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Biomedical subjects

D W Yates

Publications and source records attributed to D W Yates.

At least 73 records · Page 4Linked to original sources

Measuring the severity of injury.

Attempts have been made to improve the Injury Severity Score (ISS) system of Baker et al. (1974) using plasma lactate data obtained from 277 patients shortly after injury and before treatment. The ISS is based on the Abbreviated Injury Scale (AIS) values of the individual injuries, being the sum of the squares of the values for the three most severely injured regions. Log (plasma lactate concentration) is positively related to ISS over its whole range. It was not possible to vary the AIS values, either on clinical grounds or using a computer, in such a way that the variance of the log (plasma lactate concentration) about its regression line with ISS was significantly reduced. With a score based on the sum of the squares of the AIS values for all the patient's injuries, some improvement to the AIS values could be made but it was not statistically significant. At the present time Baker's ISS method would seem to be the best way of grading injuries for acute studies.

Humans↗

Changes in cardiac output and its distribution after non-haemorrhagic injury in the rat.

In the unanaesthetized rat cardiac output, measured by a thermodilution technique, fell rapidly following a 4h period of bilateral hind-limb ischaemia. There was a significant positive correlation between body temperature and total cardiac output after injury. There were also striking changes in the distribution of cardiac output; for example, hepatic artery flow was markedly increased, whereas splanchnic flow fell passively with the reduction in cardiac output. There were suggestions of regional differences in the reduction of blood flow within the brain.

Animals↗

Tryptophan fluorescence of (Na+ + K+)-ATPase as a tool for study of the enzyme mechanism.

1. The protein fluorescence intensity of (Na+ + K+)-ATPase is enhanced following binding of K+ at low concentrations. The properties of the response suggest that one or a few tryptophan residues are affected by a conformational transition between the K-bound form E2 . (K) and a Na-bound form E1 . Na. 2. The rate of the conformational transition E2 . (K) leads to E . Na has been measured with a stopped-flow fluorimeter by exploiting the difference in fluorescence of the two states. In the absence of ATP the rate is very slow, but it is greatly accelerated by binding of ATP to a low affinity site. 3. Transient changes in tryptophan fluorescence accompany hydrolysis of ATP at low concentrations, in media containing Mg2+, Na+ and K+. The fluorescence response reflects interconversion between the initial enzyme conformation, E1 . Na and the steady-state turnover intermediate E2 . (K). 4. The phosphorylated intermediate, E2P can be detected by a fluorescence increase accompanying hydrolysis of ATP in media containing Mg2+ and Na+ but no K+. 5. The conformational states and reaction mechanism of the (Na+ + K+)-ATPase are discussed in the light of this work. The results permit a comparison of the behaviour of the enzyme at both low and high nucleotide concentrations.

Adenosine Triphosphate↗

Elementary steps of the (Na+ + K+)-ATPase mechanism, studied with formycin nucleotides.

1. Formycin triphosphate (FTP), a fluorescent analogue of ATP, is a substrate for (Na+ + K+)-ATPase (ATP phosphohydrolase, EC 3.6.1.3), with properties similar to those of ATP. 2. FTP and formycin diphosphate (FDP) bind to the enzyme with high affinity and, on binding, the nucleotide fluorescence is enhanced 3-4-fold. It is therefore possible, with a stopped-flow fluorimeter, to measure the rates of binding and release of FTP and FDP under conditions in which turnover does not occur. 3. When the enzyme-FTP complex is exposed to conditions permitting turnover (Mg2+, Na+ +/- K+), changes in fluorescence occur which can be explained by supposing that they reflect the interconversion of states with or without bound nucleotides. A rapid fall in fluorescence, that we attribute to the rapid release of FDP from newly phosphorylated enzyme, is followed by a steady state in which low fluorescence suggests that little nucleotide is bound. Eventually, exhaustion of FTP allows rebinding of FDP to the enzyme, which is signalled by a rise in fluorescence. 4. The estimated rate of FDP release from newly formed phosphoenzyme is unaffected by the presence of K+ (0-2 mM) or the concentration of FTP (1-20 micron). 5. Experiments with [gamma-32P]FTP show that about 1 mol of 32P is incorporated per mol of enzyme. The rate of phosphorylation of the enzyme by [gamma-32P]FTP has been measured with a rapid-mixing-and-quenching apparatus. 6. Kinetic data from the fluorescence and phosphorylation experiments show that the behaviour of the enzyme, at least at the low nucleotide concentrations employed, is consistent with the Albers-Post model, and is difficult to reconcile with models in which K+ acts at or before the step in which FDP is released during turnover.

Adenosine Triphosphate↗

Conformational transitions between Na+-bound and K+-bound forms of (Na+ + K+)-ATPase, studied with formycin nucleotides.

