second early VR-DRP, like the VR-VRP, is seen to be occluded for 10-20 msec, then facilitated to supranormal amplitudes. It is concluded that motoneurone dendrites are presynaptic to both interactions.6. Evidence is presented that gallamine and TEA act by increasing the duration of activity both in axon terminals and in antidromically invaded motoneurones. Often second or multiple spikes result. The increased duration of depolarization can increase transmitter release at terminals and increase coupling at electrical junctions.7. Possible morphological correlates for the two electrical interactions are discussed. It is speculated that the motoneurone interaction arises at numerous areas of close apposition between dendrites in dendritic ;thickets', and that the early VR-DRP is mediated by fewer, lower-resistance, electrical junctions between dendrites and afferent nerve terminals.


Neuronal and subcellular localization of acetylcholine in the posterior pituitary of the rabbit. 1. Acetylcholine and neurohypophysial hormones were measured in subcellular fractions of rabbit neurohypophysis.2. Differential and density gradient centrifugation, followed by bio-assay and electron microscopy were used to separate and characterize the subcellular particles, or isolated nerve endings.3. Acetylcholine in the rabbit neurohypophysis was found to occur in small vesicles of about 40 nm diameter which had similar characteristics to the synaptic vesicles from central nervous tissue.4. Examination of intact nerve endings isolated from the rabbit neurohypophysis indicated that at least some acetylcholine and neurohypophysial hormones occurred in separate nerve endings.


A method for the selective electrical activation of tendon organ afferent fibres from the cat soleus muscle.


A method of studying fluid and solute transport across human ileum in vitro.


The origin and secretion of pancreatic juice bicarbonate. 1. The rate of secretion from a saline-perfused preparation of the cat's pancreas is directly proportional to the perfusate bicarbonate concentration. When all bicarbonate is omitted, secretion completely or almost completely ceases.2. Incorporation of [(14)C]bicarbonate into the perfusion fluid results in its prompt appearance in the juice. The radioactive label is concentrated four to five times in the juice just as the total juice bicarbonate is four to five times greater than perfusate bicarbonate.3. These two observations suggest that about 95% of pancreatic juice bicarbonate is derived from perfusate (plasma) bicarbonate.4. The inhibition of pancreatic secretion from the perfused gland by acetazolamide is similar to that observed in the intact animal.5. There is a fall in pH and rise in P(CO2) in the perfusion fluid leaving the gland which is greater during secretion than at rest.6. It is therefore suggested that during secretion, hydrogen ions pass from the gland into the perfusate (plasma), thus increasing the production of carbon dioxide from circulating bicarbonate. This carbon dioxide diffuses into the cell, is rehydrated (partly under the influence of carbonic anhydrase) and finally is secreted, thus establishing the necessary gradient for the continued diffusion of carbon dioxide into the cell.


Peripheral inhibition and muscle relaxation.


The dependence of the transmembrane salivary secretory potential on the external potassium and sodium concentration. 1. The submandibular gland of the cat was perfused with equi-osmolar Locke solutions of different cationic composition. The increase in acinar membrane potential (secretory potential), measured with a glass capillary micro-electrode, was recorded after intra-arterial injection of acetylcholine.2. When nearly all Na in the perfusion fluid was replaced by tetraethylammonium (TEA), the size of the secretory potentials was significantly (P < 0.001) greater than of those recorded during perfusion with normal Locke solution.3. When the K concentration in the TEA Locke solution was augmented, the size of the secretory potentials was greatly diminished. Thus at a [K](o) of 4 m-equiv/l. the size of the secretory potentials was 43.3 mV +/- 2.5 (n = 19) but at a [K](o) of 10 m-equiv/l. the size was only 24.7 mV +/- 2.0 (n = 13) and at a [K](o) of 20 m-equiv/l. the size of the secretory potentials was 12.0 mV +/- 1.0 (n = 21). When the submandibular gland was perfused with a K-free TEA Locke solution the size of the secretory potentials was 49.7 mV +/- 2.2 (n = 17).4. The size of the secretory potentials recorded during perfusion with normal (Na) Locke solution increased significantly (P < 0.001) when K was omitted from the perfusion fluid. The decrease of the size with increasing [K](o) was considerably less marked than that found during perfusion with TEA Locke solution. Increasing [K](o) by a factor of 5 diminished the size of the secretory potentials recorded in Na Locke solution by a factor of 2, whereas the size of the secretory potentials recorded in TEA Locke solution, with the same changes in [K](o), diminished by a factor of 3.5.5. The results seem to indicate that the increase in acinar membrane potential obtained after stimulation of the gland is due to an enhanced permeability of the basal acinar cell membrane to K. However, it seems that the permeability to Na is also enhanced so that the outwardly directed K current is partly short-circuited by an inward Na current.


Effects of Ca removal on the smooth muscle of the guinea-pig taenia coli. 1. The effects of removing the external Ca ions on the spontaneous and evoked activity of the smooth muscle of the guinea-pig taenia coli were investigated with the double sucrose-gap method.2. In Ca-free Locke solution the membrane was depolarized, the membrane resistance became low, the spike amplitude became small and the mechanical response decreased. In most preparations the electrical and mechanical activity was abolished within 10 min, but in some preparations the electrical activity continued for more than 30 min.3. In Ca-free solution containing 0.1 mM-EGTA, the membrane was depolarized and the electrical and mechanical activity was abolished within 5 min in every preparation. When NaCl was replaced with sucrose, the effects of Ca removal on the spike activity and contraction appeared very slowly and the membrane potential and membrane resistance remained unchanged.4. When Ca was replaced with Mg (2 mM) the spike was blocked within 1 min without depolarization or reduction of the membrane resistance. In Na-deficient (sucrose) solution, the presence of Mg accelerated the disappearance of the spike caused by Ca removal.5. In Ca-free solution containing 0.5 mM-Mg, a spike-like activity was observed without accompanying mechanical response. This activity was blocked by increasing the Mg concentration above 2 mM. It was Na-dependent, since it was abolished by removing Na from the external solution, but it was not influenced by tetrodotoxin (2 x 10(-6) g/ml.).6. It was concluded that calcium has at least two functions, one as current carrier for the action potential and another as controller of the Na permeability of the membrane. It was also suggested that the Ca which is bound at the membrane may be utilized as a source of Ca ions to carry the current for the action potential.


The structure of the giant fibres of earthworms, as disclosed by Procion yellow injections.


Peritoneal dialysis of cooled rats.

Peritoneal dialysis of cooled rats.


Left atrial cannulation in sheep, and prolonged atraumatic pumping of blood.


