Until the early l940's the field or protein-carbohydrate complexes was largely neglected by chemists. This fact is not surprising when one considers that typical examples of substances containing these complexes are saliva, serum, gastric mucin or better still frog spawn mucin and jellyfish protoplasm. Adequate yields of homogenous materiel, from these sources, were difficult to obtain partly because of their high degree or hydration. [...]

No description available.

No description available.

Tiam1 (for T-lymphoma invasion and metastasis-inducing protein) belongs to the Rho GEF family of proteins. In response to growth factors and cell-substrate interactions, Tiam1 selectively activates Rac. Using a two stage chemical carcinogenesis protocol (DMBA/TPA) it was previously shown that mice lacking Tiam1 are resistant to the development of Ras-induced skin tumours, suggestmg an important role for Tiam1/Rac signalling in tumourigenesis in vivo.

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The starting point of this investigation was the clinical observation that raw areas of the body resurfaced by split-thickness skin grafts contract markedly, whereas those covered by thick grafts (e.g. Wolfe grafts) contract little or not at all. The reason for this behaviour is unknown. The present work was an attempt to investigate this behaviour using fibroblasts cultured in a hydrated collagen lattice (FHCL) as a laboratory model for wound contraction in vivo. Sequential extracts of normal human dermis were prepared in water, 0.15M sodium chloride, 1M sodium chloride, 0.15M citrate buffer (pH 3.5) and 6M urea, and their effects on FHCL contraction were examined. Only citrate buffer dermal extract had a marked inhibitory effect on FHCL contraction. The effect was reversible, concentration-dependent and lasted throughout the course of the 96 hours' experiments. There was no toxic effect on the cells although their proliferation within the lattices was also inhibited. Furthermore the extracts from the deeper parts of the dermis have more inhibitory effect on the FHCL contraction than those from the more superficial layers. Preliminary attempts to characterise the citrate buffer dermal extract biochemically showed the presence of protein and proteoglycans or glycosaminoglycans with a range of molecular weights showed by gel electrophoresis, and the presence of collagen was excluded by amino acid analysis. This study shows that there is a biochemical factor (factors) present in the dermis which inhibits the ability of fibroblasts to cause lattice contraction. This factor (s) can be extracted by citrate buffer. The inhibitory effect of the citrate buffer dermal extract on lattice contraction is due to inhibition of both fibroblasts proliferation and migration.

I investigated the effect of inhibiting NO production in the psoriatic plaque. A 70% inhibition of NO was attained but overall there was no clinical benefit in 17 patients whereas with topical steroids benefit was very apparent with only 12 subjects. Immunocytochemical examination of these patients revealed a 50% reduction in endothelial cells, following L-NMMA treatment, supporting an important effect of NO in angiogenesis. ICAM-1 was also suppressed and there was an increase in CD8 positive cells and Langerhans' cells following L-NMMA. Surprisingly there was no inhibition of keratinocyte proliferation with L-NMMA. It is possible that some of the immunosuppressive effects of NO were inhibited, thus promoting some aspects of psoriasis at the same time as inhibiting others. Finally the direct effects of NO on normal skin were examined using acidified nitrite as a topically applied NO donor. In keeping with the observations in psoriasis there was a reduction in Langerhans' cells which lost dendricity and migrated from the epidermis. This suggests that NO may have some role in activating Langerhans's cells and thereby in antigen presentation. NO increased the adhesion molecules ICAM-1 and VCAM-1, attracting increased numbers of macrophages, T cells and neutrophils but had no effect on mast cell numbers. There was a tendency for higher doses of NO to produce lower levels of cellular infiltration, suggesting an immunosuppressive effect of higher doses. Nitrosotyrosine staining was not marked, suggesting only minor formation of peroxynitrite and this led to recoverable cytotoxicity manifesting as cloudy swelling of keratinocytes. There was some increase in wild type p53 in basal keratinocytes. Associated with this was an increase in apoptosis which was modest but manifested in the epidermis and dermis and was greater with the duration of exposure to NO. There was a high background level of cell proliferation and these cells were no more numerous in the NO treated skin than in the normal skin. However, there were significantly more proliferating cells in skin exposed to the higher dose of NO than those exposed to low dose suggesting that NO may promote keratinocyte proliferation at certain concentrations.

No description available.

No description available.

During the past five years a study has been made of the electrical properties of human skin in vivo both experimentally and theoretically, seeking to make a coherent whole out of the very diverse phenomenology reported in the very scattered literature. A Fourier transform method was used, employing novel electronic techniques and four non-invasive electrodes on the subject to separately determine the properties of the stratum corneum and the deeper tissues. Both linear and non-linear, A.C. and D.C. properties were investigated in this way, and the wide perspective obtained has made it possible to re-interpret the findings of previous workers and so assemble a self-consistent model of nearly all the known electrical properties of human skin. The main conclusions of this work are that: (a) The small-signal A.C. impedance properties of skin are extremely well fitted by a minor arc of a circle on the complex impedance plane, and the depression of the centre of the circle below the equivalent series resistance axis is very significantly greater in psoriatic skin and in hyper-hydrated normal skin. (b) This behaviour cannot be adequately interpreted by any extant physical model of skin, but can be adequately interpreted by considering the stratum corneum to be an inhomogeneous or amorphous semiconductor. (c) The semiconductivity of human skin has been demonstrated both in vitro and in vivo, and was found to have activation enthalpies averaging 0.46 eV (10.63 kcal/mole). (d) These insights into the mechanisms of electrical charge transport through skin may suggest new ways of characterizing the properties of skin using methods developed for the semiconductor industry. (e) The results in the literature of "phoreography" should be re-interpreted, with much greater emphasis being placed on the properties of the skin appendages.