M E Rothenberg

Summary

Affiliation: Cincinnati Children's Hospital Medical Center
Country: USA

Publications

  1. pmc Development of the Pediatric Quality of Life Inventory™ Eosinophilic Esophagitis module items: qualitative methods
    James P Franciosi
    Division of Gastroenterology, Hepatology and Nutrition, Nemours Children s Hospital, 13535 Nemours Parkway, Orlando, FL 32827, USA
    BMC Gastroenterol 12:135. 2012
  2. pmc Resistin-like molecule-α regulates IL-13-induced chemokine production but not allergen-induced airway responses
    Ariel Munitz
    Division of Allergy and Immunology, Cincinnati Children s Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH 45229, USA
    Am J Respir Cell Mol Biol 46:703-13. 2012
  3. pmc The cationic amino acid transporter 2 is induced in inflammatory lung models and regulates lung fibrosis
    Kathryn A Niese
    Division of Allergy and Immunology, Cincinnati Children s Hospital Medical Center, 3333 Burnet Ave, Cincinnati, Ohio 45229, USA
    Respir Res 11:87. 2010
  4. pmc Analysis of the CCR3 promoter reveals a regulatory region in exon 1 that binds GATA-1
    Nives Zimmermann
    Division of Allergy and Immunology, Cincinnati Children s Hospital Medical Center, Cincinnati, Ohio, USA
    BMC Immunol 6:7. 2005
  5. pmc Bone marrow cell derived arginase I is the major source of allergen-induced lung arginase but is not required for airway hyperresponsiveness, remodeling and lung inflammatory responses in mice
    Kathryn A Niese
    Division of Allergy and Immunology, Cincinnati Children s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
    BMC Immunol 10:33. 2009
  6. doi request reprint Treatment of patients with the hypereosinophilic syndrome with mepolizumab
    Marc E Rothenberg
    Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children s Hospital Medical Center, University of Cincinnati, Cincinnati, OH 45229, USA
    N Engl J Med 358:1215-28. 2008
  7. ncbi request reprint The eosinophil
    Marc E Rothenberg
    Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA
    Annu Rev Immunol 24:147-74. 2006
  8. doi request reprint Biology and treatment of eosinophilic esophagitis
    Marc E Rothenberg
    Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA
    Gastroenterology 137:1238-49. 2009
  9. ncbi request reprint Clinical and immunopathologic effects of swallowed fluticasone for eosinophilic esophagitis
    Richard J Noel
    Department of Pediatrics, Cincinnati Children s Medical Center, Universityof Cincinnati College of Medicine, OH 45229 3039, USA
    Clin Gastroenterol Hepatol 2:568-75. 2004
  10. doi request reprint 2007 E. Mead Johnson award: scientific pursuit of the allergy problem
    Marc E Rothenberg
    Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA
    Pediatr Res 64:110-5. 2008

Detail Information

Publications111 found, 100 shown here

  1. pmc Development of the Pediatric Quality of Life Inventory™ Eosinophilic Esophagitis module items: qualitative methods
    James P Franciosi
    Division of Gastroenterology, Hepatology and Nutrition, Nemours Children s Hospital, 13535 Nemours Parkway, Orlando, FL 32827, USA
    BMC Gastroenterol 12:135. 2012
    ..Therefore, the objective of this qualitative study was to further develop and finalize the items and support the content validity for the new Pediatric Quality of Life Inventory™ (PedsQL™) Eosinophilic Esophagitis Module...
  2. pmc Resistin-like molecule-α regulates IL-13-induced chemokine production but not allergen-induced airway responses
    Ariel Munitz
    Division of Allergy and Immunology, Cincinnati Children s Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH 45229, USA
    Am J Respir Cell Mol Biol 46:703-13. 2012
    ..e., epithelial cells and macrophages.) Finally, we identify a largely redundant functional role for Relm-α in acute experimental models of allergen-associated Th2 immune responses...
  3. pmc The cationic amino acid transporter 2 is induced in inflammatory lung models and regulates lung fibrosis
    Kathryn A Niese
    Division of Allergy and Immunology, Cincinnati Children s Hospital Medical Center, 3333 Burnet Ave, Cincinnati, Ohio 45229, USA
    Respir Res 11:87. 2010
    ..As such, arginine has the potential to influence diverse fundamental processes in the lung...
  4. pmc Analysis of the CCR3 promoter reveals a regulatory region in exon 1 that binds GATA-1
    Nives Zimmermann
    Division of Allergy and Immunology, Cincinnati Children s Hospital Medical Center, Cincinnati, Ohio, USA
    BMC Immunol 6:7. 2005
    ..It is therefore important to elucidate the molecular mechanisms regulating receptor expression...
  5. pmc Bone marrow cell derived arginase I is the major source of allergen-induced lung arginase but is not required for airway hyperresponsiveness, remodeling and lung inflammatory responses in mice
    Kathryn A Niese
    Division of Allergy and Immunology, Cincinnati Children s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
    BMC Immunol 10:33. 2009
    ..Arginase is significantly upregulated in the lungs in murine models of asthma, as well as in human asthma, but its role in allergic airway inflammation has not been fully elucidated in mice...
  6. doi request reprint Treatment of patients with the hypereosinophilic syndrome with mepolizumab
    Marc E Rothenberg
    Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children s Hospital Medical Center, University of Cincinnati, Cincinnati, OH 45229, USA
    N Engl J Med 358:1215-28. 2008
    ..Although most patients have a response to corticosteroids, side effects are common and can lead to considerable morbidity...
  7. ncbi request reprint The eosinophil
    Marc E Rothenberg
    Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA
    Annu Rev Immunol 24:147-74. 2006
    ..Finally, strategies for targeted therapeutic intervention in eosinophil-mediated mucosal diseases are conceptualized...