Haemodynamic and other studies in the renoprival hypertensive rat. 1. The optimal conditions for the development of hypertension after total nephrectomy were defined in the rat. Under these conditions, haemodynamic changes were then studied before and for 3 days after total nephrectomy in the unanaesthetized animal and compared with mock-nephrectomized controls.2. Changes in cardiac output were followed with an electromagnetic flowmeter chronically implanted on the ascending aorta, and mean arterial pressure with an indwelling aortic cannula.3. Haematocrit fell in animals developing hypertension, due to plasma volume expansion. Restriction of administered saline did not reduce the fall in haematocrit without also preventing development of the hypertension.4. Cardiac output and stroke volume increased significantly on the second and third days after nephrectomy. Peripheral resistance remained unchanged and pulse rate tended to fall.5. The increase in cardiac output appeared to be more than could be accounted for by anaemia alone, and it is suggested that plasma volume expansion was partly responsible.6. In another group of rats developing renoprival hypertension a correlation was found between changes in plasma volume and arterial pressure over the three days.7. Renoprival hypertension was accompanied by a slight but significant reduction in oxygen consumption in comparison with the controls.8. No relationship was found between the changes in blood pressure, and plasma sodium and potassium levels.9. It is concluded that the observed rise in cardiac output associated with renoprival hypertension as induced in this study was not attributable to anaemia nor to a rise in metabolic rate. The implications of this situation are discussed in relation to a theory of the pathogenesis of hypertension and the findings of other workers.


A simple in situ micro-electrode tester.


The initial heat production of amphibian myelinated nerve fibres.


The length-tension relationship for slowly stretched, slow skeletal muscle fibres of the frog.


How the birefringence of vertebrate rods is affected by light.


Diffusion of neutral amino acids across lipid bilayers.


Experiments on the liberation of phosphate from active human muscle, and on the action of phosphate on human blood vessels.


Rapid 'give' and the tension 'shoulder' in the relaxation of frog muscle fibres.


The effects of bovine albumin on the permeability of frog mesenteric capillaries.


Rates of uptake of amino acid from L-methionine and the peptide L-methionyl-L-methionine by rat small intestine in vitro.


Chemoreceptors, sensitive to a low pH, in the duodenum of the rabbit.


Bio-radioimmunoassay of luteinizing hormone releasing factor using untreated immature rats.


Quantitative investigation of intravascular platelet aggregation.


The effect of hypoxia on the pulmonary veins.


Fatty acid release and glucose uptake by brown adipose tissue of newborn rabbits.


The release and partitioning of mechanical energy during a maximal effort of elbow flexion.


Effects of 0-9 per cent saline infusion on urinary and renal tissue composition in the hydropaenic, normal and hydrated conscious rat. 1. Changes in water and solute outputs of hydropaenic, normal and hydrated conscious rats were determined during intravenous infusion (0.2 ml./min) of isotonic (0.9%) saline for 4 hr; renal tissue composition was determined before, and after 1 or 2 hr, infusion.2. In normal and hydrated rats increased excretion of water and sodium was such that urinary output matched intravenous input from about 2 hr. In hydropaenic rats, the diuretic and natriuretic response was much reduced; a retention of infused saline, equivalent to 15% body weight, occurred over 4 hr.3. A considerable increase in urea output and clearance, and a smaller increase in potassium and ammonium outputs, occurred in all groups.4. The corticomedullary osmolal gradients characteristic of non-diuretic rats were largely dissipated during saline infusion: by 1 hr in normal and hydrated rats, and by 2 hr in the hydropaenic group.5. These changes were ascribable mainly to an increase in tissue water content in all segments, particularly in the hydropaenic group; and to a profound decrease in urea content in all groups.6. Changes in tissue sodium content were smaller, and differed between segments and between the differently hydrated groups. A decrease in papillary content occurred in hydropaenic and normal groups and an increase in cortical and outer medullary content occurred in all groups.7. After 2 hr saline infusion, incomplete papillary-urinary osmotic equilibration was evident in all groups.8. These changes in medullary osmolality and in papillary-urinary osmotic equilibration preceded the maximal diuresis, and must contribute to the diuresis induced by saline infusion, as in water and osmotic diureses.


Cleavage of a gastric inhibitory polypeptide with cyanogen bromide and the physiological action of the C-terminal fragment.


High sensitivity isometric force transducers made with piezo-electric or piezo-resistive strain gauges.


The effect of plasma volume expansion on the cortico-medullary osmotic stratification in the cat kidney.


Isolation of two types of vesicles containing endogenous noradrenaline in sympathetic nerve terminals.


The effect of nicotinic and muscarinic antagonists on single neurones of the leech, Hirudo medicinalis.


Factors controlling compensatory renal hyperplasia.


The effect of ganglion blocking agents on release of antidiuretic hormone by carotid occlusion, suberyldicholine and haemorrhage in the cat.


Relation of movements induced by intracortical stimulation to receptive fields of points in the perirolandic and parietal cortex of the monkey.


Activity of lung irritant receptors caused by cigarette smoke, dust and histamine aerosol.


Second-order neurone inhibition in the rat cuneate nucleus evoked from the contralateral periphery.


Respiratory movements and paradoxical sleep in the foetal lamb.


Projection from low-threshold muscle afferents of hand and forearm to area 3a of baboon's cortex.


Role of non-myelinated vagal afferent fibres from the lungs in the tachypnoeic response to pulmonary micro-embolism in the rabbit.


Behavioral effects of stimulation in the region of the substantia nigra.


The duration of the increase in arterial inflow during exposure of the forearm to subatmospheric pressure.


Induction of labour in the conscious rabbit by electrical stimulation of the neural stalk.


The electron microscopy of the adenohypophysis of the vole, Microtus agrestis.


Hypothalamic influence on pituitary and serum levels of LH in the vole, Microtus agrestis.


Effects of prolonged saline exposure on water, sodium and urea transport and on electron-microscopical characteristics of the isolated urinary bladder of the toad Bufo bufo. 1. A comparison was made of various transport properties and electron-microscopical characteristics of isolated urinary bladders from toads (Bufo bufo) maintained in either tap water or 0.7% saline (0.7 g NaCl in 100 ml. H(2)O) for 10 days to 2 months.2. In the absence of Pitressin, isolated bladders from saline-adapted toads showed:(a) markedly, and significantly, lower osmotic water flow;(b) moderately, but not significantly, lower urea permeability;(c) no significant change in net sodium transport (measured as short-circuit current, I(sc)); and(d) significantly smaller intercellular space/mucosal cell ratios in electron-micrographs.3. Differences in the transport and electron-microscopical characteristics between bladders from water-exposed and saline-adapted toads became more evident in the presence of exogenous Pitressin (10 m-u./ml. serosal solution):(a) the stimulating influence of Pitressin on osmotic water flow, short-circuit current and urea permeability was considerably smaller in bladders from saline-adapted toads than in those from water-exposed toads;(b) the influence of Pitressin on short-circuit current was reduced more profoundly than that on either water flow or urea permeability;(c) the Pitressin-induced increment in intercellular space/mucosal cell ratio was significantly smaller in electron-micrographs of bladders from saline-adapted toads than in those from water exposed toads.4. The effects of saline adaptation are discussed in relation to decreased permeability of mucosal membrane barriers.


Recording aortic flow, stroke volume, cardiac output, acceleration and peripheral vascular resistance.


