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Biomedical subjects

A M Reynolds

Publications and source records attributed to A M Reynolds.

At least 19 recordsLinked to original sources

Appetitive flight patterns of male Agrotis segetum moths over landscape scales.

An analysis is presented of the first harmonic radar studies of pheromone-plume locating flights of male Agrotis segetum moths over distances of up to 500 m. Upon release most moths flew in a direction having a downwind component. The first significant changes in flight orientations occur in the immediate vicinity of a pheromone source. Moths that were initially flying downwind change course and start flying crosswind whilst those that initially flew crosswind change course and start flying upwind. It is shown that such behaviour is consistent with the adoption of an effective plume-location strategy, and conditions are identified when downwind flights would be more advantageous than crosswind ones. Additionally, some of the complex flight patterns that can arise at later times are shown to be compatible with the adoption of an optimal biased scale-free (Lévy-flight) searching strategy. It is found that disruptive doses of sex pheromone can have a marked influence upon male moth flight patterns.

Animals↗

Ballooning dispersal in arthropod taxa with convergent behaviours: dynamic properties of ballooning silk in turbulent flows.

We present a new model of ballooning behaviour in arthropods in which draglines are regarded as being extendible and completely flexible. Our numerical simulations reveal that silk draglines within turbulent flows can become twisted and stretched into highly contorted shapes. Ballooners are therefore predicted to have little control over their aerodynamic drag and their dispersal within the atmospheric boundary layer. Dragline length is crucial only at lift-off. This prediction runs counter to that of Humphrey who suggested that the length of rigid draglines can be used to control dispersal. In contrast with Humphrey's model, the new model accounts naturally for the large distances travelled by some ballooners.

Animals↗

White blood cell left shift in a neonate: a case of mistaken identity.

We present a full-term male infant who presented with tachypnea and an increased band count on his complete blood count (CBC) with an immature to total neutrophil (I:T) ratio of 0.6 raising suspicion of early onset sepsis. A blood culture was drawn and he was started on appropriate antibiotics. The patient's clinical condition rapidly improved; however, the white cell count 'left shift' persisted. When a detailed family history was obtained, it was discovered that the father, paternal uncle and the grandfather had been diagnosed with Pelger-Huet anomaly (PHA). As the urine, blood and CSF cultures were all negative in this now well-appearing infant, the left shift on the CBC was believed to be due to inheritance of the PHA. We present this case to emphasize that even in this age of sophisticated laboratory evaluation, a good clinical history, including family history, and clinical evaluation, are essential for accurate diagnosis.

Diagnostic Errors↗

Scale-free movement patterns arising from olfactory-driven foraging.

The scale-free movement patterns of some foragers has aroused considerable excitement because they are known to optimize the success of random searches when target sites are randomly and sparsely distributed. Here it is shown that scale-free movement patterns can arise from a naive response of foragers to scent concentrations within turbulent plume structures.

Animals↗

Anisotropy of acceleration in turbulent flows.

Third-order Lagrangian stochastic models for the evolution of fluid-particle hyperaccelerations (material derivatives of Lagrangian accelerations) are shown to account naturally for the anisotropy of acceleration variances in low-Reynolds-number turbulent flows and for their dependency upon the energy-containing scales of motion. Model predictions are shown to be in close accord with the results of direct numerical simulations for a turbulent channel flow and with previously acquired simulation data for a homogeneous turbulent shear flow.

Journal Article↗

Stokes number effects in Lagrangian stochastic models of dispersed two-phase flows.

The statistical properties of fluid velocities along particle trajectories in turbulent flows have a conditional dependency upon particle velocity. It is shown that the formulation of Lagrangian stochastic (LS) models for particle trajectories in terms of the well-mixed condition for these conditional velocity statistics is exactly analogous to the formulation of second-order LS models for fluid-particle trajectories. The particle aerodynamic response time is shown to be incorporated at second order, which together with the Lagrangian timescale introduced at first order, defines the Stokes number. Reynolds-number effects can be incorporated at third order. The corresponding Fokker-Planck equation is shown to be identical to that advocated by Pozorski and Minier [Phys. Rev. E 59 (1999) 855], who included the fluid velocities "seen" by a particle in the probability density function (pdf) formalism of Reeks and co-workers as a means of circumventing the closure problem (prescribing a closure for the particle flux induced by the fluid) associated with that approach. It is demonstrated that the neglect of Stokes-number effects accounts, in part, for the tendency of first-order LS models to underpredict particle deposition velocities in the diffusion-impaction regime.

Journal Article↗

Superstatistical mechanics of tracer-particle motions in turbulence.

