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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
MeSH Review


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Disease relevance of Sepsis


Psychiatry related information on Sepsis


High impact information on Sepsis

  • Treatment of human diseases with recombinant human IL-1Ra showed an absence of benefit in sepsis syndrome [11].
  • Dysfunction of endothelial protein C activation in severe meningococcal sepsis [12].
  • Plasma thrombomodulin levels in the children with meningococcal sepsis (median, 6.4 ng per liter) were higher than those in the controls (median, 3.6 ng per liter; P=0.002) [12].
  • Recombinant human activated protein C for severe sepsis [13].
  • METHODS: We assessed the integrity of the endothelium and the expression of thrombomodulin and the endothelial protein C receptor in biopsy specimens of purpuric lesions from 21 children with meningococcal sepsis (median age, 41 months), as compared with control skin-biopsy specimens [12].

Chemical compound and disease context of Sepsis


Biological context of Sepsis


Anatomical context of Sepsis


Gene context of Sepsis

  • Neutralization of proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha) or interleukin-1 (IL-1), decreases mortality in several animal models of sepsis [29].
  • Mice lacking neutrophil elastase reveal impaired host defense against gram negative bacterial sepsis [30].
  • Here we report a mutation in a gene coding for a putative transmembrane protein, PGRP-LC, which reduces survival to Gram-negative sepsis but has no effect on the response to Gram-positive bacteria or natural fungal infections [31].
  • Destructive mutations of Tlr4 predispose to the development of Gram-negative sepsis, leaving most aspects of immune function intact [32].
  • These data implicate IL-10 as a candidate for treatment of bacterial sepsis, and more generally as an effective antiinflammatory reagent [33].
  • Treatment with transcutaneous vagus nerve stimulation inhibited HMGB1 levels and improved survival in mice with polymicrobial sepsis, even when administered 24 hrs after the onset of disease [34].
  • Our data suggest that a tandem repeat polymorphism (AC)n at position -665 in the CXCL2 gene may be an independent predictor of mortality for severe sepsis [35].
  • Orally administered probiotics prevented liver and intestinal damage in a mouse model of sepsis through a PPARgamma-dependent mechanism [36].

Analytical, diagnostic and therapeutic context of Sepsis

  • In animal models, inhibition of cyclooxygenase by treatment with ibuprofen before the onset of sepsis reduces physiologic abnormalities and improves survival [16].
  • Longitudinal studies of anti-P activity in two patients with psychosis revealed that anti-P levels increased before and during the active phases of psychosis but not during sepsis or other exacerbations of SLE, and that the elevations were selective for anti-P antibodies, as opposed to anti-DNA antibodies [37].
  • Notably, blockade of TREM-1 protects mice against LPS-induced shock, as well as microbial sepsis caused by live Escherichia coli or caecal ligation and puncture [38].
  • The preliminary results of clinical trials in humans indicate possible efficacy of IL-1ra in sepsis syndrome, rheumatoid arthritis, and GVHD [39].
  • In an attempt to understand their biologic basis of action, we used a fluid-phase radioimmunoassay to measure binding between bacterial lipopolysaccharide (LPS) and two IgM mAbs directed to lipid A that are being evaluated for the treatment of gram-negative bacterial sepsis [40].


