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Genomes and Genes | Philip N HawkinsSummaryAffiliation: University College London Country: UK Publications
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Publications
Spectrum of clinical features in Muckle-Wells syndrome and response to anakinraPhilip N Hawkins
Royal Free and University College Medical School, Royal Free Hospital, London, UK
Arthritis Rheum 50:607-12. 2004..Molecular studies suggest that NALP3 is involved in the processing of interleukin-1beta (IL-1beta), prompting us to investigate whether IL-1 blockade may be therapeutic in patients with MWS...
Serum amyloid P component scintigraphy for diagnosis and monitoring amyloidosisPhilip N Hawkins
Department of Medicine, Royal Free and University College Medical School London, UK
Curr Opin Nephrol Hypertens 11:649-55. 2002..The technique is available routinely for all known or suspected cases of amyloidosis in the NHS National Amyloidosis Centre at the Royal Free Hospital, but it has not been developed commercially...
Hereditary systemic amyloidosis with renal involvementPhilip N Hawkins
National Amyloidosis Centre, Royal Free Hospital, London, UK
J Nephrol 16:443-8. 2003..DNA analysis is now performed routinely in UK National Amyloidosis Centre in patients with systemic amyloidosis in whom AA or AL fibril type cannot be definitively verified...
Association of mutations in the NALP3/CIAS1/PYPAF1 gene with a broad phenotype including recurrent fever, cold sensitivity, sensorineural deafness, and AA amyloidosisEbun Aganna
Barts and The London, Queen Mary s School of Medicine and Dentistry, University of London, London, UK
Arthritis Rheum 46:2445-52. 2002..This study was undertaken to characterize the genetic basis of FCU, MWS, and an overlapping disorder in French Canadian, British, and Indian families, respectively...
Natural history and outcome in systemic AA amyloidosisHelen J Lachmann
National Amyloidosis Centre and Centre for Amyloidosis and Acute Phase Proteins, Department of Medicine, Royal Free and University College Medical School, London
N Engl J Med 356:2361-71. 2007..Little is known about the natural history of AA amyloidosis or its response to treatment...
Efficacy of bortezomib in systemic AL amyloidosis with relapsed/refractory clonal diseaseAshutosh D Wechalekar
National Amyloidosis Centre, Department of Medicine, Royal Free and University College Medical School, Rowland Hill St, London NW3 2PF, United Kingdom
Haematologica 93:295-8. 2008..Fifteen (75%) patients experienced some degree of toxicity, which in 8 (40%) cases resulted in discontinuation of bortezomib. Bortezomib shows promise in the treatment of systemic AL amyloidosis...
Amyloidogenicity and clinical phenotype associated with five novel mutations in apolipoprotein a-IDorota Rowczenio
National Amyloidosis Centre, Centre for Amyloidosis and Acute Phase Proteins, Division of Medicine, Royal Free Campus, University College London, London, England
Am J Pathol 179:1978-87. 2011....
Diagnosis, pathogenesis, treatment, and prognosis of hereditary fibrinogen A alpha-chain amyloidosisJulian D Gillmore
National Amyloidosis Centre, CAAPP, Department of Medicine, Royal Free Campus, University College London, Rowland Hill Street, London NW3 2PF, United Kingdom
J Am Soc Nephrol 20:444-51. 2009..Survival is markedly better than observed with systemic AL amyloidosis, and outcomes with renal replacement therapy are comparable to those for age-matched individuals with nondiabetic renal disease...
Outcome of autologous stem cell transplantation for AL amyloidosis in the UKHugh J B Goodman
National Amyloidosis Centre, Centre for Amyloidosis and Acute Phase Proteins, Royal Free and University College Medical Schools, Hampstead Campus, Royal Free Hospital, London, UK
Br J Haematol 134:417-25. 2006....
Cardiac amyloidosis, a monoclonal gammopathy and a potentially misleading mutationAshutosh D Wechalekar
National Amyloidosis Centre, Centre for Amyloidosis and Acute Phase Proteins, Department of Medicine Hampstead Campus, Royal Free and University College Medical School, London, UK
Nat Clin Pract Cardiovasc Med 6:128-33. 2009..A 46-year-old Afro-Caribbean man presented with progressive dyspnea and recurrent syncope. Clinical examination revealed evidence of biventricular failure...
AL amyloidosis associated with IgM paraproteinemia: clinical profile and treatment outcomeAshutosh D Wechalekar
National Amyloidosis Centre, Centre for Amyloidosis and Acute Phase Proteins, Department of Medicine Hampstead Campus, Royal Free and University College Medical School, London, United Kingdom
Blood 112:4009-16. 2008....
