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Biomedical subjects

C S Poon

Publications and source records attributed to C S Poon.

At least 37 records · Page 2Linked to original sources
PubMed2000

NMDA receptor activity in utero averts respiratory depression and anomalous long-term depression in newborn mice.

Mutant mice lacking NMDA receptor 1 subunit (NR1) showed marked depression of respiratory and suckling activities in vivo and overexpression of synaptic long-term depression (LTD) in a brainstem cardiorespiratory-related region (nucleus tractus solitarius) in vitro. Pharmacological blockade of NMDA receptors in normal newborn mice mimicked the depression in suckling activity but not respiratory depression in vivo or brainstem LTD in vitro. Results at the behavioral and cellular levels demonstrate that NMDA receptor deficiency during prenatal development may unleash an anomalous form of NMDA receptor-independent LTD along with life-threatening respiratory depression consequences in the newborn. These findings raise the specter of cardiorespiratory dysregulation with increased risks of morbidity and mortality in the infant as a result of premature births or genetic or drug-induced NMDA receptor antagonism during pregnancy.

Animals↗
PubMed2000

High-pass filtering of carotid-vagal influences on expiration in rat: role of N-methyl-D-aspartate receptors.

Repetitive electrical stimulation of the carotid sinus nerve or vagus nerve in rats elicited abrupt reflex shortening or prolongation, respectively, of the inter-burst interval of phrenic nerve activity followed by exponential decay from the initial response. Removal of the stimuli resulted in transient post-stimulus rebound excitation or inhibition that mirrored the corresponding stimulus-evoked responses. The biphasic responses to these complementary inputs approximate the on- and off-transients of full-wave differentiators or high-pass filters. Blockade of N-methyl-D-aspartate (NMDA) receptors abolished the post-stimulus rebounds and transformed both signal pathways into integrators or low-pass filters, thus switching off part or all of the high-pass filters. We suggest that such NMDA receptor-dependent high-pass filtering effects may serve to increase the dynamic range and response speed of sensory neurotransmission to the brain, thereby enhancing closed-loop stability of sensorimotor reflex.

Animals↗
PubMed2000

Habituation and desensitization of the Hering-Breuer reflex in rat.

1. Many processes in mammalian and invertebrate central nervous systems exhibit habituation and/or sensitization of their responses to repetitive stimuli. Here, we studied the adaptive behaviours of the respiratory pattern generator in rat on repetitive vagal-afferent stimulation and compared these behaviours obtained in vivo with the reported effects of such stimuli on synaptic transmission in the corresponding signal pathway in vitro. 2. Sustained (1 min) electrical pulsed stimulation of the vagus nerve elicited the classic Hering-Breuer (HB) reflex slowing of the respiratory rhythm followed by a bi-exponential recovery, and a post-stimulus rebound (PR). The recovery from the HB reflex satisfied the classic criteria of habituation. 3. The fast component of the recovery and the PR were abolished by systemic administration of an NMDA receptor antagonist or electrolytic lesioning of the pontine Kolliker-Fuse nucleus. The characteristics of the fast recovery and PR suggest a vagally induced desensitization of the NMDA receptor-dependent pontine input to the respiratory pattern generator. 4. The slow component of recovery persist after both experimental interventions and accounted for the habituation to the vagal input. The characteristics of the slow recovery in vivo were reminiscent of the reported synaptic accommodation in vitro in the medullary region where vagal afferents terminate. 5. The habituation of vagal input and desensitization of pontine input act in concert to offset the HB reflex. Such simultaneous habituation-desensitization in parallel neural pathways with differing sensitivities to NMDA receptor activation represent a hitherto unknown pairing of dual non-associative learning processes in the mammalian brain.

Animals↗
PubMed2000

Field potential analysis of synaptic transmission in spiking neurons in a sparse and irregular neuronal structure in vitro.

