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Biomedical subjects

K Walton

Publications and source records attributed to K Walton.

54 records · Page 3Linked to original sources
PubMed1986

Ionic mechanisms underlying the firing properties of rat neonatal motoneurons studied in vitro.

Ionic mechanisms underlying the firing properties of spinal motoneurons of neonatal rats (postnatal days 3-10) have been investigated using a hemisected, in vitro spinal cord preparation. These results demonstrate the presence of a high-threshold voltage-dependent calcium response and partial sodium-dependent spikes. The calcium current is evident during the falling phase of the action potential and is the major component of the after-depolarizing potential. The subsequent increase in intracellular calcium concentration activates a calcium-dependent potassium conductance (gK-Ca), the major component of the after-hyperpolarizing potential. The gCa, by activating gK-Ca, is the primary determinant of firing rate in neonatal motoneurons. For, when gCa was blocked by Cd2+, the interspike interval decreased, the maximum firing rate and the slope of the firing frequency-injected current relation increased. The calcium current is particularly robust during the first few postnatal days; during this period, tetrodotoxin resistant action potentials can be elicited by direct stimulation under control conditions. In animals older than 5 days such calcium spikes could be elicited only after decreasing gK with intracellular Cs+ or extracellular tetraethylammonium. This was the case even when 1 mM of the bath CaCl2 was replaced with BaCl2. The rising phases of calcium spikes recorded from neurons in both age groups demonstrate several components suggesting the calcium spikes comprise several discrete events, which probably originate across the dendritic membrane. When gK was decreased by bath application of tetraethylammonium+ and Cs+, neonatal motoneurons generated prolonged Ca-dependent spikes lasting for up to 6 s. Repolarization of Ca spikes occurred in two stages, the first was rapid (-2.11 +/- 0.8 V/s, n = 6) but incomplete. The second, was slower (-0.01 +/- 0.003 V/s, n = 5) and returned the membrane potential to the resting level after about 1-2 s. It is suggested that accumulation of extracellular potassium may contribute to the slow phase of repolarization. Motoneurons from the younger age group (3-5 days old) demonstrate all-or-none partial spikes rising from the after-depolarization of directly elicited sodium-dependent action potentials. Similar partial spikes were elicited from neurons from older animals during intracellular Cs+ loading. The partial spikes had faster rates of rise than the tetrodotoxin-resistant spikes and were not seen after tetrodotoxin treatment, suggesting that they are sodium-dependent.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1986

Electrophysiological properties of neonatal rat motoneurones studied in vitro.

The electroresponsive properties of neonatal lumbar spinal motoneurones were studied using isolated, hemisected spinal cords from neonatal rats aged 3-12 days. The extracellular and intracellular responses to electrical stimulation of the ventral and dorsal root were studied as well as the intracellular response to current injection. Field potentials recorded in the lateral motor area following electrical stimulation of lumbar ventral roots had a triphasic positive-negative-positive wave form. The negative component did not return to the base line smoothly but exhibited a 'shoulder' where the negativity increased in duration. Following electrical stimulation of the dorsal root, presynaptic field potentials were recorded upon activation of the afferent axons as well as following synaptic activation of interneurones and motoneurones. The input resistances of neonatal motoneurones determined from the slope of current-voltage plots were high compared with the adult. The resistance decreased with age with a mean of 18.1 M omega for animals 3-5 days old, 8.8 M omega for animals 6-8 days old and 5.4 M omega for animals 9-11 days old. Values for the membrane time constant were similar to those in the adult with a mean of 4.5 ms. Action potentials elicited by ventral or dorsal root stimulation or by intracellular current injection were marked by a pronounced after-depolarization (a.d.p.) and an after-hyperpolarization (a.h.p.). The amplitude of the a.h.p. varied with that of the a.d.p. The amplitude of excitatory post-synaptic potentials (e.p.s.p.s) elicited by electrical stimulation of the dorsal root was affected by intracellular current injection. Two types of e.p.s.p.s were distinguished: those with a biphasic reversal (early phase first) and those in which the early phase was unaffected by inward current injection while the later phase was reversed. Unlike in the adult, the reversals could be achieved with low current levels and the amplitude of both types of e.p.s.p. was increased by inward current injection. Inhibitory post-synaptic potentials (i.p.s.p.s) were elicited by dorsal or ventral root stimulation. The amplitude of these i.p.s.p.s was diminished and reversed in sign with inward current injection and their amplitude was enhanced with outward current injection. Activation of neonatal motoneurones with long current pulses revealed that there is one steady-state firing range.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1985

