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Biomedical subjects

M B Robinson

Publications and source records attributed to M B Robinson.

100 records · Page 6Linked to original sources

Kynurenic acid as an antagonist of hippocampal excitatory transmission.

Kynurenate, an endogenous tryptophan metabolite, was bath-applied to hippocampal slices while recording extracellular synaptic field potentials. Kynurenate antagonized the medial and lateral entorhinal projections to dentate granule cells, the Schaffer collateral projections to CA1 pyramidal cells, and inputs to the CA3 stratum radiatum of regio inferior with similar potencies. Concentration-response curves for these pathways paralleled theoretical antagonist curves with a Hill coefficient of 1, and the KdS were in the range of 130-400 microM. Projections to the stratum lucidum of regio inferior were much less sensitive to kynurenate. Inputs to CA3 pyramidal cells showed varying sensitivities to kynurenate, L-2-amino-4-phosphonobutanoic acid (L-APB), and (-)-baclofen depending on the placements of the stimulating and recording electrodes. When both electrodes were located in area CA3, outside the hilus of area dentata, all responses were insensitive to inhibition by L-APB. Under these conditions, responses recorded within the stratum radiatum were sensitive to inhibition by kynurenate and baclofen, while responses recorded within the stratum lucidum were insensitive to these drugs. When the stimulating electrode was placed within the hilus of area dentata, variable patterns of sensitivity to APB, baclofen, and kynurenate were observed from recording electrodes in area CA3. These results suggest that stimulation in the hilus, while recording in the stratum lucidum, produces responses that show composite effects resulting both from direct stimulation of mossy fibers and from stimulation of neuronal elements in the hilus which produce outputs to mossy fibers.

Action Potentials↗

Coarctation of the aorta and renal artery stenosis in tuberous sclerosis.

Among neurocutaneous disorders, coarctation of the abdominal aorta and renal artery stenosis have traditionally been associated with neurofibromatosis. We report a 5-year-old girl who, during the evaluation of asymptomatic hypertension, was discovered to have bilateral renal artery stenosis, coarctation of the abdominal aorta, renal cysts and typical skin lesions of tuberous sclerosis. Renal vascular hypertension has not been reported previously in tuberous sclerosis. We conclude that the tuberous sclerosis complex should be expanded to include vascular malformations and that hypertension should not be assumed to be secondary to renal hamartomata or cysts in patients with tuberous sclerosis.

Aortic Coarctation↗

Structure - function relationships for gamma-substituted glutamate analogues on dentate granule cells.

We previously demonstrated in the Schaffer collateral-CA1 region of the hippocampus that bath-applied agonists could be distinguished from antagonists among a group of acidic amino acid analogues by extracellular recording techniques. Here we report the use of the extracellular signs of agonist activity for discerning agonists and antagonists among several gamma-substituted glutamate analogues tested in the perforant path. The two-pathway composition of the perforant path offers the advantage over CA1 in that pathway-specificity, a postulated characteristic of antagonists, may be tested. By extracellular recording, D- and L-homocysteic acid, L-serine-O-sulfate, and L-2-amino-4-(5-tetrazolyl)-butanoic acid [L-glutamate tetrazole] were identified as agonists, and all 4 analogues were more potent than L-glutamate for inhibiting synaptic field potentials. Two previously identified antagonists, L-2-amino-4-phosphonobutyric acid and L-O-phosphoserine, exhibited the pathway-specificity and inhibitory kinetics consistent with properties expected for antagonists; both compounds detected 3 perforant path components with the same rank in sensitivity, suggesting that they are acting on the same set of receptors.

Aminobutyrates↗

[Levodopa].

Explore the source record for details and available documents.

Humans↗

Substrate-induced up-regulation of Na(+)-dependent glutamate transport activity.

