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146 results on '"Esmon, Naomi L."'

8. Extracellular histones are major mediators of death in sepsis

Author

Xu, Jun, Zhang, Xiaomei, Pelayo, Rosana, Monestier, Marc, Ammollo, Concetta T., Semeraro, Fabrizio, Taylor, Fletcher B., Esmon, Naomi L., Lupul, Florea, and Esmon, Charles T.

Subjects
Histones -- Health aspects, Sepsis -- Patient outcomes, Biological sciences, Health
Abstract

Hyperinflammatory responses can lead to a variety of diseases, including sepsisl. We now report that extracellular histones released in response to inflammatory challenge contribute to endothelial dysfunction, organ failure and death during sepsis. They can be targeted pharmacologically by antibody to histone or by activated protein C (APC). Antibody to histone reduced the mortality of mice in lipopolysaccharide (LPS), tumor necrosis factor (TNF) or cecal ligation and puncture models of sepsis. Extracellular histones are cytotoxic toward endothelium in vitro and are lethal in mice. In vivo, histone administration resulted in neutrophil margination, vacuolated endothelium, intra-alveolar hemorrhage and macro- and microvascular thrombosis. We detected histone in the circulation of baboons challenged with Escherichia coli, and the increase in histone levels was accompanied by the onset of renal dysfunction. APC cleaves histones and reduces their cytotoxicity. Co-infusion of APC with E. coli in baboons or histones in mice prevented lethality. Blockade of protein C activation exacerbated sublethal LPS challenge into lethality, which was reversed by treatment with antibody to histone. We conclude that extracellular histones are potential molecular targets for therapeutics for sepsis and other inflammatory diseases., Macrophage activation leads to production of several mediators, including TNF and high-mobility group box-1 protein (HMGB1), that contribute to the severity of sepsis(l). Recombinant human APC is approved by the [...]

Published
2009

9. Thrombomodulin mutations in atypical hemolytic-uremic syndrome

Author

Delvaeye, Mieke, Noris, Marina, De Vriese, Astrid, Esmon, Charles T., Esmon, Naomi L., Ferrell, Gary, Del-Favero, Jurgen, Plaisance, Stephane, Claes, Bart, Lambrechts, Dieter' Zoja, carla, Remuzzi, Guiseppe, and Conway. Edward M.

Subjects
Anticoagulants (Medicine) -- Health aspects, Gene mutations -- Analysis, Glycoproteins -- Health aspects, Glycoproteins -- Research, Hemolytic-uremic syndrome -- Genetic aspects, Hemolytic-uremic syndrome -- Care and treatment, Protein binding -- Analysis
Abstract

A study was conducted to determine the effects of thrombomodulin which is an endothelial glycoprotein with anticoagulant, anti-inflammatory and cytoprotective properties in cases with gene mutations manifesting atypical hemolytic-uremic condition. Results revealed that mutations in genes affect the functioning of thrombomodulin in some patients who manifest hemolytic-uremic syndrome.

Published
2009

11. The effect of membrane composition on the hemostatic balance

Author

Smirnov, Michael D., Ford, David A., Esmon, Charles T., and Esmon, Naomi L.

Subjects
Protein C -- Research, Phospholipids -- Research, Prothrombin -- Research, Membranes (Biology) -- Analysis, Biological sciences, Chemistry
Abstract

A study was conducted to analyze the phospholipid composition requirements for maximum prothrombin activation and factor Va inactivation by activated protein C anticoagulant. A three-stage assay was utilized to examine factor Va inactivation. Results indicated that changes in the phospholipid composition of cells can influence procoagulant and anticoagulant reactions under normal and pathological environments.

Published
1999

12. Factor VIIa/tissue factor generates a form of factor V with unchanged specific activity, resistance to activation by thrombin, and increased sensitivity to activated protein C

Author

Safa, Omid, Morrissey, James H., Esmon, Charles T., and Esmon, Naomi L.

