Richard S Hotchkiss

Summary

Affiliation: Washington University School of Medicine
Country: USA

Publications

  1. ncbi Overexpression of Bcl-2 in transgenic mice decreases apoptosis and improves survival in sepsis
    R S Hotchkiss
    Department of Anesthesiology, Howard Hughes Medical Institute, Washington University School of Medicine, St Louis, MO 63110, USA
    J Immunol 162:4148-56. 1999
  2. ncbi Role of apoptotic cell death in sepsis
    Richard S Hotchkiss
    Department of Anesthesiology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Scand J Infect Dis 35:585-92. 2003
  3. ncbi The pathophysiology and treatment of sepsis
    Richard S Hotchkiss
    Department of Anesthesiology, Washington University School of Medicine, St Louis, MO 63110, USA
    N Engl J Med 348:138-50. 2003
  4. ncbi Depletion of dendritic cells, but not macrophages, in patients with sepsis
    Richard S Hotchkiss
    Department of Anesthesiology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA
    J Immunol 168:2493-500. 2002
  5. pmc Adoptive transfer of apoptotic splenocytes worsens survival, whereas adoptive transfer of necrotic splenocytes improves survival in sepsis
    Richard S Hotchkiss
    Department of Anesthesiology, Washington University School of Medicine, St Louis, MO 63110, USA
    Proc Natl Acad Sci U S A 100:6724-9. 2003
  6. ncbi Sepsis-induced apoptosis causes progressive profound depletion of B and CD4+ T lymphocytes in humans
    R S Hotchkiss
    Department of Anesthesiology, Washington University School of Medicine, 660 South Euclid, St Louis, MO 63110, USA
    J Immunol 166:6952-63. 2001
  7. ncbi Caspase inhibitors improve survival in sepsis: a critical role of the lymphocyte
    R S Hotchkiss
    Department of Anesthesiology, Washington University School of Medicine, St Louis, MO 63110, USA
    Nat Immunol 1:496-501. 2000
  8. ncbi Rapid onset of intestinal epithelial and lymphocyte apoptotic cell death in patients with trauma and shock
    R S Hotchkiss
    Department of Anesthesiology, Washington University School of Medicine, St Louis, MO, USA
    Crit Care Med 28:3207-17. 2000
  9. ncbi Apoptotic cell death in patients with sepsis, shock, and multiple organ dysfunction
    R S Hotchkiss
    Department of Anesthesiology, Washington University School of Medicine, St Louis, MO 63110, USA
    Crit Care Med 27:1230-51. 1999
  10. ncbi p53-dependent and -independent pathways of apoptotic cell death in sepsis
    R S Hotchkiss
    Department of Anesthesiology, Washington University School of Medicine, St Louis, MO 63110, USA
    J Immunol 164:3675-80. 2000

Detail Information

Publications86

  1. ncbi Overexpression of Bcl-2 in transgenic mice decreases apoptosis and improves survival in sepsis
    R S Hotchkiss
    Department of Anesthesiology, Howard Hughes Medical Institute, Washington University School of Medicine, St Louis, MO 63110, USA
    J Immunol 162:4148-56. 1999
    ..We conclude that overexpression of Bcl-2 provides protection against cell death in sepsis. Lymphocyte death may be detrimental in sepsis by compromising host defense...
  2. ncbi Role of apoptotic cell death in sepsis
    Richard S Hotchkiss
    Department of Anesthesiology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Scand J Infect Dis 35:585-92. 2003
    ..This new understanding of sepsis may lead to novel therapeutic approaches including pharmacological agents that block apoptosis...
  3. ncbi The pathophysiology and treatment of sepsis
    Richard S Hotchkiss
    Department of Anesthesiology, Washington University School of Medicine, St Louis, MO 63110, USA
    N Engl J Med 348:138-50. 2003
  4. ncbi Depletion of dendritic cells, but not macrophages, in patients with sepsis
    Richard S Hotchkiss
    Department of Anesthesiology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA
    J Immunol 168:2493-500. 2002
    ..The dramatic loss of DCs in sepsis may significantly impair B and T cell function and contribute to the immune suppression that is a hallmark of the disorder...
  5. pmc Adoptive transfer of apoptotic splenocytes worsens survival, whereas adoptive transfer of necrotic splenocytes improves survival in sepsis
    Richard S Hotchkiss
    Department of Anesthesiology, Washington University School of Medicine, St Louis, MO 63110, USA
    Proc Natl Acad Sci U S A 100:6724-9. 2003
    ..Necrotic cells (and likely apoptotic cells) exert their effects via modulation of IFN-gamma..
