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Biomedical subjects

P J Butler

Publications and source records attributed to P J Butler.

At least 91 records · Page 5Linked to original sources
PubMed1994

The metabolic characteristics of the locomotory muscles of grey seals (Halichoerus grypus), harbour seals (Phoca vitulina) and Antarctic fur seals (Arctocephalus gazella).

It is not known precisely how marine mammals are able to maintain muscle function during active swimming in breath-hold dives, when ventilation stops and heart rate falls. Examination of muscle biochemistry and histochemistry can provide information on the relative importance of different metabolic pathways, the contractile potential of the muscle fibres, the oxygen storage capacity of the muscle and the capillary distribution in these animals. In this study, samples of locomotory muscle were taken from wild grey seals (Halichoerus grypus), harbour seals (Phoca vitulina) and Antarctic fur seals (Arctocephalus gazella); Wistar rat muscle was analysed for comparative purposes. Activities of citrate synthase and beta-hydroxyacyl CoA dehydrogenase were higher in the harbour seal muscle than in the grey seal muscle, suggesting that harbour seals have a greater aerobic capacity. Both phocid muscles had a greater reliance on fatty acid oxidation than the fur seal or rat muscles. The myoglobin data demonstrate that the grey seals have the highest oxygen storage capacity of the three pinniped species, which correlates with their greater diving ability. Myoglobin levels were higher in all three pinniped species than in the Wistar rat. The fibre type compositions suggest that the muscles from the fur seals have higher glycolytic capacities than those of the phocid seals [fur seal pectoralis, 7% slow-twitch oxidative fibres (SO), 25% fast-twitch oxidative glycolytic fibres (FOG), 68% fast-twitch glycolytic fibres (FG); grey seal 57% SO, 5% FOG, 38% FG; area per cents]. However, the pectoralis muscle of the fur seal, although the most glycolytic of the pinniped muscles studied, has the highest capillary density, which indicates a high capacity for fuel distribution. These results show that, while pinniped muscle has an increased oxygen storage potential compared with the muscle of a typical terrestrial mammal, there are no distinct adaptations for diving in the enzyme pathways or fibre type distributions of the pinniped muscle. However, the muscle characteristics of each species can be related to its diving behaviour and foraging strategy.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1993

Molecular characterization of Limulus polyphemus C-reactive protein. I. Subunit composition.

The molecular mass of whole native C-reactive protein (CRP) from Limulus polyphemus, the horseshoe crab, was precisely determined for the first time, by analytical ultracentrifugation after measurement of its absorption coefficient, A1cm, 1% at 280 nm (15.49) and its partial specific volume (0.72 +/- 0.003 ml/g). The apparent weight-average molecular mass, in the range over which it was independent of the concentration, was 300 kDa. Limulus CRP, isolated from an individual animal, was also analyzed by electrospray mass spectrometry after dissociation into its subunits, and nine components were detected in the mass range 24935-25617 Da. Four of these components corresponded precisely to one of the previously reported protein sequences of Limulus CRP subunits which is glycosylated by a single oligosaccharide chain of composition, Man2GlcNAc2, Man3GlcNAc2, Man4GlcNAc2 or Man5GlcNAc2, the structures of which are elucidated in the accompanying paper [Amatayakul-Chantler, S., Dwek, R. A., Tennent, G. A., Pepys, M. B. & Rademacher, T. W. Molecular characterization of Limulus polyphemus C-reactive protein. II. Asparagine-linked oligosaccharides (1993) Eur. J. Biochem. 214, 99-110]. All the remaining components, except one minor component, corresponded to the analogous glycoforms of peptides of molecular mass 24281 +/- 2 Da and 24523 +/- 1 Da, neither of which have previously been characterized. These results are consistent with the presence of 12 subunits in the Limulus CRP molecule, in contrast to the number of subunits in vertebrate members of the CRP family. The CRP family members in vertebrates are known as pentraxins because of the symmetrical pentameric arrangement of their subunits. The concentration of Limulus CRP in hemolymph from 20 individual animals, measured precisely by specific electroimmunoassay, covered the wide range 0.275-6.64 mg/ml, mean (SD) = 1.83 (2.06) mg/ml. It remains to be determined whether this protein is an acute-phase reactant, like its human and some other mammalian homologues.

Animals↗
PubMed1993

Hydrogen-bonding contacts in the major groove are required for human immunodeficiency virus type-1 tat protein recognition of TAR RNA.

