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Kwan Tat S Pelletier JP Lajeunesse D Fahmi H Lavigne M Martel-Pelletier J 《Clinical and experimental rheumatology》2008,26(2):295-304
OBJECTIVE: We previously reported that human OA subchondral bone osteoblasts could be discriminated into two subpopulations identified by their levels of endogenous production (low [L] or high [H]) of PGE(2). Here, we investigated the OPG and RANKL expression levels, the histologic analysis of the subchondral bone as well as the osteoclast differentiation effect of osteoblasts on normal and both OA subpopulations (L and H), and further examined on the L OA osteoblasts the modulation of bone remodelling factors on the OPG and RANKL levels, as well as on the resorption activity. METHODS: Gene expression was determined using real-time PCR, PGE2 and OPG levels by specific ELISA, and membranous RANKL by flow cytometry. Histological observation of the subchondral bone was performed on human knee specimens. Osteoclast differentiation and formation was assayed by using the pre-osteoclastic cell line RAW 264.7. OPG and RANKL modulation on L OA osteoblasts was monitored following treatment with osteotropic factors, and the resorption activity was studied by the co-culture of differentiated PBMC/osteoblasts. RESULTS: Human OA subchondral bone osteoblasts expressed less OPG than normal. Compared to normal, RANKL gene expression levels were increased in L OA and decreased in H OA cells. The OPG/RANKL mRNA ratio was significantly diminished in L OA compared to normal or H OA (p<0.02, p<0.03), and markedly increased in H OA compared to normal. Inhibition of endogenous PGE(2) levels by indomethacin markedly decreased the ratio of OPG/RANKL on the H OA. In contrast to H OA osteoblasts, L OA cells induced a significantly higher level of osteoclast differentiation and formation (p<0.05).Histological analysis showed a reduced subchondral bone on the L OA and an increased bone mass on the H OA compared to normal. Treatment of L OA osteoblasts with osteotropic factors revealed that the OPG/RANKL mRNA expression ratio was significantly reduced by vitamin D(3) and significantly increased by TNF-alpha, PTH and PGE(2), while IL-1Beta demonstrated no effect. OPG protein levels showed similar profiles. No true effect was noted on membranous RANKL upon treatment with IL-1Beta, PGE(2) and PTH, but a significant increase was observed with vitamin D3 and TNF-alpha. The resorption activity of the L OA cells was significantly inhibited by all treatments except IL-1Beta, with maximum effect observed with vitamin D(3) and PGE(2). CONCLUSION: OPG and RANKL levels, and consequently the OPG/RANKL ratio, differed according to human OA subchondral bone osteoblast classification; it is decreased in L and increased in H OA. These findings, in addition to those showing that L OA osteoblasts have a reduced subchondral bone mass and induce a higher level of osteoclast differentiation, strongly suggest that the metabolic state of the L OA osteoblasts favours bone resorption. 相似文献
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Efficacy of artesunate + sulphadoxine/pyrimethamine and artemether + lumefantrine and dhfr and dhps mutations in Somalia: evidence for updating the malaria treatment policy 下载免费PDF全文
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Fahmi J. Farah Christopher D. Chiles 《Texas Heart Institute journal / from the Texas Heart Institute of St. Luke's Episcopal Hospital, Texas Children's Hospital》2014,41(5):543-546
Primary malignant cardiac lymphomas associated with grafts are extremely rare: to our knowledge, only 6 cases of prosthesis-associated B-cell lymphoma have been reported. Ours is the first report of recurrent diffuse large B-cell lymphoma associated with aortic valve allografts.We treated a 60-year-old man who presented in early 2007 with aortic valve endocarditis. He underwent aortic valve replacement with an allograft; the resected native valve showed active endocarditis without tumor. In January 2011, the patient underwent repeat aortic valve replacement because of symptomatic aortic regurgitation. The explanted valve specimen displayed diffuse large B-cell lymphoma. In September 2011, the patient presented with fever and a mass around the aortic valve. He died in January 2012. On autopsy, the explanted replacement valve displayed recurrent diffuse large B-cell lymphoma. The recurrent lymphoma on a new graft leads us to believe that this tumor is more aggressive than had been thought. We propose early systemic chemotherapy, in addition to tumor resection, for the possibility of a better prognosis. We discuss our patient''s case and review the relevant medical literature. 相似文献
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Torsten Pietsch Ezzeldin Metwalli Stephan Volker Roth Ronald Gebhardt Nabil Gindy Peter Müller‐Buschbaum Amir Fahmi 《Macromolecular chemistry and physics.》2009,210(10):864-878
Herein we explore the possibility to control the fabrication of non‐equilibrium nano‐patterns of spin‐coated organic‐inorganic hybrid materials based on diblock copolymers and metal nanoparticles in thin films. It is demonstrated that the type of solvent and the initial solution concentration, among other factors, can serve as tools to direct the morphology of spin‐coated thin films. The driving forces leading to the pattern formation are reviewed with respect to these parameters—type of solvents and polymer concentration. As a result well‐defined surface patterns of functional hybrid materials are obtained. Moreover, the same tools used to direct the pattern formation can be applied to gain control over the particle size and size distribution.
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Farrajota K Cheng S Martel-Pelletier J Afif H Pelletier JP Li X Ranger P Fahmi H 《Arthritis and rheumatism》2005,52(1):94-104