Extracellular field potential (FP) recording of dendritic depolarizations evoked by afferent stimulation is widely used as a quantitative measure of excitatory synaptic transmission in brain slices in-vitro for structures with high neuronal density and regularity such as hippocampus, neocortex and cerebellum. On the other hand, FP recordings of somatic depolarizations induced by orthodromic or antidromic stimulation of afferent or efferent nerves have been used in some in-vivo preparations for mapping the central projections of these nerves. In this study, we examined the applicability of somatic FPs as a measure of excitatory synaptic transmission in a sparse and irregular brain structure. Excitatory FPs were induced in nucleus tractus solitarius (NTS) in the dorsal medulla by electrical impulse stimulation of primary afferent fibers in the tractus solitarius (TS) in rat brainstem slices in vitro. The evoked FP was rapid and biphasic, and was stimulus-intensity dependent and saturable. The morphology of these somatic FPs resembled the dendritic FPs found in hippocampal and neocortical slices, with an excitatory postsynaptic component that exhibited similar pharmacological and stimulus frequency-dependent properties as found in NTS cells with intracellular or whole-cell recordings. Simultaneous FP and whole-cell recordings revealed that the postsynaptic component of FP was associated with neuronal firing rather than subthreshold membrane depolarizations. We conclude that somatic FP recording provides a simple and reliable measure of excitatory neurotransmission in the TS-NTS pathway and is a useful alternative or adjunct to intracellular or whole-cell recordings especially for studies of long-term synaptic plasticity in spiking neurons. This technique may also be applicable to other brain regions that lack the regular and dense organization of hippocampal and neocortical structures.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2000

Plasticity of cardiorespiratory neural processing: classification and computational functions.

Neural plasticity, or malleability of neuronal structure and function, is an important attribute of the mammalian forebrain and is generally thought to be a kernel of biological intelligence. In this review, we examine some reported manifestations of neural plasticity in the cardiorespiratory system and classify them into four functional categories, integral; differential; memory; and statistical-type plasticity. At the cellular and systems level the myriad forms of cardiorespiratory plasticity display emergent and self-organization properties, use- and disuse-dependent and pairing-specific properties, short-term and long-term potentiation or depression, as well as redundancy in series or parallel structures, convergent pathways or backup and fail-safe surrogate pathways. At the behavioral level, the cardiorespiratory system demonstrates the capability of associative and nonassociative learning, classical and operant conditioning as well as short-term and long-term memory. The remarkable similarity and consistency of the various types of plasticity exhibited at all levels of organization suggest that neural plasticity is integral to cardiorespiratory control and may subserve important physiological functions.

Animals↗
PubMed1999

Allelic loss on chromosome 1 is associated with tumor progression of cervical carcinoma.

BACKGROUND: Alterations in chromosome 1 are common in human malignancies. The frequency of loss of heterozygosity (LOH) on chromosome 1 in cervical carcinoma and its clinical significance are not clearly understood. METHODS: LOH on chromosome 1 was studied in 100 cervical carcinomas by the polymerase chain reaction (PCR) using 29 highly polymorphic microsatellite markers spaced approximately 10 centimorgans apart. Loci with high frequencies of LOH were identified and the findings were correlated with clinicopathologic characteristics. RESULTS: LOH on chromosome 1 at 1 or more loci was detected in 93% of tumors. The frequencies of LOH at locus D1S2829 (1p31), D1S2663 (1p36.3), and D1S2725 (1q25) exceeded 30%, and 12 other loci exhibited frequencies of LOH of 20-30%. Advanced stage tumors had a significantly higher percentage of informative microsatellite markers with LOH than early stage tumors. Of the 29 microsatellite markers studied, 4 loci had a significantly higher frequency of LOH in Stage III and IV tumors than in earlier stage tumors. CONCLUSIONS: Frequent aberrations on chromosome 1 in cervical carcinoma suggest that inactivation of tumor suppressor genes is important in cervical tumorigenesis. Higher frequencies of LOH in Stage III and IV tumors suggest that chromosome 1 changes are late events in cervical carcinoma. The findings of this study are consistent with earlier reports that suggest that tumor suppressor genes are present at 1p36.3 and 1p31. To the authors' knowledge, the high frequency of LOH mapped to 1q25 has not been reported previously. Its significance awaits further clarification.