Subjects
Tissues -- Research, Proteins -- Research, Proteolysis -- Research, Thrombin -- Research, Biological sciences, Chemistry
Abstract

A study was conducted to analyze factor V as an additional substrate for the tissue factor/VIIa complex. SDS-PAGE was carried out with the gradient acrylamide gels using the Laemmli buffer system. Factor V coagulant activity was then assayed in a one-stage clotting assay using factor V-deficient human plasma. Results indicated that the modified factor V would be resistant to activation by the low levels of thrombin in the extravascular tissue.

Published
1999

17. Ca2+ dependence of the interactions between protein C, thrombin, and the elastase fragment of thrombomodulin. Analysis by ultracentrifugation

Author

Olsen, Philip H., Esmon, Naomi L., Esmon, Charles T., and Laue, Thomas M.

Subjects
Protein C -- Research, Thrombin -- Research, Centrifuges -- Usage, Biological sciences, Chemistry
Abstract

The interactions between protein C, thrombin and the elastase fragment of rabbit thrombomodulin (elTM) were examined by analytical ultracentrifugation. The role of the protein C Gla domain in the interaction ofprotein C with thrombin and elTM was also examined by direct binding experiments and by competition studies. It was demonstrated that Ca2+ is not required for complex formation and that activated protein C is a potent inhibitor of protein C activation. Moreover, the results suggest that the Gla domain may be involved directly in the binding of protein C to both thrombin and elTM.

Published
1992

28. Neutrophil Extracellular Traps Drive Bleomycin-Induced Lung Fibrosis by Regulating TGF beta 1-Dependent Interactions of Platelets and Macrophages

Author

Riehl, Dennis R., Roewe, Julian, Klebow, Sabrina, Esmon, Naomi L., Eming, Sabine, Colucci, Giuseppe, Schaefer, Katrin, Gunzer, Matthias, Waisman, Ari, Ward, Peter A., Esmon, Charles T., Bosmann, Markus, Riehl, Dennis R., Roewe, Julian, Klebow, Sabrina, Esmon, Naomi L., Eming, Sabine, Colucci, Giuseppe, Schaefer, Katrin, Gunzer, Matthias, Waisman, Ari, Ward, Peter A., Esmon, Charles T., and Bosmann, Markus

Published
2016

29. Neutrophil Extracellular Traps Drive Bleomycin‐Induced Lung Fibrosis by Regulating TGFβ1‐Dependent Interactions of Platelets and Macrophages

Author

Riehl, Dennis R., primary, Roewe, Julian, additional, Klebow, Sabrina, additional, Esmon, Naomi L., additional, Eming, Sabine, additional, Colucci, Giuseppe, additional, Schäfer, Katrin, additional, Gunzer, Matthias, additional, Waisman, Ari, additional, Ward, Peter A., additional, Esmon, Charles T., additional, and Bosmann, Markus, additional

Published
2016
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31. Inhibition of endogenous activated protein C attenuates experimental autoimmune encephalomyelitis by inducing myeloid-derived suppressor cells1

Author

Alabanza, Leah M., Esmon, Naomi L., Esmon, Charles T., and Bynoe, Margaret S.

Subjects
CD4-Positive T-Lymphocytes, CD11b Antigen, Encephalomyelitis, Autoimmune, Experimental, Multiple Sclerosis, Arginase, Antibodies, Monoclonal, Nitric Oxide Synthase Type II, Mice, Transgenic, Lymphocyte Activation, T-Lymphocytes, Regulatory, Article, Immunophenotyping, Disease Models, Animal, Mice, Animals, Myeloid Cells, Reactive Oxygen Species, Protein C
Abstract