Pseudomonas arthritis treated with parenteral and intra-articular ceftazidime.

A 73-year-old diabetic presented with septic arthritis of the knee; Pseudomonas aeruginosa was isolated. She was successfully treated with a combination of parenteral and intra-articular ceftazidime, after failure to eradicate the organism with adequate serum levels of gentamicin and full doses of azlocillin.

Aged↗
PubMed1985

A study of two diuretic/potassium combinations in heart failure.

The effect of potassium supplements was studied in 28 patients taking long term frusemide (40-80 mg daily). Plasma potassium fell when supplements were stopped, and rose towards prior values on the potassium/frusemide combination, Diumide K. In a crossover study in 14 of these patients comparing equivalent doses of frusemide, Diumide K (frusemide 40 mg, potassium 8 mmol), bumetanide, and Burinex K (bumetanide 0.5 mg, potassium 7.7 mmol) plasma potassium was lower on frusemide than on bumetanide. On Diumide K and Burinex K plasma potassium rose significantly but did not reach the levels on prior therapy. Small doses of potassium in combined formulations seem to be effective in countering the mild hypokalaemia caused by loop diuretics.

Adult↗
PubMed1985

Clinical features, autoantibodies and HLA-DR antigens in rheumatoid arthritis.

HLA-DR4 was associated with seropositive but not seronegative disease in 105 Caucasians with rheumatoid arthritis (RA). There were no clinical or radiological differences between DR4 positive and negative RA groups, although 7 of 8 patients with early disease onset (less than 30 yr) were DR4 positive. High rheumatoid factor (RF) titers were more frequent in DR4 negative RA. A plot of the frequency distribution of RF titers in DR4 negative disease showed a bimodal distribution with seronegative and high titer groups. HLA-DR3 was not associated with high RF titers but was associated with high titers of antinuclear antibodies.

Agglutination Tests↗
PubMed1985

Genetic variants of properdin factor B (Bf) in rheumatoid arthritis.

Properdin factor B (Bf) phenotyping was carried out in 392 patients with rheumatoid arthritis (RA) and in 360 controls. In RA there were increased frequencies of both the Bf*S gene (83 vs 78%; pc = 0.0003) and the BfSS genotype 73 vs 61%; pc = 0.0002) and reduced frequencies of the Bf*F1 gene (0.5 vs 2.2%; pc = 0.03) and the BfFS genotype (20 vs 29%; pc = 0.0007). The frequencies of Bf*S in DR4 positive and DR4 negative RA were similar so that the findings were not accounted for by linkage disequilibrium between DR4 and Bf*S.

Arthritis, Rheumatoid↗
PubMed1983

Hydrogen peroxide as a source of molecular oxygen for in vitro mammalian CNS preparations.

Using an isolated neonatal rat spinal cord preparation, we have studied the ability of hydrogen peroxide to act as a source of oxygen for mammalian central nervous system (CNS) maintained in vitro. We report here that hydrogen peroxide, in low concentrations (0.001-0.004%), can effectively provide the only source, or act as a supplementary source of oxygen. This is brought about via the intracellular enzyme catalase which catalyzes the conversion of H2O2 into molecular oxygen and water.

Animals↗
PubMed1981

Presynaptic calcium currents in squid giant synapse.

A voltage clamp study has been performed in the presynaptic terminal of the squid stellate ganglion. After blockage of the voltage-dependent sodium and potassium conductances, an inward calcium current is demonstrated. Given a step-depolarization pulse, this voltage- and time-dependent conductance has an S-shaped onset. At the "break" of the voltage step, a rapid tail current is observed. From these results a kinetic model is generated which accounts for the experimental results and predicts for the time course and amplitude a possible calcium entry during presynaptic action potentials.

