Thomas J. Lawley

Cutaneous Vasculitis: Its Relationship to Systemic Disease

Necrotizing vasculitis may be localized to the skin or may involve multiple organs. Although the etiology of cutaneous necrotizing vasculitis is unknown, evidence suggests that circulating immune complexes play an important role. The most common clinical lesion seen is palpable purpura, which histologically demonstrates leukocytoclastic vasculitis. The majority of patients affected with cutaneous necrotizing vasculitis have a benign course.

Antigen presentation by a continuous human microvascular endothelial cell line, HMEC-1, to human T cells

Endothelial cells line the vessels and lymphatics of the body, acting as a barrier between the blood and extravascular tissue. These cells are, therefore, in a prime position to play a role in lymphocyte activation. Indeed, it has been shown that primary endothelial cells in culture are capable of presenting particulate and soluble antigens to T cells and that this response is not dependent on macrophages. Recently, we developed an immortalized line of human microvascular endothelial cells, CDC/EU.HMEC-1 (HMEC-1). This endothelial line has the advantage not only of being devoid of contaminating cells but also of being a continuous cell line and therefore not subject to a restricted number of useful passages. The focus of this study was to determine whether HMEC-1 cells (like primary endothelial cells) could present antigen to T cells in the absence of macrophages. We demonstrate that a cloned and purified endothelial cell line can independently provide all the necessary signals for antigen-specific T-cell activation.

Use of a Human Microvascular Endothelial Cell Line as a Model System to Evaluate Cholesterol Uptake

CDC/EU.HMEC-1 (HMEC-1) cells provide a reliable source of human microvascular endothelial cells free of mycoplasma and viral infection. This cell line has potential for use in the further study of the endothelial cell modification of low-density lipoproteins and for anticholesterol drug evaluation assays. HMEC-1 cells will fill a gap that is present for in vitro investigations of cholesterol metabolism in conjunction with previously established hepatic, monocytic, or macrophage cell lines. This paper presents a simple assay that demonstrates a linear uptake of tritiated cholesterol by he HMEC-1 cells and shows that the cellular cholesterol load can be regulated using anticholesterol drugs.

Role of Leaders in Fostering Meaningful Collaborations Between Academic Medical Centers and Industry While Also Managing Individual and Institutional Conflicts of Interest

Over at least the past 20 years, putative and real conflicts of interest (COI) at academic medical centers have been featured prominently in the lay press, often with reputational damage to individuals and institutions.1 The heightened focus of concern about alleged financial payments to physicians and academic institutions by pharmaceutical and device companies, coupled with increasing concern by medical students (most notably in the American Medical Student Association scorecard, which gave grades to medical schools ranging from A to F based on how well they performed in avoiding conflicts of interest with the pharmaceutical industry) shone a bright light on individual and institutional integrity.

The role of adhesion molecules in cutaneous inflammation.

The integrity and function of all tissues depend on the ability of their resident cells as well as cells that migrate through them to interact with each other and with matrix proteins in the tissues. These interactions rely in part on the regulated expression of cell adhesion molecules. Cell adhesion molecules are cell surface proteins, glycoproteins, or carbohydrates that play important roles in a wide variety of physiologic and pathophysiologic processes. These include inflammation, wound healing, tumor metastases, cell growth, development and differentiation, immunological responses, and leukocyte trafficking, among others. Cell adhesion molecules interact with their ligands (counterreceptors) on other cells or on structural proteins and allow binding to occur. These molecules have been the focus of tremendous scientific interest and effort in the last decade. The biochemical, functional, and molecular characterization of numerous cell adhesion molecules has enhanced our understanding of important physiologic and pathophysiologic processes that involve cell-cell and cell-matrix binding. This review will focus on a series of cell adhesion molecules relevant to the normal functioning of cutaneous cells or to the evolution of the inflammatory response in skin diseases. Selected cell adhesion molecules will be discussed in regard to their categorization in specific families, their function, and their regulation.