Genomes and Genes
N J Klein
Affiliation: University College London
- Infliximab for the treatment of intravenous immunoglobulin resistant Kawasaki disease complicated by coronary artery aneurysms: a case reportRobert J Brogan
Department of Paediatric Rheumatology, UCL Institute of Child Health and Great Ormond Street Hospital, 30 Guilford Street, London, UK
Pediatr Rheumatol Online J 7:3. 2009..This case report describes an 8 year old boy with IVIG resistant Kawasaki disease complicated by severe bilateral coronary artery aneurysms successfully treated with infliximab, a monoclonal antibody against tumour necrosis factor alpha...
- Expression of the inflammatory chemokines CCL5, CCL3 and CXCL10 in juvenile idiopathic arthritis, and demonstration of CCL5 production by an atypical subset of CD8+ T cellsDaniel S Pharoah
Rheumatology Unit, Institute of Child Health, UCL, London, UK
Arthritis Res Ther 8:R50. 2006..We believe this to be the first in depth analysis of these mediators of inflammation in JIA...
- Immunodeficiency and the gut: clues to the role of the immune system in gastrointestinal diseaseN Klein
Immunobiology Unit, Institute of Child Health, London, UK
Ital J Gastroenterol Hepatol 31:802-6. 1999..This article focuses on recent developments in this field and highlights the insights gained in understanding the complex relationship between immunodeficiency and the gut...
- Mannose-binding lectin: do we need it?N J Klein
Infectious Diseases and Microbiology Unit, Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK
Mol Immunol 42:919-24. 2005..However, the importance of MBL, in defence against infection, is still debated. This article discusses recent developments in MBL research and explores how MBL may be operating in the setting of modern medical practice...
- Basic research in endoscopyR A Kozarek
Immunobiology Unit, Institute of Child Health, London, UK
Ital J Gastroenterol Hepatol 31:743-8. 1999..The latter may include training in areas such as outcomes, physics, or biomedical engineering; and should also entail a formal mentoring process, "seed money" early in the investigator's career and protected time...
- Mannose-binding lectin regulates the inflammatory response of human professional phagocytes to Neisseria meningitidis serogroup BD L Jack
Immunobiology Unit, Institute of Child Health, University College, London, United Kingdom
J Infect Dis 184:1152-62. 2001..These results suggest that MBL not only is involved in complement activation but also is a potent regulator of inflammatory pathways and, as such, may affect the severity of meningococcal disease...
- Mannose-binding lectin accelerates complement activation and increases serum killing of Neisseria meningitidis serogroup CD L Jack
Institute of Child Health, University College London, London, United Kingdom
J Infect Dis 184:836-45. 2001..meningitidis and can modulate complement-dependent killing of the bacterium. These findings could explain the observed susceptibility to meningococcal disease of individuals genetically deficient in MBL...
- Mannose-binding lectin: targeting the microbial world for complement attack and opsonophagocytosisD L Jack
Immunobiology Unit, Institute of Child Health, University College London, UK
Immunol Rev 180:86-99. 2001..In addition, the protein also modulates disease severity, at least in part through a complex, dose-dependent influence on cytokine production. The mechanisms and signalling pathways involved in such processes remain to be elucidated...
- Platelet and leucocyte activation in childhood sickle cell disease: association with nocturnal hypoxaemiaD P Inwald
Portex Unit of Anaesthesia, Intensive Care and Respiratory Medicine, Great Ormond Street Hospital for Children NHS Trust, London, UK
Br J Haematol 111:474-81. 2000..466, P = 0.038) and monocyte CD11b (Spearman's rho -0.652, P = 0. 002). These findings provide important clues about the mechanism by which SCD patients may become predisposed to vaso-occlusive events...
- Deficiency of mannose-binding lectin and burden of infection in children with malignancy: a prospective studyO Neth
Immunobiology Unit, Institute of Child Health, 30 Guilford Street, WC1N 1EH, London, UK
Lancet 358:614-8. 2001..This finding suggests that MBL infusions could represent a new therapeutic approach which would aid the management of chemotherapy-induced complications in this population of children...