Activated protein C (PC) is an anticoagulant involved in the interactions between the coagulation and immune systems. Activated PC has broad anti-inflammatory effects that are mediated through its ability to modulate leukocyte function and confer vascular barrier protection. We investigated the influence of activated PC on the pathogenesis of experimental autoimmune encephalomyelitis (EAE), the animal model for multiple sclerosis. We modulated activated PC levels in the circulation during EAE induction through systemic administration of a mAb against PC/activated PC (anti-PC). We initially hypothesized that inhibition of activated PC may result in a heightened inflammatory environment, leading to increased EAE pathogenesis. Contrary to this hypothesis, mice treated with anti-PC Ab (anti-PC mice) exhibited attenuated EAE. Interestingly, despite reduced disease severity and minimal pathogenic conditions in the CNS, anti-PC mice exhibited considerable leukocyte infiltration in the brain, comparable to control mice with severe EAE. Furthermore, CD4(+) T cells were diminished in the periphery of anti-PC mice, whereas various CD11b(+) populations were increased, notably the myeloid-derived suppressor cells (MDSCs), a CD11b(+) subset characterized as potent T cell suppressors. MDSCs from anti-PC mice exhibited increased expression of T cell suppressive factors and effectively inhibited T cell proliferation. Overall, our findings show that activated PC inhibition affected EAE pathogenesis at multiple fronts, specifically increasing vascular barrier permeability, as evidenced by considerable leukocyte infiltration in the brain. Additionally, inhibition of activated PC modulated the functional responses of CD11b(+) cells, leading to the expansion and increased activation of MDSCs, which are suppressive to the CD4(+) T cells required for EAE progression, thereby resulting in attenuated EAE.

Published
2013

33. Extracellular histones are mediators of death through TLR2 and TLR4 in mouse fatal liver injury1

Author

Xu, Jun, Zhang, Xiaomei, Monestier, Marc, Esmon, Naomi L., and Esmon, Charles T.

Subjects
Histones, Male, Mice, Inbred C57BL, Mice, Knockout, Toll-Like Receptor 4, Disease Models, Animal, Mice, Liver, Blotting, Western, Animals, Article, Systemic Inflammatory Response Syndrome, Toll-Like Receptor 2
Abstract

We previously reported that extracellular histones are major mediators of death in sepsis. Infusion of extracellular histones leads to increased cytokine levels. Histones activate TLR 2 and 4 in a process that is enhanced by binding to DNA. Activation of TLR4 is responsible for the histone dependent increase in cytokine levels. To study the impact of histone release on pathology we used two models: a concanavalin A (ConA) triggered activation of T cells to mimic sterile inflammation and acetaminophen (APAP), to model drug induced tissue toxicity. Histones were released in both models and anti-histone antibodies were protective. TLR 2 or TLR 4 null mice were also protected. These studies imply that histone release contributes to death in inflammatory injury and in chemical induced cellular injury, both of which are mediated in part through the toll-like receptors.

Published
2011

42. Safety and efficacy of anti-human activated protein C antibody SR604 for prophylaxis of congenital factor deficiencies

Author

Jiang, Miao, Yang, Fei, Jiang, Yizhi, Cheng, Lu, Han, Jingjing, Yi, Jiawei, Zuo, Bin, Huang, Lulu, Ma, Zhenni, Li, Tianyi, Cao, Lijuan, Xia, Zhisong, Bai, Xia, Jia, Chenjun, Yang, Teddy Tat Chi, Esmon, Naomi L., Ruan, Changgeng, Xia, Lijun, Esmon, Charles T., Han, Yue, Wu, Depei, and Xu, Jun

Abstract

1.We engineered a high affinity antibody, SR604, that selectively blocks the anticoagulant activity of human activated protein C (APC).2.SR604 exhibited prophylactic and therapeutic efficacy in hemophilia A and B mice expressing human APC.

Published
2023
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44. The Protein C Pathway: New Insights

Author

Esmon, Charles T, additional, Ding, Wei, additional, Yasuhiro, Katsuura, additional, Gu, Jian-Ming, additional, Ferrell, Gary, additional, Regan, Lisa M, additional, Stearns-Kurosawa, Deborah J, additional, Kurosawa, Shimichiro, additional, Mather, Timothy, additional, Laszik, Zolton, additional, and Esmon, Naomi L, additional

Published
1997
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45. Contributors

