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Biomedical subjects

David Bennett

Publications and source records attributed to David Bennett.

24 records · Page 2Linked to original sources

The cloning and functional analysis of canine matrix metalloproteinase-13 gene promoter.

A fragment of the 5' untranslated region corresponding to the canine matrix metalloproteinase-13 (MMP-13), collagenase-3 gene promoter has been isolated and characterized in rat cardiocytes to investigate the role of MMP-13 in cardiac disease. The promoter fragment (1.5 kb) demonstrated regions of sequence homology with the collagenase gene promoter sequences already determined for other species. Conserved regions were identified and shown to correlate with DNA binding motifs including AP-1 sites, a nuclear factor (NF) B-like binding domain, GATA and Nkx2.5 sites. A consensus TATA box was identified and shown to direct transcription initiation approximately 27 bp upstream of the translation start site. The canine MMP-13 promoter fragment was sufficient to drive basal expression of a luciferase reporter gene in both Madin Darby canine kidney cells (MDCK) and primary rat cardiocytes. The activity of the promoter fragment could be significantly increased by the treatment of transfected primary rat cardiocytes with interleukin-1 (IL-1) and basic fibroblastic growth factor (bFGF), with some induction also observed with tumour necrosis factor (TNF). The canine MMP-13 promoter activity has also been compared to the basal and induced activity of the canine MMP-9, gelatinase B promoter in these cell types.

5' Flanking Region↗

Recent evidence for plateau potentials in human motoneurones.

Motoneurones in reduced animal preparations can exhibit plateau potentials that amplify their response to synaptic inputs and can persist for prolonged periods in the absence of synaptic drive. There is mounting evidence that a similar mechanism may be an integral part of the normal activation of motoneurones. Some of the work describing plateau potentials in reduced animal preparations is reviewed and then evidence that similar properties contribute to the normal activation of motoneurones in rats and humans is presented. Recent data have shown that during high-frequency electrical stimulation over human muscle, large contractions can develop which originate within the central nervous system and are present in addition to the contraction due to the direct activation of motor axons. These "extra" contractions may in part be due to plateau potentials in spinal motoneurones. It is becoming clear that intrinsic properties of human motoneurones may make a large contribution to muscle contractions during normal movements. The extent to which the nervous system uses this as a gain control mechanism to tailor motor output for a given task needs to be further explored.

Animals↗

Pulmonary artery catheter: does the problem lie in the users?

The aims of this study were to look for the variability in the treatment of circulatory shock and to assess the extent to which this variability was reduced by pulmonary artery catheterization (PAC). At three international conferences in 1997-1998 (European Society of Critical Care Medicine, French Language Society for Critical Care [Société de Réanimation de Langue Française], and Society of Critical Care Medicine), a real-life clinical case was discussed in meetings among physicians and a panel of experts, with assistance from an expert computer program. A total of 417 physicians took part in the discussions. Following the clinical presentation, only 38% of physicians suggested the same treatment as the experts, and 35% suggested potentially harmful treatments. Complete hemodynamic data from PAC significantly decreased the range of suggested treatments, improved agreement among physicians themselves as well as the agreement between physicians and experts, and decreased the number of potentially harmful propositions. However, whereas almost 80% of participants finally agreed on the treatment after one to three invasive hemodynamic sets of measurements, at least 10% persisted in suggesting potentially harmful treatments. PAC improved interphysician agreement, but our data suggest that yet greater agreement could be achieved by improving the theoretical training of practitioners.

Catheterization, Swan-Ganz↗

Health and safety management systems: liability or asset?

Health and safety management systems have a background in theory and in various interests among employers and workplace health and safety professionals. These have resulted in a number of national systems emanating from national standard-writing centres and from employers' organizations. In some cases these systems have been recognized as national standards. The contenders for an international standard have been the International Organization of Standardization (ISO) and the International Labour Organization (ILO). The quality and environmental management systems of ISO indicate what an ISO health and safety management standard would look like. The ILO Guidelines on Safety and Health Management Systems, by contrast, are stringent, specific and potentially effective in improving health and safety performance in the workplace.

Canada↗