http://hdl.handle.net/10027/28 Tue, 21 May 2013 05:04:20 GMT 2013-05-21T05:04:20Z http://hdl.handle.net/10027/9849 **not published** Low-Dose Irradiation and Constrained Revision for Severe, Idiopathic, Arthrofibrosis Following Totatl Knee Arthroplasty Farid, Yasser; Thakral, Rishi; Finn, Henry Treatment options for arthrofibrosis following total knee arthroplasty include manipulation under anesthesia, open or arthroscopic arthrolysis, and revision surgery to correct identifiable problems. We propose preoperative low-dose irradiation and Constrained Condylar or Rotating-hinge revision for severe, idiopathic arthrofibrosis. Irradiation may decrease fibro-osseous proliferation while constrained implants allow femoral shortening and release of contracted collateral ligaments. Fourteen patients underwent fifteen procedures for a mean overall motion of 46 degrees and flexion contracture of 30 degrees. One patient had worsening range of motion while thirteen patients had 57 degrees mean gain in range of motion (range 5-90 degrees). Flexion contractures decreased by a mean of 28 degrees. There were no significant complications at a mean follow up of 34 months (range 24 to 74 months). NOTICE: This is the author’s version of a work that was accepted for publication in Journal of Arthroplasty. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Journal of Arthroplasty, 2013] DOI: 10.1016/j.arth.2012.11.009 Fri, 01 Mar 2013 06:00:00 GMT http://hdl.handle.net/10027/9849 2013-03-01T06:00:00Z http://hdl.handle.net/10027/9848 Particulate matter air pollution disrupts endothelial cell barrier via calpain-mediated tight junction protein degradation Wang, Ting; Wang, Lichun; Moreno-Vinasco, Liliana; Lang, Gabriel D.; Siegler, Jessica H.; Mathew, Biji; Usatyuk, Peter V.; Samet, Jonathan M.; Geyh, Alison S.; Breysse, Patrick N.; Natarajan, Viswanathan; Garcia, Joe G. N. BACKGROUND: Exposure to particulate matter (PM) is a significant risk factor for increased cardiopulmonary morbidity and mortality. The mechanism of PM-mediated pathophysiology remains unknown. However, PM is proinflammatory to the endothelium and increases vascular permeability in vitro and in vivo via ROS generation. OBJECTIVES: We explored the role of tight junction proteins as targets for PM-induced loss of lung endothelial cell (EC) barrier integrity and enhanced cardiopulmonary dysfunction. METHODS: Changes in human lung EC monolayer permeability were assessed by Transendothelial Electrical Resistance (TER) in response to PM challenge (collected from Ft. McHenry Tunnel, Baltimore, MD, particle size >0.1 μm). Biochemical assessment of ROS generation and Ca2+ mobilization were also measured. RESULTS: PM exposure induced tight junction protein Zona occludens-1 (ZO-1) relocation from the cell periphery, which was accompanied by significant reductions in ZO-1 protein levels but not in adherens junction proteins (VE-cadherin and β-catenin). N-acetyl-cysteine (NAC, 5 mM) reduced PM-induced ROS generation in ECs, which further prevented TER decreases and atteneuated ZO-1 degradation. PM also mediated intracellular calcium mobilization via the transient receptor potential cation channel M2 (TRPM2), in a ROS-dependent manner with subsequent activation of the Ca2+-dependent protease calpain. PM-activated calpain is responsible for ZO-1 degradation and EC barrier disruption. Overexpression of ZO-1 attenuated PM-induced endothelial barrier disruption and vascular hyperpermeability in vivo and in vitro. CONCLUSIONS: These results demonstrate that PM induces marked increases in vascular permeability via ROS-mediated calcium leakage via activated TRPM2, and via ZO-1 degradation by activated calpain. These findings support a novel mechanism for PM-induced lung damage and adverse cardiovascular outcomes. © 2012 Wang et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The original version is available through BioMed Central at DOI: 10.1186/1743-8977-9-35.. Wed, 01 Aug 2012 05:00:00 GMT http://hdl.handle.net/10027/9848 2012-08-01T05:00:00Z http://hdl.handle.net/10027/9845 Statins as a novel therapeutic strategy in acute lung injury Singla, Sunit; Jacobson, Jeffrey R. Acute lung injury (ALI) is a devastating clinical condition associated with pulmonary and systemic inflammation and characterized by incompetence of the pulmonary microvascular barrier culminating in noncardiogenic pulmonary edema. An understanding of the mechanisms underlying endothelial barrier dysfunction in ALI has been facilitated by study of the effects of statins in relevant cellular and animals models. Many of the pleotropic properties of these drugs, including direct effects on endothelial cell (EC) cytoskeletal rearrangement, NADPH oxidase, and nitric oxide activity, as well as effects on differential EC gene expression, are relevant to the pathobiology of ALI and suggest a potential therapeutic role for statins in this context. Moreover, results from preclinical studies and observations in relevant patient populations support the protective potential of statins in ALI, paving the way now for definitive clinical trials. This is a copy of an article published in the Pulmonary Circulation © 2012 Medknow Publications Mon, 01 Oct 2012 05:00:00 GMT http://hdl.handle.net/10027/9845 2012-10-01T05:00:00Z http://hdl.handle.net/10027/9641 Early, nonciliary role for microtubule proteins in left-right patterning is conserved across kingdoms Lobikin, Maria; Wang, Gang; Xu, Jing-Song; Hsieh, Yi-Wen; Chuang, Chiou-Fen; Lemire, Joan M.; Levin, Michael Many types of embryos’ bodyplans exhibit consistently-oriented laterality of the heart, viscera, and brain. Errors of left-right patterning present an important class of human birth defects, and considerable controversy exists about the nature and evolutionary conservation of the molecular mechanisms that allow embryos to reliably orient the left-right axis. Here we show that the same mutations in the cytoskeletal protein tubulin that alter asymmetry in plants also affect very early steps of left-right patterning in nematode and frog embryos, as well as chirality of human cells in culture. In the frog embryo, tubulin α and tubulin γ-associated protein are required for the differential distribution of maternal proteins to the left or right blastomere at the first cell division. Our data reveal a remarkable molecular conservation of mechanisms initiating left-right asymmetry. The origin of laterality is cytoplasmic, ancient, and highly conserved across kingdoms – a fundamental feature of the cytoskeleton that underlies chirality in cells and multicellular organisms. This is a copy of an article published in the Proceedings of the National Academy of Sciences © 2012 National Academy of Sciences. The final publication is available at www.pnas.org/ doi: 10.1073/pnas.1202659109 Tue, 31 Jul 2012 05:00:00 GMT http://hdl.handle.net/10027/9641 2012-07-31T05:00:00Z