Biomedical subjects

D Marston

Publications and source records attributed to D Marston.

15 recordsLinked to original sources

PubMed2006

Molecular epidemiology of rabies viruses in Europe.

Several different strains of classical rabies virus co-circulate in Europe. In order to investigate the roles of the host species and topography on the molecular epidemiology of these viruses, a 400 bp region of the nucleoprotein gene was sequenced and compared with more than 500 European virus isolates. Viruses from 21 European countries were represented including some unique panels of archived isolates from the former Republic of Yugoslavia, Estonia, the Czech Republic, Poland and Austria. Phylogenetic analysis of 198 unique sequences demonstrated numerous groups of viruses clustered at both geographical and host-species levels.

Animals↗

PubMed2006

Development of a real-time, differential RT-PCR TaqMan assay for lyssavirus genotypes 1, 5 and 6.

A number of RT-PCR methods have been reported for the detection of rabies and rabies-related viruses. Here, a single, closed tube, non-nested RT-PCR TaqMan assay to distinguish between Classical rabies virus and European bat lyssaviruses 1 and 2 in real time is described. The TaqMan assay is rapid, sensitive, specific and allows for the genotyping of unknown isolates concomitant with the RT-PCR. It can be applied quantitatively and the use of an internal control enables the quality of the isolated template to be assessed. The efficiency and dynamic range of the PCR has been established using isolated viral RNA and cloned control template. Comparative performance of the TaqMan assay against other diagnostic methodologies for the detection of rabies virus has been determined and the assay validated against a panel of archival samples and virus of unknown genotype from both Germany and the Sudan. Despite sequence heterogeneity between the different genotypes in the N-gene, a universal forward and reverse primer set have been designed allowing simplification of previously described assays. Rapid genotyping of two recent EBLV2 cases in the U.K. in Daubenton's bats and a recently imported human case of rabies has been performed using this test.

Animals↗

PubMed2005

Development of a real-time, TaqMan reverse transcription-PCR assay for detection and differentiation of lyssavirus genotypes 1, 5, and 6.

Several reverse transcription-PCR (RT-PCR) methods have been reported for the detection of rabies and rabies-related viruses. These methods invariably involve multiple transfers of nucleic acids between different tubes, with the risk of contamination leading to the production of false-positive results. Here we describe a single, closed-tube, nonnested RT-PCR with TaqMan technology that distinguishes between classical rabies virus (genotype 1) and European bat lyssaviruses 1 and 2 (genotypes 5 and 6) in real time. The TaqMan assay is rapid, sensitive, and specific and allows for the genotyping of unknown isolates concomitant with the RT-PCR. The assay can be applied quantitatively and the use of an internal control enables the quality of the isolated template to be assessed. Despite sequence heterogeneity in the N gene between the different genotypes, a universal forward and reverse primer set has been designed, allowing for the simplification of previously described assays. We propose that within a geographically constrained area, this assay will be a useful tool for the detection and differentiation of members of the Lyssavirus genus.

Animals↗

PubMed1996

Identification and pharmacological characterization of [125I]L-750,667, a novel radioligand for the dopamine D4 receptor.

We identified a novel azaindole derivative, L-750,667, that has high affinity (Ki = 0.51 nM) and >2000-fold selectivity for D4 dopamine receptors compared with its activity at D2 and D3 dopamine receptors. L-750,667 had little affinity for rat D1/D5 dopamine receptors, sigma binding sites, or 5-hydroxytryptamine1A or 5-hydroxytryptamine2 receptors. In functional studies, L-750,667 exhibited high affinity antagonist activity at D4 receptors, reversing dopamine (1 microM)-induced inhibition of cAMP accumulation in human embryonic kidney (HEK) cells expressing the human D4 receptor (hD4 HEK) with an EC50 value of 80 nM. The radioiodinated form of L-750,667 bound specifically to the human dopamine D4 receptor expressed in HEK cells and saturation analysis revealed a single high affinity binding site for [125I]L-750,667 (Kd = 0.16 +/- 0.06 nM). The maximum number of binding sites (Bmax) estimated using [125I]L-750,667 in hD4 HEK cells was 251 +/- 71 fmol/mg, which correlated well with the Bmax value determined using [3H]spiperone (227 +/- 83 fmol/mg) in the same membrane preparations. The pharmacological profile of [125I]L-750,667 binding to hD4 HEK cells was evaluated using known dopamine receptor agonists and antagonists. The rank order of potencies for dopamine receptor agonists was dopamine > quinpirole > 6,7-aminodihydroxytetralin > 5,6-aminodihydroxytetralin. Dopamine receptor antagonists also showed high affinity, with a rank order of haloperidol > chlorpromazine > domperidone > (+)-butaclamol > (-)-sulpiride = (+)-sulpiride > (+)-SCH23390 > (-)-butaclamol. [125I]L-750,667, bound to D4 receptors in a stereoselective manner with (+)-butaclamol showing higher activity than its respective enantiomer (-)-butaclamol. These results show that [125I]L-750,667 is a novel, highly selective radioligand for dopamine D4 receptors and may be used to investigate the dopamine D4 receptor population in the central nervous system.