The effect of hypercapnia on myocardial blood flow and metabolism. 1. In closed-chest dogs anaesthetized with trichlorethylene, the inhalation of carbon dioxide sufficient to increase the arterial P(CO2) from 40 to about 100 mm Hg, increased myocardial blood flow (measured using a (133)Xe clearance technique) and right atrial pressure. There were no consistent changes in mean arterial blood pressure, heart rate or cardiac output.2. The effect of hypercapnia on myocardial blood flow was not influenced by the previous administration of atropine and propranolol or of bretylium. It can be concluded, therefore, that the elevated arterial P(CO2) has a direct vasodilator effect on the myocardial microcirculation.3. During hypercapnia the coronary sinus P(O2) was increased and the coronary arteriovenous oxygen content difference, and calculated myocardial oxygen consumption, reduced. It is suggested that this latter effect may be the result of myocardial depression produced by the decrease in arterial blood pH.4. There was no evidence of myocardial glucose uptake either before or during hypercapnia. The myocardial extraction of lactate and pyruvate at rest varied between 0 and 55%. During acute hypercapnia the extraction of lactate usually fell.5. When the arterial P(CO2) was maintained at 100 mm Hg for a period of 1 hr the effects on myocardial blood flow and on oxygen consumption were not sustained.6. Stepwise increments and decrements in arterial P(CO2) of 10-20 mm Hg produced corresponding increases and decreases in myocardial blood flow and demonstrated that changes in arterial P(CO2) of 20-30 mm Hg can markedly affect blood flow in the myocardium.


The persistence of stable bonds between actin and myosin filaments of intrafusal muscle fibres following their activation.


Activities of anterior cingulate gyrus on anterior thalamic nuclei in cat.


The fine structure of interstitial gland cells in rabbit ovaries.


Clinical, epidemiological and irological studies on mumps.


The use of silica gel impregnanted glass fiber sheets in plasma estriol assays.


Competitive inhibition of primate brain corticosteroid acetyltransferase by triamcinolone and related 16alpha-hydroxysteroids.


Comparative anti-inflammatory properties of systemically administered betamethasone 17-benzoate and 6 alpha, 9 alpha difluoroprednisolone 21-acetate 17-butyrate.


The local anti-inflammatory properties of betamethasone 17-benzoate and 6 alpha, 9 alpha difluoroprednisolone 21-acetate 17-butyrate.


Effect of betamethasone 17-benzoate and 6 alpha, 9 alpha difluoroprednisolone 21-acetate 17-butyrate on the survival of adrenalectomized rats.


Preparation of steroid heptafluorobutyrates for gas liquid chromatography utilizing vapor phase derivatization.


Progesterone in uterus and plasma. IV. Progesterone receptor(s) in guinea pig uterus cytosol.


Metabolism of 4-14C-estradiol-17 beta by the newborn puppy.


Synthetic approaches to steroidal alkaloids II (1). Preparation and reactions of 12-oxo-dinorcholanic acids.


Feto-maternal transfer and production of cortisol in the sheep.


Further studies of the specificity of the sex hormone-binding globulin of human plasma.


The stability of L-asparaginase with respect ot protein denaturants.


A proteinase from human erythrocyte membranes.


Purification and some properties of beta-1,3-glucan glucanohydrolase from the crystalline style of bivalvia, Spisula sachalinensis.


Studies on gamma-glutamyl carboxypeptidase. I. The solid phase synthesis of analogs of polyglutamates of folic acid and their effects on human liver gamma-glutamyl carboxypeptidase.


The inactivation and dissociation of Escherichia coli succinyl-CoA synthetase by sulfhydryl reagents.


Observations of the effect of diethylnitrosamine on glucuronide formation.


Activation of the D to I form conversion of glycogen synthetase by glucose 6-phosphate in bovine spleen.


The subcellular localization of alcohol dehydrogenase activities in Astasia longa.


The influence of sodium taurocholate on the pancreatic lipase-substrate adsorption and activity.


Transfer of N-acetylneuraminic acid to neuraminidase-treated alkaline phosphatase from sheep brain.


Some studies on the thermic phosphorylation of activated nucleoside by phosphate anion and nucleotide anion.


Brain hexokinase: a kinetic comparison of soluble and particulate forms.


Adenosine deaminases of two different molecular sizes in human tissues.


Tosylarginine methylester hydrolase activity in sea urchin egg membrane.


The regulation of rat liver xanthine oxidase: conversion of type D (dehydrogenase) into type O (oxidase) by a thermolabile factor, and reversibility by dithioerythritol.


Storage stability of water-insoluble enzymes convalently coupled to organic and inorganic carriers.


Purification and properties of homoserine dehydrogenase from Neurospora crassa.


Forms of ceruloplasmin in developing piglets.


7-Hydroxylation of thymine in a Neurospora strain coupled to oxidative decarboxylation of 2-ketoglutarate.


Number and reactivity of the sulfhydryl groups of alpha-isopropylmalate synthase of Salmonella typhimurium.


Partial purification of hepatic UDP-glucuronyltransferase. Studies of some of its properties.


Alcohol dehydrogenase activity in the yeast Lipomyces starkeyi.


Substrate specificity of pancreatic lipase. Influence of the structure of fatty acids on the reactivity of esters.


The concept of mental representation in psychoanalysis.


Four years' presidency: a personal view.


Perspective, Rome: the 'viewpoint' of the psychoanalyst. Remarks of the incoming president.


Panel on 'psychoanalysis and psychotherapy'.


Inhibition of RNA synthesis by actinomycin D: characteristic dose-response of different RNA species.


Further studies on the biological properties of Friend virus-induced leukemic cells differentiating along the erythrocytic pathway.


The influence of diffusion in the external medium upon the determination of cytoplasmic diffusion coefficients.


Further studies on the differentiation of a cell line of myeloid leukemia.


Correlation of adenosine phosphate levels with cellular morphology in Dictyostelium discoideum amoebae.


Argon laser micro-irradiation of mitochondria in rat myocardial cells in tissue culture.


Selection of synchronous Chlorella cells by centrifugation to equilibrium in aqueous Ficoll.


The effect of drugs on the rate of proteolysis in vitro within secondary liver lysosomes.


Changes in state of water in proteinaceous systems.


Some micellar properties of long-chain acylcarnitines.


The effect of temperature and hydrocarbon chain structures on the titration properties of lecithin and some related phospholipids.


Cytoarchitectonics of the lobus pyriformis in the cow.


A proposed method for establishing homologies among the lobules of the anterior lobe in the Mammalian Cerebellum.


