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D Noble

Publications and source records attributed to D Noble.

At least 55 records · Page 3Linked to original sources
PubMed1995

Artificial blood.

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Biological Transport↗
PubMed1995

Novel squalestatins produced by biotransformation.

Microorganisms were screened for the ability to modify the squalene synthase inhibitor squalestatin 1. Biotransformation of 1 by two actinomycetes, S15106 and S15138, yielded three products hydroxylated on the 4,6-dimethyl-oct-2-enoyl side chain either at the 6 position (5) or 7 position (4 two diastereoisomers), and lacking the acetyl ester from the C-1 side chain. Many strains were found to hydrolyse the 4,6-dimethyl-oct-2-enoyl or acetyl esters to yield squalestatins 2 or 3. The 3-methyl ester (6) of 1 was obtained using Fusarium sp. F13945. This fungus also produced a farnesoic acid derivative, possibly in response to inhibition of its squalene synthase by 1. The biotransformation products of 1 all retained potent squalene synthase inhibitory activity.

Actinomycetales↗
PubMed1994

Effects of rapid changes of external Na+ concentration at different moments during the action potential in guinea-pig myocytes.

1. A rapid solution-changing system using a solenoid was set up. The half-time for changing the external solution surrounding a ventricular cardiac cell was 7.2 +/- 1.4 ms, whereas the time needed to change 90% of this solution was 48.5 +/- 7.9 ms. This rapid switching system was used to reduce the external sodium concentration at different moments during the action potential (recorded using the whole-cell method) to 50% of its original value. This was performed in order to investigate the effect on the shape and duration of the action potential of modifying the activity of the sodium-calcium exchanger. 2. A diminution of the action potential duration was seen irrespective of the substitute used for reducing the NaCl concentration from 140 to 70 mM. The magnitude of this diminution depended on the presence or absence of EGTA (5 mM) in the pipette solution and also on the moment during the action potential at which the NaCl substitution occurred. 3. Some differences were observed depending on whether the NaCl substitute used was lithium chloride or choline chloride. When choline chloride or N-methyl-D-glucamine was used as the NaCl substitute, the amplitude of the action potential was slightly reduced (by 2-5 mV) when the solution was changed 40 ms before the action potential was triggered. This reduction was never observed when LiCl was used as the NaCl substitute. 4. The effects on the shape of the action potential of changing from a solution containing 140 mM NaCl to one containing 70 mM NaCl and 70 mM LiCl were much more rapid when these changes occurred at a later stage during the action potential. The rate of repolarization was more than doubled when the change occurred at a late stage of the action potential but was hardly changed at the beginning of the plateau. 5. These experiments confirm the role of the sodium-calcium exchange current in determining the duration of the mammalian ventricular action potential. However, it is also possible that the sodium background current plays a significant role in determining the shape of the action potential.

Action Potentials↗
PubMed1994

High selectivity of the i(f) channel to Na+ and K+ in rabbit isolated sinoatrial node cells.

The ionic selectivity of the hyperpolarization-activated inward current (i(f)) channel to monovalent cations was investigated in single isolated sinoatrial node cells of the rabbit using the whole-cell patch-clamp technique. With a 140 mM K+ pipette, replacement of 90% external Na+ by Li+ caused a -24.5 mV shift of the fully activated current/voltage I/V curve without a significant decrease of the slope conductance. With a 140 mM Cs+ pipette, the i(f) current decreased almost proportionally to the decrease in external [Na+]o as Li+ was substituted. These responses are practically the same as those observed with N-methyl glucamine (NMG+) substitution, suggesting that the relative permeability of Li+ compared with Na+ for the i(f) channel is as low as that of NMG+. When Cs+ or Rb+ was substituted for internal K+, the fully activated I/V relationship for i(f) showed strong inward rectification with a positive reversal potential, indicating low permeability of the i(f) channel for Cs+ and Rb+. These results show that the i(f) channel is highly selective for Na+ and K+ and will not pass the similar ions Li+ and Rb+. Such a high degree of selectivity is unique and may imply that the structure of the i(f) channel differs greatly from that of other Na+ and K+ conducting channels.

Animals↗
PubMed1994

The influence of dietary creatine supplementation on performance during repeated bouts of maximal isokinetic cycling in man.

The effect of dietary creatine (Cr) supplementation on performance during 3, 30 s bouts maximal isokinetic cycling and on plasma ammonia and blood lactate accumulation during exercise was investigated. Placebo (P) ingestion had no effect on peak power output (PPO), mean power output (MPO) and total work output during each bout of exercise. Cr ingestion (4 x 5 g.day-1 for 5 days) significantly increased PPO in exercise bout 1 (p < 0.05) and MPO and total work output in exercise bouts 1 (p < 0.05, p < 0.05, respectively) and 2 (p < 0.05, p < 0.05, respectively). Cr ingestion had no effect on any of the measures of performance during exercise bout 3. No difference was observed in peak plasma ammonia accumulation before (146 + 30 mumol.l-1) and after (122 +/- 17 mumol.l-1) P ingestion, however the corresponding concentration was lower following Cr ingestion (129 +/- 22 mumol.l-1) compared with before Cr ingestion (160 +/- 18 mumol.l-1, p < 0.05), despite subjects performing more work. No difference in peak blood lactate accumulation was observed before and after P or Cr ingestion. The results demonstrate that Cr ingestion can increase whole body exercise performance during the initial two, but not a third, successive bout of maximal exercise lasting 30 s. The lower accumulation of plasma ammonia under these conditions suggests this response is achieved by an effect on muscle ATP turnover.

