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Biomedical subjects

P J Butler

Publications and source records attributed to P J Butler.

At least 19 recordsLinked to original sources
PubMed1992

Direct visualization of the structure of the "20 S" aggregate of coat protein of tobacco mosaic virus. The "disk" is the major structure at pH 7.0 and the Proto-helix at lower pH.

We have employed the rapid-freeze technique to prepare specimens for electron microscopy of a coat protein solution of tobacco mosaic virus at equilibrium at pH 7.0 and 6.8, ionic strength 0.1 M and 20 degrees C. The former are the conditions for the most rapid assembly of the virus from its isolated protein and RNA. At both pH values, the equilibrium mixture contains approximately 80% of a "20 S" aggregate and 20% of a "4 S" aggregate (the so-called A-protein). The specimens were prepared either totally unstained or positively stained with methyl mercury nitrate, which binds to an amino acid residue (Cys27) internally located within the subunit, which we show not to affect the virus assembly. The images in the electron microscope are compatible only with the major structure for the "20 S" aggregate at pH 7.0 containing two rings of subunits and these aggregates display the same binding contacts as those seen between the aggregate that forms the asymmetric unit in the crystal, which has been shown by X-ray crystallography to be a disk containing two rings, each of 17 subunits, oriented in the same direction. In contrast, the images from specimens prepared at pH 6.8 show the major structure to be a proto-helix at this slightly lower pH, demonstrating that the technique of cryo-electron microscopy is capable of distinguishing between these aggregates of tobacco mosaic virus coat protein. The main structure in solution at pH 7.0 must therefore be very similar to that in the crystal, although slight differences could occur and there are probably other, minor, components in a mixture of species sedimenting around 20 S under these conditions. The equilibrium between aggregates is extremely sensitive to conditions, with a drop of 0.2 pH unit tipping the disk to proto-helix ratio from approximately 10:1 at pH 7.0 to 1:10 at pH 6.8. This direct determination of the structure of the "20 S" aggregate in solution, under conditions for virus assembly, contradicts some recent speculation that it must be helical, and establishes that, at pH 7.0, it is in fact predominantly a two-layer disk as it had been modelled before.

Capsid↗
PubMed1992

High frequency jet ventilation for microlaryngeal laser surgery. An improved technique.

The use of a triple lumen central venous catheter, which can be shielded from laser irradiation by metal tape, as a conduit for high frequency jet ventilation in six children, is described. The problems of anaesthesia for laryngeal laser surgery and the advantages of the technique described in this paper are discussed.

Catheterization, Central Venous↗
PubMed1992

Prediction of difficult laryngoscopy: an assessment of the thyromental distance and Mallampati predictive tests.

Two hundred and fifty patients were assessed preoperatively using the Mallampati classification and by measuring their thyromental distances. The ease or difficulty of direct laryngoscopy was assessed at the time of induction of anaesthesia. Retrognathia was seen in 15.6% of patients and the incidence of difficult laryngoscopy without external laryngeal pressure was 8.2%. It was found that both assessments predicted less than two in three difficult laryngoscopies and had high false positive rates. It was found that external laryngeal pressure often improved the view of the glottis in difficult laryngoscopies.

Adolescent↗
PubMed1992

The synchronization of ventilation and locomotion in horses (Equus caballus).

Ciné film and synchronized records of respiratory flow were obtained from Thoroughbred racehorses cantering on a treadmill at speeds of 9 and 11 m s-1. Horses and some other galloping and hopping mammals link their breathing and locomotion, taking exactly one breath per stride. Three theoretical mechanisms by which the movements of locomotion might drive ventilation are considered. (i) Flexion of the lumbosacral joint and the resulting forward sweep of the pelvis pushes the viscera against the diaphragm. However, back flexion lags behind ventilation at 11 m s-1 and could not exclusively drive ventilation at this speed. (ii) Loading of the thorax by the impact of the forelimbs with the ground might force air out of the lungs. If the respiratory system were damped sufficiently to perform as this mechanism requires, the work of driving ventilation would make up approximately 15% of the total work of running. In comparison with other estimates of the work of ventilation this seems improbably high. (iii) The observed phase relationship between displacements of the viscera, caused by the accelerations of the body during running, and respiratory airflow is not consistent with a tuned visceral piston mechanism driving breathing. Thus, it would seem likely that back flexion is likely to contribute towards driving ventilation but loading of the thorax and the visceral piston mechanism do not.