The glycogenolytic response to stimulation of the splanchnic nerves in adrenalectomized calves. 1. The effects of stimulation of the peripheral ends of one or both splanchnic nerves have been investigated in adrenalectomized calves at different ages.2. During the first 24 hr after birth unilateral splanchnic nerve stimulation led to a prompt rise in the plasma glucose concentration and this response was more than doubled when both nerves were stimulated simultaneously. Under these latter conditions hyperglycaemia was found to be associated with a measurable loss of glycogen from the liver.3. Both the glycogenolytic and hyperglycaemic effects of splanchnic stimulation became more pronounced with age; at 5 weeks of age liver glycogen was depleted by approximately 2/3 and plasma glucose raised by about 200 mg/100 ml. after stimulation of the right splanchnic nerve for 9 min.4. Splanchnic stimulation also caused a rise in mean arterial blood pressure and haematocrit during the period of stimulation at all ages studied; the rise in haematocrit was greatest in the oldest animals.5. The hyperglycaemic response to splanchnic stimulation persisted after pancreatectomy and was also demonstrated in calves in which the whole of the portal effluent blood flow was collected during splanchnic stimulation. The plasma from blood collected in this way had no apparent hyperglycaemic effect when infused into a branch of the mesenteric vein in recipient calves.6. In adrenalectomized calves in which the liver had been partially denervated before stimulation both the hyperglycaemic and the glycogenolytic responses were substantially reduced, although the rise in haematocrit was unaffected, during stimulation of both splanchnic nerves.7. It is concluded that glycogenolysis occurs in the liver as a result of stimulation via the hepatic innervation in the new-born calf and that this response increases with age during the first few weeks after birth.


Cat colour vision: evidence for more than one cone process. 1. The ability of cats to distinguish colours was investigated at mesopic and photopic levels to test the hypothesis that cats discriminate wavelength by using rods in conjunction with a single type of cone.2. Cats were trained to distinguish red from cyan, and orange from cyan at the mesopic level. They retained the ability to make this discrimination when the coloured stimuli were placed against a background bright enough to saturate the rods.3. One cat was also tested after being exposed to a bright white light of 9000 cd/m(2) for a period of 5 min, and found able to distinguish red from cyan.4. These results suggest that cats have more than one type of cone. Subsequent recordings from single units in the lateral geniculate nucleus showed that there are rare opponent colour units in layer B with input from a green-absorbing cone and a blue-absorbing cone.


Thyroxine utilization in the new-born lamb. 1. From previous studies on foetal thyroid function in various mammalian species it would appear that the foetal pituitary-thyroid axis is capable of function before birth. Few studies are available to indicate the level of function before birth and in the immediate post-natal period.2. Plasma thyroxine levels, thyroxine pool and utilization rate of thyroxine have been followed in new-born Welsh mountain lambs from birth to 39 days of age.3. Plasma thyroxine levels are high within the first hour of life after birth (18.2 +/- 2.0 mug/100 ml.) and fall steadily to a minimum of 5.1 +/- 1.1 on day 11 and 12 of post-natal life. Thereafter they fluctuate about a mean of 6.1 mug/100 ml. The significance of these changes is discussed in respect to foetal thyroxine levels, placental permeability to thyroxine, and foetal and neonatal thyroid and pituitary function.4. Thyroxine utilization rate is high both in absolute terms and relative to unit body weight on days 1-4 of post-natal life. The utilization rate/kg remains fairly constant from days 10-39 of post-natal life.5. Thyroxine utilization in the new-born lamb is compared with that in the new-born calf in which the post-natal growth curve is very different.6. The various factors such as levels of free thyroxine, diet and environmental changes which influence thyroxine utilization are discussed and the rate of utilization is compared with other indices of thyroid function in new-born and adult animals of different species.


Stimulus-response curves for the pulmonary vascular bed to hypoxia and hypercapnia. 1. In anaesthetized open-chest cats and dogs, blood flow and gas tensions were measured in a circuit inserted into a pulmonary vein while ventilating the lobe which it drained with low O(2) and high CO(2) mixtures.2. Both hypoxic and hypercapnic mixtures caused a reduction in blood flow from the lobe.3. Stimulus-response curves relating blood flow to pulmonary venous P(O2) and P(CO2) were obtained. Those for hypoxia were usually asymptotic in shape; the curves became steep below 100 torr and flow sometimes fell to zero. The mean reduction in blood flow for every 20 torr fall in P(O2) was 15.7% in cats and 11.8% in dogs. Those for hypercapnia were steep at first but levelled out at high P(CO2) values; the maximum reduction in flow was 40-60% as vasoconstriction was only observed over a limited P(CO2) range.4. Hypoventilation of the lobe led to a reduction in blood flow. This was mainly attributable to hypoxia though other factors such as hypercapnia may sometimes have contributed.5. Total occlusion of the bronchus of an O(2)-filled lobe caused blood flow to fall in two phases. The first phase could be attributed to a rise in P(CO2) and the second to a fall in P(O2).6. The results confirm the hypothesis that hypoxia is an important factor regulating local blood flow in relation to local ventilation.


Temperature dependence of non-electrolyte and sodium permeability in giant axon of squid. 1. The efflux of [(14)C]urea was measured in micro-injected axons at 18 degrees C. A permeability constant for urea of (0.55 +/- 0.18) x 10(-6) cm/sec was calculated from these experiments.2. The influxes of urea, thiourea, ethylene glycol, urethane and toluene were measured in perfused axons at 18 +/- 1 degrees C. The permeability constants obtained from these determinations increased in the order listed, from (0.76 +/- 0.19) x 10(-6) cm/sec for urea to 0.80 x 10(-4) cm/sec for toluene.3. The influxes of tritiated water and sodium ions at 18 degrees C were measured in perfused axons. An average permeability of (0.78 +/- 0.22) x 10(-4) cm/sec for titriated water and an average influx of 23 +/- 6 p-mole/cm(2) sec for sodium were obtained.4. Lowering the temperature of the external sea-water bathing the axon from 18 to 5 degrees C produced a decrease of 12% in the permeability of toluene, 30% for tritiated water and urethane, 55% for ethylene glycol and urea and 60% for thiourea. There was a 50% reduction in the influx of sodium for this same temperature change.5. The results obtained with the effect of temperature on permeabilities suggest that the axonal membrane has a non-homogeneous composition. A model based on the assumption of structured aqueous channels in the membrane is postulated.


Effect of stimulation and hyperpolarization on non-electrolyte and sodium permeability in perfused axons of squid. 1. The permeability for micro-injected [(3)H]ethylene glycol was measured in resting state and during stimulation at 100/sec in squid giant axons. No detectable changes during electrical activity were observed.2. The influxes of urethane, tritiated water, ethylene glycol, urea and sodium were measured in internally perfused squid axons. Ethylene glycol and urea influxes were determined simultaneously with sodium influxes. The electrical stimulation of the fibre produced an increase in the influx of sodium but did not alter the influxes of the non-electrolytes listed above.3. Experiments were done with the combined voltage clamp-perfusion technique. The influxes of ethylene glycol and sodium were simultaneously measured in resting state and during maximum sodium current under stimulation at 10/sec. The influx of sodium increased in these conditions but the influx of ethylene glycol remained constant. In some experiments, the fibre was hyperpolarized to 10 or 20 mV, above the resting potential and the influxes of ethylene glycol and sodium were measured. The sodium influx decreased to 60% at 20 mV above the resting potential whereas the influx of ethylene glycol remained constant.4. These results indicate that in the giant axons of the squid Dosidicus gigas, sodium and non-electrolytes fluxes are not coupled.


