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Biomedical subjects

R Miles

Publications and source records attributed to R Miles.

At least 19 recordsLinked to original sources
PubMed2001

Interneurons, spike timing, and perception.

Rhythmic gamma oscillations at 30-70 Hz in cortical and hippocampal slices depend on a maintained excitation and on interactions between interneurons and pyramidal cells. These interactions include gap-junctional connections between inhibitory cells and fast excitatory and inhibitory chemical synapses. Spike timing with precision in the range of several ms may be assured by biphasic signaling mechanisms operating at these different connections. Such temporal precision may be important in cognitive processing.

Action Potentials↗
PubMed2001

Choline blocks AMPA-induced dark cell degeneration of Purkinje neurons: potential role of the alpha7 nicotinic receptor.

The objective of the present study was to assess the contribution of sodium influx to development of dark cell degeneration (DCD) in Purkinje neurons (PNs) following AMPA (DL-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid) receptor activation. During the course of these experiments, we observed inconsistent protection against DCD by Na(+) ion substitutes leading us to consider other potential mechanisms. A 30 min application of AMPA (30 microM, induction or trigger phase) followed by a 90-120 min AMPA-free expression period produced DCD in the majority of PNs. Substitution of NaCl with choline chloride (120 mM) produced a marked suppression of AMPA-induced toxicity. Suppression of DCD by choline was concentration dependent. Concentrations of choline as low as 10 mM effectively attenuated DCD when substituted on an equimolar basis for NaCl in the artificial cerebrospinal fluid (ACSF). Unlike choline, substitution of NMDG for NaCl failed to suppress AMPA-induced DCD. Lidocaine and TTX (tetrodotoxin), two agents that inhibit Na(+) influx failed to significantly alter DCD. Because choline is a prototypical alpha7 nicotinic receptor selective agonist, methyllycaconitine (MLA), an alpha7 receptor antagonist was tested and significantly attenuated the protective effects of choline in a concentration-dependent manner. Nicotine (100 microM) added to normal ACSF was effective in attenuating AMPA-induced toxicity. These findings suggest that DCD is not heavily dependent on Na(+)-mediated phenomena and that nicotinic alpha7 receptor activation may be neuroprotective against some types of excitotoxicity that are mediated by active cellular programs.

Aconitine↗
PubMed2001

Exploring the relationship between proper name anomia and word retrieval: a single case study.

We report the results of an investigation of the spoken word retrieval abilities of a patient, BG, with proper name anomia. Our investigations reveal that she is impaired in retrieving common nouns as well as proper names. Common noun retrieval was influenced by age-of-acquisition, word familiarity and name agreement. Cued retrieval of proper names was influenced by age-of-acquisition, although effects of other linguistic variables were not excluded. It is claimed that an explanation in terms of a 'continuum of word retrieval difficulty' rather than of proper names as 'pure referring expressions' can best account for the findings. However, this proposal is unlikely to be able to explain all cases of proper name anomia. Nonetheless, it is suggested that similar findings may be observed in other people with proper name anomia, and that it is necessary for future studies to investigate not only proper name but also common noun retrieval. We also provide evidence that Plausible Phonology and Specificity hypotheses of proper name anomia cannot account for BG's naming abilities.

Aged↗
PubMed2000

Homocysteine inhibits retinoic acid synthesis: a mechanism for homocysteine-induced congenital defects.

Hyperhomocysteinemia is frequently associated with congenital defects of the heart and neural tube and is a suspected pathogenic factor in atherosclerosis and neoplasia. Results in the present report show homocysteine treatment disrupts normal development of avian embryos; and this effect is prevented by retinoic acid. Based on this, we hypothesize that homocysteine may exert its teratogenic effects by disrupting retinoic acid signaling during development. A reporter cell line transfected with a retinoic acid response element (RARE) linked to a lacZ reporter gene was used to identify the site of retinoid inhibition. Using this reporter cell line, we show that homocysteine inhibits the oxidation of retinal to retinoic acid with concentrations of homocysteine that are in the pathophysiological range (.05 to 0.5 mM). In contrast, homocysteine concentrations as high as 5 mM are unable to inhibit the induction of lacZ by retinoic acid. We show that cellular uptake of homocysteine is sensitive to the specific L-system transport inhibitor, bicycloheptane, and bicycloheptane blocks the inhibition of retinoic acid synthesis by homocysteine, demonstrating that this inhibition occurs intracellularly. These results suggest that homocysteine-induced congenital defects are due to the specific ability of homocysteine to inhibit conversion of retinal to retinoic acid.