Animals↗
PubMed1992

Relationship between heart rate and oxygen consumption during steady-state swimming in California sea lions.

Heart rate (fH) and rate of oxygen uptake (VO2) were measured in six subadult California sea lions Zalophus californianus while they were at rest and while they were swimming for 15 min at controlled speeds of up to 1.4 m s-1 and pulling loads of up to 3 kg. There was a good linear relationship between fH and VO2 in all six sea lions. The slopes of the individual regression lines varied between 2.66 and 4.36 beats ml-1 O2 kg-1, the intercepts varied between 48.2 and 63.0 beats min-1 and r2 varied between 0.82 and 0.93. The mean relationship for all six sea lions is fH = (57.4 +/- 2.0) + (3.58 +/- 0.23) VO2, r2 = 0.89 +/- 0.01. The mean of the lowest VO2 values was 5.1 +/- 0.4 ml min-1 kg-1 and the mean of the highest VO2 values was 26.9 +/- 1.9 ml min-1 kg-1. The means of the lowest and highest values of fH were less extreme, being 72 +/- 3 beats min-1 and 155 +/- 5 beats min-1, respectively. It is concluded that, by using data storage devices and grouped data, fH could be used in otariids as an indicator of aerobic metabolism under field conditions, in particular for breeding females during the period of lactation.

Animals↗
PubMed1990

Pentraxin-chromatin interactions: serum amyloid P component specifically displaces H1-type histones and solubilizes native long chromatin.

Pure serum amyloid P component (SAP) and native long chromatin, mixed together at wt/wt ratios between 1:1 and 1:2 in the presence of physiological concentrations of NaCl and calcium, both remained in solution, whereas each alone precipitates rapidly under these conditions. This solubilization accompanies the binding of SAP to chromatin and the displacement of H1-type histones, which are essential for condensation and higher order folding of chromatin. Such binding of SAP to chromatin is remarkable since displacement of H1 and H5 by salt alone requires approximately 0.5 M NaCl. SAP also bound to nucleosome core particles forming soluble complexes with an apparent stoichiometry of 1:2, a result that is compatible with attachment of SAP at the nucleosome dyad, the site of H1 in intact chromatin. SAP thus undergoes a specific, avid interaction with chromatin that promotes its solubilization and may thereby contribute to the physiological handling of chromatin released from cells in vivo. In contrast, C-reactive protein (CRP) did not bind significantly to either chromatin or to core particles at physiological ionic strength. Incubation of chromatin with either normal serum, or acute phase human serum containing raised levels of CRP, did not induce complement activation regardless of the presence of added SAP or CRP, nor was any cleavage of DNA observed.

Animals↗
PubMed1990

Mechanics of breathing during strenuous exercise in Thoroughbred horses.

The changes induced by exercise on the mechanics of breathing, as well as the simultaneous changes occurring in arterial blood gas tensions and in respiratory gas exchange were investigated in 6 healthy thoroughbred horses, performing a treadmill exercise of increasing intensity. Respiratory airflow and tidal volume (VT) were measured with ultrasonic flowmeters. Pleural pressure changes were measured by an oesophageal balloon catheter. Gas concentration of the expired air was analysed with a mass spectrometer; the oxygen consumption (VO2) and the carbon dioxide output (VCO2) were computed breath-by-breath. Arterial blood gas values were obtained by sampling from the carotid artery. Between rest and fast gallop VT, respiratory frequency, expired minute ventilation (VE), VO2, VCO2, total pulmonary resistance (RL), mechanical work of breathing (Wrm) and PaCO2 increased significantly while PaO2 decreased significantly. The Wrm.VO2(-1) ratio in galloping horses increased exponentially with VE. This, together with the relationship between the changes in PaO2 and in PaCO2 and the increase in the ventilatory mechanics parameters, suggests that the mechanics of breathing may be one of the factors constraining further increase in ventilation in exercising healthy horses.