The relation between calcium and contraction kinetics in skinned muscle fibres. 1. Segments of skinned frog muscle fibres were immersed in solutions in which the calcium ion concentration, and therefore the steady isometric force, was controlled with an EGTA buffer system. The contraction kinetics were measured when the load was quickly reduced to values less than the isometric force.2. The velocity of shortening following release from steady force was a hyperbolic function of relative load. The minimum quick displacement required to reduce the force from the steady isometric value to half this value was about 1% of the fibre segment length.3. The relative force-velocity relation was independent of pCa in the range 5.0-6.75. Thus calcium ions appear to control the number of sites at which cross-bridges can be formed but have no significant effect on the kinetic properties of an individual bridge.4. Cross-bridges along the length of a myofilament appear to act independently of each other.5. The force-velocity relations reported for intact muscle fibres during relaxation, when compared with those of skinned fibres at different calcium levels, indicate that the time course of the fall in force after a stimulus is essentially that of calcium removal from the myofilaments.


Response characteristics of muscle afferents in the domestic duck. 1. Response patterns of 116 muscle stretch receptor units isolated from the sciatic nerve of the duck have been studied, and the units classified as muscle spindles and tendon organs.2. Units classified as spindles had low threshold tensions for maintained discharge. From conduction-velocity measurements, the calculated fibrediameter spectrum appears to be unimodal, ranging from 5 to 11-12 mum.3. Spindle units showed essentially ;in parallel' behaviour, though increase in initial tension often led to the appearance of ;in series' responses. Although apparent ;alpha-excitation' during maximal tetanic contractions was a common occurrence, no direct evidence of alpha-innervation of spindles was obtained.4. Evidence has been obtained for motor innervation of spindles by fibres distinct from those constituting the alpha supply to extrafusal muscle fibres. Afferent response attributable to this fusimotor innervation is influenced by initial tension and stimulus-frequency. Electrical thresholds for fusimotor responses ranged from 1.1 to 4.03 times alpha maximum.5. Tendon organ units consistently showed ;in series' response patterns during muscle contractions. They were not influenced by stimulation of the high-threshold efferent nerve supply to the muscles.6. Threshold tensions required for maintained discharge in tendon organ units from m. gastrocnemius pars lateralis were characteristically high; however, many units from m. flexor perforans et perforatus d. 3 had unexpectedly low mechanical thresholds. The calculated fibre-diameter spectrum for tendon organ units is unimodal, ranging from 4-7 to 10-11 mum. As in mammals, they contribute to the coarse-fibre component in the muscle nerve and include the fastest fibres present.


Selective reinnervation of two cell populations in the adult pigeon ciliary ganglion. 1. Presynaptic fibres innervating the adult pigeon ciliary ganglion were cut 2 mm proximal to the ganglion. The modification of transmission in the ciliary and choroid cell populations was studied after periods of 6 hr-100 days.2. Transmission failed after 2 days and for the next 10 days there was no transmission through the ganglion. Long latency responses in both ciliary and choroid nerves were first observed at 13-15 days, and the latency decreased toward control values in 40 days. Electrical transmission reappeared in the ciliary population in about 26 days.3. Presynaptic fibres innervating the ciliary population have higher conduction velocities and lower electrical thresholds than those innervating the choroid group. This relation was maintained throughout the reinnervation process. Fibres innervating the extraocular muscles also regenerated and achieved conduction velocities similar to their control values.4. In two experiments out of seventeen, a few fast conducting, low threshold fibres, presumably stray ciliary fibres, innervated choroid cells and induced electrical transmission.5. It is concluded that each group of cells, ciliary and choroid, was reinnervated in a highly selective manner by its original class of presynaptic fibres, and that the presynaptic ciliary elements cause the specializations necessary for electrical transmission.


Mechanism of action of pyrogen.

Mechanism of action of pyrogen. 1. In unanaesthetized rabbits the cerebral ventricles were perfused for 30-75 min from left lateral ventricle to cisterna magna with solutions of different composition, whilst rectal temperature was continuously recorded.2. Temperature did not rise during the perfusion when the perfusing fluid consisted of artificial c.s.f.; it did rise, however, when the perfusing fluid consisted merely of a 0.9% sodium chloride solution.3. Temperature fell, though not in all rabbits, during the perfusion when the calcium in the perfusing fluid was increased from 1.25 mM, the concentration in c.s.f. to 5 mM.4. Magnesium chloride had only a weak action, in comparison to calcium, in preventing the rise produced during perfusion with 0.9% sodium chloride solution. In a concentration of 1.25 mM it had no effect, but in a concentration of 5 mM it delayed and greatly reduced the rise.5. Temperature did not rise during perfusion with an isotonic sucrose solution.6. The rise in temperature produced by an intravenous injection of leucocyte pyrogen was not prevented when the injection was made during a perfusion with artificial c.s.f., but it was prevented when the calcium concentration in the perfusing fluid was raised to 5 mM or when the perfusing fluid consisted of isotonic sucrose solution. Again, magnesium had only a weak action in comparison to calcium.7. These results support the theory put forward recently (Feldberg, Myers & Veale, 1970) that the constancy of temperature depends upon the physiological balance of sodium and calcium ions in the anterior hypothalamus, that the calcium ions act as a kind of ;brake' preventing the sodium ions from exerting their temperature raising effect, and that pyrogen acts by removing the ;calcium brake', the pyrogen fever thus being a sodium fever.


Selective hypersensitivity to bradykinin in salivary glands with ligated ducts. 1. In submandibular salivary glands of cats in which the ducts have been tied for at least 3 days, the kallikrein activity of ;chorda' saliva is much reduced; but it is never absent, even after prolonged sympathetic stimulation.2. The relationship between the extent of the vasodilatation accompanying secretory activity and frequency of chorda stimulation is similar in normal glands and those with ducts ligated for 3 days, though, in the latter group, the variability is much greater.3. In glands of which the ducts have been tied for 3 days, the responses to close arterial injections of bradykinin are greatly increased, the dose-response curve being steeper and shifted to the left. This appears to be a selective increase in sensitivity, as the responses to the close arterial injections of ACh are, if anything, less than those in normal glands.4. In glands with ligated ducts, prolonged sympathetic stimulation reduces the vasodilatation following chorda stimulation.5. These results strengthen the conclusion that kinins participate in the vasodilatation accompanying glandular activity.


Voltage clamp of the Aplysia giant neurone: early sodium and calcium currents. 1. The membrane properties of the Aplysia giant neurone were studied under controlled voltage conditions. Emphasis was placed on the early transient currents resulting from step polarizations applied while the ganglion was immersed in different test solutions.2. Early inward-going currents were observed when the neurone was bathed in normal saline (containing both Na and Ca), in Ca-free (Na-containing) saline, in Na-free (Ca-containing) saline, and in the normal saline to which tetrodotoxin 10(-5) g/ml. was added. When both Na and Ca are absent from the bathing solution no evidence for early inward-going current could be found.3. When tetrodotoxin is added to the normal saline, the maximum inward-going current is reduced, and no further reduction of this current is observed when the external Na-concentration is subsequently halved in the presence of the drug. When the external Ca-concentration is increased fivefold in the presence of the drug, the maximum transient current increases significantly.4. Hyperpolarizing prepulses result in a membrane inactivation in the presence of tetrodotoxin or in the absence of Na. In the presence of Na (and absence of tetrodotoxin) no such voltage-dependent inactivation occurs, and for this case, inactivation results only from depolarizing prepulses.