Abnormalities, Drug-Induced↗
PubMed2000

Contributions of intrinsic and synaptic activities to the generation of neuronal discharges in in vitro hippocampus.

1. Extracellular and intracellular records were made from guinea-pig hippocampal slices to examine the contributions of intrinsic cellular properties and synaptic events to the generation of neuronal activity. Extracellular signals were filtered to pass action potentials, which could be detected within a distance of about 80 microm from a discharging cell. 2. Spontaneous action potentials were invariably detected in records from the stratum pyramidale of CA3 region. Blocking excitatory synaptic transmission with NBQX and APV reduced their frequency by 23 +/- 35 %. Suppressing synaptic inhibition, while excitation was already blocked, increased the rate of spike discharge to 177 +/- 71 % of its control value. 3. Most action potentials recorded intracellularly from CA3 pyramidal cells were initiated in the absence of a detectable synaptic event. In contrast, most action potentials generated by inhibitory cells located close to stratum pyramidale were preceded by an EPSP. 4. In 31 simultaneous recordings, intracellular pyramidal cell action potentials appeared consistently to initiate extracellular spikes with a mean latency of 2.2 +/- 1.0 ms. Single inhibitory cell action potentials could initiate a reduction in the frequency of extracellular spikes of duration 10-30 ms. 5. Some identified extracellular spikes (n = 9) consistently preceded intracellularly recorded IPSPs. IPSPs were initiated monosynaptically with latencies of 0.9-1.5 ms. In reciprocal interactions, single pyramidal cell action potentials could trigger the discharge of an identified unit that in turn appeared to initiate an IPSP in the same pyramidal cell. 6. These data suggest that intrinsic cellular mechanisms underly much of the spontaneous activity of pyramidal cells of the CA3 region of the hippocampus in vitro. Both synaptic inhibition and a strong excitation of inhibitory cells by pyramidal cells act to reduce population activity.

Action Potentials↗
PubMed2000

EPSP amplification and the precision of spike timing in hippocampal neurons.

The temporal precision with which EPSPs initiate action potentials in postsynaptic cells determines how activity spreads in neuronal networks. We found that small EPSPs evoked from just subthreshold potentials initiated firing with short latencies in most CA1 hippocampal inhibitory cells, while action potential timing in pyramidal cells was more variable due to plateau potentials that amplified and prolonged EPSPs. Action potential timing apparently depends on the balance of subthreshold intrinsic currents. In interneurons, outward currents dominate responses to somatically injected EPSP waveforms, while inward currents are larger than outward currents close to threshold in pyramidal cells. Suppressing outward potassium currents increases the variability in latency of synaptically induced firing in interneurons. These differences in precision of EPSP-spike coupling in inhibitory and pyramidal cells will enhance inhibitory control of the spread of excitation in the hippocampus.

Action Potentials↗
PubMed2000

Improving hand hygiene in community healthcare settings: the impact of research and clinical collaboration.

Observation of nursing activities and bacteriological studies undertaken with a sample of nurses employed in a community NHS trust indicated that considerable scope for cross infection existed during domiciliary visits. Poor conditions in patients' homes compromised nurses' ability to perform hand hygiene effectively, increasing risks. A clinical trial indicated that carriage of medically significant bacteria likely to contribute to cross infection could be reduced by applying an antiseptic cream which exhibited residual effectiveness. An audit of hand hygiene throughout the inner city trust indicated the need to pay greater attention to hand hygiene, especially during home nursing visits. The situation was less acute in a rural trust where a second audit was performed for comparative purposes. The motivation of clinical staff to improve hand hygiene precautions was high.

Anti-Infective Agents, Local↗
PubMed1999

An outbreak of Campylobacter enteritis on an island resort, north Queensland.

An outbreak of Campylobacter enteritis among staff on a resort island in north Queensland is reported. Untreated rainwater and food from the staff dining room were initially suspected as possible sources of infection but Campylobacter species were not isolated from any environmental samples. Faecal contamination was detected in four rainwater tanks. A case control study involved a total of 23 cases (7 confirmed and 16 probable), 3 of whom required hospitalisation. There was a strong association between gastrointestinal illness and consumption of water from a dispenser in the staff restaurant that had probably been filled from one of the contaminated tanks. We conclude that this was probably a waterborne outbreak and postulate that Campylobacter species were introduced into one or more of the tanks by contamination with the faeces of wild animals.