  8. doi request reprint Biology and treatment of eosinophilic esophagitis
    Marc E Rothenberg
    Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA
    Gastroenterology 137:1238-49. 2009
    ..Therefore, eosinophilic esophagitis is a disease with unique features that include chronic esophagitis, atopy, immune sensitization to oral antigens, reversibility, and familial association...
  9. ncbi request reprint Clinical and immunopathologic effects of swallowed fluticasone for eosinophilic esophagitis
    Richard J Noel
    Department of Pediatrics, Cincinnati Children s Medical Center, Universityof Cincinnati College of Medicine, OH 45229 3039, USA
    Clin Gastroenterol Hepatol 2:568-75. 2004
    ..Eosinophilic esophagitis (EE) is a recently recognized clinical disorder that is understood poorly. We aimed to determine the efficacy of swallowed fluticasone propionate on the immunopathologic features associated with EE...
  10. doi request reprint 2007 E. Mead Johnson award: scientific pursuit of the allergy problem
    Marc E Rothenberg
    Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA
    Pediatr Res 64:110-5. 2008
    ....
  11. pmc IL-13 receptor α1 differentially regulates aeroallergen-induced lung responses
    Marc E Rothenberg
    Division of Allergy and Immunology, Cincinnati Children s Hospital Medical Center, Cincinnati, OH 45229, USA
    J Immunol 187:4873-80. 2011
    ....
  12. ncbi request reprint Gastrointestinal eosinophils
    M E Rothenberg
    Department of Pediatrics, Children s Hospital Medical Center, Cincinnati, Ohio 45229 3039, USA
    Immunol Rev 179:139-55. 2001
    ..We propose that eosinophils are integral members of the gastrointestinal immune system and are likely to be important in innate, regulatory and inflammatory immune responses...
  13. ncbi request reprint A pathological function for eotaxin and eosinophils in eosinophilic gastrointestinal inflammation
    S P Hogan
    Division of Pulmonary Medicine, Allergy and Clinical Immunology, Department of Pediatrics, Children s Hospital Medical Center, Cincinnati, OH 45229, USA
    Nat Immunol 2:353-60. 2001
    ..These results establish a critical pathological function for eotaxin and eosinophils in gastrointestinal allergic hypersensitivity...
  14. pmc An etiological role for aeroallergens and eosinophils in experimental esophagitis
    A Mishra
    Division of Pulmonary Medicine, Allergy and Clinical Immunology, Department of Pediatrics, Children's Hospital Medical Center, Cincinnati, Ohio, USA
    J Clin Invest 107:83-90. 2001
    ..These results establish a pathophysiological connection between allergic hypersensitivity responses in the lung and esophagus and demonstrate an etiologic role for inhaled allergens and eosinophils in gastrointestinal inflammation...
  15. ncbi request reprint IL-13 induces eosinophil recruitment into the lung by an IL-5- and eotaxin-dependent mechanism
    S M Pope
    Division of Pulmonary Medicine, Allergy and Clinical Immunology, Department of Pediatrics, Children s Hospital Medical Center, Cincinnati, Ohio 45229, USA
    J Allergy Clin Immunol 108:594-601. 2001
    ..IL-13 induces several characteristic features of asthma, including airway eosinophilia, airway hyperresponsiveness, and mucus overproduction; however, the mechanisms involved are largely unknown...
  16. pmc Distinct roles for IL-13 and IL-4 via IL-13 receptor alpha1 and the type II IL-4 receptor in asthma pathogenesis
    A Munitz
    Division of Allergy and Immunology, Cincinnati Children s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA
    Proc Natl Acad Sci U S A 105:7240-5. 2008
    ..Taken together, our data provide a comprehensive mechanistic analysis of the critical role by which IL-13Ralpha1 mediates allergic lung pathology and highlight unforeseen roles for the type II IL-4R...
  17. ncbi request reprint The alpha4bbeta7-integrin is dynamically expressed on murine eosinophils and involved in eosinophil trafficking to the intestine
    E B Brandt
    Division of Allergy and Immunology, Cincinnati Children s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA
    Clin Exp Allergy 36:543-53. 2006
    ..Most studies have focused on the role of the alpha4beta1-adhesion complex, but eosinophils also express the alpha4beta7-integrin complex...
  18. pmc Local B cells and IgE production in the oesophageal mucosa in eosinophilic oesophagitis
    M Vicario
    Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
    Gut 59:12-20. 2010
    ....
  19. pmc Periostin facilitates eosinophil tissue infiltration in allergic lung and esophageal responses
    C Blanchard
    Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
    Mucosal Immunol 1:289-96. 2008
    ....
  20. ncbi request reprint Inhibition of human interleukin-13-induced respiratory and oesophageal inflammation by anti-human-interleukin-13 antibody (CAT-354)
    C Blanchard
    Department of Pediatrics, Division of Allergy and Immunology, Cincinnati Children s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA
    Clin Exp Allergy 35:1096-103. 2005
    ....
  21. ncbi request reprint Murine eotaxin-2: a constitutive eosinophil chemokine induced by allergen challenge and IL-4 overexpression
    N Zimmermann
    Division of Pulmonary Medicine, Allergy, and Clinical Immunology, Department of Pediatrics, Children s Hospital Medical Center, University of Cincinnati, OH 45229, USA
    J Immunol 165:5839-46. 2000
    ..Thus, murine eotaxin-2 is a constitutively expressed eosinophil chemokine likely to be involved in homeostatic, allergen-induced, and IL-4-associated immune responses...