Consumption of kininogen in the submandibular salivary gland when activated by chorda stimulation. 1. A method is described for determination of kininogen 1 (substrate mainly for plasma kallikrein) and kininogen 2 (substrate for glandular kallikrein) independently in cat plasma.2. In anaesthetized cats the arterial inflow to, and venous outflow from, the submandibular salivary gland were isolated: a roller pump giving constant volume inflow was interposed in the arterial circuit.3. Venous blood was collected at rest, during and after stimulation of the chorda tympani, and its content of kininogens 1 and 2 were estimated. Kininogen 2 was reduced up to 60% by chorda stimulation, whereas the level of kininogen 1 was unchanged.4. On close arterial infusion of bradykinin or histamine in amounts which produce large vascular effects, including increased capillary permeability, the venous blood levels of both kininogens 1 and 2 were unchanged.5. It is concluded that the selective loss of kininogen 2 on chorda stimulation results from the release of kallikrein into the tissue spaces and reflects the extent of kinin formation within the gland.


Afferent vagal fibres with an expiratory discharge in the rabbit. 1. An investigation was undertaken in the spontaneously breathing, anaesthetized rabbit to observe the response of vagal sensory endings to inflation and deflation stimuli which were sufficient to produce Hering-Breuer reflexes.2. When artificial changes in lung volume were produced by applying step changes in intratracheal pressure, activity in pulmonary stretch receptors increased with inflation and decreased with deflation.3. A small number of vagal afferent fibres were encountered which exhibited a discharge with a respiratory modulation consisting of an increase in activity during the phase of expiration. This pattern of discharge was accentuated when the animal was artificially ventilated with the chest either open or closed.4. These expiratory receptors were stimulated by step changes in intratracheal pressure of -5 and +15 mm Hg to produce a high frequency, slowly adapting discharge which persisted for the 10 sec period of the pressure application. The endings were localized in the extrapulmonary bronchi and lung parenchyma and the afferent fibres were myelinated with conduction velocities of 10.6-29.5 m/sec.5. The pronounced effect of deflation stimuli on the endings indicates that they probably act as one of the afferent mechanisms in the Hering-Breuer deflation reflex.


Permeation and distribution of deuterated and tritiated water in smooth and striated muscle. 1. The diffusion of deuterated water (HDO) into and out of isolated guinea-pig taenia coli and frog sartorius was followed by means of a recording electronic microbalance.2. A comparison was made of the rates of efflux of deuterated and tritiated (HTO) water using the microbalance and a standard tracer technique.3. The time course of the exchange of HDO in both smooth and striated muscle was fitted to the sum of two exponential functions; however, it was not possible to correlate sizes of the intra- and extracellular spaces in the muscles with the sizes of the two compartments in model systems based on compartmental theory of tracer kinetics.4. The efflux of HDO, which was measured by means of the microbalance under stagnant conditions, occurred at a rate approximately 3 times slower than the efflux of HTO which took place while muscles were agitated vigorously in their bathing media.5. There was a marked deviation at short times from a double exponential time course during the efflux of HTO.6. Values of the tracer water permeability, P(d), of smooth and striated muscle fibres, and the extracellular space, E, of the muscles were obtained using a computer to numerically evaluate the series solutions of the equations describing the permeation of labelled water in the muscles.7. It was necessary to assume a value for the diffusion coefficient of the tracer in extracellular fluid in order to compute a unique fit to an exchange curve.8. Values of P(d) and E given by the analysis depended upon the method used for monitoring the exchange, and an interpretation of this dependence was made difficult by the variation in the thickness of unstirred layers on the surface of the muscles under the different experimental conditions.


Effect of environmental temperature on the turnover of 5-hydroxytryptamine in various areas of rat brain. 1. Rats were exposed to environmental temperatures of 9, 24 or 32 degrees C and the turnover of 5-hydroxytryptamine (5-HT) was estimated in various areas of brain by two different methods in separate series of experiments. In the first method, small amounts of tritium labelled 5-HT, [(3)H]5-HT, were injected into the c.s.f. in order to label radioactively the endogenous 5-HT in the brain. The rates of disappearance of [(3)H]5-HT from discrete areas of brain were taken as indices of the rates of turnover of endogenous 5-HT in these areas. In the second method, the rate of accumulation of endogenous 5-HT after inhibition of monoamine oxidase by pargyline was taken as an estimate of 5-HT turnover.2. The results obtained by each method were in agreement. The turnover of 5-HT increased with increasing environmental temperature from 9 to 32 degrees C in specific brain areas. During the first hour of exposure to 32 degrees C, the turnover of 5-HT increased in the preoptic area, hypothalamus and cortex + hippocampus, but not in striatum or midbrain. During the subsequent 2 hr at 32 degrees C, however, the turnover of 5-HT in the preoptic area and hypothalamus fell while that in the striatum showed a delayed rise.3. It is concluded that 5-HT is involved in several different cerebral pathways which increase their activity upon exposure of the rat to heat. These pathways are not located exclusively in the preoptic area and hypothalamus.


The carotid body in the duck and the consequences of its denervation upon the cardiac responses to immersion. 1. The anatomy of the carotid body and its afferent nerve supply was studied in the duck and a method of denervating the carotid body which ensures a satisfactory post-operative course is described.2. The effect of denervating the carotid body upon the cardiac response to immersion of the head in water was studied in ten ducks which at the time of the test were unanaesthetized.3. When the nerves were intact, immersion of the head caused a fall in heart rate after a latent period of between 1 and 9 sec to an average of 24% of the resting rate after 30 sec. Simultaneous measurement of arterial oxygen tension (P(a, O2)) in the brachiocephalic artery showed a rapid initial fall during the initial 10 sec from control levels, 93-103 mm Hg, to between 42 and 47 mm Hg, followed by a gradual fall of 3-5 mm Hg for each subsequent 30 sec period of submergence.4. Following carotid body denervation, the latent period before heart rate started to fall was no different from control but the average fall in heart rate was now to 90% of the resting rate and brachiocephalic P(a. O2) continued to fall steadily during submergence reaching levels of between 10 and 21 mm Hg by the end of the second minute.5. Stimulation of the central end of branches of the IXth (glossopharyngeal) nerve supplying the glottis caused apnoea and bradycardia.6. It is concluded that apnoea and bradycardia during submergence in the duck is initiated reflexly from receptors in the nares, pharynx and glottis but that the profound degree of bradycardia and mechanisms which maintain a relatively high P(a, O2) are regulated by peripheral chemoreceptor activity.


