Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0039483 (giant cell arteritis)
 3,204 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Giant cell arteritis (GCA) is a relatively common granulomatous arteritis of unknown etiology which mainly occurs in elderly people. Using histopathological findings from-seven biopsy cases of temporal artery and one autopsy case of GCA, and performing immunocytochemical staining for matrix metalloproteinase (MMP)-2 and -9 and tissue inhibitor of matrix metalloproteinase (TIMP)-1 and -2, we tested the hypothesis that an imbalance between MMPs and TIMPs may be a critical determinant in developing severe intimal hyperplasia and luminal stenosis. All biopsy cases revealed nearly complete luminal occlusion of the temporal artery with active lymphocytic infiltrate, fragmentation of internal lamina and median elastic fibers. Four of seven cases revealed typical GCA. The autopsy case was systematically sampled for histological examination, revealing GCA in the ascending aorta, main branches of aorta and coronary artery. Immunocytochemical staining revealed intense staining for MMP-2 and -9 in fragmented media of the aorta and artery, and less positive staining for TIMP-1 and -2 at the MMP-positive media. In situ hybridization revealed intense positive staining for TIMPs in GCA despite weak immunocytochemical staining for TIMPs. Control cases were negative for TIMPs by immunocytochemical staining whereas RNA message level was mildly positive at a lesser intensity than that of GCA. Granulomatous tissue of fibroblasts and giant cells were most intensely positive for MMPs. The presence of markedly increased MMPs and less increased TIMPs in GCA may implicate an MMPs-TIMPs imbalance in the pathogenesis of GCA.
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PMID:Matrix metalloproteinases and tissue inhibitors of metalloproteinases in giant cell arteritis: an immunocytochemical study. 953 7

Among matrix metalloproteinases (MMPs), the subfamily of gelatinases (MMP-2, MMP-9) is of particular interest due to their ability to degrade type IV collagen and other non-fibrillar collagen domains and proteins such as fibronectin and laminin. Whilst malignant cells often over-express various MMPs, the gelatinases have been most consistently detected in malignant tissues and associated with tumor growth, metastatic potential and angiogenesis. Radiosynthesis of carboxylic (1') and hydroxamic (2') MMPIs resulted in radiochemical yields of 70 +/- 5% (n = 6) and 60 +/- 5% (n = 4), respectively. Evaluation in A549-inoculated athymic mice showed a tumor uptake of 2. 0+/- 0.7%ID/g (3 h p.i.), a tumor/blood ratio of 0.5 and a tumor/muscle ratio of 4.6 at 48 h p.i. for 1'. For compound 2' a tumor uptake of 0.7 +/- 0.2%ID/g (3 h p.i.), a tumor/blood ratio of 1.2 and a tumor/muscle ratio of 1.8 at 24 h p.i. were observed. HPLC analysis of the blood (plasma) showed no dehalogenation or other metabolites of 1' 2 h p.i. For compound 2', 65.4% of intact compound was found in the blood (plasma) and one polar metabolite (31%) was detected whereas in the tumor 91.8% of the accumulated activity was caused by intact compound and only 8.1% by the metabolite. Planar imaging, using a Toshiba GCA-9300A/hg SPECT camera, showed that tumor tissue could be visualized and that image quality improved by decreasing specific activity resulting in lower liver uptake, indicating some degree of saturable binding in the liver. In vivo evaluation of these radioiodinated carboxylic and hydroxamic MMP inhibitor tracers revealed that MMP inhibitors could have potential as tumor imaging agents, but that further research is necessary.
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PMID:Valine-based biphenylsulphonamide matrix metalloproteinase inhibitors as tumor imaging agents. 1654 98