PubMed Health⌕ Search

Biomedical subjects

M T Pugh

Publications and source records attributed to M T Pugh.

8 recordsLinked to original sources
PubMed1993

The role of infection in juvenile chronic arthritis.

Juvenile chronic arthritis covers a heterogeneous group of arthritides for which there appears to be a genetically determined susceptibility. The exact events which trigger or perpetuate an arthritic disease have yet to be defined. There is circumstantial clinical evidence that JCA can be initiated by environmental factors such as infection, and indirect laboratory evidence that immune responses to infectious agents are associated with ongoing JCA; such immune responses seem particularly vigorous within the joint space. Although the weight of evidence favours the hypothesis that the intra-articular inflammatory process is antigen-driven, none of the critical antigens have been identified, and it is still unclear whether they are derived from infectious agents or are true auto-antigens. We can however expect progress to be made, since techniques are now available for defining the antigenic specificity and TCR usage of synovial T cell populations, while PCR allows exquisitely sensitive detection of infectious agents deposited in the synovial space. Application of these techniques should lead to an enhanced understanding of whether (or in what circumstances) infectious agents are involved in the pathogenesis of arthritis in children.

Antigens, Bacterial↗
PubMed1986

Locomotor behaviors in response to new selective D-1 and D-2 dopamine receptor agonists, and the influence of selective antagonists.

With the introduction of the selective D-1 dopamine receptor agonist and antagonist benzazepines, especially as enantiomeric pairs, there is now a range of D-1 compounds to complement the previously available selective D-2 agents. These have been used to investigate whether sub-types of dopamine receptors might be differentially involved in locomotor behavior. Stereotyped locomotion induced by the non-selective D-2 agonist apomorphine and by the selective D-2 agonist RU 24213 were blocked by the selective D-2 antagonists metoclopramide and Ro 22-2586 [-)-piquindone). Responses to either D-2 agonist were also blocked by the selective D-1 antagonists SCH 23390 and R-(but not S-) SK&F 83566. Non-stereotyped locomotion was induced by R- but not S-SK&F 38393, a stereoselective D-1 agonist, and was blocked by SCH 23390. Responses to the D-1 agonist were also antagonised by metoclopramide. Such results suggest concerted D-1:D-2 interplay in the regulation of at least some dopaminergic behaviors, such as locomotion.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1985

Effects of the putative D-1 antagonist SCH 23390 on stereotyped behaviour induced by the D-2 agonist RU24213.

The effects of the putative selective dopamine D-1 antagonist benzazepine SCH 23390 and of the selective dopamine D-2 antagonist Ro22-2586 on stereotypy induced by the selective D-2 agonist RU24213 were compared. RU24213 (0.5-15 mg/kg) dose-dependently induced stereo-typed behaviour characterised by continuous downward sniffing and locomotion. These responses were antagonised, as expected, by 40-200 micrograms/kg Ro22-2586, but surprisingly blocked by 40-200 micrograms/kg SCH 23390. The selectivities of these compounds for dopamine receptor subtypes were verified in terms of their relative abilities to displace the in vitro binding of 3H-piflutixol to striatal D-1 receptors and of 3H-spiperone to D-2 receptors. As SCH 23390 fails to influence D-2 mediated prolactin secretion or emesis in vivo, there appears to be no significant formation of an active metabolite of SCH 23390 with D-2 antagonist activity. Because SCH 23390 has some affinity for 5-hydroxytryptamine receptors, any effect on the serotonergic behavioural syndrome induced by 10 mg/kg 5-methoxy-N,N-dimethyltryptamine was also studied. The serotonergic responses of hind limb abduction, reciprocal forepaw treading and Straub tail were unaltered after 40-200 micrograms/kg SCH 23390, indicating no significant 5-HT blockade or non-specific depressant action at these doses which might influence the expression of stereotypy. Thus, these data are consistent with blockade of tonic D-1 dopaminergic activity that may influence the expression of behaviours initiated by D-2 dopaminergic stimulation.

Animals↗
PubMed1985

Association of intellectual impairment, negative symptoms, and aging with tardive dyskinesia: clinical and animal studies.

It is not known why some schizophrenic patients receiving long-term neuroleptic treatment develop abnormal involuntary orofacial movements, while others do not. Schizophrenic patients with orofacial dyskinesia were found to be more intellectually impaired, more likely to show negative symptoms, and older than those without such movements. These features are characteristic of the "defect state," wherein structural brain changes may be demonstrable. Prolonged long-term neuroleptic treatment of young rats was associated with late-onset orofacial movements; however, such movements occurred spontaneously in untreated senescent rats. Structural brain changes consequent to aging and disease processes may be associated with the emergence of orofacial dyskinesia, even in the absence of exposure to neuroleptics. These movements do not appear to have their basis in striatal dopamine receptor supersensitivity.

Aged↗