The effect of carotid body denervation upon the respiratory response to hypoxia and hypercapnia in the duck. 1. Respiratory responses to altered P(a, O2) at constant P(a, CO2) and altered P(a, CO2) at constant P(a, O2) were measured in fourteen unanaesthetized ducks 5-9 weeks old.2. All the ducks responded to the inhalation of a few breaths of 100% O(2) with a fall in V(E) of between 11 and 17% of control, and to the reduction in P(a, O2) from control levels (93-101 mm Hg) to 38-47 mm Hg with an average increase in V(E) of 190% of control which was potentiated by raising the level of CO(2).3. Ventilation approximately doubled when P(a, CO2) was raised to 55 mm Hg, the greatest sensitivity to changes in P(a, CO2) being over the range 40-45 mm Hg.4. Carotid body denervation was carried out in nine ducks and the respiratory responses were modified. The fall in V(E) with inhalation of 100% O(2) was abolished in all ducks and the rise in V(E) with hypoxia was abolished in six. The increase in V(E) as P(a, CO2) was altered in steps was unaffected but the rate at which V(E) increased in response to 4% CO(2) was markedly reduced.5. It is concluded that the chemoreceptor regulation of respiration in ducks is similar to that observed in non-diving animals.


The effect of ions on the photoresponses of pigeon cones. 1. Pigeon cone receptor potentials have been identified in a preparation of isolated, incubated retina.2. There is an approximately linear relationship between response amplitude and sodium concentration of the bathing medium.3. A decrease of chloride ions produces results equivalent to a decrease of sodium ions. The response amplitude is a power function of the product of the sodium and chloride concentrations. For most experiments, the exponent is ca. 1.4. After treatment of the retina with ouabain, responses vanish, but can be temporarily restored, in normal, or inverted polarity, by appropriate changes in sodium or chloride concentration.5. Ammonium and potassium ions can substitute quantitatively for sodium ions. Lithium ions initially carry response currents, but later block all responses. Bromide, nitrate and thiocyanate can substitute for chloride ions.6. The response wave form, and the amplitude/light intensity relationship are independent of ions.7. Models of the photoreceptor are discussed. It is concluded that the membrane potential of the cone in light is chiefly determined by the distribution of anions across the membrane, and in darkness there is an increase in outer limb cation permeability.


The role of hypothalamic temperature in the control of panting in the chicken exposed to heat. 1. In unanaesthetized chickens, the temperatures of the hypothalamus, colon and skin have been recorded in relation to the onset and cessation of thermally induced panting.2. During control conditions, hypothalamic temperature showed fluctuations associated with arousal and movement. It was lower than colonic temperature by about 0.9 degrees C but this difference generally decreased during exposure to heat.3. When the birds were exposed abruptly to 40 degrees C, or to ambient temperatures increasing gradually from 20 to 52 degrees C, there was a delay of 15-65 min and marked increases in both peripheral and central body temperatures before panting commenced.4. Infra-red irradiation of the thorax and abdomen caused vasodilatation in the comb and toe before detectable increases in the deep body temperatures. Increasing the colonic temperature by up to 2 degrees C did not cause panting until hypothalamic temperature was also raised. This inhibitory effect of normal hypothalamic temperature was enhanced by low ambient temperature.5. Infra-red irradiation of the head increased hypothalamic temperature by up to 3.5 degrees C and caused vasodilatation in the toe without changes in colonic temperature. Panting, however, did not occur so long as colonic temperature was within the normal range. The inhibitory effect of normal colonic temperature was again enhanced by low ambient temperature.6. In anaesthetized chickens, selective heating of the head and body caused panting only after increases in both the hypothalamic and colonic temperatures.7. Repeated exposure of birds to 40 degrees C did not reduce the time delay before panting started.8. It is concluded that panting in the fowl requires an increase in some extracranial deep body temperature as well as in that of the hypothalamus.


Inotropic changes in the left ventricle: the effect of changes in heart rate, aortic pressure and end-diastolic pressure. 1. Under conditions where heart rate, mean aortic pressure and enddiastolic pressure in the left ventricle are held constant, the intravenous infusion of isoprenaline is accompanied by large changes in dP/dt max in the left ventricle.2. Under similar conditions, during stepwise increments in the rate of infusion of isoprenaline the changes in dP/dt max (measured at a constant paced heart rate) were proportional to changes in the free (intrinsic) heart rate. It is concluded that dP/dt max is a quantitative index of inotropic changes in the left ventricle.3. In comparison to dP/dt max, three other variables which have been used to indicate inotropic changes in the heart (peak pressure in the left ventricle, duration of systole and stroke work at constant end-diastolic pressure), were shown to be unreliable indices of inotropic changes.4. Using dP/dt max to indicate inotropic changes, alteration in the heart rate while mean aortic pressure and end-diastolic pressure in the left ventricle were held constant, and in mean aortic pressure while heart rate ane end-diastolic pressure in the left ventricle were held constant, were each shown to be accompanied by small inotropic changes in the heart.5. Under similar conditions, changes in end-diastolic pressure in the left ventricle alone were not accompanied by inotropic changes as indicated by dP/dt max.


Effects of calcium on the contraction of the hypodynamic frog heart. 1. The time course of build-up or decline of twitch tension in response to enhancement or reduction of the external calcium concentration was determined in frog heart ventricles, in the hypodynamic state as well as under non-hypodynamic conditions.2. The tension build-up induced by high calcium was greatly slowed when the heart passed into the hypodynamic state, whereas the decline in low calcium was little altered by this condition.3. The tension decline consisted of two approximately exponential phases, an initial rapid phase (t((1/2)) between 3 and 10 sec) and a later slow phase (t((1/2)) between 50 and 180 sec).4. A similar composite time course of tension build-up only occurred under certain conditions: (a) in ventricles in which the hypodynamic state had not developed; (b) after a conditioning period of exposure to enhanced calcium or reduced sodium concentrations.5. The results are explained on the assumption that contraction is brought about by the co-operative action inside heart cells of two calcium compounds whose concentrations change at different rates after variation of the external calcium concentration.6. Formal relationships describing the dependence of twitch tension on the concentration of these two hypothetical compounds are obtained.A tentative explanation of the development of the hypodynamic state is also proposed.


Interaction between heart rate and calcium concentration in the control of contractile strength of the frog heart. 1. The changes in twitch tension during the ascending and descending staircase of the frog heart have been examined under various experimental conditions including the hypodynamic and prehypodynamic state.2. The descending staircase resembles the tension change after reduction of external calcium concentration in showing two consecutive phases, an initial rapid and later slow phase of tension decline.3. The time course of the ascending staircase depends on the condition of the heart; it is slow after, and rapid before, development of the hypodynamic state. It is also rapid when elicited after conditioning periods of increased heart rate.4. The tension transients in response to brief concentration steps of external calcium concentration were examined at various levels of heart rate. The results indicate that at high heart rates the sensitivity of heart cells to external calcium is increased.5. The results are interpreted along the lines of a previous hypothesis relating tension development to the cooperative action of two intracellular calcium compounds. The additional assumption is made that an intermediary exists which facilitates calcium movements in heart cells to an extent depending on the level of heart rate.