Action Potentials↗
PubMed1981

Relationship between presynaptic calcium current and postsynaptic potential in squid giant synapse.

The relationship between calcium current and transmitter release was studied in squid giant synapse. It was found that the voltage-dependent calcium current triggers the release of synaptic transmitter in direct proportion to its magnitude and duration. Transmitter release occurs with a delay of approximately 200 mus after the influx of calcium. A model is presented which describes these relations formally.

Action Potentials↗
PubMed1980

Transmission in the squid giant synapse: a model based on voltage clamp studies.

1. Voltage clamp studies were performed in squid giant synapse after blockage of the voltage-dependent sodium and potassium conductances. 2. Presynaptic depolarization under these conditions demonstrates the presence of voltage-dependent calcium conductance change for the duration of the voltage step, and a tail current at the break of the pulse. 2. This calcium current triggers a postsynaptic response which can be measured directly at the postsynaptic fiber. 4. These voltage clamp experiments have allowed the development of a mathematical model that describes the kinetics of the calcium current and the relationship between calcium current and transmitter release.

Animals↗
PubMed1976

Presynaptic calcium currents and their relation to synaptic transmission: voltage clamp study in squid giant synapse and theoretical model for the calcium gate.

A voltage clamp study of the presynaptic terminal in squid stellate ganglion has given quantitative results relating inward Ca2+ current to presynaptic membrane potential and postsynaptic response to inward Ca2+ current. The results indicate an S-shaped curve for the relationship between presynaptic potential and Ca2+ current and a linear relationship between Ca2+ current and postsynaptic potential. A similar S-shaped curve was found for the time-dependent properties of the Ca2+ conductance. Based on these results a mathematical model was developed which accounts for the experimental results in this and previously published papers by other authors. The model suggests that five subunits are involved in the Ca2+ gate and that the subunits change noncooperatively from an inactive to an active form upon membrane depolarization.

Animals↗
PubMed1975

Inferior olive: its role in motor learing.

Specific chemical lesion of the rat inferior olive by intraperitoneal administration of 3-acetylpyridine prevents recuperation from motor abnormalities generated by unilateral labyrinthine lesion. Moreover, in animals that have recuperated from the balyrinthine lesion, 3-acetylpyridine produces a reversal of the symptoms within 2 hours of administration. These results indicate that the integrity of the olivo-cerebellar system is necessary for the acquisition and retention of this form of motor learning, but that the cerebellum itself is not the seat of such learning.

Animals↗
PubMedDate not supplied

Mathematical modelling and quantitative methods.

The present review reports on the mathematical methods and statistical techniques presently available for hazard characterisation. The state of the art of mathematical modelling and quantitative methods used currently for regulatory decision-making in Europe and additional potential methods for risk assessment of chemicals in food and diet are described. Existing practices of JECFA, FDA, EPA, etc., are examined for their similarities and differences. A framework is established for the development of new and improved quantitative methodologies. Areas for refinement, improvement and increase of efficiency of each method are identified in a gap analysis. Based on this critical evaluation, needs for future research are defined. It is concluded from our work that mathematical modelling of the dose-response relationship would improve the risk assessment process. An adequate characterisation of the dose-response relationship by mathematical modelling clearly requires the use of a sufficient number of dose groups to achieve a range of different response levels. This need not necessarily lead to an increase in the total number of animals in the study if an appropriate design is used. Chemical-specific data relating to the mode or mechanism of action and/or the toxicokinetics of the chemical should be used for dose-response characterisation whenever possible. It is concluded that a single method of hazard characterisation would not be suitable for all kinds of risk assessments, and that a range of different approaches is necessary so that the method used is the most appropriate for the data available and for the risk characterisation issue. Future refinements to dose-response characterisation should incorporate more clearly the extent of uncertainty and variability in the resulting output.

Animals↗