  6. ncbi Sepsis-induced apoptosis causes progressive profound depletion of B and CD4+ T lymphocytes in humans
    R S Hotchkiss
    Department of Anesthesiology, Washington University School of Medicine, 660 South Euclid, St Louis, MO 63110, USA
    J Immunol 166:6952-63. 2001
    ..Similar loss of lymphocytes may be occurring in critically ill patients with other disorders...
  7. ncbi Caspase inhibitors improve survival in sepsis: a critical role of the lymphocyte
    R S Hotchkiss
    Department of Anesthesiology, Washington University School of Medicine, St Louis, MO 63110, USA
    Nat Immunol 1:496-501. 2000
    ..Thus, caspase inhibitors enhance immunity by preventing lymphocyte apoptosis and lymphocytes act rapidly, within 24 h, to control infection...
  8. ncbi Rapid onset of intestinal epithelial and lymphocyte apoptotic cell death in patients with trauma and shock
    R S Hotchkiss
    Department of Anesthesiology, Washington University School of Medicine, St Louis, MO, USA
    Crit Care Med 28:3207-17. 2000
    ..The purpose of this study was to determine whether apoptosis is a major mechanism of cell death in intestinal epithelial cells and lymphocytes in patients who sustained trauma, shock, and ischemia/ reperfusion injury...
  9. ncbi Apoptotic cell death in patients with sepsis, shock, and multiple organ dysfunction
    R S Hotchkiss
    Department of Anesthesiology, Washington University School of Medicine, St Louis, MO 63110, USA
    Crit Care Med 27:1230-51. 1999
    ..The purpose of this study was to determine whether apoptosis is a major mechanism of cell death in patients with sepsis. The activities of caspase-3 and the antiapoptotic protein, BCL-2, were investigated also...
  10. ncbi p53-dependent and -independent pathways of apoptotic cell death in sepsis
    R S Hotchkiss
    Department of Anesthesiology, Washington University School of Medicine, St Louis, MO 63110, USA
    J Immunol 164:3675-80. 2000
    ..The fact that p53-/- lymphocytes of an identical subtype (CD8-CD4+) were protected in thymi but not in spleens indicates that cell susceptibility to apoptosis differs depending upon other unidentified factors...
  11. pmc Prevention of lymphocyte cell death in sepsis improves survival in mice
    R S Hotchkiss
    Department of Anesthesiology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA
    Proc Natl Acad Sci U S A 96:14541-6. 1999
    ..Caspase inhibitors may represent a treatment strategy in this highly lethal disorder...
  12. pmc IL-15 prevents apoptosis, reverses innate and adaptive immune dysfunction, and improves survival in sepsis
    Shigeaki Inoue
    Department of Anesthesiology, Washington University School of Medicine, St Louis, MO 63110, USA
    J Immunol 184:1401-9. 2010
    ..IL-15 represents a potentially novel therapy of this highly lethal disorder...
  13. ncbi High-dose exogenous iron following cecal ligation and puncture increases mortality rate in mice and is associated with an increase in gut epithelial and splenic apoptosis
    Pardis Javadi
    Department of Surgery, Washington University School of Medicine, St Louis, MO, USA
    Crit Care Med 32:1178-85. 2004
    ....
  14. pmc CD4+ lymphocytes control gut epithelial apoptosis and mediate survival in sepsis
    Paul E Stromberg
    Department of Surgery, Washington University School of Medicine, 660 South Euclid Ave, St Louis, MO 63110, USA
    FASEB J 23:1817-25. 2009
    ..Thus, sepsis unmasks CD4(+) lymphocyte control of gut apoptosis that is not present under homeostatic conditions, which acts as a key determinant of both cellular survival and host mortality...
  15. ncbi Surviving sepsis: bcl-2 overexpression modulates splenocyte transcriptional responses in vivo
    Tracey H Wagner
    Department of Anesthesiology, School of Medicine, Washington University in St Louis, St Louis, MO 63110, USA
    Am J Physiol Regul Integr Comp Physiol 292:R1751-9. 2007
    ..In addition, our data suggest that the ability of bcl-2 overexpression to improve survival in sepsis in this model is related in part to prevention of sepsis-induced alterations in spleen transcriptional responses...
  16. pmc Cancer causes increased mortality and is associated with altered apoptosis in murine sepsis
    Amy C Fox
    Departments of Surgery, Washington University School of Medicine, St Louis, MO, USA
    Crit Care Med 38:886-93. 2010
    ..Malignancy is the most common comorbidity associated with sepsis. The purpose of this study was to determine whether mice with cancer have a different response to sepsis than healthy animals...