Adenosine Triphosphate↗
PubMed1994

Effects of gap junction conductance on dynamics of sinoatrial node cells: two-cell and large-scale network models.

A computational model of single rabbit sinoatrial (SA) node cells has been revised to fit data on regional variation of rabbit SA node cell oscillation properties. The revised model simulates differences in oscillation frequency, maximum diastolic potential, overshoot potential, and peak upstroke velocity observed in cells from different regions of the node. Dynamic properties of electrically coupled cells, each with different intrinsic oscillation frequency, are studied as a function of coupling conductance. Simulation results demonstrate at least four distinct regimes of behavior as coupling conductance is varied: a) independent oscillation (Gc < 1 pS); b) complex oscillation (1 < or = Gc < 220 pS); c) frequency, but not waveform entrainment (Gc > or = 220 pS); and d) frequency and waveform entrainment (Gc > or = 50 nS). The conductance of single cardiac myocyte gap junction channels is about 50 pS. These simulations therefore show that very few gap junction channels between each cell are required for frequency entrainment. Analyses of large-scale SA node network models implemented on the Connection Machine CM-200 supercomputer indicate that frequency entrainment of large networks is also supported by a small number of gap junction channels between neighboring cells.

Algorithms↗
PubMed1994

Mechanosensitive fibroblasts in the sino-atrial node region of rat heart: interaction with cardiomyocytes and possible role.

The positive chronotropic response of the heart to stretch of the right atrium is one of the major mechanisms adjusting the heart rate to variations in venous return on a beat-by-beat basis. The precise pathway of this mechano-electric feedback and its cellular basis are uncertain. In this study, a possible contribution of mechanosensitive fibroblasts, abundant in the sino-atrial node region, was investigated using a mathematical model of the electrical interaction of a mechanosensitive fibroblast and a sino-atrial pacemaker cell. Electrophysiological evidence for a bio-electrical interaction of mechanosensitive fibroblasts with surrounding cardiomyocytes has been studied in (i) the isolated spontaneously beating atrium of rat hearts, and (ii) cell cultures of the neonatal rat heart. These investigations were performed using (i) double-barrelled floating microelectrodes for intracellular potential registrations, and (ii) the double whole cell patch-clamp technique. It was shown that cardiac fibroblasts and surrounding cardiomyocytes can be either electrically well isolated from each other, or coupled both capacitively and electrotonically. The electrophysiological data obtained were incorporated into the OXSOFT HEART program. Assuming that equivalent coupling may occur between mechanosensitive fibroblasts and sino-atrial pacemaker cells, a heterologous cell pair consisting of one fibroblast and one sino-atrial node myocyte connected by ten to thirty single gap junctional channels with a conductance of 30 pS was modelled. The model of the electrotonic interaction of these cells showed that stretch of the fibroblast during atrial diastole, simulating increased atrial wall tension during atrial filling, can raise the spontaneous depolarization rate of the pacemaker cell in a stretch-dependent manner by up to 24%. These results show that cardiac mechanosensitive fibroblasts could form a cellular basis for the positive chronotropic response of the heart to stretch of the right atrium.

Animals↗
PubMed1994

Discrimination of transiently applied mechanical loads: breathing vs. pulling.

Two groups of 24 subjects each attempted to discriminate between large elastic and resistive loads during 50 randomized presentations of each load. Breathers inspired from the loads through a J valve, whereas pullers reciprocally stroked the plunger of a 2-liter syringe connected to the J valve. A range of load durations was obtained in each subject by prematurely unloading approximately one-half of the trials at graded times from their onset. Breathers produced random discrimination scores [50.8 +/- 2.5% (SE) correct] when loaded inspirations were shorter than unloaded inspirations [trials in which both loads induced equal airway pressure (and probably respiratory muscle tension) waveforms] and nonrandom discrimination scores (65.7 +/- 2.8% correct) when loaded inspirations were longer than unloaded inspirations (trials in which both loads induced different waveforms). In contrast, pullers produced nonrandom discrimination scores (62.2 +/- 2.9% correct) when loaded airflow durations were shorter than unloaded inspirations [trials in which both loads induced equal line pressure (and therefore limb muscle tension) waveforms]. Supplemental audio feedback related to instantaneous airflow (an expression of movement) improved load perception in breathers (to 64.2 +/- 3.0% correct; P < 0.01), indicating that airflow feedback introduced load-specific information that was lacking during breathing but redundant during pulling. In support of this hypothesis, airflow feedback by itself enabled a third group of listeners to identify load type with equal accuracy as pullers but with greater accuracy than breathers. These findings suggest that 1) uniformed subjects rely heavily on feedback from airway pressure and/or muscle tension receptors to perceive added loads to breathing and 2) limb mechanoreceptors provide a more sensitive appreciation of movement than do respiratory mechanoreceptors.

Acoustic Stimulation↗