- Absence of platelet CD40L identifies patients with X-linked hyper IgM syndromeD P Inwald
Portex Department of Anaesthesia, Intensive Therapy and Respiratory Medicine and Immunobiology Unit, Institute of Child Health, London, UK
Clin Exp Immunol 120:499-502. 2000..We have demonstrated that this technique is useful in neonatal screening, in rapid diagnosis and in determining reconstitution by donor bone marrow post-transplantation...
- Investigation of platelet-neutrophil interactions in whole blood by flow cytometryM J Peters
Department of Immunobiology, Institute of Child Health, London, UK
J Immunol Methods 209:125-35. 1997..This straightforward technique is simple, reproducible, and allows assessment of platelet-neutrophil interactions and activation of neutrophils. It may also provide a method for estimating platelet activation in whole blood...
- Staphylococcal toxins in sudden unexpected death in infancy: experience from a single specialist centreM A Weber
Department of Paediatric Histopathology, Great Ormond Street Hospital For Children and UCL Institute of Child Health, London, UK
Forensic Sci Med Pathol 7:141-7. 2011..These data are consistent with the hypothesis that a subset of otherwise unexplained SUDI may be related to the presence of S aureus colonization/infection, but do not indicate routine testing for toxin-associated genotypes...
- Mannose-binding lectin is present in the infected airway: a possible pulmonary defence mechanismK J Fidler
Infectious Diseases and Microbiology Unit, Institute of Child Health, London, UK
Thorax 64:150-5. 2009..The mechanism is uncertain, and could relate either to systemic or local effects. The aim of this study was to determine, in a large cohort of children, whether MBL is present on the airway surface in health or disease...
- Mannose-binding lectin binds to a range of clinically relevant microorganisms and promotes complement depositionO Neth
Immunobiology Unit, Institute of Child Health, University College London, NHS Trust, London, United Kingdom
Infect Immun 68:688-93. 2000..Bound MBL was able to promote C4 deposition in a concentration-dependent manner. We conclude that MBL may be of importance in first-line immune defense against several important pathogens...
- High-level endothelial E-selectin (CD62E) cell adhesion molecule expression by a lipopolysaccharide-deficient strain of Neisseria meningitidis despite poor activation of NF-kappaB transcription factorG L J Dixon
Immunobiology Unit, Institute of Child Health, London, UK
Clin Exp Immunol 135:85-93. 2004..These signals may explain the potent effects of N. meningitidis on CD62E expression on vascular endothelium and provide a basis for the complex endothelial dysregulation seen in meningococcal sepsis...
- Vbeta-restricted T cell adherence to endothelial cells: a mechanism for superantigen-dependent vascular injuryP A Brogan
Institute of Child Health, London, UK
Arthritis Rheum 50:589-97. 2004..To investigate the potential for endothelial cells to operate as superantigen-presenting cells for T cells and the potential for such an interaction to cause endothelial cell activation and injury...
- Randomized clinical trial of glutamine-supplemented versus standard parenteral nutrition in infants with surgical gastrointestinal diseaseE G p Ong
Department of Paediatric Surgery, University College London Institute of Child Health and Great Ormond Street Hospital for Children, London, UK
Br J Surg 99:929-38. 2012..The aim of this trial was to determine whether glutamine supplementation of parenteral nutrition in infants requiring surgery would reduce the time to full enteral feeding and/or decrease the incidence of sepsis and septicaemia...
- Endothelial injury and repair in systemic vasculitis of the youngL A Clarke
Institute of Child Health, University College London and Great Ormond Street Hospital National Health Service Trust, London, UK
Arthritis Rheum 62:1770-80. 2010..The purpose of this study was to assess how indices of endothelial injury and repair change during different stages of disease activity in children with primary systemic vasculitis (PSV)...