  17. pmc Sigma-2 receptor ligands potentiate conventional chemotherapies and improve survival in models of pancreatic adenocarcinoma
    Hiroyuki Kashiwagi
    Department of Surgery, Washington University School of Medicine, 660 S, Euclid Avenue, Campus Box 8109, St, Louis, MO 63110, USA
    J Transl Med 7:24. 2009
    ..Here, we examined whether sigma-2 receptor ligands potentiate conventional chemotherapies such as gemcitabine and paclitaxel...
  18. pmc Streptococcus pneumoniae and Pseudomonas aeruginosa pneumonia induce distinct host responses
    Kevin W McConnell
    Departments of Surgery, Washington University School of Medicine, St Louis, MO, USA
    Crit Care Med 38:223-41. 2010
    ..The purpose of this study was to determine whether host response is similar after disparate infections with similar mortalities...
  19. ncbi Antibiotics improve survival and alter the inflammatory profile in a murine model of sepsis from Pseudomonas aeruginosa pneumonia
    Craig M Coopersmith
    Department of Surgery, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Shock 19:408-14. 2003
    ..These results indicate that both gentamicin and imipenem increase survival at least 10-fold in a model of pneumonia-induced monomicrobial sepsis, and this is predominantly associated with a down-regulation of proinflammatory cytokines...
  20. pmc Targeting AKT with the proapoptotic peptide, TAT-CTMP: a novel strategy for the treatment of human pancreatic adenocarcinoma
    Peter O Simon
    Department of Surgery, Washington University School of Medicine, St Louis, MO 63110, USA
    Int J Cancer 125:942-51. 2009
    ..001). These data indicate that inhibiting AKT with CTMP may be of therapeutic benefit in the treatment of pancreatic adenocarcinoma and, when combined with established therapies, may result in an increase in tumor cell death...
  21. pmc Mechanisms of decreased intestinal epithelial proliferation and increased apoptosis in murine acute lung injury
    Kareem D Husain
    Departments of Surgery, Washington University School of Medicine, St Louis, MO, USA
    Crit Care Med 33:2350-7. 2005
    ..The relationship between severity and timing of lung injury to intestinal pathology was also examined...
  22. ncbi Bim siRNA decreases lymphocyte apoptosis and improves survival in sepsis
    Steven J Schwulst
    Department of Surgery, Washington University School of Medicine, St Louis, MO 63110, USA
    Shock 30:127-34. 2008
    ..05). Treatment with Bim siRNA in vivo has the potential to be an effective therapy in the treatment of sepsis...
  23. pmc Characterization and modulation of the immunosuppressive phase of sepsis
    Jared T Muenzer
    Department of Pediatrics, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, Missouri 63110, USA
    Infect Immun 78:1582-92. 2010
    ..However, by 7 days post-CLP, the host's immune system has recovered sufficiently to mount an effective immune response. Modulation of the immunosuppressive phase of sepsis may aid in the development of new therapeutic strategies...
  24. pmc Intestine-specific overexpression of IL-10 improves survival in polymicrobial sepsis
    Saju Rajan
    Department of Surgery, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Shock 29:483-9. 2008
    ....
  25. pmc Sepsis induces extensive autophagic vacuolization in hepatocytes: a clinical and laboratory-based study
    Eizo Watanabe
    Department of Anesthesiology, Washington University School of Medicine, St Louis, MO 63110, USA
    Lab Invest 89:549-61. 2009
    ..However, it is not possible to determine whether the increase in autophagic vacuolization is an adaptive response or a harbinger of cell death...
  26. ncbi Agonistic monoclonal antibody against CD40 receptor decreases lymphocyte apoptosis and improves survival in sepsis
    Steven J Schwulst
    Department of Surgery, Washington University School of Medicine, St Louis, MO 63110, USA
    J Immunol 177:557-65. 2006
    ..05). In conclusion, anti-CD40 treatment increases Bcl-x(L), provides nearly complete protection against sepsis-induced lymphocyte apoptosis, and improves survival in sepsis...
  27. pmc Modulation of the Bcl-2 family blocks sepsis-induced depletion of dendritic cells and macrophages
    Octavia M Peck-Palmer
    Department of Anesthesiology, Washington University School of Medicine, St Louis, Missouri, USA
    Shock 31:359-66. 2009
    ..We conclude that sepsis induces a major depletion of developing M Phi as well as DCs, and this depletion may be an important mechanism of immune suppression in sepsis...
