No description available.

This thesis describes the use of a model of cell deformation to measure the effect of stretch on mediator release or expression by airway epithelial cells, and to assess the method of mechanotransduction in these cells. Cells were cyclically stretched using the Flexercell system delivering biaxial stretch. IL-8 release by BEAS 2B cells was increased by cytokine stimulation and stretch, in a dose, time and rate dependent manner, whereas RANTES levels in the cell supernatant and cell surface ICAM-1 expression decreased after stretch. 30% elongation at 20 cycles/minute for 24 hours increased IL-8 levels by over 100% (p<0.01). Changes in IL-8 and RANTES RNA correlated with the effect on protein levels. Stretch did not adversely effect cell viability. The novel use of primary bronchial epithelial cells in stretch experiments is reported, with, in contrast to the BEAS 2B cell line, no effect of stretch on IL-8 release by these cells.;To interpret how the cells were sensing the stretch stimulus, signalling via integrins was blocked using an inhibitor of Rho (R&barbelow;as Homologous) associated kinases, which inhibited the effect of stretch on IL-8 release by the BEAS 2B cells, but not the effect on RANTES release or ICAM-1 expression. Blocking individual integrins did not affect the stretch response. Paxillin was visualised by indirect immunofluorescence to study the effect of stretch on the distribution of focal contacts and the organisation of the actin cytoskeleton. This demonstrated that stretch caused dramatic disassembly of focal adhesions and resulted in the redistribution of paxillin to the peri-nuclear region.

Respiration is a complex activity. If the relationship between all neurological and skeletomuscular interactions was perfectly understood, an accurate dynamic model of the respiratory system could be developed and the interaction between different inputs and outputs could be investigated in a straightforward fashion. Unfortunately, this is not the case and does not appear to be viable at this time. In addition, the provision of appropriate sensor signals for such a model would be a considerable invasive task. Useful quantitative information with respect to respiratory performance can be gained from non-invasive monitoring of chest and abdomen motion. Currently available devices are not well suited in application for spirometric measurement for ambulatory monitoring. A sensor matrix measurement technique is investigated to identify suitable sensing elements with which to base an upper body surface measurement device that monitors respiration. This thesis is divided into two main areas of investigation; model based and geometrical based surface plethysmography. In the first instance, chapter 2 deals with an array of tactile sensors that are used as progression of existing and previously investigated volumetric measurement schemes based on models of respiration. Chapter 3 details a non-model based geometrical approach to surface (and hence volumetric) profile measurement. Later sections of the thesis concentrate upon the development of a functioning prototype sensor array. To broaden the application area the study has been conducted as it would be fore a generically configured sensor array. In experimental form the system performance on group estimation compares favourably with existing system on volumetric performance. In addition provides continuous transient measurement of respiratory motion within an acceptable accuracy using approximately 20 sensing elements. Because of the potential size and complexity of the system it is possible to deploy it as a fully mobile ambulatory monitoring device, which may be used outside of the laboratory. It provides a means by which to isolate coupled physiological functions and thus allows individual contributions to be analysed separately. Thus facilitating greater understanding of respiratory physiology and diagnostic capabilities. The outcome of the study is the basis for a three-dimensional surface contour sensing system that is suitable for respiratory function monitoring and has the prospect with future development to be incorporated into a garment based clinical tool.