Adenocarcinoma↗
PubMed1999

Somatic mutations in the BRCA1 gene in Chinese sporadic breast and ovarian cancer.

Inherited mutations in the BRCA1 gene confer increased susceptibility to breast and ovarian cancer. Its role in sporadic carcinogenesis is not well defined. Somatic mutations in breast cancers have not been reported and to date there are only three reports of somatic mutations in sporadic ovarian cancers. To investigate the contribution of BRCA1 mutations to sporadic breast and ovarian cancer in the Chinese population, we analysed 62 samples from Chinese women using the protein truncation test. There were 40 cases of breast cancer under age 50 and 22 cases of ovarian cancer, all unselected for family history. There was no age selection for the ovarian cancers. We found two somatic BRCA1 mutations in exon 11, one in a breast cancer and the other in an ovarian cancer, both of which result in truncated proteins. Our results indicate that somatic BRCA1 mutations, like somatic mutations in the BRCA2 gene, though very rare, can be found in both breast and ovarian cancers and support a tumor suppressor function for BRCA1 in sporadic tumors.

Adult↗
PubMed1999

Short-term potentiation of carotid chemoreflex: an NMDAR-dependent neural integrator.

Repetitive stimulation of the carotid sinus nerve (CSN) elicits a short-term potentiation (STP) of the reflex response in respiratory motor output in mammals. The input-output transformation approximates a leaky integrator with a time constant of several seconds. Here, we showed that STP induced by CSN stimulation in rats was manifested in the reflex response in the amplitude of rhythmic phrenic nerve activity as well as its duration. Moreover, pharmacological blockade of NMDA receptors (NMDAR) resulted in marked increases in the time constants of the equivalent neural integrator in both the STP induction phase (by 10- to 20-fold) and recovery phase (by 1- to 5-fold). Thus, NMDAR serves as a molecular switch that facilitates the integrative processing of CSN inputs by STP.

Animals↗
PubMed1999

Indoor air quality investigation on commercial aircraft.

Sixteen flights had been investigated for indoor air quality (IAQ) on Cathay Pacific aircraft from June 1996 to August 1997. In general, the air quality on Cathay Pacific aircraft was within relevant air quality standards because the average age of aircraft was less than 2 years. Carbon dioxide (CO2) levels on all flights measured were below the Federal Aviation Administration (FAA) standard (30,000 ppm). The CO2 level was substantially higher during boarding and de-boarding than cruise due to low fresh air supply. Humidity on the aircraft was low, especially for long-haul flights. Minimum humidity during cruise was below the American Society of Heating, Refrigerating, and Air-Conditioning Engineers (ASHRAE) minimum humidity standard (20%). The average temperature was within a comfortable temperature range of 23 +/- 2 degrees C. The vertical temperature profile on aircraft was uniform and below the International Standard Organization (ISO) standard. Carbon monoxide levels were below the FAA standard (50 ppm). Trace amount of ozone detected ranged from undetectable to 90 ppb, which was below the FAA standard. Particulate level was low for most non-smoking flights, but peaks were observed during boarding and de-boarding. The average particulate level in smoking flights (138 micrograms/m3) was higher than non-smoking flights (7.6 micrograms/m3). The impact on IAQ by switching from low-mode to high-mode ventilation showed a reduction in CO2 levels, temperature, and relative humidity.

Air Pollution, Indoor↗
PubMed1998

Hebbian learning in parallel and modular memories.