1. Fluorescence measurements have shown that formycin triphosphate (FTP) or formycin diphosphate (FDP) bound to (Na+ + K+)-ATPase (ATP phosphohydrolase, EC 3.6.1.3) in Na+-containing media can be displaced by the following ions (listed in order of effectiveness): Tl+, K+, Rb+, NH4+, Cs+. 2. The differences between the nucleotide affinities displayed by the enzyme in predominantly Na+ and predominantly K+ media in the absence of phosphorylation, are thought to reflect changes in enzyme conformation. These changes can therefore be monitored by observing the changes in fluorescence that accompany net binding or net release of formycin nucleotides. 3. The transition from a K+-bound form (E2-(K)) to an Na+-bound form (E1-Na) is remarkably slow at low nucleotide concentrations, but is accelerated if the nucleotide concentration is increased. This suggests that the binding of nucleotide to a low-affinity site on E2-(K) accelerates its conversion to E1-Na; it supports the hypothesis that during the normal working of the pump, ATP, acting at a low affinity site, accelerates the conversion of dephosphoenzyme, newly formed by K+-catalysed hydrolysis of E2P, to a form in which it can be phosphorylated in the presence of Na+. 4. The rate of the reverse transformation, E1-Na to E2-(K), varies roughly linearly with the K+ concentration up to the highest concentration at which the rate can be measured (15 mM). Since much lower concentrations of K+ are sufficient to displace the equilibrium to the K-form, we suggest that the sequence of events is: (i) combination of K+ with low affinity (probably internal) binding sites, followed by (ii) spontaneous conversion of the enzyme to a form, E2-(K), containing occluded K+. 5. Mg2+ or oligomycin slows the rate of conversion of E1-Na to E2-(K) but does not significantly affect the rate of conversion of E2-(K) to E1-Na. 6. In the light of these and previous findings, we propose a model for the sodium pump in which conformational changes alternate with trans-phosphorylations, and the inward and outward fluxes of both Na+ and K+ each involve the transfer of a phosphoryl group as well as a change in conformation between E1 and E2 forms of the enzyme or phosphoenzyme.

Antibiotics, Antineoplastic↗

Measuring the severity of injury.

The injury severity score as a method for measuring the severity of injury has been found useful for epidemiological and metabolic research. Comparison with plasma cortisol concentrations confirmed that the method could distinguish between minor and moderate injuries. Before using the method one must decide on the need to weight the score for age. This is necessary when studying some relationships--for example, mortality and severity--but not others--for example, plasma cortisol concentration and severity.

Adolescent↗

Airway patency in fatal accidents.

The state of the airway in patients who had fatal accidents over a five-year period was correlated with the severity of injury sustained. Necropsy of patients dying in hospital up to 72 hours after an accident showed that those with obstruction of the airway had less severe injuries than those in whome no such obstruction could be found. This suggests that airway obstruction contributed to their death. A similar distinction could not be shown for the patients who died before they reached hospital, indicating that airway management before arrival at hospital was probably satisfactory.

Age Factors↗

The binding of nucleotides and bivalent cations to the calcium-and-magnesium ion-dependent adenosine triphosphatase from rabbit muscle sarcoplasmic reticulum.

The binding of MgATP to purified Ca2+Mg2+-dependent adenosine triphosphatase from rabbit muscle sarcoplasmic reticulum was studied by using a flow-dialysis method. Phosphoryl-enzyme formation and catalytic activity were also measured, and all three processes demonstrated negative co-operativity, with half-saturation of all three parameters at a MgATP concentration of 40-50muM, and a Hill coefficient (h) of 0.8. The variation of the binding constant with with pH was measured and showed tighter binding of MgATP with increasing pH over the range 6.8-8.5. Binding parameters for ATP analogues were also measured. The binding of Ca2+ in the presence and absence of ATP analogues gave half saturation at a Ca2+ concentration of 1.2-1.3muM. Hill plots of Ca2+-binding data gave a slope of 0.8. These results show that the binding of MgATP and Ca2+ can occur in a random manner, with neither substrate influencing the affinity of the enzyme for the other.

Adenosine Triphosphatases↗

Complications of fractures of the clavicle.

Most fractures of the clavicle unite without incident. The number and diversity of the methods of treatment in use suggest that in most cases good results are obtained despite medical supervision. Yet occasionally complications do arise. This paper describes two such cases and reviews the literature in search of a common factor to account for these complications. Cases presenting with early and late complications of fractures of the clavicle are described and the literature on the subject reviewed. The incidence of complications is highest in cases of direct violence to the shoulder region producing comminuted fractures. Surgical management is outlined in general terms. It is suggested that more prolonged and rigorous immobilization of cases "at risk" may reduce the incidence of non-union and prevent late neurovascular complications.

Adolescent↗