Animals↗
PubMed1990

Life-threatening complications during anaesthesia in a patient with a ventriculo-atrial shunt and pulmonary hypertension.

A 6-year-old patient with hydrocephalus who underwent revision of a ventriculo-atrial shunt is described. Anaesthesia was complicated by the occurrence of systemic hypertension and arterial hypoxaemia. The patient was subsequently found to have pulmonary hypertension secondary to recurrent pulmonary thromboembolism. The pathophysiological mechanisms for the patient's deterioration are discussed and the anaesthetic management of children with pulmonary hypertension is outlined. It is concluded that patients with a ventriculo-atrial shunt who present for surgery should be screened carefully for the presence of pulmonary hypertension.

Anesthesia, General↗
PubMed1989

Assembly of hybrid RNAs with tobacco mosaic virus coat protein. Evidence for incorporation of disks in 5'-elongation along the major RNA tail.

We have shown that during the reassembly of tobacco mosaic virus (TMV) RNA, with the coat protein supplied as a "disk preparation", the lengths of RNA protected from nuclease are "quantized" with steps which correspond to incorporation of the subunits from either a single or, more commonly, both rings of a disk. This interpretation has been challenged and it was suggested that the pattern was due to special, though unspecified features of the sequence of TMV RNA. To test whether the specific sequence of TMV RNA is important during the elongation, rather than just during nucleation, we have now followed growth of particles containing hybrid RNAs, with the TMV RNA origin of assembly but otherwise non-TMV sequences. We have prepared in vitro RNA transcripts containing heterologous RNA 5' to the origin of assembly sequence from TMV RNA, i.e. with a heterologous RNA tail in place of the natural major 5'-tail and no minor tail, and used these for assembly experiments. In each case we observe a banding pattern very similar to that which we had found with native TMV RNA and with a dominant quantum step of just over 100 bases, and sometimes also a step of 50 bases, strongly suggesting that this is not due to any feature of the TMV RNA. This same repeat is also visible even with a heterologous RNA chosen because it had a sequence repeat of 135 or 136 bases, confirming that the quantization is due to a feature of the elongation reaction and in no way to the RNA sequence being encapsidated. We have also followed elongation with the origin of assembly located 5' to the heterologous RNA. This leads to a slower elongation along this 3'-tail, after the initial rapid encapsidation of the origin RNA, which lacks any quantization of length protected. These results are fully compatible with the hypothesis we had advanced earlier, that the major growth along the 5'-tail is from performed aggregates ("disks") while the minor growth along the 3'-tail is from subunits in the "A-protein" adding singly or a few at a time.

Base Sequence↗
PubMed1988

The tobacco mosaic virus assembly origin RNA. Functional characteristics defined by directed mutagenesis.

The in vitro reassembly of tobacco mosaic virus (TMV) begins with the specific recognition by the viral coat protein disk aggregate of an internal TMV RNA sequence, known as the assembly origin (Oa). This RNA sequence contains a putative stem-loop structure (loop 1), believed to be the target for disk binding in assembly initiation, which has the characteristic sequence AAGAAGUCG exposed as a single strand at its apex. We show that a 75-base RNA sequence encompassing loop 1 is sufficient to direct the encapsidation by TMV coat protein disks of a heterologous RNA fragment. This RNA sequence and structure, which is sufficient to elicit TMV assembly in vitro, was explored by site-directed mutagenesis. Structure analysis of the RNA identified mutations that appear to effect assembly via a perturbation in RNA structure, rather than by a direct effect on coat protein binding. The binding of the loop 1 apex RNA sequence to coat protein disks was shown to be due primarily to its regularly repeated G residues. Sequences such as (UUG)3 and (GUG)3 are equally effective at initiating assembly, indicating that the other bases are less functionally constrained. However, substitution of the sequences (CCG)3, (CUG)3 or (UCG)3 reduced the assembly initiation rate, indicating that C residues are unfavourable for assembly. Two additional RNA sequences within the 75-base Oa sequence, both of the form (NNG)3, may play subsidiary roles in disk binding. RNA structure plays an important part in permitting selective protein-RNA recognition, since altering the RNA folding close to the apex of the loop 1 stem reduces the rate of disk binding, as does shortening the stem itself. Whereas the RNA sequence making up the hairpin does not in general affect the specificity of the protein-RNA interaction, it is required to present the apex signal sequence in a special conformation. Mechanisms for this are discussed.