- T cell activation profiles in Kawasaki syndromeP A Brogan
Department of Rheumatology, Institute of Child Health and Great Ormond St Hospital for Children, London, UK
Clin Exp Immunol 151:267-74. 2008....
- Natural human antibodies to pneumococcus have distinctive molecular characteristics and protect against pneumococcal diseaseH E Baxendale
Infectious Diseases and Microbiology Unit, Institute of Child Health, University College London, London, UK
Clin Exp Immunol 151:51-60. 2008..4 (+/-4.2) and selective use of IGHD6 (P < 0.001) and IGHJ6 (P < 0.01) family genes. The clones expressing IGHV1-69 and IGHV 3-21 provided significant passive protection against invasive pneumococcal disease in vivo...
- Contribution of inflammation to the pathology of idiopathic pulmonary arterial hypertension in childrenS Hall
Infectious Diseases and Microbiology, Institute of Child Health, London WC1N 1EH, UK
Thorax 64:778-83. 2009..002). This study shows that pulmonary inflammation is present in the lungs of children with IPAH. This may indicate a role for inflammation in the pathobiology of IPAH and provide the rationale for novel therapeutic intervention...
- Quantitative detection of circulating endothelial cells in vasculitis: comparison of flow cytometry and immunomagnetic bead extractionL A Clarke
Department of Rheumatology, Institute of Child Health UCL and Great Ormond Street Hospital NHS Trust, London, UK
J Thromb Haemost 6:1025-32. 2008..Reports suggest that there is good agreement between these methods for CEC quantification...
- Endothelial and platelet microparticles in vasculitis of the youngP A Brogan
Department of Nephrourology, Institute of Child Health, London, UK
Arthritis Rheum 50:927-36. 2004....
- Circulating aldosterone levels are unexpectedly low in children with acute meningococcal diseaseE J Lichtarowicz-Krynska
The London Centre for Paediatric Endocrinology and Metabolism and Great Ormond Street Hospital for Children NHS Trust, London, UK
J Clin Endocrinol Metab 89:1410-4. 2004..Further work is needed to elucidate the mechanisms underlying this finding and to examine its clinical implications...
- Gram-negative bacteria induce proinflammatory cytokine production by monocytes in the absence of lipopolysaccharide (LPS)H Uronen
Immunobiology Unit, Institute of Child Health, University College London, London and Edward Jenner Institute for Vaccine Research, Compton, UK
Clin Exp Immunol 122:312-5. 2000..meningitidis does not require the presence of LPS. Therapeutic strategies designed to block LPS alone may not therefore be sufficient for interrupting the inflammatory response in severe meningococcal disease...
- Endothelial adhesion molecule expression and its inhibition by recombinant bactericidal/permeability-increasing protein are influenced by the capsulation and lipooligosaccharide structure of Neisseria meningitidisG L Dixon
Immunobiology Unit, Institute of Child Health, London, United Kingdom
Infect Immun 67:5626-33. 1999..These findings could have important implications for the use of antiendotoxin therapy in meningococcal disease...
- Demystified...adhesion molecule deficienciesD Inwald
Portex Department of Anaesthesia, Intensive Care and Respiratory Medicine, Institute of Child Health, London, UK
Mol Pathol 54:1-7. 2001..This review describes these leucocyte adhesion defects and discusses how they have provided important insights into the function of these molecules...
- Ischemic preconditioning prevents endothelial injury and systemic neutrophil activation during ischemia-reperfusion in humans in vivoR K Kharbanda
Centre for Clinical Pharmacology and Therapeutics, University College London, London, UK
Circulation 103:1624-30. 2001..We studied the effects of experimental IR on endothelial and neutrophil function in the human forearm in vivo and examined the protection afforded by IPC...