The Lagrangian stochastic model of Reynolds [Phys. Fluids 15, L1-4 (2003)]] for the accelerations of fluid particles in turbulence is shown to predict precisely the observed Reynolds-number dependency of the distribution of Lagrangian accelerations and the exponents characterizing the observed extended self-similarity scaling of the Lagrangian velocity structure functions. Departures from superstatistics of the log-normal kind are accounted for and their impact upon model predictions is quantified.

Journal Article↗

Effects of periodicity on flow and dispersion through closely packed fixed beds of spheres.

A lattice-Boltzmann formulation is used to investigate the effects of "periodicity" (geometry) on fluid flow and tracer-particle dispersion through fixed beds of spheres comprising of closely packed layers. In the "period-1" arrangement, spheres in the adjacent layers contact at their poles while the "period-2" and "period-3" arrangements correspond to hexagonal and faced-centered cubic close packing. For all three packing arrangements, there is a transition with increasing Reynolds number from a power law to a log-normal distribution of kinetic energies and, velocity and vorticity become more closely aligned giving rise to helical tracer-particle trajectories. It is suggested that these flow characteristics, unlike the stability of flow and the distribution of helicity, are largely insensitive to geometry, even when the geometry creates direct channels through the pack bed orientated along the gradient in applied pressure. For steady flows and strongly turbulent flows, such channels are predicted to provide direct routes for dispersion through a packed bed, while for weakly turbulent flows they influence dispersion primarily by destabilizing the flow and thereby promoting dispersion throughout a bed. The dispersion of tracer-particles released from a source located on or close to a "stagnation streamline" is predicted to be faster than ballistic in the near field and the transition to long-time Fickian diffusion is predicted to be distinguished by a regime of subdiffusion.

Journal Article↗

Effects of endothelin-1 on K(+) currents from rat ventricular myocytes.

It has been suggested that the positive inotropic effect of the vasoactive peptide hormone, endothelin-1 (ET-1), involves inhibition of cardiac K(+) currents. In order to identify the K(+) currents modulated by ET-1, the outward K(+) currents of isolated rat ventricular myocytes were investigated using whole-cell patch-clamp recording techniques. Outward currents were elicited by depolarisation to +40 mV for 200 ms from the holding potential of -60 mV. Currents activated rapidly, reaching a peak (I(pk)) of 1310 +/- 115 pA and subsequently inactivating to an outward current level of 1063 +/- 122 pA at the end of the voltage-pulse (I(late)) (n = 11). ET-1 (20 nM) reduced I(pk) by 247.6 +/- 60.7 pA (n = 11, P < 0.01) and reduced I(late) by 323.2 +/- 43.9 pA (P < 0.001). The effects of ET-1 were abolished in the presence of the nonselective ET receptor antagonist, PD 142893 (10 microM, n = 5). Outward currents were considerably reduced and the effects of ET-1 were not observed when K(+) was replaced with Cs(+) in the experimental solutions; this indicates that ET-1 modulated K(+)-selective currents. A double-pulse protocol was used to investigate the inactivation of the currents. The voltage-dependent inactivation of the currents from potentials positive to -80 mV was fitted by a Boltzmann equation revealing the existence of an inactivating transient outward component (I(to)) and a noninactivating steady-state component (I(ss)). ET-1 markedly inhibited I(ss) by 43.0 +/- 3.8% (P < 0.001, n = 7) and shifted the voltage-dependent inactivation of I(to) by +3.3 +/- 1.2 mV (P < 0.05). Although ET-1 had little effect on the onset of inactivation of the currents elicited from a conditioning potential of -70 mV, the time-independent noninactivating component of the currents was markedly inhibited. In conclusion, the predominant effect of ET-1 was to inhibit a noninactivating steady-state background K(+) current (I(ss)). These results are consistent with the hypothesis that I(ss) inhibition contributes to the inotropic effects of ET-1.

Animals↗

Tachykinin-induced bronchoconstriction in sheep is NK-1 receptor mediated and exhibits tachyphylaxis.

