The goals of this research are to gain a better understanding of the organization and ultrastructure of the normal human cutaneous microcirculation so that it may be applied to dermatoses in which the microvasculature plays a significant role such as psoriasis, diabetes mellitus, sun damage and telangiectases. We intend to reconstruct the 3-dimensional relationships between the elements of the microvascular unit (endothelial cell, pericyte, mural basement membrane material, mast cell and veil cell) by a computer graphics system of our own design. We shall study the 3-dimensional configuration of the myofilamentous bundles in the endothelial cells and see how they relate to the surrounding elastic fiber network and whether they participate in vasodilatation and vasoconstriction. We will map out the lymphatic capillary network in relation to the blood vascular system and we shall investigate whether there are vascular fields produced in the dermis by the microvasculature. Using human and psoriatic skin grafted onto Nude mice; we will study the differentiated microdomains on the endothelial surface with tracers as the initial studies of macromolecular transport in the human microvasculature. We plan to measure cutaneous blood flow by laser Doppler velocimetry in psoriatic lesions under therapy to correlate flow with ultrastructural changes in the capillary loops, labeling index of basal cells and histologic features to further study the modulating effect of the microvasculature on the initiation and regression of psoriatic lesions. We shall also be studying the morphological events in the development of the endothelial cell gaps in psoriatic vessels and in histamine activated venules. We shall be reconstructing in 3-dimensions a variety of common vascular abnormalities in order to learn more about their organization.
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