  28. doi Lymphocyte phenotyping to distinguish septic from nonseptic critical illness
    Steven J Schwulst
    Department of Surgery, Washington University School of Medicine, St Louis, MO, USA
    J Am Coll Surg 206:335-42. 2008
    ..In this study, we hypothesized that lymphocyte phenotype can distinguish between septic and nonseptic critical illness...
  29. ncbi Age disproportionately increases sepsis-induced apoptosis in the spleen and gut epithelium
    Isaiah R Turnbull
    Department of Surgery, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Shock 22:364-8. 2004
    ....
  30. ncbi Both gram-negative and gram-positive experimental pneumonia induce profound lymphocyte but not respiratory epithelial cell apoptosis
    Torsten Schreiber
    Department of Anesthesiology, Washington University School of Medicine, St Louis, MO, USA
    Shock 26:271-6. 2006
    ..Increased lymphocyte but not bronchial cell apoptosis occurs in both gram-positive and gram-negative pneumonia and probably involves both the extrinsic and intrinsic pathway...
  31. ncbi Inhibition of intestinal epithelial apoptosis and survival in a murine model of pneumonia-induced sepsis
    Craig M Coopersmith
    Department of Surgery, Washington University School of Medicine, 660 S Euclid Ave, Campus Box 8109, St Louis, MO 63110, USA
    JAMA 287:1716-21. 2002
    ..Increased intestinal epithelial apoptosis is present in both human autopsy studies and animal models of sepsis. Whether altering gut apoptosis decreases mortality in sepsis induced by pathogenic bacteria outside the gut is unknown...
  32. ncbi Bcl-2 inhibits gut epithelial apoptosis induced by acute lung injury in mice but has no effect on survival
    Kareem D Husain
    Department of Surgery, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Shock 20:437-43. 2003
    ....
  33. ncbi Sepsis induces apoptosis and profound depletion of splenic interdigitating and follicular dendritic cells
    Kevin W Tinsley
    Department of Anesthesiology, Washington University School of Medicine, St Louis, MO 63110, USA
    J Immunol 171:909-14. 2003
    ..IDC death occurred by caspase 3-mediated apoptosis. Such profound apoptosis induced loss of FDCs and IDCs may significantly compromise B and T cell function and impair the ability of the host to survive sepsis...
  34. ncbi Sequence makes a difference: paradoxical effects of stress in vivo
    Joseph J Wizorek
    Cellular Injury and Adaptation Laboratory, Department of Surgery, Washington University, St Louis, Missouri 63130, USA
    Shock 22:229-33. 2004
    ..The cellular mechanisms responsible for these "stressor" paradoxes in vivo are not known, but do not involve altered sepsis-induced apoptosis...
  35. pmc Sepsis-induced apoptosis leads to active suppression of delayed-type hypersensitivity by CD8+ regulatory T cells through a TRAIL-dependent mechanism
    Jacqueline Unsinger
    Department of Anesthesiology, Washington University School of Medicine, St Louis, MO 63110, USA
    J Immunol 184:6766-72. 2010
    ..These results establish a link between apoptotic cells and immune suppression during sepsis and suggest TRAIL may be a viable therapeutic target for boosting the adaptive immune response following sepsis...
  36. ncbi Sepsis from Pseudomonas aeruginosa pneumonia decreases intestinal proliferation and induces gut epithelial cell cycle arrest
    Craig M Coopersmith
    Department of Surgery, Washiongton University School of Medicine, St Louis, MO, USA
    Crit Care Med 31:1630-7. 2003
    ..To evaluate whether the up-regulation in sepsis-induced gut epithelial apoptosis is balanced by an increase in intestinal proliferation and to assess mechanisms affecting the gut's regenerative response to overwhelming infection...
  37. ncbi Accelerated lymphocyte death in sepsis occurs by both the death receptor and mitochondrial pathways
    Richard S Hotchkiss
    Department of Anesthesiology, Washington University School of Medicine, St Louis, MO 63110, USA
    J Immunol 174:5110-8. 2005
    ..Lymphocyte loss occurs by both death receptor and mitochondrial-mediated apoptosis, suggesting that there may be multiple triggers for lymphocyte apoptosis...
  38. ncbi Pneumonia after cecal ligation and puncture: a clinically relevant "two-hit" model of sepsis
    Jared T Muenzer
    Department of Pediatrics, Washington University School of Medicine, 660 S Euclid Avenue, St Louis, MO 63110, USA
    Shock 26:565-70. 2006
    ....