OBJECTIVE: Tachykinins are mediators of airway hyper-reactivity and inflammation. There is in vitro evidence that ovine responses to tachykinins correlate closely to human responses. This study was designed to characterize the effect of intravenously administered tachykinins on sheep lung resistance in vivo to determine the effect of dose timing on reproducibility of responses and the induction of tachyphylaxis. We then used this information to help further characterize the response with several pharmacological agents. METHODOLOGY: Substance P (SP) was administered by infusion to conscious merino ewes and lung resistance (RL) was measured. Infusions were given at 30, 60, 120 min and 24 h intervals. The effect of various agents on the response to SP was then assessed. RESULTS: Substance P led to a transient increase in RL, mean (+/- SEM) 754.8 (+/- 139)% of baseline, with marked tachyphylaxis at 30, 60 and 120 min. Phosphoramidon increased the peak response to 1151.5 +/- 196%. Atropine and CP 96 345 abolished the response to SP, while indomethacin, sodium cromoglycate and pyrilamine had no significant effect. Substance P had a greater effect on RL than did neurokinin A. CONCLUSIONS: Substance P increases RL in sheep via a cholinergic mechanism which is mediated by NK-1 receptors, and is subject to tachyphylaxis. These findings have implications for the design of studies using the ovine model in the evaluation of tachykinin antagonists as potential therapeutic agents.

Airway Resistance↗

Nicotinic agonists stimulate acetylcholine release from mouse interpeduncular nucleus: a function mediated by a different nAChR than dopamine release from striatum.

Acetylcholine release stimulated by nicotinic agonists was measured as radioactivity released from perfused synaptosomes prepared from mouse interpeduncular nucleus (IPN) that had been loaded with [(3)H]choline. Agonist-stimulated release was dependent upon external calcium and over 90% of released radioactivity was acetylcholine. The release process was characterized by dose response curves for 13 agonists and inhibition curves for six antagonists. alpha-Conotoxin MII did not inhibit this release, while alpha-conotoxin AuIB inhibited 50% of agonist-stimulated release. Comparison of this process with [(3)H]dopamine release from mouse striatal synaptosomes indicated that different forms of nicotinic acetylcholine receptors (nAChRs) may mediate these processes. This was confirmed by assays using mice homozygous for the beta 2 subunit null mutation. The deletion of the beta 2 subunit had no effect on agonist-stimulated acetylcholine release, but abolished agonist-stimulated release of dopamine from striatal synaptosomes. Mice heterozygous for the beta 2 subunit null mutation showed decreased dopamine release evoked by L-nicotine with no apparent change in EC(50) value, as well as similar decreases in both transient and persistent phases of release with no changes in desensitization rates.

Acetylcholine↗

Modulation of the synaptic Ca2+ current in salamander photoreceptors by polyunsaturated fatty acids and retinoids.

Synaptic transmission between retinal photoreceptors and second-order neurones is controlled by an L-type Ca2+ conductance (gCa) in the photoreceptor inner segment. Modulation of this conductance therefore influences the flow of visual information to higher centres. Possible modulation of gCa by retinal factors was investigated using patch clamp and Ca2+ imaging. No significant modulation of gCa by retinal neurotransmitters nor by intracellular signalling pathways was found. gCa was inhibited by retinoids (all-trans retinal) and by polyunsaturated fatty acids (PUFAs) such as arachidonic acid and docosahexaenoic acid, which are known to be released in the retina by exposure to light. Some PUFAs tested are physiological substrates for the cyclo-oxygenase, lipoxygenase and epoxygenase pathways, but specific inhibitors of these pathways had no effect on the inhibition of gCa. Treatments designed to activate or inhibit G-protein-coupled pathways or protein kinases A and C similarly had no effect on the inhibition by PUFAs nor on gCa itself. Inhibitors of phosphatases 1 and 2A were also largely ineffective. The inhibition by PUFAs is, however, dependent on membrane potential, suggesting that it arises from a direct interaction of fatty acids with the Ca2+ channel. The effect was not use or frequency dependent, suggesting that the effect does not depend on channel gating state. Control by retinoids and by PUFAs may be an important mechanism by which the Ca2+ conductance, and consequently the transmission of the visual signal, is modulated at the first retinal synapse.

Adaptation, Ocular↗

Laparoscopic management of neonatal ovarian cysts.

A laparoscopic approach was used in four infants with antenatally diagnosed ovarian cysts requiring surgical intervention. Operating time ranged from 60 to 90 minutes, there were no intraoperative or postoperative complications, and all infants were discharged within 23 hours after surgery. If performed by experienced practitioners, microendoscopy is an alternative to laparotomy in neonates requiring surgical intervention for ovarian cysts.

Female↗

Cytokines enhance airway smooth muscle contractility in response to acetylcholine and neurokinin A.

