Limited number of studies that directly measure reactive species or oxidative stress in patients with ARDS are presently. A major limitation for measuring reactive species is their short half life in biological systems. Since reactive species modify biological molecules such as proteins, lipids and DNA, measurement of the modified targets provide the experimental tools for their detection and quantification. Protein carbonyls are derived by the direct oxidation of amino acid residues or conjugation of aldehydes that are formed by the oxidation of unsaturated lipids or sugars. Overall plasma protein carbonyls indicate the formation of oxidants. Nitration of protein tyrosine residues results in the formation of 3-nitrotyrosine. Previous we found that the reaction of peroxynitrate with C02 provides the necessary nitrating agent that explains the formation of plasm protein 3-nitrotyrosine. Peroxynitrate is formed by the nearly diffusion limited reaction of nitric oxide and superoxide. Urinary isoprostanes are generated by reactive species attack on arachidonate in lipid bilayers and is selective and sensitive indicator of lipid peroxidation. Therefore, the main function of the analytical chemistry core (Core C) is to measure the levels of modified plasma proteins (carbonyls and 3-nitrotyrosine) and urinary isoprostanes in the human samples for Project 3. Protein carbonyls will be also measured in cell lysates, lung tissue, perfusate and plasma in samples generated in Project 4. Core C will also function as a central processing, storage and distribution facility for the samples collected in Project 3. The analytical chemistry will be located at the Institute for Environmental Medicine. Strengths of Core C include the established protocols for clinical specimen collection, processing and storage, the experience of the investigators with measuring these biological markers and the understanding of the biochemical origin of these biological markers.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Specialized Center (P50)
Project #
5P50HL060290-02
Application #
6202610
Study Section
Project Start
1999-09-01
Project End
2000-08-31
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Type
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Ferguson, Jane F; Meyer, Nuala J; Qu, Liming et al. (2015) Integrative genomics identifies 7p11.2 as a novel locus for fever and clinical stress response in humans. Hum Mol Genet 24:1801-12
Reilly, John P; Meyer, Nuala J; Shashaty, Michael G S et al. (2014) ABO blood type A is associated with increased risk of ARDS in whites following both major trauma and severe sepsis. Chest 145:753-761
Chatterjee, Shampa; Nieman, Gary F; Christie, Jason D et al. (2014) Shear stress-related mechanosignaling with lung ischemia: lessons from basic research can inform lung transplantation. Am J Physiol Lung Cell Mol Physiol 307:L668-80
Reilly, John P; Bellamy, Scarlett; Shashaty, Michael G S et al. (2014) Heterogeneous phenotypes of acute respiratory distress syndrome after major trauma. Ann Am Thorac Soc 11:728-36
Shashaty, Michael G S; Kalkan, Esra; Bellamy, Scarlett L et al. (2014) Computed tomography-defined abdominal adiposity is associated with acute kidney injury in critically ill trauma patients*. Crit Care Med 42:1619-28
Meyer, Nuala J; Feng, Rui; Li, Mingyao et al. (2013) IL1RN coding variant is associated with lower risk of acute respiratory distress syndrome and increased plasma IL-1 receptor antagonist. Am J Respir Crit Care Med 187:950-9
Christie, Jason D; Wurfel, Mark M; Feng, Rui et al. (2012) Genome wide association identifies PPFIA1 as a candidate gene for acute lung injury risk following major trauma. PLoS One 7:e28268
Holena, Daniel N; Netzer, Giora; Localio, Russell et al. (2012) The association of early transfusion with acute lung injury in patients with severe injury. J Trauma Acute Care Surg 73:825-31
Meyer, Nuala J; Daye, Zhongyin John; Rushefski, Melanie et al. (2012) SNP-set analysis replicates acute lung injury genetic risk factors. BMC Med Genet 13:52
Tejera, Paula; Meyer, Nuala J; Chen, Feng et al. (2012) Distinct and replicable genetic risk factors for acute respiratory distress syndrome of pulmonary or extrapulmonary origin. J Med Genet 49:671-80

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