- Dendritic cell activation and cytokine production induced by group B Neisseria meningitidis: interleukin-12 production depends on lipopolysaccharide expression in intact bacteriaG L Dixon
Immunobiology Unit, Institute of Child Health, London WC1N 1EH, Windeyer Institute, University College London, London WC1E 6BT, United Kingdom
Infect Immun 69:4351-7. 2001..These findings may be useful in assessing components of N. meningitidis as potential vaccine candidates...
- Kawasaki disease: an evidence based approach to diagnosis, treatment, and proposals for future researchP A Brogan
Nephrourology Department, Institute of Child Health, London, UK
Arch Dis Child 86:286-90. 2002..Future research as proposed by the London Kawasaki Disease Research Group is outlined, and clinicians are invited to prospectively enroll their suspected cases into this collaborative research project...
- T cell Vbeta repertoires in childhood vasculitidesP A Brogan
Department of Nephrourology, Institute of Child Health, 30 Guilford St, London, UK, WC1N 1EH
Clin Exp Immunol 131:517-27. 2003..While these data provide impetus for further research into this contentious field, they do not resolve unequivocally the question of the role of SAgs in childhood vasculitic syndromes...
- Growth hormone enhances proinflammatory cytokine production by monocytes in whole bloodH Uronen-Hansson
Institute of Child Health, Immunobiology, 30 Guilford Street, London WC1N 1EH, UK
Growth Horm IGF Res 13:282-6. 2003..Our results show that GH enhances IL1-alpha, IL-6 and TNF-alpha production by LPS activated monocytes in whole blood. The modulation of cytokines by GH may be responsible for the adverse consequences of GH in critically ill patients...
- Endotoxin immunity and the development of the systemic inflammatory response syndrome in critically ill childrenR C M Stephens
Critical Care Group, Portex Unit, Institute of Child Health, 30 Guilford Street, WC1N 1EH, London, UK
Intensive Care Med 32:286-94. 2006..Because of the existing literature we defined two sub-groups according to the primary reason for ICU admission: infection and non-infection...
- Aberrant response to commensal Bacteroides thetaiotaomicron in Crohn's disease: an ex vivo human organ culture studyL A Edwards
Centre for Paediatric Gastroenterology, Lower Ground Floor, Royal Free Hospital, London, UK
Inflamm Bowel Dis 17:1201-8. 2011..The aim of the present study was to compare and contrast the early innate immune response of pediatric "healthy" versus CD mucosa to pathogenic, probiotic, and commensal bacteria...
- Susceptibility to infection in patients with neutropenia: the role of the innate immune systemO W Neth
Infectious Diseases and Microbiology Unit, Institute of Child Health and Great Ormond Street Hospital NHS Trust, London, UK
Br J Haematol 129:713-22. 2005..frequency one in 10). Here, we review the potential role of the innate immune system in determining susceptibility to infections in patients with neutropenia...
- A critical role for ATF2 transcription factor in the regulation of E-selectin expression in response to non-endotoxin components of Neisseria meningitidisM C Jacobsen
Infection, Inflammation and Rheumatology Section, Institute of Child Health, University College London, London, UK
Cell Microbiol 18:66-79. 2016....
- Management of Kawasaki diseaseD Eleftheriou
Paediatric Rheumatology Infectious Diseases and Microbiology Unit, Institute of Child Health and Great Ormond Street Hospital NHS Foundation Trust, London, UK
Arch Dis Child 99:74-83. 2014..This paper summarises recent advances in the understanding of KD pathogenesis and therapeutics, and provides an approach for managing KD patients in the UK in the light of these advances. ..
- Is there a role for mannan/mannose-binding lectin (MBL) in defence against infection following chemotherapy for cancer?N J Klein
Institute of Child Health, University College London, London, UK
Clin Exp Immunol 138:202-4. 2004
- Immunohistochemical expression of inflammatory markers in sudden infant death; ancillary tests for identification of infectionJ W Pryce
Department of Histopathology, Camelia Botnar Laboratories, Great Ormond Street Hospital for Children NHS Trust, London, UK UCL Institute of Child Health, London, UK
J Clin Pathol 67:1044-51. 2014..This study investigates the role of inflammatory markers in SUDI autopsies for determining cause of death...