  22. ncbi request reprint Interleukin-5-mediated allergic airway inflammation inhibits the human surfactant protein C promoter in transgenic mice
    A Mishra
    Division of Pulmonary Medicine, Allergy and Clinical Immunology, Department of Pediatrics, Children s Hospital Medical Center, Cincinnati, Ohio 45229, USA
    J Biol Chem 276:8453-9. 2001
    ..These results suggest that alterations in surfactant protein levels may contribute to immune and airway dysfunction in asthma...
  23. ncbi request reprint Chemokines and chemokine receptors: their role in allergic airway disease
    M E Rothenberg
    Department of Pediatrics, Children s Hospital Medical Center, Cincinnati, Ohio 45229 3039, USA
    J Clin Immunol 19:250-65. 1999
    ..In this regard, chemokines are attractive new therapeutic targets for the treatment of allergic disease. This article focuses on recently emerging data on the importance of chemokines and their receptors in allergic airway inflammation...
  24. pmc Eosinophils and CCR3 regulate interleukin-13 transgene-induced pulmonary remodeling
    Patricia C Fulkerson
    Deparmtnet of Molecular Genetics, Division of Allergy and Immunology, Cincinnati Children s Hospital Medical Center, University of Cincinnati College of Medicine, 3333 Burnet Ave, MLC 7028, Cincinnati, OH 45229, USA
    Am J Pathol 169:2117-26. 2006
    ..Taken together, these data definitively identify a functional contribution by eosinophils on the effects of chronic IL-13 expression in the lung...
  25. pmc The FIP1L1-PDGFRA fusion gene cooperates with IL-5 to induce murine hypereosinophilic syndrome (HES)/chronic eosinophilic leukemia (CEL)-like disease
    Yoshiyuki Yamada
    Division of Allergy and Immunology, Cincinnati Children s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA
    Blood 107:4071-9. 2006
    ..These results suggest that F/P is not sufficient to induce a HES/CEL-like disease but requires a second event associated with IL-5 overexpression...
  26. ncbi request reprint IL-5 promotes eosinophil trafficking to the esophagus
    Anil Mishra
    Division of Allergy and Immunology, Department of Pediatrics, Children s Hospital Medical Center, Cincinnati, OH 45229, USA
    J Immunol 168:2464-9. 2002
    ..In conclusion, these studies demonstrate a central role for IL-5 in inducing eosinophil trafficking to the esophagus...
  27. pmc Anti-IL-5 (mepolizumab) therapy reduces eosinophil activation ex vivo and increases IL-5 and IL-5 receptor levels
    Miguel L Stein
    Division of Allergy and Immunology, Cincinnati Children s Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA
    J Allergy Clin Immunol 121:1473-83, 1483.e1-4. 2008
    ..Anti-IL-5 might be a useful therapeutic agent for eosinophilic disorders, yet its immunologic consequences have not been well characterized...
  28. pmc A central regulatory role for eosinophils and the eotaxin/CCR3 axis in chronic experimental allergic airway inflammation
    Patricia C Fulkerson
    Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine, 231 Bethesda Avenue, Cincinnati, OH 45257 0524, USA
    Proc Natl Acad Sci U S A 103:16418-23. 2006
    ..In summary, we present multiple lines of independent evidence that eosinophils via CCR3 have a central role in chronic allergic airway disease...
  29. ncbi request reprint Epicutaneous antigen exposure primes for experimental eosinophilic esophagitis in mice
    Hiroko Saito Akei
    Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA
    Gastroenterology 129:985-94. 2005
    ..Data are emerging that atopic skin may provide an early entry point for antigen sensitization. We aimed to test the hypothesis that epicutaneous exposure to antigen primes for subsequent respiratory antigen-induced EE...
  30. pmc Resistin-like molecule alpha enhances myeloid cell activation and promotes colitis
    Ariel Munitz
    Division of Allergy and Immunology, Cincinnati Children s Hospital Medical Center, Cincinnati, OH 45229, USA
    J Allergy Clin Immunol 122:1200-1207.e1. 2008
    ..Relm-alpha is highly induced by allergic inflammatory triggers and perceived to promote tissue repair. Yet the function of Relm-alpha remains unknown...
  31. ncbi request reprint Expression and regulation of small proline-rich protein 2 in allergic inflammation
    Nives Zimmermann
    Division of Allergy and Immunology, Cincinnati Children s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA
    Am J Respir Cell Mol Biol 32:428-35. 2005
    ..Thus, SPRR2 is an allergen- and IL-13-induced gene in experimental allergic responses that may be involved in disease pathophysiology...
  32. ncbi request reprint Anti-IL-5 (mepolizumab) therapy for eosinophilic esophagitis
    Miguel L Stein
    Division of Allergy and Immunology, Cincinnati Children s Hospital Medical Center, Cincinnati, OH 45229, USA
    J Allergy Clin Immunol 118:1312-9. 2006
    ..IL-5 promotes eosinophil trafficking to the esophagus, and positively regulates eosinophil growth, activation, survival, and tissue recruitment...
  33. ncbi request reprint Critical role for adaptive T cell immunity in experimental eosinophilic esophagitis in mice
    Anil Mishra
    Department of Pediatrics, Cincinnati Children s Hospital Medical Center, University of Cincinnati, College of Medicine, OH 45229, USA
    J Leukoc Biol 81:916-24. 2007
    ..Taken together, these studies indicate a role for CD4+ and CD4- cell populations in EE pathogenesis and demonstrate that experimental allergen-induced EE is dependent on adaptive T cell immunity...