Author

Abrahm, Janet L., Abrams, Charles S., Abrams, Donald I., Ackerman, Steven J., Adams, Sharon, Adewoye, Adeboye H., Allen, Carl, Ambinder, Richard F., Anasetti, Claudio, Anastasi, John, Anderson, Julia A., Andreeff, Michael, Antin, Joseph H., Antony, Aśok C., Apostolakis, Stavros, Armstrong, Scott A., Arnold, Donald M., Artz, Andrew S., Awan, Farrukh T., Banchereau, Jacques, Barker, Juliet N., Baum, Linda G., Benson, Don M., Jr., Benz, Edward J., Jr., Berliner, Nancy, Bhagat, Govind, Bhalla, Kapil N., Bhardwaj, Nina, Bhatia, Ravi, Bhatia, Smita, Blinderman, Craig D., Bollard, Catherine M., Brenner, Malcolm K., Brittenham, Gary M., Brodsky, Robert A., Broxmeyer, Hal E., Brummel-Ziedins, Kathleen, Buadi, Francis K., Butterfield, Joseph H., Byrd, John C., Caimi, Paolo F., Caligiuri, Michael A., Campagnaro, Erica, Canaani, Jonathan, Canavan, Michelle, Cantor, Alan B., Carcao, Manuel, Carroll, Michael C., Carty, Shannon A., Champlin, Richard E., Chan, Anthony K.C., Choate, Jacquelyn D., Chung, Peter, Chute, John P., Cines, Douglas B., Clark, David B., Coates, Thomas D., Cogle, Christopher R., Connell, Nathan T., Cooke, Elizabeth, Cooley, Sarah, Corradini, Paolo, Creager, Mark A., Creger, Richard J., Cromwell, Caroline, Cunningham, Regina S., Cushing, Melissa M., Cutler, Corey, Dahl, Gary V., Dang, Chi V., Danial, Nika N., Dave, Sandeep S., DeAngelo, Daniel J., Desai, Madhav V., Dey, Bimalangshu R., Diehl, Volker, Dinauer, Mary C., Diz-Küçükkaya, Reyhan, Donato, Michele L., Dorshkind, Kenneth, Dotti, Gianpietro, Dror, Yigal, Dunleavy, Kieron, Ebert, Benjamin L., Eck, Michael J., Eichenauer, Dennis A., Eikelboom, John W., Engert, Andreas, Ershler, William B., Esmon, Charles T., Esmon, Naomi L., Evans, William E., Faderl, Stefan, Ferrara, James L.M., Filipovich, Alexandra Hult, Freedman, Melvin H., Fuller, Stephen J., Gailani, David, Gallagher, Patrick G., Gardner, Lawrence B., Gee, Adrian P., Gerson, Stanton L., Gertz, Morie A., Giardina, Patricia J., Golan, Karin, Golub, Todd R., Gottschalk, Stephen, Grant, Steven, Green, David L., Gribben, John G., Guitart, Joan, Gur-Cohen, Shiri, Gurbuxani, Sandeep, Gutierrez, Alejandro, Hari, Parameswaran, Harlan, John M., Hartwig, John H., Hayman, Suzanne R., Hayward, Catherine P.M., Hebbel, Robert P., Heslop, Helen E., Hillyer, Christopher D., Hockenbery, David M., Hoffman, Ronald, Horowitz, Mary, Horwitz, Edwin M., Hromas, Robert A., Huang, Franklin W., Isenman, David E., Italiano, Joseph E., Jr., Jaffe, Elaine S., Jagannath, Sundar, Jäger, Ulrich, Jain, Nitin, James, Paula, Jeha, Sima, Jordan, Michael B., Josephson, Cassandra, Jung, Moonjung, Kager, Leo, Kamdar, Kala Y., Kanakry, Jennifer A., Kantarjian, Hagop M., Karafin, Matthew S., Karsan, Aly, Katz, Louis M., Kaufman, Randal J., Kaufman, Richard M., Keller, Frank G., Kelly, Kara M., Kelton, John, Kessler, Craig M., Key, Nigel S., Khandoga, Alexander G., Khanna-Gupta, Arati, Klein, Harvey G., Kollet, Orit, Konkle, Barbara A., Kontoyiannis, Dimitrios P., Koreth, John, Koretzky, Gary A., Kremyanskaya, Marina, Küppers, Ralf, Kuzel, Timothy M., Kwak, Larry W., Lakshmanan, Viswanathan, Landier, Wendy, Lapid, Kfir, Lapidot, Tsvee, Larson, Peter