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Biomedical subjects

P G Nelson

Publications and source records attributed to P G Nelson.

At least 19 recordsLinked to original sources
PubMed1991

Revised trauma score: a triage tool in the accident and emergency department.

We evaluated the Revised Trauma Score (RTS) for the rapid identification of severely injured patients on their arrival at the accident and emergency department. A total of 1407 consecutively injured patients admitted to the Accident and Emergency Department of the Royal Victoria Hospital, Belfast, had their RTSs calculated on arrival. A trauma team, consisting of experienced senior doctors, was summoned for all patients with an abnormal RTS of 11 or less. Each patient also had their Injury Severity Score (ISS) calculated later, and this was compared with their RTS on admission. It was found that 53 patients had an ISS of 16 or above, indicating severe injury. The RTS identified 42 of these. Of the remaining 11, five had incurred penetrating trauma and three spinal cord injuries. Clinical examination revealed actual or potentially serious injuries in all eight patients. However, serious injuries were not recognized initially in three patients due to physiological compensation and/or a short time lapse between injury and arrival at hospital. On admission 49 patients had an abnormal RTS, but their final ISS was less than 16. Forty had injuries warranting urgent resuscitation or a period of observation. Of the remaining nine patients, five had fractures with an elevated respiratory rate, presumably due to pain, and the other four had a depressed level of consciousness which could be accounted for by alcohol intoxication alone. Our results reinforce some well-known points. First, alcohol alone should not be assumed to be the only cause for a depressed level of consciousness in patients with head injuries. Second, systolic hypotension following trauma is an important sign of serious injury. We recommend the use of the RTS as an aid to junior doctors in the recognition of seriously injured patients in the accident and emergency department. Furthermore, the score should be recalculated at frequent intervals while the patient remains in the department.

Blood Pressure↗
PubMed1991

General surgical manpower, Victoria, Australia.

To provide information for the planning of general surgical manpower in Victoria for the next 2 decades, an attempt was made to establish a statewide profile of surgical practices and an analysis of surgical activity to determine whether surgeons' and the community's needs were being met. Of 343 practising general surgeons, 280 furnished returns to a questionnaire--a return rate of 81.6%. Responses to the questionnaire reveal that the current surgeon-to-population ratio is optimal, although certain imbalances and concerns exist. Surgeons are fully occupied regardless of age, location of practice or type of practice, and they work long hours. Most surgeons regard themselves as not overworked and most are satisfied, although not all do the type of work they would prefer. Current surgical training programmes, however, appear inadequate for future needs.

Adult↗
PubMed1991

Calcium, network activity, and the role of NMDA channels in synaptic plasticity in vitro.

Functionally effective neuronal circuits are constructed through a competitive process that requires patterned neuronal activity elicited by structured input from the environment. To explore the mechanisms of this activity-dependent synaptic restructuring, we have developed an in vitro preparation of mouse spinal cord neurons maintained in a 3-chambered cell-culture system. Sensory afferents that received chronic electrical stimulation for 3-5 d developed stronger synaptic connections than unstimulated afferents converging onto the same postsynaptic spinal cord neuron. Exposure to 100 microM DL-2-amino-5-phosphonovaleric acid (APV), an antagonist of the NMDA channel, during the stimulation period prevented the competitive advantage associated with electric stimulation. However, when APV was applied with a higher concentration of calcium (3 mM), activity-dependent synaptic plasticity was no longer inhibited by the NMDA receptor antagonist. This reversal of APV block of the plasticity was not impaired by reducing transmitter release with 3 mM magnesium (in addition to 3 mM calcium and APV). A suppressant effect of APV on spontaneous activity was observed, which was attributed to loss of the NMDA component of the EPSP. Activity-dependent plasticity was also blocked if spontaneous activity was suppressed with dilute tetrodotoxin (TTX; 5-10 nM), a dosage that reduces excitability of neurons but is insufficient to block sodium-dependent action potentials. These experiments bring into question how NMDA channel activation is involved in the processes of synaptic remodeling during development. The data suggest that postsynaptic activity is required for synaptic remodeling, but this activity need not involve NMDA receptor activation specifically for activity-evoked synaptic plasticity. Instead, the mechanism for plasticity appears to operate through calcium-dependent processes in general.

2-Amino-5-phosphonovalerate↗
PubMed1990

N-methyl-D-aspartate receptors influence neuronal survival in developing spinal cord cultures.