  34. ncbi request reprint Anti-interleukin-5 (mepolizumab) therapy for hypereosinophilic syndromes
    Jennifer K Garrett
    Department of Pediatrics, Cincinnati Children s Hospital Medical Center, Cincinnati, Ohio 45229, USA
    J Allergy Clin Immunol 113:115-9. 2004
    ..As such, IL-5 may be involved in the pathogenesis of hypereosinophilic syndromes, a group of poorly treated diverse disorders characterized by sustained peripheral blood and/or tissue eosinophilia...
  35. ncbi request reprint Review article: The eosinophil as a therapeutic target in gastrointestinal disease
    S P Hogan
    Cincinnati Children s Hospital Medical Center, Division of Allergy and Immunology, University of Cincinnati College of Medicine, Cincinnati, OH 45229 3039, USA
    Aliment Pharmacol Ther 20:1231-40. 2004
    ....
  36. pmc Siglec-F antibody administration to mice selectively reduces blood and tissue eosinophils
    N Zimmermann
    Division of Allergy and Immunology, Cincinnati Children s Hospital Medical Center and Department of Pediatrics, University of Cincinnati School of Medicine, Cincinnati, OH 45229, USA
    Allergy 63:1156-63. 2008
    ..We therefore hypothesized that Siglec-F engagement would affect levels and viability of eosinophils in vivo...
  37. doi request reprint Chemotactic factors associated with eosinophilic gastrointestinal diseases
    Carine Blanchard
    Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children s Hospital Medical Center, 3333 Burnet Avenue, MLC 7028, Cincinnati, OH 45229 3039, USA
    Immunol Allergy Clin North Am 29:141-8, xi. 2009
    ..Eosinophilic GI diseases are characterized by an increased number of eosinophil infiltrates with no identified cause. This article describes the past and present knowledge regarding the chemotactic factors involved in GI eosinophilia...
  38. ncbi request reprint Interplay of adaptive th2 immunity with eotaxin-3/c-C chemokine receptor 3 in eosinophilic esophagitis
    Jennifer Z Bullock
    Division of Allergy and Immunology, Cincinnati Children s Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229 3039, USA
    J Pediatr Gastroenterol Nutr 45:22-31. 2007
    ..Although studies of esophageal tissue suggest that Th2 cytokines and eotaxin-3 may be crucial in disease pathogenesis, little is known about the systemic immunological phenotypes of children with EE...
  39. ncbi request reprint Resistin-like molecule-beta is an allergen-induced cytokine with inflammatory and remodeling activity in the murine lung
    Anil Mishra
    Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children s Hospital Medical Center, Cincinnati, OH 45229, USA
    Am J Physiol Lung Cell Mol Physiol 293:L305-13. 2007
    ..In vitro experiments demonstrated that RELM-beta had fibroblast motogenic activity. These results identify RELM-beta as a Th2-associated cytokine with potent inflammatory and remodeling activity...
  40. pmc Cationic amino acid transporter 2 regulates inflammatory homeostasis in the lung
    Marc E Rothenberg
    Division of Allergy and Immunology, Cincinnati Children s Hospital and University of Cincinnati College of Medicine, 3333 Burnet Avenue, Cincinnati, OH 45229 3039, USA
    Proc Natl Acad Sci U S A 103:14895-900. 2006
    ..This process was accompanied by an increase in the number of memory T cells. Thus, our data suggest that CAT2 regulates anti-inflammatory processes in the lungs via regulation of dendritic cell activation and subsequent T cell responses...
  41. pmc A dual activation and inhibition role for the paired immunoglobulin-like receptor B in eosinophils
    Ariel Munitz
    Division of Allergy and Immunology, Cincinnati Children s Hospital Medical Center, OH 45229, USA
    Blood 111:5694-703. 2008
    ..These data change the conventional wisdom that inhibitory receptors are restricted to inhibitory signals; we therefore propose that a single receptor can have dual functionality in distinct cell types after unique cellular signals...
  42. pmc Esophageal remodeling develops as a consequence of tissue specific IL-5-induced eosinophilia
    Anil Mishra
    Division of Allergy and Immunology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
    Gastroenterology 134:204-14. 2008
    ..We hypothesized that the development of EE in patients and in an experimental murine model would be associated with eosinophil-mediated tissue remodeling...
  43. doi request reprint Surfactant protein D alters allergic lung responses in mice and human subjects
    Eric B Brandt
    Division of Allergy and Immunology, Cincinnati Children s Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA
    J Allergy Clin Immunol 121:1140-1147.e2. 2008
    ..Surfactant protein (SP) D has been proposed to be protective in allergic airway responses...
  44. pmc IL-9- and mast cell-mediated intestinal permeability predisposes to oral antigen hypersensitivity
    Elizabeth E Forbes
    Division of Allergy and Immunology, Cincinnati Children s Hospital Medical Center, USA
    J Exp Med 205:897-913. 2008
    ..These observations demonstrate a central role for IL-9 and mast cells in experimental intestinal permeability in oral antigen sensitization and suggest that IL-9-mediated mast cell responses have an important role in food allergy...
  45. pmc Intestinal macrophage/epithelial cell-derived CCL11/eotaxin-1 mediates eosinophil recruitment and function in pediatric ulcerative colitis
    Richard Ahrens
    Division of Allergy and Immunology, Department of Pediatrics, University of Cincinnati College of Medicine, CCHMC, Cincinnati, OH 45229, USA
    J Immunol 181:7390-9. 2008
    ....
  46. ncbi request reprint Expression and regulation of a disintegrin and metalloproteinase (ADAM) 8 in experimental asthma
    Nina E King
    Division of Allergy and Immunology, Cincinnati Children s Hospital Medical Center, University of Cincinatti College of Medicine, Cincinnati, OH 45229, USA
    Am J Respir Cell Mol Biol 31:257-65. 2004
    ..Taken together with the role of ADAM33 in asthma, these results suggest that allergic lung responses involve the interplay of diverse members of the ADAM family...