  39. ncbi Splenic CD4+ T cells have a distinct transcriptional response six hours after the onset of sepsis
    Jonathan E McDunn
    Cellular Injury and Adaptation Laboratory, Department of Surgery, Washington University School of Medicine, St Louis, MO 63110, USA
    J Am Coll Surg 203:365-75. 2006
    ..The molecular mechanism(s) for the phenotypic changes of splenic CD4+ T cells in sepsis are not well understood...
  40. doi Deletion of MyD88 markedly attenuates sepsis-induced T and B lymphocyte apoptosis but worsens survival
    Octavia M Peck-Palmer
    Department of Anesthesiology, Division of Laboratory and Genomic Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
    J Leukoc Biol 83:1009-18. 2008
    ..MyD88 was effective in blocking apoptosis, as it is essential in mediating most pathogen recognition pathways; however, MyD88 is also critical for host survival in a model of severe peritonitis...
  41. pmc Immunosuppression in patients who die of sepsis and multiple organ failure
    Jonathan S Boomer
    Department of Medicine, Washington University School of Medicine, 660 S Euclid, St Louis, MO 63110, USA
    JAMA 306:2594-605. 2011
    ..Whether this hyperinflammatory phase is followed by immunosuppression is controversial. Animal studies suggest that multiple immune defects occur in sepsis, but data from humans remain conflicting...
  42. pmc Epidermal growth factor treatment decreases mortality and is associated with improved gut integrity in sepsis
    Jessica A Clark
    Department of Surgery, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Shock 30:36-42. 2008
    ..Mortality decreased from 60% to 30% in mice treated with EGF after the onset of sepsis (P < 0.05). Thus, EGF may be a potential therapeutic agent for the treatment of sepsis in part due to its ability to protect intestinal integrity...
  43. pmc Targeted delivery of siRNA to cell death proteins in sepsis
    Pavan Brahmamdam
    Department of Surgery, Washington University in St Louis, School of Medicine, St Louis, Missouri 63110, USA
    Shock 32:131-9. 2009
    ....
  44. pmc IL-7 promotes T cell viability, trafficking, and functionality and improves survival in sepsis
    Jacqueline Unsinger
    Department of Anesthesiology, Washington University School of Medicine, St Louis, MO 63110, USA
    J Immunol 184:3768-79. 2010
    ..If additional animal studies support its efficacy in sepsis and if current clinical trials continue to confirm its safety in diverse settings, rhIL-7 should be strongly considered for clinical trials in sepsis...
  45. pmc Sepsis-induced human lymphocyte apoptosis and cytokine production in "humanized" mice
    Jacqueline Unsinger
    Department of Anesthesiology, Washington University School of Medicine, St Louis, MO 63110, USA
    J Leukoc Biol 86:219-27. 2009
    ..Therefore, it represents an advanced, clinically relevant model for mechanistic studies of sepsis and testing of novel therapies...
  46. pmc Effects of aging on the immunopathologic response to sepsis
    Isaiah R Turnbull
    Department of Surgery, Washington University School of Medicine, St Louis, MO, USA
    Crit Care Med 37:1018-23. 2009
    ..The purpose of this study was to determine whether this represents a fundamental age-based difference in the host response or is secondary to the increased mortality seen in aged hosts...
  47. ncbi Multiple triggers of cell death in sepsis: death receptor and mitochondrial-mediated apoptosis
    Katherine C Chang
    Department of Anesthesiology, Washington University School of Medicine, St Louis, MO 63110, USA
    FASEB J 21:708-19. 2007
    ..If siRNA becomes practical therapeutically, proapoptotic proteins would be potential targets...
  48. doi Delayed administration of anti-PD-1 antibody reverses immune dysfunction and improves survival during sepsis
    Pavan Brahmamdam
    Department of Surgery, Washington University School of Medicine, 660 S Euclid Ave, St Louis, MO 63110, USA
    J Leukoc Biol 88:233-40. 2010
    ....
  49. pmc Early antibiotic administration but not antibody therapy directed against IL-6 improves survival in septic mice predicted to die on basis of high IL-6 levels
    Dinesh Vyas
    Washington University School of Medicine, 660 South Euclid Ave, Campus Box 8109, St Louis, MO 63110, USA
    Am J Physiol Regul Integr Comp Physiol 289:R1048-53. 2005
    ..These results demonstrate that earlier systemic therapy can improve outcome in a subset of mice predicted to die in sepsis, but we are unable to demonstrate any benefit in similar animals using targeted therapy directed at IL-6...