Sodium-dependent transporters regulate extracellular glutamate in the CNS. Recent studies suggest that the activity of several different neurotransmitter transporters can be rapidly regulated by a variety of mechanisms. In the present study, we report that pre-incubation of primary 'astrocyte-poor' neuronal cultures with glutamate (100 microM) for 30 min nearly doubled the V(max) for Na(+)-dependent accumulation of L-[(3)H]-glutamate, but had no effect on Na(+)-dependent [(3)H]-glycine transport. Pre-incubation with glutamate also increased the net uptake of non-radioactive glutamate, providing evidence that the increase in accumulation of L-[(3)H]-glutamate was not related to an increase in intracellular glutamate and a subsequent increase in exchange of intracellular non-radioactive glutamate for extracellular radioactive glutamate. The glutamate receptor agonists, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate, quisqualate, and (1 S, 3R)-1-aminocyclopentane-1,3-dicarboxylic acid did not mimic the effect of pre-incubation with glutamate and the glutamate-induced increase was not blocked by receptor antagonists. However, compounds known to interact with the transporters, including L-aspartate, D-aspartate, L-(-)-threo-3-hydroxyaspartate (L-THA) and L-trans-pyrrolidine-2,4-dicarboxylate (L-trans-PDC), caused variable increases in transport activity and attenuated the increase induced by glutamate, suggesting that the increase is related to the interaction of glutamate with the transporters. Several studies were attempted to define the mechanism of this regulation. We found no evidence for increases in transporter synthesis or cell surface expression. Inhibitors of signaling molecules known to regulate other neurotransmitter transporters had no effect on this stimulation. Using a variety of cultures, evidence is provided to suggest that this substrate-induced up-regulation of glutamate transport is specific for the GLT-1 and GLAST subtypes and does not influence transport mediated by EAAC1. These studies suggest that the interaction of glutamate with some of the subtypes of glutamate transporters causes an increase in transport activity. Conceivably, this phenomenon provides an endogenous mechanism to increase the clearance of glutamate during periods of prolonged elevations in extracellular glutamate.

ATP-Binding Cassette Transporters↗

Data base for stroke rehabilitation using computerized English text discharge summaries.

A data processing system programmed in a terminal-oriented language called APL is described. This user-oriented system features the print-out of English text discharges summaries for patients treated in a stroke rehabilitation unit. The variables contained in the summaries are stored in the computer for statistical analysis, allowing continous monitoring of the unit's activities. Seventy-eight percent of patients with moderate to severe hemiparesis were able to return home after an average length of stay of 44 days. The value of the described system is suggested for muliticenter, cooperative studies on stroke.

Cerebrovascular Disorders↗

Junior doctors and clinical audit.

OBJECTIVES: To assess the extent of junior doctor involvement in clinical audit, the degree of support from audit staff, and the perceived value of the resulting audits. DESIGN: Postal survey of National Health Service (NHS) junior doctors. SUBJECTS AND SETTINGS: 704 junior doctors in central Leeds hospitals, June 1996. RESULTS: Questionnaires were returned by 232 respondents (33%), 211 (31%) were completed; 157 respondents (74%) had personally performed audit. Mean (+/- SD) duration since last audit project was 14.9 (14.1) (range 0-84) months. Of the respondents who had personally performed audit, 88 (56%) did not use the hospital audit department, 60 (38%) received no guidance and only 19 (12%) were involved in re-auditing the same project. Mean (+/- SD) time spent per audit project was 27.8 (37.7), (range 2-212) hours. Seventy-five junior doctors (48%) were aware of subsequent change in clinical practice, 41 (26%) perceived a negative personal benefit from audit, 33 (21%) perceived a negative departmental benefit, and 42 (27%) felt that audit was a waste of time. CONCLUSIONS: A large proportion of junior doctors are involved in audit projects that do not conform to established good practice and which have a low impact on clinical behaviour. Although junior doctors feel that there is inadequate assistance and poor supervision whilst performing audit, they still support the principle of audit. There is a need to improve the quality and supervision of audit projects performed by junior doctors.

Attitude of Health Personnel↗