  47. ncbi request reprint Experimental gastrointestinal allergy enhances pulmonary responses to specific and unrelated allergens
    Eric B Brandt
    Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA
    J Allergy Clin Immunol 118:420-7. 2006
    ..Gastrointestinal allergy often precedes or coexists with respiratory allergy...
  48. pmc Negative regulation of eosinophil recruitment to the lung by the chemokine monokine induced by IFN-gamma (Mig, CXCL9)
    Patricia C Fulkerson
    Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine, 231 Bethesda Avenue, Cincinnati, OH 45257 0524, USA
    Proc Natl Acad Sci U S A 101:1987-92. 2004
    ..The identification of a naturally occurring eosinophil inhibitory chemokine pathway in vivo provides a strategic basis for future therapeutic consideration...
  49. doi request reprint MiR-375 is downregulated in epithelial cells after IL-13 stimulation and regulates an IL-13-induced epithelial transcriptome
    T X Lu
    Division of Allergy and Immunology, Cincinnati Children s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
    Mucosal Immunol 5:388-96. 2012
    ..Taken together, our results support a key role of miRNAs, particularly miR-375, in regulating and fine-tuning IL-13-mediated responses...
  50. pmc Basic pathogenesis of eosinophilic esophagitis
    Carine Blanchard
    Division of Allergy and Immunology, Cincinnati Children s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA
    Gastrointest Endosc Clin N Am 18:133-43; x. 2008
    ....
  51. pmc Mast cells are required for experimental oral allergen-induced diarrhea
    Eric B Brandt
    Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA
    J Clin Invest 112:1666-77. 2003
    ..These results demonstrate that oral allergen-induced diarrhea associated with experimental Th2 intestinal inflammation is largely mast cell, IgE, serotonin, and PAF dependent...
  52. pmc Gastrointestinal eosinophilia
    Li Zuo
    Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children s Hospital Medical Center, University of Cincinnati, College of Medicine, 3333 Burnet Avenue, Cincinnati, OH 45229 3039, USA
    Immunol Allergy Clin North Am 27:443-55. 2007
    ..All three groups of gastrointestinal eosinophila are described in this article, although the focus is on primary gastrointestinal eosinophilia...
  53. ncbi request reprint Eosinophilic gastrointestinal disorders (EGID)
    Marc E Rothenberg
    Department of Pediatrics, Cincinnati Children s Hospital Medical Center, Cincinnati, Ohio 45229 3039, USA
    J Allergy Clin Immunol 113:11-28; quiz 29. 2004
    ..An essential question is to determine the cellular and molecular basis for each of these clinical problems and the best treatment regimen, which is the main subject of this review...
  54. doi request reprint FIP1L1/PDGFRalpha synergizes with SCF to induce systemic mastocytosis in a murine model of chronic eosinophilic leukemia/hypereosinophilic syndrome
    Yoshiyuki Yamada
    Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children s Hospital Medical Center, OH 45229 3039, USA
    Blood 112:2500-7. 2008
    ..The increased proliferation and survival correlated with increased SCF-induced Akt activation. In summary, F/P synergistically promotes MC development, activation, and survival in vivo and in vitro in response to SCF...
  55. pmc Dissection of experimental asthma with DNA microarray analysis identifies arginase in asthma pathogenesis
    Nives Zimmermann
    Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children s Hospital Medical Center, Cincinnati, Ohio 45229, USA
    J Clin Invest 111:1863-74. 2003
    ..Based on the ability of arginase to regulate generation of NO, polyamines, and collagen, these results provide a basis for pharmacologically targeting arginine metabolism in allergic disorders...
  56. pmc Dissociation between symptoms and histological severity in pediatric eosinophilic esophagitis
    Scott Pentiuk
    Department of Pediatrics, Cincinnati Children s Hospital Medical Center, University of Cincinnati College of Medicine, OH, USA
    J Pediatr Gastroenterol Nutr 48:152-60. 2009
    ..The relation between patient symptoms and histological severity of eosinophilic esophagitis (EE) is not known. We created a pediatric EE symptom score (PEESS) and compared the results with histological findings in the esophagus...
  57. ncbi request reprint Trefoil factor-2 is an allergen-induced gene regulated by Th2 cytokines and STAT6 in the lung
    Nikolaos M Nikolaidis
    Division of Allergy and Immunology, Cincinnati Children s Hospital Medical Center, 3333 Burnet Avenue, MLC 7028 Cincinnati, OH 45229, USA
    Am J Respir Cell Mol Biol 29:458-64. 2003
    ....
  58. ncbi request reprint Chemokines in asthma: cooperative interaction between chemokines and IL-13
    Nives Zimmermann
    Divisions of Allergy and Immunology, Department of Pediatrics, Cincinnati Children s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229 3039, USA
    J Allergy Clin Immunol 111:227-42; quiz 243. 2003
    ....
  59. ncbi request reprint Eosinophil-associated gastrointestinal disorders: a world-wide-web based registry
    Jesus R Guajardo
    Division of Allergy and Immunology, Department of Pediatrics, Children s Hospital Medical Center, Cincinnati, Ohio 45229, USA
    J Pediatr 141:576-81. 2002
    ....
  60. pmc Allergy and eosinophil-associated gastrointestinal disorders (EGID)
    Charles W Debrosse
    Division of Allergy and Immunology, Cincinnati Children s Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United States
    Curr Opin Immunol 20:703-8. 2008
    ..In the article herein, we will review the most recent scientific advances influencing our understanding of EGID with special emphasis on the role of allergens in the pathogenesis of EGID...