  50. pmc A genetically encoded multifunctional TRAIL trimer facilitates cell-specific targeting and tumor cell killing
    Dirk Spitzer
    Department of Surgery, Washington University School of Medicine, and Siteman Cancer Center, St Louis, Missouri 63110, USA
    Mol Cancer Ther 9:2142-51. 2010
    ..More importantly, the ability to target TR3 to a cell surface presents the opportunity to create a cancer-selective drug with fewer off-target toxicities and enhanced killing capacities...
  51. pmc Use of multifunctional sigma-2 receptor ligand conjugates to trigger cancer-selective cell death signaling
    Dirk Spitzer
    Department of Surgery, Alvin J Siteman Cancer Center, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Cancer Res 72:201-9. 2012
    ..Our findings define a simple platform technology to increase the tumor-selective delivery of small molecule therapeutics via σ-2 ligands, permitting chemotherapeutic synergy that can optimize efficacy and patient benefit...
  52. pmc Differential lymphopenia-induced homeostatic proliferation for CD4+ and CD8+ T cells following septic injury
    Jacqueline Unsinger
    Washington University School of Medicine, 660 S Euclid, St Louis, MO 63110, USA
    J Leukoc Biol 85:382-90. 2009
    ..Restoration of homeostatic control mechanisms might be a rational therapy for this disorder...
  53. ncbi Antibiotics improve survival in sepsis independent of injury severity but do not change mortality in mice with markedly elevated interleukin 6 levels
    Isaiah R Turnbull
    Department of Surgery, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Shock 21:121-5. 2004
    ..Furthermore, there is a threshold IL-6 level that can be identified 6 h after sepsis above which animals are destined to die, and antibiotic treatment does not alter their outcome...
  54. pmc Selective sigma-2 ligands preferentially bind to pancreatic adenocarcinomas: applications in diagnostic imaging and therapy
    Hiroyuki Kashiwagi
    Department of Surgery, Washington University School of Medicine, Saint Louis, USA
    Mol Cancer 6:48. 2007
    ..The sigma-2 receptor has been found to be over-expressed in some types of malignant tumors, and, recently, small molecule ligands to the sigma-2 receptor were found to induce cancer cell apoptosis...
  55. ncbi Characterization and evaluation of two novel fluorescent sigma-2 receptor ligands as proliferation probes
    Chenbo Zeng
    Department of Radiology, Washington University School of Medicine, St Louis, MO, USA
    Mol Imaging 10:420-33. 2011
    ....
  56. pmc Peptide-mediated activation of Akt and extracellular regulated kinase signaling prevents lymphocyte apoptosis
    Jonathan E McDunn
    Department of Anesthesiology, Washington University School of Medicine, St Louis, MO, 63110, USA
    FASEB J 22:561-8. 2008
    ..Molecular approaches to activate the antiapoptotic Akt and ERK signaling pathways may provide a novel tool to study these signaling pathways, as well as a new antiapoptotic strategy for the treatment of sepsis and other acute injuries...
  57. ncbi The role of TCR engagement and activation-induced cell death in sepsis-induced T cell apoptosis
    Jacqueline Unsinger
    Department of Anesthesiology, Washington University School of Medicine, St Louis, MO 63110, USA
    J Immunol 177:7968-73. 2006
    ..We conclude that lymphocyte apoptosis in sepsis does not require proliferation, TCR engagement, or AICD. Thus the immunosuppression observed in sepsis cannot be the result of T cell deletion via the TCR...
  58. pmc Cecal ligation and puncture followed by methicillin-resistant Staphylococcus aureus pneumonia increases mortality in mice and blunts production of local and systemic cytokines
    Enjae Jung
    Department of Surgery, Washington University School of Medicine, St Louis, Missouri, USA
    Shock 37:85-94. 2012
    ....
  59. pmc Bim-Bcl-2 homology 3 mimetic therapy is effective at suppressing inflammatory arthritis through the activation of myeloid cell apoptosis
    John C Scatizzi
    St Louis University School of Medicine, St Louis, MO, USA
    Arthritis Rheum 62:441-51. 2010
    ....
  60. pmc An anti-apoptotic peptide improves survival in lethal total body irradiation
    Jonathan E McDunn
    Department of Anesthesiology, Washington University School of Medicine, Saint Louis, MO 63110, USA
    Biochem Biophys Res Commun 382:657-62. 2009
    ....
  61. pmc Iron dysregulation combined with aging prevents sepsis-induced apoptosis
    Pardis Javadi
    Department of Surgery, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Surg Res 128:37-44. 2005
    ..Sepsis, iron loading, and aging cause independent increases in gut epithelial and splenic apoptosis. It is unknown how their combination will affect apoptosis and systemic cytokine levels...