Animals↗

PubMed1993

Effects of transitory cognitive impairment on psychosocial functioning of children with epilepsy: a therapeutic trial.

The authors report a trial of the use of anti-epileptic medication to treat possible cognitive deficits due to subclinical epileptiform EEG discharges in 10 children with psychosocial and educational problems associated with epilepsy. Medication intended to suppress the EEG discharges was added to the children's existing drug regime. In all instances, epileptiform activity, assessed by 24-hour periods of ambulatory monitoring, was reduced on active medication compared with placebo. In general, there was improvement of psychosocial function on active treatment: eight children improved, there was no change in one and one deteriorated. No psychosocial deterioration attributable to adverse effects of the medication was detected in those completing the trial. Despite possible confounding factors, the findings are in accordance with the view that subclinical EEG discharges can impair psychosocial function, which may be ameliorated by anti-epileptic medication.

Adolescent↗

PubMed1992

Cognitive correlates of interictal discharges.

Interictal discharges can occur silently without apparent simultaneous clinical manifestations. Nevertheless, formal testing during electroencephalographic (EEG) recording may demonstrate transitory cognitive impairment (TCI). The probability of demonstrating TCI is related to the nature of the test employed and the type of epileptiform discharge. Difficult tasks are more useful to detect TCI, and working memory and language tests may be particularly sensitive. Generalized 3-Hz spike-wave bursts lasting at least 3 s are most likely to produce demonstrable TCI, but they can also be found during briefer and even focal discharges. The latter exhibit some specificity: left-sided focal spiking more frequently produces errors in verbal tasks, whereas right-sided discharges are more often accompanied by impairment in handling nonverbal material. TCI may adversely affect the patient's psychosocial functioning in daily life, as has been shown by some studies pointing out an impairment of educational skill in epileptic children and of driving performance in motorists. Our study on benign childhood epilepsy with Rolandic spikes also detected TCI in the majority of the patients. Nevertheless, it is not possible to claim that everyone with subclinical EEG discharges has TCI that adversely affects their psychosocial functioning. It may be possible to treat TCI by antiepileptic drugs.

Anticonvulsants↗

PubMed1991

Cooperative teaching project: a model for students at risk.

This article describes an innovative teaching model designed to impact students at risk with the cooperative efforts of regular and special education in Grades K-3. Evaluation outcomes are presented that show the model has a positive effect on individual student performance, total building progress as measured by curriculum based measurement, special education referrals, and attitudes of participating teachers.

Child↗

PubMed1990

Learning disabilities in epilepsy: neurophysiological aspects.

Subclinical generalized spike-wave discharges are often accompanied by transitory cognitive impairment, demonstrable by psychological testing during EEG recording. Transitory cognitive impairment is demonstrated most readily by difficult tasks and during generalized regular spike-wave bursts lasting for more than 3 s, but can also be found during briefer and even focal discharges. That this is not simply a consequence of global inattention is shown by the fact that focal discharges exhibit some specificity: left-sided focal spiking is more likely to produce errors on verbal tasks, for instance, whereas right-sided discharges are more often accompanied by impairment in handling nonverbal material. Both learning difficulties in general and specific abnormal patterns of cognitive functioning are well documented in children with epilepsy and are most pronounced in those with frequent interictal discharges. However, there is now evidence that intermittent cognitive impairment due to the discharges themselves contributes significantly to such neurophysiological abnormalities. The significance of transitory cognitive impairment accompanying subclinical EEG discharges for everyday functioning is uncertain, but there is experimental evidence that subclinical discharges may be accompanied by disruption of educational skills in children or by impairment of driving performance in motorists. In some individuals, suppression of discharges by antiepileptic drugs has demonstrably improved psychological function, but further work is required to determine the indications for such treatment.

Animals↗

PubMed1989

Distribution of temporal spikes in relation to the sphenoidal electrode.

Sphenoidal EEG recordings were performed in 111 patients with epilepsy, who showed antero-mesial temporal epileptiform discharges. In 6, a multipolar sphenoidal electrode showed a shallow potential gradient between the standard sphenoidal site and the surface. In 17 patients a superficial electrode at the site of entry of the sphenoidal wire recorded all discharges seen at the sphenoidal. Out of 165 foci, in only 2 instances were less than 90% of sphenoidal discharges recognisable on the surface. In 39 patients who underwent surgery, lesions confined to mesial temporal structures were found to be associated with inter-ictal discharges maximal at the sphenoidal electrode. A mid-temporal maximum was always associated with diffuse non-specific, or lateral temporal pathology. It is concluded that sphenoidal recording offers no advantage over suitably placed scalp contacts for detecting inter-ictal epileptiform discharges. It may be of some value for differentiating between mesial and lateral temporal foci.

Electrodes↗

PubMed1988