- Tumor necrosis factor-alpha inhibits epithelial differentiation and morphogenesis in the mouse metanephric kidney in vitroC M Cale
Developmental Biology and Nephrourology, Institute of Child Health, London, United Kingdom
Int J Dev Biol 42:663-74. 1998..In addition, TNF-alpha mRNA and protein were expressed by clonal renal mesenchymal cells in vitro, suggesting that these cells are a source of TNF-alpha in vivo...
- Activation of complement by mannose-binding lectin on isogenic mutants of Neisseria meningitidis serogroup BD L Jack
Immunobiology Unit, Institute of Child Health, London, United Kingdom
J Immunol 160:1346-53. 1998..Our results suggest that MBL may bind to and activate complement on these encapsulated organisms, and the major determinants of these effects are the LOS structure and sialylation...
- Infection and sudden unexpected death in infancy: a systematic retrospective case reviewM A Weber
Department of Paediatric Pathology, Great Ormond Street Hospital for Children and the Institute of Child Health, University College London, London, UK
Lancet 371:1848-53. 2008..The cause and mechanism of most cases of sudden unexpected death in infancy (SUDI) remain unknown, despite specialist autopsy examination. We reviewed autopsy results to determine whether infection was a cause of SUDI...
- Decreased monocyte class II MHC expression following major abdominal surgery in children is related to operative stressM McHoney
Department of Paediatric Surgery, Great Ormond Street Hospital for Children and the Institute of Child Health, 30 Guilford Street, WC1N 1EH, London, UK
Pediatr Surg Int 22:330-4. 2006..Class II MHC depression was related to magnitude of surgical trauma, implying that more severe immuneparesis follows surgery of greater magnitude. This may predispose to postoperative infection...
- Severe meningococcal disease is characterized by early neutrophil but not platelet activation and increased formation and consumption of platelet-neutrophil complexesM J Peters
Infection and Microbiology Unit and Portex Unit Critical Care Group, Institute of Child Health, London, United Kingdom
J Leukoc Biol 73:722-30. 2003..Therefore, in severe MD, PMNL activation is likely to promote PNC formation, and we suggest that the reduced levels of PNC seen in established MD reflect rapid loss of PNC from the circulation rather than reduced formation...
- Interleukin-4 increases the permeability of human endothelial cells in cultureK Kotowicz
Immunobiology and Infectious Diseases and Microbiology Units, Institute of Child Health, London, UK
Clin Exp Allergy 34:445-9. 2004..Although some observations suggest that IL-4 may mediate increased vascular permeability, which is a characteristic feature of allergic inflammation, evidence for a direct effect on endothelial cell permeability is lacking...
- Influence of mannose-binding lectin genotypes and serostatus in allo-SCT: analysis of 131 recipients and donorsO W Neth
Infectious Diseases and Microbiology Unit, Institute of Child Health and Great Ormond Street Hospital, London, UK
Bone Marrow Transplant 45:13-9. 2010..Donors' MBL genotypes did not influence infection rates. Prospective studies should clarify the importance of MBL as a prelude for MBL replacement after SCT...
- The role of the collectin system in pulmonary defenceJ Davies
Department of Paediatric Respiratory Medicine, Royal Brompton Hospital and Department of Gene Therapy, Imperial College, London, UK
Paediatr Respir Rev 2:70-5. 2001..The role of MBL in human pulmonary disease is less well established, although accumulating evidence suggests that it is a modifier for lung disease in tuberculosis and cystic fibrosis...
- The link between rotavirus vaccination and intussusception: implications for vaccine strategiesC M Cale
Department of Immunology, Great Ormond Street Hospital for Children NHS Trust, London, UK Immunobiology Unit, Institute of Child Health, London, UK
Gut 50:11-2. 2002