The binding site for tat on TAR RNA was analysed by preparing a series of model RNA substrates carrying site-specific functional group modifications. The test RNAs were prepared by annealing two short synthetic oligoribonucleotides to form a duplex structure with a U-rich bulge and flanking sequences identical to TAR RNA. Tat binds these duplex RNAs with approximately half the affinity for wild-type TAR RNA. Substitution at positions U23 or U25 by the base analogue, O4-methyl-dT, which is deficient in its ability to hydrogen-bond at the N3 position reduces tat affinity more than 20-fold. Modifications to purines in the stem of TAR RNA that affect hydrogen-bonding ability in either the major or the minor groove of duplex RNA were also tested. Removal of the nitrogen atom at either the N7 position of G26 or at the N7 position of A27 reduces tat affinity 10- to 20-fold. By contrast removal of the exocyclic amino group in the minor groove at position G26, by substitution with inosine, does not affect tat binding significantly. A single methylphosphonate substitution at the phosphate bond between A22 and U23 also leads to a significant loss of tat binding ability, whereas all other methylphosphonate substitutions in the U-rich bulge are not harmful to tat binding. We conclude that tat forms multiple specific hydrogen bonds to a series of dispersed sites displayed in the major groove of the TAR RNA molecule. These include the N3-H of U23, the N7 of G26, the N7 of A26 and the phosphate between A22 and U23.

Base Sequence↗
PubMed1993

Stride length and respiratory tidal volume in exercising thoroughbred horses.

The purpose of this study was to test the hypothesis that locomotor-respiratory coupling in horses may provide a basis for the appropriate matching of lung ventilation to running speed and metabolic power. This was achieved by determining the effect on respiratory frequency and tidal volume in thoroughbred horses of changing running speed while maintaining a constant metabolic demand by also varying the incline of the treadmill. This procedure was performed at three different speeds at two different levels of metabolic rate. It appears that, in response to metabolic demands which are not directly related to speed, horses can control tidal volume independently of stride length but they do not vary respiratory frequency independently of stride frequency. When running at 0 degrees incline, however, they probably do not operate an elevated tidal volume, because of the increased energetic costs such an elevated tidal volume would incur.

Animals↗
PubMed1993

The central localization of the vagus nerve in the ferret (Mustela putorius furo) and the mink (Mustela vison).

The location of vagal preganglionic neurones (VPN) has been determined in nine ferrets (Mustela putorius furo) and seven mink (M. vison) using neuronal tract-tracing techniques employing horseradish peroxidase (HRP) and wheat-germ agglutinin conjugated HRP (WGA-HRP) mixtures injected into the nodose ganglion of the vagus nerve. Labelled VPN were located ipsilaterally in the dorsal motor nucleus of the vagus (DmnX), nucleus ambiguus (nA), and reticular formation (rf) of the medulla oblongata. In four of the ferrets, labelled VPN were also identified in the nucleus dorsomedialis (ndm) and the nucleus of the spinal accessory nerve (nspa). In a single mink a few labelled cells were observed in the ndm but no labelled VPN were found in the nspa. Labelling of afferent components of the vagus nerve was seen in two ferrets and two mink with the best labelling obtained following an injection of an HRP/WGA-HRP mixture into the nodose ganglion. Labelled afferents were observed to cross the ipsilateral spinal trigeminal tract (SpV) before entering the tractus solitarius (TS) in regions separate from the motor axons which exit the medulla in separate fasicles. Sensory terminal fields were identified bilaterally in the nucleus of the tractus solitarius (nTS) in both species and bilaterally in the area postrema (ap) of the ferret; however, the contralateral labelling was sparse in comparison to the densely labelled ipsilateral nTS/ap. Maximal terminal labelling was seen in regions just rostral and caudal to obex in both species.

Animals↗
PubMed1993

Lung management during cardiopulmonary bypass: is continuous positive airways pressure beneficial?

It is not clear if the use of continuous positive airway pressure (CPAP) during cardiopulmonary bypass (CPB) improves lung function after cardiac surgery. We have measured alveolar-arterial oxygen partial pressure difference (PAO2-PaO2) in 61 patients undergoing elective coronary artery bypass surgery. We studied three groups of patients: in group 1 the lungs were disconnected from the breathing system (no CPAP) during CPB; in group 2, 5 cm H2O CPAP with air was applied to the lungs; in group 3, 5 cm H2O of CPAP was applied with 100% oxygen. (PAO2-PaO2) was measured before CPB and then at 30 min, 4 h and 8 h after CPB. Compared with group 1 (no CPAP), (PAO2-PaO2) was significantly smaller in groups 2 and 3 at 30 min (P = 0.036), but not at 4 h and 8 h after CPB (P = 0.32, P = 0.96). The time to extubation (P = 0.42) and early extubation (P = 0.87) were not affected by the use of CPAP. The results of this study do not support the use of CPAP during CPB as a mechanism of improving lung function after cardiac surgery.