  61. pmc Origin, regulation and physiological function of intestinal oeosinophils
    Patricia C Fulkerson
    Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA
    Best Pract Res Clin Gastroenterol 22:411-23. 2008
    ..In addition, the regulation of oeosinophil survival by inhibitory and death receptors and the expanding role for oeosinophils in health and disease are reviewed...
  62. ncbi request reprint Hypereosinophilic syndromes and new therapeutic approaches including anti-IL-5
    Miguel L Stein
    University of Cincinnati College of Medicine, Division of Allergy and Immunology, Cincinnati Children s Hospital Medical Center, 3333 Burnet Avenue, MLC 7028, Cincinnati, OH 45229, USA
    Expert Rev Clin Immunol 1:633-44. 2005
    ..This review will analyze the etiology, classification and new options for the treatment of the hypereosinophilic syndromes, with particular emphasis on anti-interleukin-5 therapy...
  63. ncbi request reprint Pediatric patients with eosinophilic esophagitis: an 8-year follow-up
    Amal H Assa'ad
    Division of Allergy and Immunology, Cincinnati Children s Hospital Medical Center, Cincinnati, OH 45229, USA
    J Allergy Clin Immunol 119:731-8. 2007
    ..Eosinophilic esophagitis (EE) is a gastrointestinal disorder that is increasingly diagnosed in pediatric patients...
  64. pmc Arginase I suppresses IL-12/IL-23p40-driven intestinal inflammation during acute schistosomiasis
    De Broski R Herbert
    Research Service, Cincinnati Veterans Administration Medical Center, Cincinnati, OH 45220, USA
    J Immunol 184:6438-46. 2010
    ..Thus, macrophage-derived Arg I protects hosts against excessive tissue injury caused by worm eggs during acute schistosomiasis by suppressing IL-12/IL-23p40 production and maintaining the Treg/Th17 balance within the intestinal mucosa...
  65. pmc IL-13 induces esophageal remodeling and gene expression by an eosinophil-independent, IL-13R alpha 2-inhibited pathway
    Li Zuo
    Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children s Hospital Medical Center, Cincinnati, OH 45229, USA
    J Immunol 185:660-9. 2010
    ..Notably, we identified a pathway that induces EE-like changes and is IL-13-driven, eosinophil-independent, and suppressed by IL-13Ralpha2...
  66. ncbi request reprint Eosinophil Function in Eosinophil-associated Gastrointestinal Disorders
    Simon P Hogan
    Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229 3039, USA
    Curr Allergy Asthma Rep 6:65-71. 2006
    ..We summarize recent experimental analysis examining the underlying contribution of eosinophils to disease pathogenesis and discuss possible therapeutic approaches for the treatment of these diverse diseases...
  67. doi request reprint Biology of the eosinophil
    Carine Blanchard
    Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229 3039, USA
    Adv Immunol 101:81-121. 2009
    ..The mechanisms and consequences of eosinophil responses in experimental inflammatory models and human diseases are discussed...
  68. pmc Persistent effects induced by IL-13 in the lung
    Patricia C Fulkerson
    Department of Molecular Genetics, Biochemistry and Microbiology, Cincinnati Children s Hospital Medical Center, University of Cincinnati College of Medicine, 3333 Burnet Avenue, Cincinnati, Ohio 45229 3039, USA
    Am J Respir Cell Mol Biol 35:337-46. 2006
    ..Thus, several hallmark features of IL-13-induced lung pathology persist and are dissociated from eosinophilia after IL-13 overexpression ceases...
  69. ncbi request reprint Eosinophilic esophagitis: concepts, controversies, and evidence
    Philip E Putnam
    Division of Gastroenterology, Hepatology, and Nutrition, University of Cincinnati College of Medicine, Cincinnati Children s Hospital Medical Center, Cincinnati Center for Eosinophilic Disorders, Cincinnati, OH 45229, USA
    Curr Gastroenterol Rep 11:220-5. 2009
    ..Intense investigations to explain the underpinnings of the disorder and to discover effective therapy are ongoing...
  70. doi request reprint Murine model of hypereosinophilic syndromes/chronic eosinophilic leukemia
    Yoshiyuki Yamada
    Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children s Hospital Medical Center, Cincinnati, Ohio, USA
    Int Arch Allergy Immunol 149:102-7. 2009
    ....
  71. ncbi request reprint Suppressive effect of IL-4 on IL-13-induced genes in mouse lung
    Fred D Finkelman
    Division of Immunology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA
    J Immunol 174:4630-8. 2005
    ..These results provide a potential explanation for the dominant role of IL-13 in induction of goblet cell hyperplasia and airway hyperresponsiveness in asthma...
  72. doi request reprint Acquired coenzyme Q10 deficiency in children with recurrent food intolerance and allergies
    Michael V Miles
    Division of Pathology and Laboratory Medicine, Department of Pediatrics, Cincinnati Children s Hospital Medical Center and University of Cincinnati College of Medicine, ML 2015, 3333 Burnet Ave, Cincinnati, OH 45229 3039, USA
    Mitochondrion 11:127-35. 2011
    ..69; p = 0.012; n = 23). Children with recurrent food intolerance and allergies may acquire CoQ10 deficiency with disease progression...
  73. pmc A critical role for eotaxin in experimental oral antigen-induced eosinophilic gastrointestinal allergy
    S P Hogan
    Division of Pulmonary Medicine, Allergy and Clinical Immunology, Department of Pediatrics, Children s Hospital Medical Center, Cincinnati, OH 45229, USA
    Proc Natl Acad Sci U S A 97:6681-6. 2000
    ..Furthermore, eotaxin is identified as a critical regulator of antigen-induced eosinophilic inflammation in the gastrointestinal tract...