Base Sequence↗
PubMed1988

Chemoreceptor control of heart rate and behaviour during diving in the tufted duck (Aythya fuligula).

1. The role of chemoreceptors in the control of heart rate and behaviour during diving activity in the tufted duck was investigated in two ways. In a closed-loop experiment, ducks were exposed to ambient gas mixtures of varied composition during diving activity in an indoor tank. Characteristics of diving behaviour, heart rate and deep body temperature were monitored under hypoxic, hyperoxic and hypercapnic conditions and compared with those in air. Secondly, in an open-loop experiment the role of the carotid body (CB) chemoreceptors in the control of the responses to altered inspired gas composition and in the cardiac responses to extended and enclosed dives (Stephenson, Butler & Woakes, 1986) was investigated by chronic bilateral denervation of these receptors. 2. Heart rate during submersion was unaffected by inspired gas composition in control (data from intact and sham-operated ducks combined) and CB-denervated ducks, though diving behaviour was significantly modified in both groups of animals in response to altered inspired gas composition. Hypoxia and hypercapnia resulted in an increase in the proportion of total diving time spent breathing at the surface. The main effect of hypoxia (9-10% O2) was to reduce dive duration in control ducks and this effect was almost completely abolished after CB denervation. Hypercapnia (5-6% CO2) reduced dive duration less markedly than hypoxia but it greatly increased the duration of the inter-dive interval, effects which were not significantly influenced by CB denervation. Hyperoxia (40-45% O2) had very little effect on either behaviour or heart rate during diving, although deep body temperature was significantly elevated in this gas mixture during diving activity. There was also a less marked, but nevertheless significant, apparent hyperthermia during diving activity in air on an indoor tank but not on an outdoor pond. Conversely, there was a significant apparent hypothermia during diving activity under hypoxic conditions. 3. The CB chemoreceptors were shown to play a role in cardiac control during diving under certain circumstances. The duration of pre-dive tachycardia was significantly increased in hypoxia and this increase was abolished after CB denervation. The rate of development of bradycardia during extended and enclosed dives was slowed following CB denervation, though the initiation of the responses in extended and enclosed dives and the eventual attainment of sub-resting heart rates in enclosed dives were not prevented, indicating that other, as yet unidentified, sensory inputs are involved in cardiac control under these conditions.

Animals↗
PubMed1988

Effect of training on maximal oxygen uptake and aerobic capacity of locomotory muscles in tufted ducks, Aythya fuligula.

1. The effects of artificial swim training on maximal oxygen consumption and heart rate, as well as on the capillarity and oxidative capacity of locomotory muscles, have been studied in the tufted duck, Aythya fuligula. 2. The artificial training programme resulted in a 27% increase in maximal oxygen consumption, mainly as a result of an increase in muscle capillarity (20% increase in capillary/fibre ratio). In addition, activity of an oxidative enzyme, citrate synthase, increased (by 42%) and there was a significant transformation of fibre types in the lateral gastrocnemius muscle. 3. Altering the duration and nature of the training stimulus, for example flying and diving, can bring about different degrees of muscular adaptation, particularly in oxidative capacity.

Adaptation, Physiological↗
PubMed1988

The aerobic capacity of locomotory muscles in the tufted duck, Aythya fuligula.

The locomotory muscles of the tufted duck, Aythya fuligula (L.), were analysed for mass, aerobic and anaerobic enzyme activities, fibre-type proportions, capillarity, mitochondrial and myoglobin content. The estimated aerobic capacity of the muscles correlated well with the muscles' maximal oxygen uptake both when measured during swimming and when predicted for steady-state flight. The results suggest that exercise performance in birds cannot be predicted purely on the basis of muscle mass (see Butler & Woakes, 1985); the specific enzyme complement of each muscle must also be taken into account. The delivery of oxygen to mitochondria is facilitated by the dense capillarity and high myoglobin content of the muscles.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1988

Regional distribution of blood flow during swimming in the tufted duck (Aythya fuligula).

