The Journal of investigative dermatology
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J. Invest. Dermatol. · Jun 1994
ReviewEpidemiologic approaches to the study of toxic epidermal necrolysis.
The appropriate epidemiologic strategy for studying the etiology of toxic epidermal necrolysis is determined by the characteristics of the disease, particularly its rarity and the fact that it is caused by numerous drugs. Although information about drugs as risk factors can in principal be obtained from case reports and experimental studies, the former are subject to bias and the latter are impractical because toxic epidermal necrolysis is so rare. Cohort studies are also impractical because of the rarity of the outcome. ⋯ As of June, 1993, 459 cases and 1299 controls have been enrolled. At the scheduled end of data collection in 1995, the projected totals are 691 cases and 1956 controls. These large numbers will allow for the detailed evaluation of even relatively uncommonly used drugs, for the evaluation of more commonly used drugs in relation to subtypes of toxic epidermal necrolysis/Stevens-Johnson syndrome, and for the comparison of results between countries.
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J. Invest. Dermatol. · Jun 1994
Expression of 72-kDa gelatinase (MMP-2), collagenase (MMP-1), and tissue metalloproteinase inhibitor (TIMP) in primary pig skin fibroblast cultures derived from radiation-induced skin fibrosis.
In addition to producing matrix degradation for normal tissue remodeling and repair, matrix metalloproteinases (MMPs) are also involved in various pathologic processes. MMPs and the tissue inhibitor of MMPs (TIMP) were investigated in primary cultures of pig fibroblasts from radiation-induced dermal fibrosis and compared to normal dermal fibroblasts. The free gelatinolytic, collagenolytic, and caseinolytic activities secreted into the culture medium were evaluated against specific 3H denatured collagen type I, native helical collagen, and casein alpha, respectively. ⋯ These results indicate that in addition to accumulating large amounts of collagen, proteoglycans, and fibronectin, pig fibroblasts from radiation-induced dermal fibrosis also promote connective tissue matrix formation by repressing MMP-1 and stimulating TIMP expression at the transcriptional level, and by reducing overall free MMP and catheptic collagenolytic activities at the post-transcriptional level. In contrast, enzymography assays and automated image analysis demonstrated no significant change in the 72-kDa type IV collagenase activity of fibrotic pig skin fibroblasts. This opposite regulation of 72-kDa collagenase type IV to that of MMP-1 seems to indicate that it has a specific role in remodeling the extracellular matrix during wound healing, fibrogenesis, and angiogenesis.