J., Lechner, Klaus, Lee, Andrea, Lee, William M.F., Levi, Marcel, Lewis, Russell E., Liebman, Howard A., Lillicrap, David, Lim, Wendy, Lin, Thomas S., Lindblad, Robert, Lip, Gregory Y.H., Little, Jane A., Loh, Mignon L., Look, A. Thomas, López, José A., Luscinskas, Francis W., Macartney, Christine A., Maciejewski, Jaroslaw P., Maitta, Robert W., Majhail, Navneet S., Manches, Olivier, Mandle, Robert, Mann, Kenneth G., Manno, Catherine S., Marchi, Enrica, Mariani, Guglielmo, Marincola, Francesco M., Marks, Peter W., Mascarenhas, John, Massberg, Steffen, Mauch, Peter M., McCorkle, Ruth, McCrae, Keith R., McEver, Rodger P., McGrath, Emer, McKinney, Matthew S., Meacham, Amy, Menitove, Jay E., Merlini, Giampaolo, Migliaccio, Anna Rita, Miller, Jeffrey S., Mims, Martha P., Mondoro, Traci Heath, Moorehead, Paul, Munshi, Nikhil C., Najfeld, Vesna, Nazi, Ishac, Neff, Anne T., Ness, Paul M., Ng, Andrea K., Notarangelo, Luigi D., O'Brien, Sarah H., O'Connor, Owen A., Donghaile, Diarmaid Ó, O'Donnell, Martin, Otis, Stavroula, Ou, Zhishuo, Pai, Sung-Yun, Palucka, Karolina, Pande, Reena L., Papayannopoulou, Thalia, Pardanani, Animesh, Paredes, Nethnapha, Patriquin, Christopher, Petersdorf, Effie W., Pittaluga, Stefania, Plow, Edward F., Ponce, Doris M., Popolo, Laura, Powell, Leland D., Price, Elizabeth A., Pui, Ching-Hon, Puigserver, Pere, Quintás-Cardama, Alfonso, Rak, Janusz, Ramos, Carlos A., Rand, Jacob H., Ravandi, Farhad, Rawlings, David J., Reddy, Pavan, Reding, Mark T., Rhee, Charles, Rice, Lawrence, Riese, Matthew J., Ritchey, Arthur Kim, Rivella, Stefano, Roberts, David J., Romaguera, Jorge E., Roman, Elizabeth, Rooney, Cliona M., Rosen, Steven T., Rosenthal, David S., Rosovsky, Rachel, Rowley, Scott D., Rydz, Natalia, Sadler, J. Evan, Sandlund, John T., Jr., Sauk, Steven, Saunthararajah, Yogen, Scadden, David, Schaefer, Kristen G., Schiffman, Fred J., Schmaier, Alvin H., Schrier, Stanley L., Schuchman, Edward H., Scullion, Bridget Fowler, Selvaggi, Kathy J., Shaheen, Montaser, Shaz, Beth H., Sheehan, Andrea M., Shelburne, Samuel A., Shlomchik, Mark J., Shurin, Susan B., Silberstein, Leslie E., Silberstein, Lev, Silverstein, Roy L., Sloan, Steven R., Smith, Franklin O., Smith, James, Snyder, Edward L., Soff, Gerald A., Spitzer, Thomas R., Steinberg, Martin H., Stock, Wendy, Stone, Richard M., Storry, Jill R., Strauss, Ronald G., Stroncek, David F., Szczepiorkowski, Zbigniew M., Tiu, Ramon V., Toltl, Lisa J., Toms, Angela, Tormey, Christopher A., Treon, Steven P., Tulpule, Anil, Vedantham, Suresh, Verneris, Michael R., Vichinsky, Elliott P., von Andrian, Ulrich H., Wagner, Andrew J., Wang, Ena, Wang, Jia-huai, Wang, Michael, Warkentin, Theodore E., Wasserstein, Melissa P., Wei, Michael C., Weinstein, Howard J., Weisdorf, Daniel J., Weitz, Jeffrey I., Westhoff, Connie M., Wiley, James S., Williams, David A., Wilson, Wyndham H., Wolfe, Joanne, Wolgast, Lucia R., Wood, Deborah, Wu, YanYun, Yee, Donald L., Young, Ken H., Young, Neal S., Zeldenrust, Steven R., Zhang, Liang, and Zhou, Ming-Ming

Published
2013
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