Characterising pattern asymmetry in pigmented skin lesions

Abstract. In clinical diagnosis of pigmented skin lesions asymmetric pigmentation is often indicative of melanoma. This paper describes a method and measures for characterizing lesion symmetry. The estimate of mirror symmetry is computed first for a number of axes at different degrees of rotation with respect to the lesion centre. The statistics of these estimates are the used to assess the overall symmetry. The method is applied to three different lesion representations showing the overall pigmentation, the pigmentation pattern, and the pattern of dermal melanin. The best measure is a 100% sensitive and 96% specific indicator of melanoma on a test set of 33 lesions, with a separate training set consisting of 66 lesions

Expression and regulation of monocyte chemoattractant protein-3 (MCP-3) in fibrosis

Systemic sclerosis is a multisystem connective tissue disease characterised by skin thickening and widespread, but variable, visceral fibrosis. The aetiopathogenesis is likely to involve immunological activation and microvascular dysfunction leading to excessive accumulation of extracellular matrix (ECM) with increased production of collagen type I in lesional tissues. This implies a dysregulated repair process probably as a consequence of aberrant crosstalk between fibroblasts and inflammatory cells. It has been proposed that a hierarchical cascade of soluble mediators in which initial induction of proinflammatory cytokines expressed by the inflammatory infiltrate may lead to expression of profibrotic mediators including TGFβ. A salient feature of the inflammatory response is directional migration of leucocytes into subendothelial tissues orchestrated by chemokines in a spatially and temporally-regulated multistep process. Work described in this thesis explores the expression of chemokine, monocyte chemoattractant protein-3 (MCP-3/CCL7) in SSc and in murine models for SSc: type 1 tight skin mouse (Tsk1) and a transgenic mouse strain (TβRIIΔk) in which there is fibroblast-directed disruption of TGFβ signalling. The hypothesis that crosstalk between MCP-3 and TGFβ may modulate the signalling response in the fibrotic microenvironment was also explored. Overexpression of MCP-3 was demonstrated on cDNA expression profiling and protein analysis of neonatal Tsk1 and TβRIIΔk fibroblasts. This was supported by immunohistochemical studies on dermal tissues. Similar upregulation dermal patterns of MCP-3 protein expression were observed in the early stage of diffuse cutaneous SSc. Activation of collagen reporter genes by MCP-3 in transgenic mouse fibroblasts and wildtype neonatal mouse fibroblasts harbouring proα2(Ι)collagen promoter reporter gene constructs is mediated via sequences within the proximal promoter and is partly dependent on TGFβ. This coinduction between the two factors in the fibrotic response is also demonstrated by activation of TGFβ signalling pathways by MCP-3 leading to type I collagen secretion. In addition, MCP-3 gene expression is stimulated by TGFβ. Comparison of downstream signalling pathways that regulate collagen gene activation by both cytokines confirms the central role of MAPK pathway activation in mediating the effects of both factors. An additive effect of these two agonists was demonstrated for key TGFβ-regulated genes on comparative microarray analysis. Overall, these results demonstrate that overexpression of MCP-3 is a key biochemical feature of early stage SSc and murine models of SSc, and suggest a novel role for this chemokine as a profibrotic mediator in addition to its role in regulating leucocyte recruitment. Furthermore, there is a potentially important interplay between MCP-3 and TGFβ in modulation of the signalling response in the fibrotic microenvironment.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Fractal vasculature and vascular network growth modeling in normal and tumor tissue

Thesis (Ph. D.)--Massachusetts Institute of Technology, Whitaker College of Health Sciences and Technology, 1996.Includes bibliographical references (p. 177-187).by Yuval Gazit.Ph.D

Glaucoma

This book addresses the basic and clinical science of glaucomas, a group of diseases that affect the optic nerve and visual fields and is usually accompanied by increased intraocular pressure. The book incorporates the latest development as well as future perspectives in glaucoma, since it has expedited publication. It is aimed for specialists in glaucoma, researchers, general ophthalmologists and trainees to increase knowledge and encourage further progress in understanding and managing these complicated diseases

Enhancement of Temporally Variable Features in Nailfold Capillary Patterns

Analysis of the condition of blood capillaries in the nailfold is complicated by the fact that gaps in the flow of blood cells results in temporal variability in their appearance. At a single instant the capillaries may be incomplete, but integration of the information from several successive video frames renders the whole capillary visible. This paper shows that combining the information from the video frame sequence by subtracting a multiple of the standard deviation from the mean value for each pixel, improves the signal to noise ratio of variable features when compared with the mean image or using minimum projection