Adolescent↗
PubMed1999

Biochemical diversity of Mycoplasma fermentans strains.

In this study, the metabolism of a diverse range of Mycoplasma fermentans strains was investigated. It was shown that the ability to utilise glucose, fructose and N-acetylglucosamine differentiated strains, and that the patterns and kinetics of substrate utilisation were correlated with the site of isolation, i.e. joint fluid, respiratory tract, urinary tract or cell culture. Interestingly, isolates from the urogenital tract of AIDS patients used fructose in preference to glucose. There was also some correlation of fructose and N-acetylglucosamine utilisation of isolates with M. fermentans sub-groups, identified in an independent study, and based on the distribution of insertion sequence-like elements in the M. fermentans genome.

Acetylglucosamine↗
PubMed1999

Cell-attached measurements of the firing threshold of rat hippocampal neurones.

1. The cell-attached configuration of the patch-clamp technique was used to assess resting membrane potential and firing threshold of CA1 pyramidal cells and interneurones of rat hippocampal slices. 2. Resting potential was inferred from the reversal potential of voltage-gated K+ currents with symmetrical intracellular and pipette K+ concentrations. Its mean value was -74 +/- 9 mV for silent interneurones (mean +/- s.d.; n = 17) and -84 +/- 7 mV for silent pyramidal cells (n = 8). Spontaneous action currents occurred in thirteen out of thirty-two interneurones and two out of ten pyramidal cells. In active cells, membrane potential values fluctuated by up to 20 mV, due in part to the large hyperpolarizations that followed an action current. 3. Membrane potential values determined from K+ current reversal were 13 +/- 6 mV more hyperpolarized than those measured in whole-cell recordings from the same neurones (n = 8), probably due to a Donnan equilibrium potential between pipette and cytoplasm. 4. Firing threshold of silent cells was determined by elevating external K+ until action currents were generated, while membrane potential was monitored from the cell-attached K+ current reversal. Spike threshold was attained at -49 +/- 8 mV for interneurones (n = 17) and at -60 +/- 8 mV for pyramidal cells (n = 8). Increasing external Ca2+ from 2 to 4 mM shifted the neuronal voltage threshold by +5 mV, without affecting resting potential. 5. For comparison with these values, we examined how the rate of membrane polarization influenced firing threshold in whole-cell records. Ramp current injections, of duration 15-1500 ms, revealed that current threshold followed a classical strength-duration relationship. In contrast voltage threshold, determined from current injection or by elevating extracellular K+, varied little with the rate of membrane polarization. 6. The state of activation and inactivation of Na+ and K+ currents might contribute to the stability of the voltage threshold. Cell-attached records showed that 79 +/- 10 % of Na+ channels and 64 +/- 10 % of K+ channels were available for activation at resting potential in silent cells (n = 8). As cells were depolarized to threshold, Na+ current availability was reduced to 23 +/- 10 %, and K+ current availability to 31 +/- 12 %. 7. The speed of transition into the inactivated states also appears to contribute to the invariance of threshold for all but the fastest depolarizations. At potentials close to threshold, the rate of inactivation of Na+ and K+ followed a double exponential time course, such that Na+ currents were 62 % inactivated and K+ currents were 63 % inactivated within 15 ms.

Action Potentials↗
PubMed1999

Noninvasive measurements of the membrane potential and GABAergic action in hippocampal interneurons.

Neurotransmitters affect the membrane potential (Vm) of target cells by modulating the activity of receptor-linked ion channels. The direction and amplitude of the resulting transmembrane current depend on the resting level of Vm and the gradient across the membrane of permeant ion species. Vm, in addition, governs the activation state of voltage-gated channels. Knowledge of the exact level of Vm is therefore crucial to evaluate the nature of the neurotransmitter effect. However, the traditional methods to measure Vm, with microelectrodes or the whole-cell current-clamp technique, have the drawback that the recording pipette is in contact with the cytoplasm, and dialysis with the pipette solution alters the ionic composition of the interior of the cell. Here we describe a novel technique to determine the Vm of an intact cell from the reversal potential of K+ currents through a cell-attached patch. Applying the method to interneurons in hippocampal brain slices yielded more negative values for Vm than subsequent whole-cell current-clamp measurements from the same cell, presumably reflecting the development of a Donnan potential between cytoplasm and pipette solution in the whole-cell mode. Cell-attached Vm measurements were used to study GABAergic actions in intact CA1 interneurons. In 1- to 3-week-old rats, bath-applied GABA inhibited these cells by stabilizing Vm at a level depending on contributions from both GABAA and GABAB components. In contrast, in 1- to 4-d-old animals, only GABAA receptors were activated resulting in a depolarizing GABA response.