  62. ncbi Molecular diagnostics in sepsis: from bedside to bench
    T Philip Chung
    Department of Surgery, School of Medicine, Washington University, St Louis, MO 63110, USA
    J Am Coll Surg 203:585-598. 2006
    ..Based on recent in vitro data, we tested the hypothesis that microarray expression profiles can be used to diagnose sepsis, distinguishing in vivo between sterile and infectious causes of systemic inflammation...
  63. ncbi Anti-apoptotic peptides protect against radiation-induced cell death
    Kevin W McConnell
    Department of Surgery, Washington University School of Medicine, St Louis, MO 63110, USA
    Biochem Biophys Res Commun 355:501-7. 2007
    ..Thus, by targeting steps within the apoptosis signaling pathway it is possible to develop post-exposure treatments to protect radio-sensitive tissues...
  64. pmc Adoptive transfer of dying cells causes bystander-induced apoptosis
    Steven J Schwulst
    Department of Surgery, Washington University School of Medicine, St Louis, MO 63110, USA
    Biochem Biophys Res Commun 353:780-5. 2007
    ..05). Therefore, this data suggests that dying cells emit signals triggering cell death in neighboring non-Bcl-2 overexpressing cells, i.e., a "trans" destructive effect...
  65. ncbi Subcellular localization of sigma-2 receptors in breast cancer cells using two-photon and confocal microscopy
    Chenbo Zeng
    Department of Radiology, Division of Radiological Sciences, Washington University School of Medicine, 510 S Kingshighway Boulevard, St Louis, MO 63110, USA
    Cancer Res 67:6708-16. 2007
    ....
  66. ncbi Sepsis gene expression profiling: murine splenic compared with hepatic responses determined by using complementary DNA microarrays
    J Perren Cobb
    Department of Surgery, Washington University School of Medicine, St Louis, MO 63110, USA
    Crit Care Med 30:2711-21. 2002
    ....
  67. ncbi TAT-Bim induces extensive apoptosis in cancer cells
    Hiroyuki Kashiwagi
    Department of Surgery, Washington University School of Medicine, St Louis, MO 63110, USA
    Ann Surg Oncol 14:1763-71. 2007
    ..Since apoptosis is executed by intracellular proteins, molecular approaches must incorporate a method to deliver the treatment into the tumor cells...
  68. ncbi Overexpression of Bcl-2 in the intestinal epithelium improves survival in septic mice
    Craig M Coopersmith
    Department of Surgery, Washington University School of Medicine, St Louis, MO 63110, USA
    Crit Care Med 30:195-201. 2002
    ..The roles of the antiapoptotic protein Bcl-2 and the "executioner" protease caspase-3 in sepsis-induced gut cell death also were evaluated...
  69. ncbi Prevention of lymphocyte apoptosis--a potential treatment of sepsis?
    Richard S Hotchkiss
    Department of Anesthesiology, Washington University School of Medicine, St Louis, MO 63110, USA
    Clin Infect Dis 41:S465-9. 2005
    ..A variety of strategies to inhibit apoptosis may ultimately provide an effective therapy for this highly lethal disorder...
  70. ncbi TAT-BH4 and TAT-Bcl-xL peptides protect against sepsis-induced lymphocyte apoptosis in vivo
    Richard S Hotchkiss
    Department of Anesthesiology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA
    J Immunol 176:5471-7. 2006
    ..In conclusion, TAT-conjugated antiapoptotic Bcl-2-like peptides may offer a novel therapy to prevent apoptosis in sepsis and improve survival...
  71. ncbi Role of CuZn superoxide dismutase in regulating lymphocyte apoptosis during sepsis
    B D Freeman
    Department of Surgery, Washington University School of Medicine, St Louis, MO 63110, USA
    Crit Care Med 28:1701-8. 2000
    ....
  72. pmc Neutrophil depletion causes a fatal defect in murine pulmonary Staphylococcus aureus clearance
    Charles M Robertson
    Department of Surgery, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Surg Res 150:278-85. 2008
    ..Staphylococcus aureus is the most common cause of healthcare-associated pneumonia. Despite the significant morbidity and mortality associated with the disease, animal models of S. aureus pneumonia are rare...
  73. pmc Neutrophils employ the myeloperoxidase system to generate antimicrobial brominating and chlorinating oxidants during sepsis
    J P Gaut
    Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
    Proc Natl Acad Sci U S A 98:11961-6. 2001
    ..Thus, myeloperoxidase plays an important role in host defense against bacterial pathogens, and bromide might be a previously unsuspected component of this system...