Many cognitive and sensorimotor functions in the brain involve parallel and modular memory subsystems that are adapted by activity-dependent Hebbian synaptic plasticity. This is in contrast to the multilayer perceptron model of supervised learning where sensory information is presumed to be integrated by a common pool of hidden units through backpropagation learning. Here we show that Hebbian learning in parallel and modular memories is more advantageous than backpropagation learning in lumped memories in two respects: it is computationally much more efficient and structurally much simpler to implement with biological neurons. Accordingly, we propose a more biologically relevant neural network model, called a tree-like perceptron, which is a simple modification of the multilayer perceptron model to account for the general neural architecture, neuronal specificity, and synaptic learning rule in the brain. The model features a parallel and modular architecture in which adaptation of the input-to-hidden connection follows either a Hebbian or anti-Hebbian rule depending on whether the hidden units are excitatory or inhibitory, respectively. The proposed parallel and modular architecture and implicit interplay between the types of synaptic plasticity and neuronal specificity are exhibited by some neocortical and cerebellar systems.

Cerebellum↗
PubMed1998

Entrainment, instability, quasi-periodicity, and chaos in a compound neural oscillator.

We studied the dynamical behavior of a class of compound central pattern generator (CPG) models consisting of a simple neural network oscillator driven by both constant and periodic inputs of varying amplitudes, frequencies, and phases. We focused on a specific oscillator composed of two mutually inhibiting types of neuron (inspiratory and expiratory neurons) that may be considered as a minimal model of the mammalian respiratory rhythm generator. The simulation results demonstrated how a simple CPG model--with a minimum number of neurons and mild nonlinearities--may reproduce a host of complex dynamical behaviors under various periodic inputs. In particular, the network oscillated spontaneously only when both neurons received adequate and proportionate constant excitations. In the presence of a periodic source, the spontaneous rhythm was overridden by an entrained oscillation of varying forms depending on the nature of the source. Stable entrained oscillations were inducible by two types of inputs: (1) anti-phase periodic inputs with alternating agonist-antagonist drives to both neurons and (2) a single periodic drive to only one of the neurons. In-phase inputs, which exert periodic drives of similar magnitude and phase relationships to both neurons, resulted in varying disruptions of the entrained oscillations including magnitude attenuation, harmonic and phase distortions, and quasi-periodic interference. In the absence of significant phasic feedback, chaotic motion developed only when the CPG was driven by multiple periodic inputs. Apneic episodes with repetitive alternation of active (intrinsic oscillation) and inactive (cessation of oscillation) states developed when the network was driven by a moderate periodic input of low frequency. Similar results were demonstrated in other, more complex oscillator models (that is, half-center oscillator and three-phase respiratory network model). These theoretical results may have important implications in elucidating the mechanisms of rhythmogenesis in the mature and developing respiratory CPG as well as other compound CPGs in mammalian and invertebrate nervous systems.

Animals↗
PubMed1998

Pendelluft flow in symmetric airway bifurcations.

We propose a mathematical model for pendelluft flow in a single airway bifurcation. The model is motivated by an apparatus used in an experimental study of the pendelluft by Ultman et al. (1988). We derive differential equations governing the fluid flow, which directly connect physiological parameters to the variables determining the pendelluft; this approach allows us to include nonlinearity in the model. If nonlinearity is neglected, our model is identical to the R-I-C circuits used by previous investigators. If nonlinearity is retained, we show that pendelluft can occur even in perfectly symmetric airway bifurcations. For the specific apparatus used in the experiments of High et al. (1991), we demonstrate that two qualitatively different pendelluft flows can occur in the system.

Airway Resistance↗
PubMed1998

A miniature mechanical ventilator for newborn mice.

Transgenic/knockout mice with pre-defined mutations have become increasingly popular in biomedical research as models of human diseases. In some instances, the resulting mutation may cause cardiorespiratory distress in the neonatal or adult animals and may necessitate resuscitation. Here we describe the design and testing of a miniature and versatile ventilator that can deliver varying ventilatory support modes, including conventional mechanical ventilation and high-frequency ventilation, to animals as small as the newborn mouse. With a double-piston body chamber design, the device circumvents the problem of air leakage and obviates the need for invasive procedures such as endotracheal intubation, which are particularly important in ventilating small animals. Preliminary tests on newborn mice as early as postnatal day O demonstrated satisfactory restoration of pulmonary ventilation and the prevention of respiratory failure in mutant mice that are prone to respiratory depression. This device may prove useful in the postnatal management of transgenic/knockout mice with genetically inflicted respiratory disorders.