  74. pmc CD44--a sticky target for asthma
    Marc E Rothenberg
    Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children s Hospital Medical Center, Cincinnati, Ohio 45229, USA
    J Clin Invest 111:1460-2. 2003
  75. ncbi request reprint Identification of a cooperative mechanism involving interleukin-13 and eotaxin-2 in experimental allergic lung inflammation
    Samuel M Pope
    Division of Allergy and Immunology, Cincinnati Children s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA
    J Biol Chem 280:13952-61. 2005
    ..Taken together, these results demonstrate a cooperative mechanism between IL-13 and eotaxin-2. In particular, IL-13 mediates allergen-induced eotaxin-2 expression, and eotaxin-2 mediates IL-13-induced airway eosinophilia...
  76. pmc Paired immunoglobulin-like receptor B (PIR-B) negatively regulates macrophage activation in experimental colitis
    Ariel Munitz
    Division of Allergy and Immunology, Cincinnati Children s Hospital Medical Center, Cincinnati, Ohio 45229, USA
    Gastroenterology 139:530-41. 2010
    ..We examined the role of the inhibitory receptor paired immunoglobulin-like receptor B (PIR-B) in the regulation of macrophage function in innate intestinal immunity...
  77. doi request reprint Importance of cytokines in murine allergic airway disease and human asthma
    Fred D Finkelman
    Department of Medicine, Cincinnati Veterans Affairs Medical Center, Cincinnati, OH 45220, USA
    J Immunol 184:1663-74. 2010
    ..Results of these analyses establish the importance of specific cytokines in MAAD and human asthma and have therapeutic implications...
  78. ncbi request reprint The eotaxin chemokines and CCR3 are fundamental regulators of allergen-induced pulmonary eosinophilia
    Samuel M Pope
    Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children s Hospital Medical Center, Cincinnati, OH 45229, USA
    J Immunol 175:5341-50. 2005
    ..These results imply that successful blockade of Ag-induced pulmonary eosinophilia will require antagonism of multiple CCR3 ligands...
  79. ncbi request reprint Potential of blood eosinophils, eosinophil-derived neurotoxin, and eotaxin-3 as biomarkers of eosinophilic esophagitis
    Michael R Konikoff
    Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Cincinnati Children s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229 3039, USA
    Clin Gastroenterol Hepatol 4:1328-36. 2006
    ..The aim of this study was to identify noninvasive biomarkers that correlated with disease activity and response to treatment as measured by esophageal eosinophilia...
  80. ncbi request reprint Intratracheal IL-13 induces eosinophilic esophagitis by an IL-5, eotaxin-1, and STAT6-dependent mechanism
    Anil Mishra
    Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children s Hospital Medical Center, Cincinnati, OH 45229, USA
    Gastroenterology 125:1419-27. 2003
    ..We aimed to determine whether delivery of a Th2 cytokine (interleukin [IL]-13) to the lung was sufficient for induction of EE...
  81. pmc Involvement of mast cells in eosinophilic esophagitis
    J Pablo Abonia
    Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children s Hospital Medical Center, Cincinnati, Ohio 45229, USA
    J Allergy Clin Immunol 126:140-9. 2010
    ..Eosinophilic esophagitis (EE) is an emerging disorder with poorly understood pathogenesis...
  82. ncbi request reprint Pulmonary chemokine expression is coordinately regulated by STAT1, STAT6, and IFN-gamma
    Patricia C Fulkerson
    Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine, Cincinnati, OH 45257, USA
    J Immunol 173:7565-74. 2004
    ..Collectively, we demonstrate that allergen-induced inflammation involves coordinate regulation by STAT1, STAT6, and IFN-gamma...
  83. ncbi request reprint Analysis of the CC chemokine receptor 3 gene reveals a complex 5' exon organization, a functional role for untranslated exon 1, and a broadly active promoter with eosinophil-selective elements
    N Zimmermann
    Division of Pulmonary Medicine, Allergy and Clinical Immunology, Department of Pediatrics, Children s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA
    Blood 96:2346-54. 2000
    ..Thus, the human CCR3 gene has a complex 5' exon structure, a conserved promoter with strong activity in multiple cell types, and a functional 5' untranslated exon...
  84. doi request reprint Quality of life in paediatric eosinophilic oesophagitis: what is important to patients?
    J P Franciosi
    Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children s Hospital Medical Center, Cincinnati, OH 45229 3039, USA
    Child Care Health Dev 38:477-83. 2012
    ..The primary objective of this study was to identify key patient-reported and parent proxy outcome elements of EoE disease-specific HRQOL...
  85. pmc Eotaxin is required for the baseline level of tissue eosinophils
    A N Matthews
    Division of Pulmonary Medicine, Allergy, and Clinical Immunology, Children s Hospital Medical Center, Cincinnati, OH 45229, USA
    Proc Natl Acad Sci U S A 95:6273-8. 1998
    ..Because a variety of chemokines are constitutively expressed, their involvement in the baseline trafficking of leukocytes into nonhematopoietic tissue should now be considered...
  86. pmc Clinical, pathologic, and molecular characterization of familial eosinophilic esophagitis compared with sporadic cases
    Margaret H Collins
    Division of Pathology and Laboratory Medicine, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati Children s Hospital Medical Center, Cincinnati, Ohio 45229, USA
    Clin Gastroenterol Hepatol 6:621-9. 2008
    ..Eosinophilic esophagitis (EE) occurs in families...
  87. ncbi request reprint ICAM-1-dependent pathways regulate colonic eosinophilic inflammation
    Elizabeth Forbes
    Allergy and Inflammation Research Group, Division of Biochemistry and Molecular Biology, The John Curtin School of Medical Research, Australian National University, Canberra, Australia
    J Leukoc Biol 80:330-41. 2006
    ..These studies demonstrate that beta2 -integrin/ICAM-1-dependent pathways are integral to eosinophil recruitment into the colon during GI inflammation associated with colonic injury...