The distribution of blood flow to a number of organs and tissues of the tufted duck was determined (by the microsphere technique) before and while the birds were swimming at close to their maximum sustainable velocity (i.e. at 0.69 +/- 0.01 ms-1). During swimming, oxygen uptake was twice the pre-exercise value. Cardiac output increased by 70%, there was no significant change in arterial blood pressure and total systemic conductance increased by 44%. There were no significant changes in blood flow to the brain, liver, adrenal glands, spleen and respiratory muscles. Not surprisingly, there were increases in blood flow to the heart (30% increase) and to the muscles of the hindlimbs (to 3.1 times the pre-exercise value). Significant reductions in flow occurred to various parts of the gastrointestinal tract (although not to the gastrointestinal tract as a whole), to the pancreas and to the pectoralis muscles. In the case of the flight musculature as a whole, the reduction was to approximately 40% of the values in the ducks before exercise. Thus, despite the fact that cardiac output was some three times lower than it would have been during flight, there was a clear redistribution of blood away from some visceral organs and inactive muscles during surface swimming in the tufted duck. This lends support to the suggestion that blood is selectively directed to the legs, as well as to the brain and central nervous system (CNS) and away from the visceral organs and inactive muscles during voluntary diving in these birds.

Animals↗
PubMed1987

Serum amyloid P component is the major calcium-dependent specific DNA binding protein of the serum.

Serum amyloid P component (SAP), a member of the highly conserved pentraxin family of plasma proteins, was found to be the only protein in whole normal or acute phase serum which underwent specific calcium-dependent binding to either single or double-stranded DNA immobilised on gel. Isolated purified SAP also bound to long chromatin, to H1-stripped chromatin and to native DNA in solution at physiological ionic strength. Pure SAP which had been immobilised on gel, specifically bound nucleosome core particles from solution. These observations strongly suggest that SAP may bind to extracellular chromatin and DNA in vivo and that this may be its physiological role.

Animals↗
PubMed1987

Heart rate in humans during underwater swimming with and without breath-hold.

Heart rate was monitored, by way of radiotelemetry, from 6 male subjects of mean age (+/- SE) 24 +/- 1 years and of mean mass 73.5 +/- 2.5 kg. Measurements were made in a 25 m pool at a water temperature of 28 degrees C. Resting heart rate was 67 +/- 3.7 beats X min-1 and when the subjects submerged themselves completely in the pool, but remained inactive, there was a prompt, gradual reduction in heart rate which reached 48 +/- 2.6 beats X min-1 within 30 sec and 40 +/- 2.6 beats X min-1 within 59 +/- 5.6 sec (maximum duration). When they propelled themselves under water for 33 sec by kicking their legs and breathed through a snorkel tube, heart rate increased progressively to a value of 118 +/- 4.1 beats X min-1 at 28 sec. However, when they performed the same manoeuvre while holding their breath, there was an initial increase in heart rate to 106 +/- 5.7 beats X min-1 within the first 10 sec. This was followed by a decline in heart rate which was more rapid than that recorded during inactive submersion and which eventually reached 48 +/- 4.4 beats X min-1 at mean underwater duration of 33 +/- 1.8 sec. It is concluded that during the first 10-15 sec of underwater breath-hold swimming in humans, the cardiovascular response (as indicated by heart rate) is similar to that seen during a similar level of exercise while breathing air. From then on there is a progressively more intense bradycardia which is probably indicative of an oxygen conserving response consisting of reduced perfusion of most of the body except the heart, CNS and active locomotory muscles. The degree and rate of onset of this proposed oxygen conserving response are influenced by the intensity of the exercise performed while under water and whether or not the period of underwater breath-hold swimming is preceded by exercise.

Adaptation, Physiological↗