Adult↗
PubMed1993

End-tidal oxygen measurement compared with patient factor assessment for determining preoxygenation time.

Time to adequate preoxygenation was assessed in 200 elective surgical patients, using measurement of end-tidal oxygen concentration. A variety of patient factors were assessed as to their ability to predict the time required to preoxygenate a patient. Of the 200 patients, 23 (11.5%) were unable to be adequately preoxygenated; most of these cases were due to a poor mask fit. The average time for preoxygenation was 154 seconds (range 43-364 seconds). Of those patients who could be preoxygenated, 46 (23%) required more than three minutes. Although a regression equation could be constructed to calculate time required for preoxygenation, the wide standard errors of the coefficients preclude a clinically useful predictive equation. We thus found that we could not accurately predict time required for preoxygenation and that a routine three minutes preoxygenation may not be sufficient for many patients. However, the measurement of end-tidal oxygen concentration is a very useful method of determining the end-point for preoxygenation.

Adolescent↗
PubMed1993

Respiratory and cardiovascular adjustments during exercise of increasing intensity and during recovery in thoroughbred racehorses.

A new design of flowmeter is described and used in a comprehensive study of the respiratory and cardiovascular adjustments that occur during a standardised exercise test in Thoroughbred horses. The flowmeter system and associated lightweight, fibreglass mask (total mass, 0.7 kg) have a maximum dead space of 500 ml and negligible resistance to airflow. They have no systematic effect on blood gases and, together with a rapidly responding mass spectrometer, enable an accurate computation of gas exchange to be performed together with breath-by-breath determination of other respiratory variables. At the highest level of exercise (12 ms-1 on a 3 degrees incline), the rate of oxygen uptake (VO2) and carbon dioxide production (VCO2) increased to 29.4 times and 36.8 times their resting values, respectively. Respiratory minute volume (VE) increased to 27.0 times its resting value, with respiratory frequency (fR) making the major contribution at the walk and trot. However, with increasing cantering speeds, fR changed little as it was locked in a 1:1 fashion to stride frequency, and tidal volume (VT) then made the major contribution to the increase in VE. The ratio of ventilatory dead space (VD) to VT in resting horses was lower than that previously reported in the literature and this could be the result of the different respiratory recording systems that were used. There was a close relationship between VT and stride length at increasing cantering speeds. Despite the fact that alveolar ventilation (VA) was well matched to VO2, there was a significant reduction in arterial PO2 (PaO2) when the horses cantered at 8 ms-1 and this eventually fell to 34% below the resting value. The present data tend to support the idea that VA/Vb (where Vb is cardiac output) inequalities are important in causing this hypoxaemia. However, the reduction in PaO2 was more than compensated for by an increase in haemoglobin concentration, [Hb], so the concentration of oxygen in the arterial blood (CaO2) was significantly above the resting value at all levels of exercise. Both lactate concentration and PaCO2 increased during exercise, causing substantial reductions in pH of both arterial and mixed venous blood. This would have inevitably shifted the oxygen equilibrium curve of the Hb to the right, desaturating the arterial blood and thus exacerbating the effect of the hypoxaemia, as would the almost 4 degrees C rise in blood temperature. The tight respiratory/locomotor linkage might prevent the acidosis and hyperthermia having the stimulatory effects on VE that they have in humans at high work loads.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Studies of the structure and binding properties of hamster female protein.

We report here the characterization of hamster female protein (FP), a member of the pentraxin family of plasma proteins, as a molecule composed of glycosylated subunits of 25,655 MW containing a single intrachain disulphide bridge. In the presence of EDTA the subunits are non-covalently associated as pentamers of mass approximately 128,000 MW, and in the presence of calcium they aggregate further, probably to form decamers. This pentamer-decamer transition at physiological ionic strength has not been described in other pentraxins. As previously reported, FP shares the capacity of C-reactive protein (CRP) in other species to bind phosphocholine and we show here that it also resembles human CRP in binding only weakly to agarose, to human AA amyloid fibrils in vitro, and to mouse AA amyloid deposits in vivo. It thus differs markedly from human and mouse serum amyloid P component (SAP) but it is nevertheless deposited in hamster AA amyloid in vivo and clearly is the hamster counterpart of SAP in other species. These results illustrate the subtle diversity among members of the otherwise conserved pentraxin family of vertebrate plasma proteins.

Alpha-Globulins↗
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↗