  88. ncbi request reprint IL-17E upregulates the expression of proinflammatory cytokines in lung fibroblasts
    Severine Letuve
    Meakins Christie Laboratories, Department of Pathology and Medicine, McGill University, Montreal, Quebec, Canada
    J Allergy Clin Immunol 117:590-6. 2006
    ..IL-17E proinflammatory activity has been proposed to involve induction of cytokine and chemokine production. Recruitment of inflammatory cells may be mediated by tissue-resident cells...
  89. ncbi request reprint Anti-IL-5 and hypereosinophilic syndromes
    Steven A Sutton
    Division of Allergy and Immunology, Cincinnati Children s Hospital Medical Center, 3333 Burnet Avenue, MLC 7028, Cincinnati, OH 45229, USA
    Clin Immunol 115:51-60. 2005
    ..This review will discuss the etiology, classification, and treatment options for the hypereosinophilic syndromes, with particular emphasis on anti-interleukin-5 therapy...
  90. pmc CXCL9 inhibits eosinophil responses by a CCR3- and Rac2-dependent mechanism
    Patricia C Fulkerson
    Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati College of Medicine, OH 45229 3039, USA
    Blood 106:436-43. 2005
    ..These results establish evidence that distinct chemokines can use CCR3 to induce opposing signals in eosinophils...
  91. ncbi request reprint Eotaxin-1-regulated eosinophils have a critical role in innate immunity against experimental Brugia malayi infection
    Jonathan E Simons
    School of Biological Sciences, University of Manchester, Manchester, UK
    Eur J Immunol 35:189-97. 2005
    ..Thus, our data show that the presence of eosinophils is critical for innate clearance of B. malayi Mf infection, whereas rapid clearance of secondary infections is independent of both eotaxin-1 and IL-5...
  92. ncbi request reprint T helper-2 immunity regulates bronchial hyperresponsiveness in eosinophil-associated gastrointestinal disease in mice
    Elizabeth Forbes
    Allergy and Inflammation Research Group, Division of Molecular Bioscience, The John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory, Australia
    Gastroenterology 127:105-18. 2004
    ....
  93. ncbi request reprint Experimental analysis of eosinophil-associated gastrointestinal diseases
    Simon P Hogan
    Division of Biochemistry and Molecular Biology, John Curtin School of Medical Research, Australian National University, Canberra, Australia
    Curr Opin Allergy Clin Immunol 2:239-48. 2002
    ....
  94. ncbi request reprint Chemokines in eosinophil-associated gastrointestinal disorders
    Simon P Hogan
    Division of Molecular Bioscience, John Curtin School of Medical Research, Australian National University, PO Box 334, Canberra, Australia 0200
    Curr Allergy Asthma Rep 4:74-82. 2004
    ..In this review, we describe the role of CD4+ T cells and eosinophils in the clinical manifestations of EGDs and discuss the current understanding of the role of chemokines in the recruitment of these cells in the expression of diseases...
  95. ncbi request reprint Eotaxin-2 and IL-5 cooperate in the lung to regulate IL-13 production and airway eosinophilia and hyperreactivity
    Ming Yang
    Division of Molecular Biosciences, The John Curtin School of Medical Research, Australian National University, Canberra, ACT
    J Allergy Clin Immunol 112:935-43. 2003
    ..However, the contribution of eotaxin-2 to the development of defined pathogenic features of allergic disease remains to be defined...
  96. ncbi request reprint Constitutive overexpression of IL-5 induces extramedullary hematopoiesis in the spleen
    Sophia Khaldoyanidi
    Division of Vascular Biology, La Jolla Institute for Molecular Medicine, San Diego, CA 92121, USA
    Blood 101:863-8. 2003
    ..Overall, our results suggest that constitutive overexpression of IL-5 can potentially induce colonization of spleen with MSP cells, which provides the necessary microenvironment for establishment of hematopoiesis in extramedullary sites...
  97. pmc Intrinsic defect in T cell production of interleukin (IL)-13 in the absence of both IL-5 and eotaxin precludes the development of eosinophilia and airways hyperreactivity in experimental asthma
    Joerg Mattes
    Division of Biochemistry and Molecular Biology, The John Curtin School of Medical Research, Australian National University, Canberra, ACT 0200, Australia
    J Exp Med 195:1433-44. 2002
    ....
  98. ncbi request reprint The role of Th2 cytokines, chemokines and parasite products in eosinophil recruitment to the gastrointestinal mucosa during helminth infection
    Helen Dixon
    Faculty of Life Sciences, University of Manchester, Manchester, UK
    Eur J Immunol 36:1753-63. 2006
    ..spiralis and T. muris products, suggest that CCL11 is the salient but not the sole eosinophil chemoattractant of biological significance during gastrointestinal helminth infection...
  99. ncbi request reprint Eosinophilic esophagitis
    Richard J Noel
    Division of Pediatric Gastroenterology and Nutrition, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
    Curr Opin Pediatr 17:690-4. 2005
    ..In the last 3 years, the research focus has evolved into understanding its immunologic and demographic features as well as the development of efficacious therapies...
  100. doi request reprint Eosinophils: biological properties and role in health and disease
    Simon P Hogan
    Clin Exp Allergy 38:709-50. 2008
    ..Finally, strategies for targeted therapeutic intervention in eosinophil-mediated mucosal diseases are conceptualized...
  101. doi request reprint Mitochondrial missile defense
    Victor Nizet
    Nat Med 14:910-2. 2008