Neuronal cell death, which exhibits precise spatial and temporal regulation, serves to remodel and optimize function in the developing nervous system. The mechanisms underlying neuronal cell death are poorly understood, but electrical activity and trophic substances appear to be among the important determinants of survival. We find that N-methyl-D-aspartate (NMDA) receptor antagonists induce neuronal cell death in developing spinal cord cultures. The magnitude of cell death is similar in amount to that produced by blocking action potentials with tetrodotoxin (TTX). The NMDA antagonists and TTX accelerate neuronal death in 2-week-old cultures but not in those that are 1 month old. Low concentrations of NMDA increased neuronal survival under conditions of electrical blockade with TTX. In addition, treatment with low levels of a calcium ionophore also decreased cell death associated with TTX. These results suggest that the NMDA receptor is an important determinant of neuronal survival and that this influence is stage-dependent and likely to be calcium-mediated.

2-Amino-5-phosphonovalerate↗
PubMed1990

Multi-determinate regulation of neuronal survival: neuropeptides, excitatory amino acids and bioelectric activity.

Neuronal survival of dorsal root ganglion-spinal cord cultures was determined after treatment with vasoactive intestinal peptide (VIP) and an antagonist to the N-methyl-D-aspartate receptor (NMDA). Blockade of NMDA receptors with 2-amino 5-phosphonovaleric acid (AP5) produced a biphasic response on neuronal survival: low concentrations (0.1 microM) resulting in greater survival and higher concentrations (100 microM) causing cell death. VIP, a substance with demonstrated neurotrophic properties in vitro, prevented the neuronal cell death associated with high concentrations of AP5, while having no additive effect on the survival-promoting action of low levels of AP5. Electrophysiological studies indicated that AP5, although reducing high frequency bursting activity, did not significantly reduce the abundant on-going asynchronous activity present in these cultures of high density neuronal networks. These data indicate that excitatory amino acids have more than one action that can influence neuronal survival during development and that VIP can increase neuronal survival in bioelectrically active cultures when NMDA channels are blocked. Together with previous studies, these data suggest that multiple neurochemical inputs serve to determine the survival of spinal cord neurons during development, perhaps through one final common pathway: intracellular calcium regulation.

2-Amino-5-phosphonovalerate↗
PubMed1979

Evidence for an intracellular calcium store releasable by surface stimuli ifibroblasts (L cells).

A spontaneously occurring or electrically elicited hyperpolarizing activation (HA) in L cells was previously shown to be due to a specific increase in the membrane K+ permeability (Nelson et at. 1972. J. Gen. Physiol. 60:58--71). Intracellular injection of Ca++ elicits an identical hyperpolarizing response which suggests that the increased K+ permeability associated with the HA is mediated by an increase in cytoplasmic Ca++. In zero-Ca, EGTA-containing saline the proportion of cells in which HA's can be evoked decreases, but the amplitude of those HA's that are produced is comparable to that of HA's in normal Ca saline. Co++ does block the HA but only after a period of 2 h or longer; D-600 does not affect the HA. The observations, with others, suggest that the primary source of the Ca mediating the HA response is intracellular. In L cells the endoplasmic reticulum forms morphologically specialized appositions with the surface membrane which resemble structures at the triads of muscle that are thought to mediate coupling between surface membrane electrical activity and contraction via Ca release from the sarcoplasmic reticulum. The similar structures in L cells may mediate coupling between surface membrane electrical, mechanical, or chemical stimuli and the HA response via release of Ca from the endoplasmic reticulum. Surface-coupled release of Ca from intracellular stores might also regulate a number of other intracellular functions in nonmuscle cells.

Calcimycin↗
PubMed1979

Oscillatory membrane potential changes in cells of mesenchymal origin: the role of an intracellular calcium regulating system.

A number of mesenchymal cells (fibroblasts, macrophages and megakaryocytes) respond to a variety of stimuli with large hyperpolarizations lasting several seconds (the H.A. response). The H.A. responses can occur as repetitive trains or oscillations. These hyperpolarizations are due to an increase of the surface membrane permeability to potassium ions which is probably mediated by an increase in the cytoplasmic free calcium ion concentration. Evidence is discussed which suggests that the source of this increased calcium, is least in part, an intracellular sequestering system, probably the endoplasmic reticulum. A model capable of producing oscillatory changes in membrane potential is proposed based on such an intracellular calcium sequestering and releasing system.

Calcium↗
PubMed1978

Intracellular horseradish peroxidase injection for correlation of light and electron microscopic anatomy with synaptic physiology of cultured mouse spinal cord neurons.