Animals↗
PubMed1997

Decrease of cardiac chaos in congestive heart failure.

The electrical properties of the mammalian heart undergo many complex transitions in normal and diseased states. It has been proposed that the normal heartbeat may display complex nonlinear dynamics, including deterministic chaos, and that such cardiac chaos may be a useful physiological marker for the diagnosis and management of certain heart trouble. However, it is not clear whether the heartbeat series of healthy and diseased hearts are chaotic or stochastic, or whether cardiac chaos represents normal or abnormal behaviour. Here we have used a highly sensitive technique, which is robust to random noise, to detect chaos. We analysed the electrocardiograms from a group of healthy subjects and those with severe congestive heart failure (CHF), a clinical condition associated with a high risk of sudden death. The short-term variations of beat-to-beat interval exhibited strongly and consistently chaotic behaviour in all healthy subjects, but were frequently interrupted by periods of seemingly non-chaotic fluctuations in patients with CHF. Chaotic dynamics in the CHF data, even when discernible, exhibited a high degree of random variability over time, suggesting a weaker form of chaos. These findings suggest that cardiac chaos is prevalent in healthy heart, and a decrease in such chaos may be indicative of CHF.

Adult↗
PubMed1997

Phasic and long-term depression in brainstem nucleus tractus solitarius neurons: differing roles of AMPA receptor desensitization.

One important question concerning the homeostatic regulation of many physiological processes is whether the control mechanisms are purely reflexogenic or whether they may involve neural adaptation in the form of learning and memory in the brainstem. Using a brainstem slice preparation in the rat, we studied the modifiability of neural transmission in the first-order synapses of the medial and commissural nucleus tractus solitarius of the medulla. Sustained low-frequency stimulation (5 Hz) of primary afferent fibers in the tractus solitarius resulted in a phasic depression (accommodation) of synaptic strength as reflected by a concomitant decrease in the evoked excitatory postsynaptic potentials. In one group of neurons (type I), synaptic strength recovered rapidly after low-frequency stimulation, whereas in another group of neurons (type II), synaptic strength remained depressed for >30 min, i.e., manifesting long-term depression (LTD). The latter was switched into a short-term depression lasting 15-25 min after pharmacological blockade of NMDA receptor channels with D-APV or chelation of intracellular calcium ions with EGTA, whereas the accommodation phase was unaffected. Application of an AMPA receptor anti-desensitization agent cyclothiazide abolished the LTD, but not the accommodation response. These results suggest the presence of separate postsynaptic sites for the induction of LTD and accommodation, one being sensitive to cyclothiazide, whereas the other is not. Moreover, the maintenance of LTD is dependent on the level of intracellular Ca2+. These phasic and long-term synaptic plasticity in the nucleus tractus solitarius may play a role in the homeostatic regulation of cardiorespiratory functions.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1997

Negative-impedance ventilation and pressure support ventilation: a comparative study.

Negative impedance ventilation (NIV) is a novel mode of assisted mechanical ventilation (AMV) in which the pressure support is regulated to continuously track inspiratory flow and/or volume. In this study, we have evaluated the efficacies of NIV and inspiratory pressure support (IPS) ventilation in a model of central airway obstruction in six rabbits. For both AMV modes there was an inverse relationship between the intrinsic work of breathing and alveolar pressure. Compared to IPS, NIV was found to: (1) achieve the same degree of ventilatory unloading and similar level of pulmonary ventilation with considerably lower alveolar pressure; (2) better restore the normal tidal volume and respiratory frequency; (3) yield a shorter inspiratory duty cycle, thereby helping to rest the respiratory muscles and preclude intrinsic positive end-expiratory pressure. We conclude that NIV is more efficacious than IPS in negating airway obstruction and offers a better trade-off between the risks of respiratory muscle fatigue and pressure induced complications.

Airway Resistance↗