Biomedical subjects
T W Stone
Publications and source records attributed to T W Stone.
Cholinergic mechanisms in the rat somatosensory cerebral cortex.
1. The responses of identified cells in the rat cerebral cortex to cholinomimetic and anticholinergic substances has been investigated.2. Acetylcholine and muscarinic agonists have an excitatory action on 80% of pyramidal tract cells. This response is found especially on cells responding to specific thalamic stimulation and the burst of spikes evoked from this site can sometimes be blocked by the iontophoresis of atropine. This strongly suggests an excitatory transmitter function for acetylcholine in a specific thalamocortical pathway.3. Experiments on non-pyramidal tract cells have detected a muscarinic depression of some cells, and a nicotinic excitation of some cells above a depth of 600 mu in the cortex.4. It is suggested that the increased release of acetylcholine from the cortex produced by atropine administration may be due to an excess of muscarinic inhibitory over excitatory synapses in the cortex.
Cholinergic mechanisms in the rat cerebral cortex.
Explore the source record for details and available documents.
Are noradrenaline excitations artefacts?
Explore the source record for details and available documents.
Kynurenic acid antagonism of kainate following mossy fibre lesions of rat hippocampus.
Cells in the CA3 region of rat hippocampal slices were approximately five times more sensitive to kainate than CA1 cells. After destruction of mossy fibres the sensitivity of CA3 cells was significantly diminished. Kynurenic acid antagonized the excitation of CA1 neurones by kainate, N-methyl-D-aspartate (NMDA) and quisqualate, but in CA3 of normal slices it blocked responses to NMDA selectively. After colchicine treatment kynurenate blocked responses to kainate and NMDA. The results confirm that the excitatory effect of kainate in CA3 is partly due to a presynaptic action. However they also raise the possibility that postsynaptic and presynaptic kainate receptors are pharmacologically distinguishable, only the former being sensitive to antagonism by kynurenate.
Levels of lipid peroxidation products in a chronic inflammatory disorder.
We have examined the plasma levels of the lipid peroxidation products 4-hydroxy-nonenal and malondialdehyde in a carefully controlled study of age and sex-matched subjects with rheumatoid arthritis in whom potentially confounding influences such as disease modifying anti-rheumatic drugs (DMARDs), self-medication and vitamin supplements were eliminated. The plasma concentrations of the antioxidants uric acid and vitamin E were also measured. The results reveal a strong and consistent inverse correlation between the levels of lipid peroxidation products in the plasma and erythrocyte sedimentation rate (ESR). There is no indication that vitamin E or urate function as the major antioxidant agent in arthritis, as has been suggested in more seriously affected patients. It is concluded that there is no evidence that vitamin E is more important, and urate less important as an antioxidant in mild arthritis. The correlation between lipid peroxidation and ESR suggests a more complex relationship than has been assumed.
Modulation of cytokine release by purine receptors in patients with rheumatoid arthritis.
OBJECTIVE: Since adenosine receptors are known to modulate the release of some inflammatory mediators in control subjects, we have examined the effects of the mixed A1 and A2 adenosine receptor agonist 5'-N-ethylcarboxamidoadenosine (NECA) on basal and lipopolysaccharide (LPS)-induced cytokine release in diluted whole blood cultures from rheumatoid arthritis (RA) patients and healthy volunteers. METHODS: Twenty-eight patients with rheumatoid arthritis aged 18-75 years gave their voluntary consent to participate and give a blood sample. Basal levels of tumour necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) were measured by ELISA, and whole blood cultures were prepared to assess the effects of LPS activation. RESULTS: Following a 40-hour incubation, activation of adenosine receptors by NECA, added to the cell cultures from rheumatoid arthritis patients, was found to suppress both the basal and LPS-induced release of TNF-alpha and IL-1beta, while causing an increase in the release of both basal and LPS-induced IL-6. In healthy volunteers basal cytokines were undetectable, but NECA alone induced the release of all three cytokines. Stimulated levels of TNF-alpha were more than double those in patients. In the control blood cultures, NECA suppressed LPS-induced release of TNF-alpha and IL-1beta, but increased IL-6 release. CONCLUSIONS: Adenosine receptor stimulation has a differential effect on the release of pro-inflammatory cytokines, and may induce cytokine release in normal subjects. Stimulated release of TNF-alpha is substantially lower in patients with rheumatoid arthritis than in control subjects, possibly indicating saturation, exhaustion or down-regulation of the release process.