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Arthritis and rheumatism (1)
BMJ Case Reports (1)
Miller, Mary-Clare (2)
Bowles, Philippe (1)
Cartwright, Samuel (1)
Dudhia, Jayesh (1)
Essex, David (1)
Itoh, Yoshifumi (1)
Jain, Abhilash (1)
Jones, Martin (1)
Manning, Hugh B. (1)
Nagase, Hideaki (1)
Nanchahal, Jagdeep (1)
Sandison, Ann (1)
Seiki, Motoharu (1)
Troeberg, Linda (1)
Year of Publication
Presentation of Mycobacterium abscessus infection following rhytidectomy to a UK plastic surgery unit
BMJ Case Reports
We report the presentation of a patient to a UK plastic surgery unit with Mycobacterium abscessus infection following a facelift surgery in Southern India. Treatment was protracted requiring surgical debridement and 6 months of antibiotics including a 3-week hospital admission for intravenous antibiotic therapy. We describe the clinical presentation, diagnosis and treatment of this unusual microorganism with reference to more familiar pyogenic infections.
MT1-MMP is a crucial promotor of synovial invasion in human rheumatoid arthritis
Manning, Hugh B.
Arthritis and rheumatism
A hallmark of rheumatoid arthritis (RA) is invasion of the synovial pannus into cartilage and this step requires degradation of the collagen matrix. The aim of this study was to explore the role of one of the collagen-degrading matrix metalloproteinases (MMPs), membrane-type 1 MMP (MT1-MMP), in synovial pannus invasiveness.
Expression and localization of MT1-MMP in human RA pannus were investigated by Western blot analysis of primary synovial cells and immunohistochemistry of RA joints specimens. The functional role of MT1-MMP was analyzed by 3D collagen invasion assays and a cartilage invasion assay in the presence or absence of tissue inhibitor of metalloproteinase (TIMP)-1, TIMP-2, or GM6001. The effect of adenoviral expression of a dominant negative MT1-MMP construct lacking a catalytic domain was also examined.
MT1-MMP was highly expressed at the pannus-cartilage junction of RA joints. Freshly isolated rheumatoid synovial tissues and isolated RA synovial fibroblasts invaded into a 3D collagen matrix in an MT1-MMP-dependent manner. Invasion was blocked by TIMP-2 and GM6001, but not by TIMP-1. It was also inhibited by the over-expression of a dominant negative MT1-MMP which inhibits collagenolytic activity and proMMP-2 activation by MT1-MMP on the cell surface. Synovial fibroblasts also invaded into cartilage in an MT1-MMP-dependent manner. This process was further enhanced by removing aggrecan from the cartilage matrix.
MT1-MMP is an essential collagen-degrading proteinase during pannus invasion in human RA. Specific inhibition of MT1-MMP-dependent invasion may form a novel therapeutic strategy for RA.
MT1-MMP; synovial pannus; rheumatoid arthritis
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