OBJECTIVE: In vivo airway hyperresponsiveness has been demonstrated following inhalation of specific cytokines in normal individuals. Whether this airway hyperresponsiveness results from a direct effect of cytokines on airway smooth muscle contractility, or via changes in airway wall structure is not known. The aim of the present study was to determine the effect of the pro-inflammatory cytokines interleukin-1beta (IL-1beta) and tumour necrosis factor-alpha (TNF-alpha) on airway smooth muscle contractility in vitro. METHODOLOGY: Ovine tracheal smooth muscle strips were incubated for 18 h at room temperature in Dulbecco's modified Eagle's medium, supplemented with antibiotics, with IL-1beta (10 ng/mL) and TNF-alpha (100 ng/mL), in an atmosphere of 5%CO2:95%O2. Following incubation cumulative concentration-response curves to acetylcholine (ACh) and neurokinin A (NKA) were obtained. Antagonist affinity studies were performed to determine whether the cytokine-induced enhanced contractility to ACh and NKA resulted from a functional alteration to specific M3 and NK2 receptors. Cumulative concentration-response curves to NKA were performed in the presence of phosphoramidon to determine if the enhanced contractility to NKA following cytokine exposure was due to a reduction in endogenous neutral endopeptidase activity. To assess the calcium dependence of the hyperresponsiveness, cumulative concentration-responses to ACh were conducted in calcium-free Krebs'-Henseleit solution. RESULTS: Pre-incubation with TNF-alpha and IL-1beta caused a significant leftward shift, and an increase in the magnitude, of the concentration-response curves to both ACh and NKA. No difference in M3 and NK2 receptor antagonist affinity (pA2) values between the control and cytokine-treated tissue was observed. Neurokinin A contractility in the presence of phosphoramidon indicated that the enhanced contractility following cytokine exposure was not due to a reduction in endogenous neutral endopeptidase activity. Removal of extracellular calcium ions attenuated the contractile response to low concentrations of ACh in the control and cytokine-pretreated tissue. However, enhanced contractility following TNF-alpha and IL-1beta pretreatment was still present. CONCLUSION: Pro-inflammatory cytokines induce in vitro hyperresponsiveness in normal airway smooth muscle via a mechanism involving intracellular calcium mobilization.

Acetylcholine↗

Effects of sevoflurane anaesthesia on recovery in children: a comparison with halothane.

We prospectively studied one hundred ASA physical status I-II children, ages six months to six years, undergoing myringotomy surgery. Children were randomly assigned to one of four anaesthetic groups receiving either halothane or sevoflurane for anaesthesia and oral midazolam premedication or no premedication. We found that children anaesthetized with sevoflurane had significantly faster recovery times and discharge home times than those who received halothane. Patients given oral midazolam premedication had significantly longer recovery times, but no delay in discharge home compared with those not premedicated. However, children anaesthetized with sevoflurane and no premedication had an unacceptably high incidence (67%) of postoperative agitation. The use of oral midazolam preoperatively did decrease the amount of postoperative agitation seen with sevoflurane. We conclude that although sevoflurane does shorten recovery times, the degree of associated postoperative agitation makes it unacceptable as a sole anaesthetic for myringotomy surgery.

Administration, Oral↗

Tachykinin NK2 receptors predominantly mediate tachykinin-induced contractions in ovine trachea.

In vitro studies were conducted to characterize the contractile effects of tachykinins in normal ovine trachea with a view in the future to compare tachykinin contractile responses in allergic tissue. Tracheal smooth muscle strips were prepared for in vitro studies of isometric contraction in response to cumulative addition of carbachol, acetylcholine, histamine, neuropeptide gamma, substance P, neurokinin A, neurokinin B, [Sar9, Met(O2)11]substance P, [Nle10]neurokinin A-(4-10), and [Succinyl-Asp6, Me-Phe8]substance P-(6-11) (senktide). The rank order of potency was neuropeptide gamma > carbachol > neurokinin A > or = [Nle10]neurokinin A-(4-10) > acetylcholine > or = histamine. Phosphoramidon enhanced the contractile response to neurokinin A and substance P, but not to neuropeptide gamma, [Sar9, Met(O2)11]substance P or senktide. Repeated cumulative concentration responses for acetylcholine, substance P, neurokinin A, [Sar9, Met(O2)11]substance P and histamine were also conducted to test for tachyphylaxis. No tachyphylaxis to acetylcholine, substance P, or neurokinin A was observed, however, [Sar9, Met(O2)11]substance P and histamine did exhibit tachyphylaxis. Atropine had no effect on tracheal contractions to neurokinin A and substance P, while [Sar9, Met(O2)11]substance P contractions were atropine sensitive. Pyrilamine did not affect substance P-induced tracheal smooth muscle contractions, indicating that the response to substance P was not mediated by histamine release. These results show that, in vitro, natural tachykinins induce tracheal smooth muscle contraction predominantly by a direct effect mediated by tachykinin NK2 receptors, and a small tachykinin NK1 receptor mediated cholinergic mechanism.

Acetylcholine↗