Synaptic interactions between spinal cord neurons grown in dissociated cell culture were studied electrophysiologically, and presynaptic cells were subsequently injected by intracellular iontophoresis with horseradish peroxidase (HRP). Following histochemical processing, injected cells were filled with dense reaction product which facilitated the light and electron microscopic identification of the individual physiologically typed neurons. This technique applied to neurons in monolayer culture allowed the visualization of complex intercellular relationships in essentially two dimensions. The number and distribution of morphologically defined synaptic contacts was determined for correlation with individual evoked postsynaptic potentials. HRP-filling of inhibitory and excitatory neurons revealed differences with respect to cellular geometry, axonal projection, and the number, location and ultrastructure of synaptic contacts.

Animals↗
PubMed1978

Formation of synapses between cells of a neuroblastoma X glioma hybrid clone and mouse myotubes.

Synapses form between cells of a neuroblastoma X glioma hybrid clone and cultured mouse skeletal myotubes. The synapses are cholinergic, and the acetylcholine release mechanism is dependent on calcium ions. The transmitter output of the synapses is low, with considerable variability in the latency and amplitude of the postsynaptic responses to presynaptic action potentials. The fine structure of physiologically identified functional junctions was examined electron microscopically. Small (50 nm) clear vesicles were seen presynaptically and there were areas with a wide (approx. 50 nm) gap containing basement membrane-like material between the pre- and postsynaptic cells. In addition, in some regions there was a densely staining material lining the muscle membrane and some suggestion of infolding of the muscle membrane. In none of the cases, however, have areas been found where small, clear vesicles cluster around pre- and postsynaptic membrane densities. Thus, functional synapses can occur in the absence of the highly organized synaptic structure seen at mature synapses.

Action Potentials↗
PubMed1978

Pharmacologic responses of cells of a neuroblastoma X glioma hybrid clone and modulation of synapses between hybrid cells and mouse myotubes.

Cells of the hybrid clone NG108-15 responded to 5-hydroxytryptamine (5-HT), dopamine or acetylcholine with graded depolarizations involving membrane conductance increases. Responses desensitized during continuous application of the neurotransmitters, and responses to 5-HT and dopamine cross-desensitized: a desensitizing application of one neurotransmitter also desensitized the hybrd cell to the other neurotransmitter. 5-HT and acetylcholine did not cross-desensitize. The hybrid cell 5-HT response was not attenuated by D-LSD, and was blocked by 10(-5) M morphine, although not via binding to naloxone-sensitive opiate receptors. 5-HT or the prostaglandin PGF2alpha caused the release of acetylcholine at the synapses of hybrid cells with mouse myotubes. Application of 5-HT or PGF2alpha also facilitated the synaptic release elicited by hybrid cell action potentials. Following treatment with the antimitotic agent cytosine arabinoside, co-cultures of hybrid cells and mouse myotubes exhibited plentiful synaptic connections only if maintained in medium containing 1 mM dibutyryl cAMP (dBcAMP). After X-irradiation, co-cultures were synaptically active even in the absence of dBcAMP. Thus, methods have been found to regulate both the short-term and long-term synaptic activity of NG108-15 hybrid cells.

Acetylcholine↗
PubMed1978

Specific-opiate-induced depression of transmitter release from dorsal root ganglion cells in culture.

The opiate etorphine depresses monosynaptic excitatory postsynaptic potentials (EPSP's) elicited in spinal cord cells by activation of dorsal root ganglion cells in murine neuronal cell culture. The depression is reversed by naloxone. Statistical analysis of the synaptic responses reveals that the opiate reduces EPSP quantal content at this synapse without altering quantal size. Therefore, the opiate action is presynaptic and affects transmitter release rather than postsynaptic responsiveness.

Cells, Cultured↗
PubMed1978

A factor from neurons increases the number of acetylcholine receptor aggregates on cultured muscle cells.

There is an increase in the number of acetylcholine (AcCho) receptor aggregates on striated embryonic mouse myotubules when they are cocultured with clonal neuroblastoma-glioma hybrid cells. Medium conditioned by hybrid cells contains a factor which increases the number of AcCho receptor aggregates on myotubes cultured from mouse, rat or chick muscle. AcCho receptor-aggregating activity was present in medium conditioned by the neuroblastoma parent clone but was not detected in medium conditioned by cells of the parent glioma clone, fibroblasts, or HeLa cells. The factor increased the aggregation of AcCho receptors within 24 hr without a significant increase in the total number of AcCho receptors, and its action did not depend on myotube protein synthesis. The factor appears to rearrange the distribution of myotube AcCho receptors either by aggregating mobile AcCho receptors or by stabilizing labile receptor aggregates.

Cells, Cultured↗