Animals↗
PubMed1999

The object-based representation of partially occluded surfaces in short-term visual memory: evidence from image combination.

Distinct short-term and longer term visual representations of form allow people to combine mental images of separately presented pictures in order to identify a novel object (see, e.g., Brandimonte, Hitch, & Bishop, 1992; Hitch, Brandimonte, & Walker, 1995; Walker, Hitch, Dewhurst, Whiteley, & Brandimonte, 1997). The present study focuses on the short-term representation and asks whether it describes the 2-D features in a picture or the depicted surfaces in 3-D space (see Nakayama, He, & Shimojo, 1995). To-be-combined figures were sometimes partially occluded by irrelevant forms, and it was determined whether image combination was contingent on the directly visible regions of the figures or on the perceptually completed figures. Results showed that image combination was not impeded by partial occlusion, though it was impeded if an occluder was removed from a picture and only the previously visible regions of the figure were presented. It is concluded that the short-term visual representation supporting image combination is not a pictorial code, but is an object-based description of completed surfaces in 3-D space.

Adolescent↗
PubMed1998

How many subtypes of inhibitory cells in the hippocampus?

Hippocampal inhibitory cells are diverse. It is supposed that they fall into functionally distinct subsets defined by a similar morphology and physiology. Switching between functions could be accomplished by activating receptors for modulating transmitters expressed selectively by different subsets of interneurons. We tested this hypothesis by comparing morphology, physiology, and neurotransmitter receptor expression for CA1 hippocampal interneurons. We distinguished 16 distinct morphological phenotypes and 3 different modes of discharge. Subsets of inhibitory cells were excited or inhibited by agonists at receptors for noradrenaline, muscarine, serotonin, and mGluRs. Most cells responded to 2 or 3 agonists, and 25 different response combinations were detected. Subsets defined by morphology, physiology, and receptor expression did not coincide, suggesting that hippocampal interneurons cannot easily be segregated into a few well-defined groups.

2-Amino-5-phosphonovalerate↗
PubMed1998

AMPA receptor-mediated alterations of intracellular calcium homeostasis in rat cerebellar Purkinje cells in vitro: correlates to dark cell degeneration.

In the rat cerebellar slice preparation in vitro, excessive DL-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA)-receptor activation elicits a characteristic type of excitotoxicity of Purkinje cells (PCs) known as dark cell degeneration (DCD). DCD models neurotoxicity of PCs and hippocampal pyramidal neurons in vivo following hyperexcitable states. The intent of this study was to: a) determine whether AMPA-induced neurotoxicity of PCs is correlated with temporally and spatially restricted rises in intracellular Ca2+ and b) whether GYKI 52466 and nominal external Ca2+, conditions that reduced expression of AMPA-elicited DCD, altered the induced Ca2+ patterns. Employing the Ca2+-sensitive dye Fluo-3 and a confocal laser scanning microscope, we evaluated changes in intracellular Ca2+ within PCs in a cerebellar slice preparation. AMPA application alone (30 microM for 30 min) caused a significant initial rise in perinuclear and cytoplasmic Ca2+ that returned to control levels during the latter part of the AMPA exposure period. Following removal of AMPA (expression period), perinuclear and cytoplasmic Ca2+ displayed a significant delayed rise peaking transiently 60 min after AMPA removal. The efficacy of GYKI 52466 and nominal external Ca2+ conditions to attenuate AMPA-induced DCD was correlated to reductions in AMPA-induced transient elevations in perinuclear and cytoplasmic Ca2+ levels during the expression phase and to a lesser extent during the exposure period. The present data suggest that during the expression phase, the delayed perinuclear and cytoplasmic Ca2+ transient may be the harbinger of impending loss of Ca2+ homeostasis and cell damage.

Aniline Compounds↗