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  11. Interleukin-1 receptor antagonist: role in biology. Arend, W.P., Malyak, M., Guthridge, C.J., Gabay, C. Annu. Rev. Immunol. (1998) [Pubmed]
  12. Dysfunction of endothelial protein C activation in severe meningococcal sepsis. Faust, S.N., Levin, M., Harrison, O.B., Goldin, R.D., Lockhart, M.S., Kondaveeti, S., Laszik, Z., Esmon, C.T., Heyderman, R.S. N. Engl. J. Med. (2001) [Pubmed]
  13. Recombinant human activated protein C for severe sepsis. Ott, A., Verbrugh, H.A. N. Engl. J. Med. (2001) [Pubmed]
  14. Double-blind comparison of the nephrotoxicity and auditory toxicity of gentamicin and tobramycin. Smith, C.R., Lipsky, J.J., Laskin, O.L., Hellmann, D.B., Mellits, E.D., Longstreth, J., Lietman, P.S. N. Engl. J. Med. (1980) [Pubmed]
  15. Ibuprofen in patients with sepsis. Zimmerli, W., Widmer, A.F. N. Engl. J. Med. (1997) [Pubmed]
  16. The effects of ibuprofen on the physiology and survival of patients with sepsis. The Ibuprofen in Sepsis Study Group. Bernard, G.R., Wheeler, A.P., Russell, J.A., Schein, R., Summer, W.R., Steinberg, K.P., Fulkerson, W.J., Wright, P.E., Christman, B.W., Dupont, W.D., Higgins, S.B., Swindell, B.B. N. Engl. J. Med. (1997) [Pubmed]
  17. Medication errors with inhalant epinephrine mimicking an epidemic of neonatal sepsis. Solomon, S.L., Wallace, E.M., Ford-Jones, E.L., Baker, W.M., Martone, W.J., Kopin, I.J., Critz, A.D., Allen, J.R. N. Engl. J. Med. (1984) [Pubmed]
  18. High-dose corticosteroids in patients with the adult respiratory distress syndrome. Bernard, G.R., Luce, J.M., Sprung, C.L., Rinaldo, J.E., Tate, R.M., Sibbald, W.J., Kariman, K., Higgins, S., Bradley, R., Metz, C.A. N. Engl. J. Med. (1987) [Pubmed]
  19. Angiopoietin-2 is increased in severe sepsis: correlation with inflammatory mediators. Orfanos, S.E., Kotanidou, A., Glynos, C., Athanasiou, C., Tsigkos, S., Dimopoulou, I., Sotiropoulou, C., Zakynthinos, S., Armaganidis, A., Papapetropoulos, A., Roussos, C. Crit. Care Med. (2007) [Pubmed]
  20. TREM-1: a new regulator of innate immunity in sepsis syndrome. Nathan, C., Ding, A. Nat. Med. (2001) [Pubmed]
  21. Inhibition of intestinal epithelial apoptosis and survival in a murine model of pneumonia-induced sepsis. Coopersmith, C.M., Stromberg, P.E., Dunne, W.M., Davis, C.G., Amiot, D.M., Buchman, T.G., Karl, I.E., Hotchkiss, R.S. JAMA (2002) [Pubmed]
  22. Tumor necrosis factor-alpha blockade prevents neutrophil CD18 receptor upregulation and attenuates acute lung injury in porcine sepsis without inhibition of neutrophil oxygen radical generation. Windsor, A.C., Walsh, C.J., Mullen, P.G., Cook, D.J., Fisher, B.J., Blocher, C.R., Leeper-Woodford, S.K., Sugerman, H.J., Fowler, A.A. J. Clin. Invest. (1993) [Pubmed]
  23. Interleukin 1 inhibits contraction of vascular smooth muscle. Beasley, D., Cohen, R.A., Levinsky, N.G. J. Clin. Invest. (1989) [Pubmed]
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  25. Protective effects of C5a blockade in sepsis. Czermak, B.J., Sarma, V., Pierson, C.L., Warner, R.L., Huber-Lang, M., Bless, N.M., Schmal, H., Friedl, H.P., Ward, P.A. Nat. Med. (1999) [Pubmed]
  26. Lipid IVA inhibits synthesis and release of tumor necrosis factor induced by lipopolysaccharide in human whole blood ex vivo. Kovach, N.L., Yee, E., Munford, R.S., Raetz, C.R., Harlan, J.M. J. Exp. Med. (1990) [Pubmed]
  27. Induction of diaphragmatic nitric oxide synthase after endotoxin administration in rats: role on diaphragmatic contractile dysfunction. Boczkowski, J., Lanone, S., Ungureanu-Longrois, D., Danialou, G., Fournier, T., Aubier, M. J. Clin. Invest. (1996) [Pubmed]
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  29. Monocyte deactivation in septic patients: restoration by IFN-gamma treatment. Döcke, W.D., Randow, F., Syrbe, U., Krausch, D., Asadullah, K., Reinke, P., Volk, H.D., Kox, W. Nat. Med. (1997) [Pubmed]
  30. Mice lacking neutrophil elastase reveal impaired host defense against gram negative bacterial sepsis. Belaaouaj, A., McCarthy, R., Baumann, M., Gao, Z., Ley, T.J., Abraham, S.N., Shapiro, S.D. Nat. Med. (1998) [Pubmed]
  31. The Drosophila immune response against Gram-negative bacteria is mediated by a peptidoglycan recognition protein. Gottar, M., Gobert, V., Michel, T., Belvin, M., Duyk, G., Hoffmann, J.A., Ferrandon, D., Royet, J. Nature (2002) [Pubmed]
  32. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Poltorak, A., He, X., Smirnova, I., Liu, M.Y., Van Huffel, C., Du, X., Birdwell, D., Alejos, E., Silva, M., Galanos, C., Freudenberg, M., Ricciardi-Castagnoli, P., Layton, B., Beutler, B. Science (1998) [Pubmed]
  33. Interleukin 10 protects mice from lethal endotoxemia. Howard, M., Muchamuel, T., Andrade, S., Menon, S. J. Exp. Med. (1993) [Pubmed]
  34. Transcutaneous vagus nerve stimulation reduces serum high mobility group box 1 levels and improves survival in murine sepsis. Huston, J.M., Gallowitsch-Puerta, M., Ochani, M., Ochani, K., Yuan, R., Rosas-Ballina, M., Ashok, M., Goldstein, R.S., Chavan, S., Pavlov, V.A., Metz, C.N., Yang, H., Czura, C.J., Wang, H., Tracey, K.J. Crit. Care Med. (2007) [Pubmed]
  35. A CXCL2 polymorphism is associated with better outcomes in patients with severe sepsis. Villar, J., Pérez-Méndez, L., Flores, C., Maca-Meyer, N., Espinosa, E., Muriel, A., Sangüesa, R., Blanco, J., Muros, M., Kacmarek, R.M. Crit. Care Med. (2007) [Pubmed]
  36. Probiotic bacteria prevent hepatic damage and maintain colonic barrier function in a mouse model of sepsis. Ewaschuk, J., Endersby, R., Thiel, D., Diaz, H., Backer, J., Ma, M., Churchill, T., Madsen, K. Hepatology (2007) [Pubmed]
  37. Association between lupus psychosis and anti-ribosomal P protein antibodies. Bonfa, E., Golombek, S.J., Kaufman, L.D., Skelly, S., Weissbach, H., Brot, N., Elkon, K.B. N. Engl. J. Med. (1987) [Pubmed]
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  39. Interleukin-1 receptor antagonist. Arend, W.P. Adv. Immunol. (1993) [Pubmed]
  40. Assessment of ability of murine and human anti-lipid A monoclonal antibodies to bind and neutralize lipopolysaccharide. Warren, H.S., Amato, S.F., Fitting, C., Black, K.M., Loiselle, P.M., Pasternack, M.S., Cavaillon, J.M. J. Exp. Med. (1993) [Pubmed]
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