  74. ncbi NADPH oxidase of neutrophils elevates o,o'-dityrosine cross-links in proteins and urine during inflammation
    S Bhattacharjee
    Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA
    Arch Biochem Biophys 395:69-77. 2001
    ....
  75. ncbi Apoptosis and caspases regulate death and inflammation in sepsis
    Richard S Hotchkiss
    Department of Anesthesiology, Washington University School of Medicine, Campus Box 8054, 660 South Euclid, St Louis, Missouri 63110, USA
    Nat Rev Immunol 6:813-22. 2006
    ....
  76. ncbi Intravital microscopy comparing T lymphocyte trafficking to the spleen and the mesenteric lymph node
    Mitchell H Grayson
    Division of Allergy and Immunology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Am J Physiol Heart Circ Physiol 284:H2213-26. 2003
    ....
  77. ncbi Confocal fluorescent intravital microscopy of the murine spleen
    M H Grayson
    Division of Allergy and Immunology, Washington University School of Medicine, Campus Box 8122, 660 South Euclid Avenue, St Louis, MO 63110, USA
    J Immunol Methods 256:55-63. 2001
    ..This is the first report of intravital microscopy of the spleen using a method that allows for easy identification of transferred cells...
  78. ncbi Costimulatory blockade-mediated lung allograft acceptance is abrogated by overexpression of Bcl-2 in the recipient
    M Okazaki
    Department of Surgery, Washington University in St Louis, St Louis, Missourri 63110 1013, USA
    Transplant Proc 41:385-7. 2009
    ..Thus, our results show that perioperative blockade of the CD40/CD40L and CD28/B7 costimulatory pathways markedly ameliorates acute rejection of lung allografts in wild type but not Bcl-2 transgenic recipients...
  79. ncbi Endothelial cell apoptosis in sepsis
    Richard S Hotchkiss
    Department of Anesthesiology, Washington University School of Medicine, St Louis, MO, USA
    Crit Care Med 30:S225-8. 2002
    ..To discuss a potential role for endothelial cell apoptosis in the pathogenesis of sepsis...
  80. ncbi Effects of age on mortality and antibiotic efficacy in cecal ligation and puncture
    Isaiah R Turnbull
    Department of Surgery, Washington University School of Medicine, St Louis, Missouri 63110 1093, USA
    Shock 19:310-3. 2003
    ..However, high IL-6 was predictive of mortality at any age. Mice appear to have age-dependent responses to intra-abdominal sepsis and to appropriate therapy...
  81. ncbi Injury in the era of genomics
    J P Cobb
    Department of Surgery, School of Medicine, Washington University, St. Louis, Missouri, USA
    Shock 15:165-70. 2001
    ..We conclude that efforts to apply genomics to the study of injury are best coordinated by multi-disciplinary groups, because of the extensive expertise required...
  82. ncbi Differential modulation of endotoxin responsiveness by human caspase-12 polymorphisms
    Maya Saleh
    Department of Biochemistry, Molecular Biology and Pharmacology, Merck Frosst Centre for Therapeutic Research, Montreal, Quebec H9H 3L1, Canada
    Nature 429:75-9. 2004
    ..Thus, Csp12-L attenuates the inflammatory and innate immune response to endotoxins and in doing so may constitute a risk factor for developing sepsis...
  83. ncbi Akt decreases lymphocyte apoptosis and improves survival in sepsis
    Ursula Bommhardt
    Institute of Virology and Immunobiology, University of Wurzburg, Wurzburg, Germany
    J Immunol 172:7583-91. 2004
    ..Findings from this study strengthen the concept that a major defect in sepsis is impairment of the adaptive immune system, and suggest that strategies to prevent lymphocyte apoptosis represent a potential important new therapy...
  84. ncbi Endothelial cell apoptosis in sepsis: a case of habeas corpus?
    Richard S Hotchkiss
    Crit Care Med 32:901-2. 2004
  85. pmc Myeloperoxidase produces nitrating oxidants in vivo
    Joseph P Gaut
    Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Clin Invest 109:1311-9. 2002
    ..This article was published online in advance of the print edition. The date of publication is available from the JCI website, http://www.jci.org...
  86. pmc Prevention of immune cell apoptosis as potential therapeutic strategy for severe infections
    Janie Parrino
    National Institutes of Health, Bethesda, Maryland 20892, USA
    Emerg Infect Dis 13:191-8. 2007
    ..These findings suggest that interventions aimed at reducing the extent of immune cell apoptosis could improve outcomes for a variety of severe human infections, including those caused by emerging pathogens and bioterrorism agents...