The localization of pupilloconstrictor function within the mid-brain of the cat. 1. Electrical stimulation techniques have been used to examine the localization of pupilloconstrictor function in the mid-brain of the cat.2. The results show the preganglionic pupilloconstrictor neurones to be localized to a discrete part of the small celled component of the oculomotor nucleus.3. The area described comprises both the Edinger-Westphal and anteromedian nuclei at the level where they adjoin and the caudal continuation of the anteromedian nucleus. It does not include the rostral anteromedian nucleus or the Edinger-Westphal nucleus caudal to the level where its cells are continuous with those of the anteromedian nucleus. These regions do not appear to relate to pupilloconstrictor function.4. The preganglionic nature of the pupilloconstrictor area within the small celled component was verified by an examination of the distribution of the antidromic evoked potential produced by stimulation of the preganglionic fibres at the ciliary ganglion.5. The distribution of pupilloconstrictor responses obtained from extranuclear structures suggested the presence of an excitatory tract from the region of the posterior commissure to the pupilloconstrictor nucleus.6. There was no indication of a lateral division of function within the pupilloconstrictor nucleus. All the responses obtained from nuclear or supranuclear structures were bilaterally equal.


Effects of tetraethylammonium chloride on the membrane activity of guinea-pig stomach smooth muscle. 1. The effects of tetraethylammonium (TEA) on the membrane activity of the antral circular muscle of the guinea-pig stomach were investigated with micro-electrode and double sucrose gap methods.2. In a concentration of 1-1.5 x 10(-3) g/ml. (3-5 mM), the membrane potential was not influenced; the membrane resistance measured by inward current pulses remained the same but the rectifying property of the membrane was suppressed.3. TEA (1-1.5 x 10(-3) g/ml.) enhanced the spike amplitude markedly even from fibres which generated graded responses.4. TEA (1-1.5 x 10(-3) g/ml.) did not increase the maximum rate of rise of the spike but decreased the maximum rate of fall of the spike markedly.5. In Na-free (Tris or sucrose) solution, in K-deficient and excess-K solutions, TEA (1-1.5 x 10(-3) g/ml.) suppressed the rectifying property of the membrane and enhanced the spike amplitude.6. Atropine (10(-6) g/ml.) had no effect on the enhancement of the spike amplitude produced by TEA.7. The minimum concentration of Ca ions required for the effect of TEA on the spike amplitude was one fifth of the normal concentration. TEA also enhanced the spike amplitude in Sr-Krebs.8. The possible role of TEA on the membrane activity is considered to be due to suppression of the K conductance when the membrane is depolarized. Alternative possible roles of TEA on the spike amplitude are also discussed.


The effect on respiration of abrupt changes in carotid artery pH and PCO2 in the cat. 1. An in vivo pH monitoring technique was used to assess changes in pH, and by inference changes in P(CO2), in the carotid artery of anaesthetized cats. The changes in carotid artery pH and respiration following abrupt injections of various acids into the carotid artery or aorta were investigated.2. Injections of saline equilibrated with 100% CO(2), timed to produce changes at the carotid body chemoreceptors during early inspiration caused an increase in the tidal volume of that breath. The amplitude and rate of change of the pH changes so produced were comparable with those of the oscillations in pH produced by respiration itself.3. The respiratory responses to injection of saline equilibrated with 100% CO(2) occurred whether the animal was breathing air or 100% O(2).4. Injections of lactic or hydrochloric acid were without an effect on respiration, except when pH changes larger than 0.1 pH unit were produced. A NaHCO(3) solution equilibrated with 30% CO(2) stimulated respiration, even though the solution was alkaline to the cat's arterial blood and induced an alkaline change in arterial pH.5. Infiltration of the carotid sinus nerve area with procaine temporarily abolished the respiratory response to injections of saline equilibrated with 100% CO(2).


Changes in axon birefringence during the action potential. 1. Observations have been made on the changes in optical retardation accompanying the passage of impulses along crab leg nerves and squid giant axons.2. The nerves were mounted on the stage of a polarizing microscope, at 45 degrees to the planes of polarization and analysis, brightly illuminated with white light. During the nerve impulse the intensity of the light passing the analyser decreased temporarily by 1 part in 10(3)-10(6). Signal-averaging techniques were used to obtain an acceptable ratio of signal to noise.3. The changes in light intensity recorded under these conditions were shown to arise almost entirely from alterations in retardation, with little or no interference from scattering, absorption, linear dichroism or optical rotation effects; the occurrence of stimulus and coupling artifacts was also ruled out.4. In the squid giant axon, the retardation change was shown to be located in a thin cylinder immediately surrounding the axoplasm, and to have a radially oriented optic axis.5. The time course of the decrease in optical retardation was very similar to that of the action potential recorded with an intracellular electrode, suggesting that the retardation closely followed the electrical potential across the membrane.


The uptake of tritiated ouabain by monolayers of cultured cells under various conditions.


Effects of extracellular adenosine triphosphate--a multiple study.


An arrangement for investigating the relationship between the cardiovascular and ventilatory responses of the cat to moderate hypoxia.


Changes in the spatial distribution of synaptic vesicles within degenerating endings of locust motoneurones.


Structure and function of phasic and tonic muscle fibres in locusts and grasshoppers.


A simple method for investigating the functional relationship of the longitudinal and circular layers of the muscularis externa of the rabbit bowel, using a 'flat' preparation.


A critical evaluation of a nitrogen rebreathing method for the estimation of PvO2.


The effect of cocaine and normetanephrine on the overflow of noradrenaline from the isolated blood-perfused cat spleen.


Motor neurone activity during walking in insects.


Action of pilocarpine on sweat glands and sudomotor transmission.


Basic polyelectrolytes and protein transport across the new-born pig intestine.


Functional role of an aminergic nucleus (locus coeruleus).


Striate and extra-striate origins of pattern-related visual evoked potential (VEP) components.


Inhibition by a combination of oestradiol 17-beta and oestriol of uterine muscle contractility.


Changes in electrical conductance of the cat pancreas on vagal stimulation.


Increased chloride permeability of insect muscle fibres on exposure to ibotenic acid.


The effect of meat extract (Oxo) on plasma gastrin concentration in human subjects.


Hyperplasia of the gastric mucosa during pregnancy and lactation in the rat.


Cutaneous receptive properties of single fibres in the cat's medial lemniscus.


The measurement of acetylcholine released from mammalian skeletal muscle in the presence of curare.


Autoregulation of blood flow in the denervated carotid body of the cat.


The anion permeability of frog skeletal muscle in fluoride solutions.


Mode of action of 'depolarizing' neuromuscular blockers.


Excitation of cortical cells by barium.

Excitation of cortical cells by barium.


Change in Z-disk structure with muscle contraction.


The effects of probenecid and salicylate on uric acid flux across red cell membranes.


A new technique for thyroxine secretion rate demonstrating the effect of phenobarbitone in rats.