Safety and efficacy of risk-adapted cyclophosphamide, thalidomide, and dexamethasone in systemic AL amyloidosisAshutosh D Wechalekar
National Amyloidosis Centre, Department of Medicine, Royal Free and University College Medical School, Rowland Hill St, London NW3 2PF, UK
Blood 109:457-64. 2007..The clonal response rates to CTD reported here are higher than any previously reported nontransplantation regimen in AL amyloidosis, and risk adaptation allows its use in poorer risk patients. CTD merits prospective randomized study...
In vivo regulation of interleukin 1beta in patients with cryopyrin-associated periodic syndromesHelen J Lachmann
National Amyloidosis Centre, Royal Free and University College Medical School, London NW3 2PF, England, UK
J Exp Med 206:1029-36. 2009..Together, the study allowed new insights into the production and regulation of IL-1beta in man. It also indicated that CAPS is entirely mediated by IL-1beta and that canakinumab treatment restores physiological IL-1beta production...
Sustained pharmacological depletion of serum amyloid P component in patients with systemic amyloidosisJulian D Gillmore
Centre for Amyloidosis and Acute Phase Proteins and the National Amyloidosis Centre, University College London Medical School, London, UK
Br J Haematol 148:760-7. 2010..These promising clinical observations merit further study...
Abnormal tumor necrosis factor receptor I cell surface expression and NF-kappaB activation in tumor necrosis factor receptor-associated periodic syndromeBelinda Nedjai
Barts and The London, Queen Mary s School of Medicine and Dentistry, University of London, London, UK
Arthritis Rheum 58:273-83. 2008....
Images in cardiovascular medicine. Intermittent loss of second heart soundJayshree Joshi
National Amyloidosis Centre, Royal Free and University College Medical School, Rowland Hill Street, London, NW3 2PF United Kingdom
Circulation 114:e612-3. 2006
Outcome in systemic AL amyloidosis in relation to changes in concentration of circulating free immunoglobulin light chains following chemotherapyHelen J Lachmann
The National Amyloidosis Centre and Centre for Amyloidosis and Acute Phase Proteins, Department of Medicine, Royal Free and University College Medical School, London, UK
Br J Haematol 122:78-84. 2003..Clinical improvement following chemotherapy in AL amyloidosis is delayed, but treatment strategies can be guided by their early effect on serum FLC concentration...
AA amyloidosis complicating hyperimmunoglobulinemia D with periodic fever syndrome: a report of two casesHelen J Lachmann
Royal Free and University College Medical School, London, UK
Arthritis Rheum 54:2010-4. 2006..We report 2 further cases of patients with AA amyloidosis in HIDS, both of whom developed dialysis-dependent renal failure, and we describe the outcome of the first renal transplant in this setting...
Targeting C-reactive protein for the treatment of cardiovascular diseaseMark B Pepys
Centre for Amyloidosis and Acute Phase Proteins, Department of Medicine, Royal Free and University College Medical School, University College London, Rowland Hill Street, London NW3 2PF, UK
Nature 440:1217-21. 2006....
Sequential heart and autologous stem cell transplantation for systemic AL amyloidosisJulian D Gillmore
National Amyloidosis Centre, Department of Medicine, Royal Free and University College Medical School, London, United Kingdom
Blood 107:1227-9. 2006..Heart transplantation followed by SCT is feasible in selected patients with cardiac AL amyloidosis and may confer substantial survival benefit...
Heterogeneity among patients with tumor necrosis factor receptor-associated periodic syndrome phenotypesEbun Aganna
Barts and London, Queen Mary s School of Medicine and Dentistry, London, UK
Arthritis Rheum 48:2632-44. 2003..To investigate the prevalence of tumor necrosis factor receptor-associated periodic syndrome (TRAPS) among outpatients presenting with recurrent fevers and clinical features consistent with TRAPS...
Response to anakinra in a de novo case of neonatal-onset multisystem inflammatory diseasePhilip N Hawkins
Royal Free and University College, Medical School, London, UK
Arthritis Rheum 50:2708-9. 2004
Misdiagnosis of hereditary amyloidosis as AL (primary) amyloidosisHelen J Lachmann
National Amyloidosis Centre, Department of Medicine, Royal Free and University College Medical School, Royal Free Campus, London, United Kingdom
N Engl J Med 346:1786-91. 2002....
Human plasma fibrinogen is synthesized in the liverGlenys A Tennent
Centre for Amyloidosis and Acute Phase Proteins, Department of Medicine, Royal Free and University College Medical School, London, United Kingdom
Blood 109:1971-4. 2007..After transplantation, only the wild-type sequence was detected, and the liver is thus the source of at least 98% of the circulation fibrinogen...
Systemic amyloidosis and the gastrointestinal tractPrayman T Sattianayagam
National Amyloidosis Centre, Centre for Amyloidosis and Acute Phase Proteins, Division of Medicine Royal Free Campus, University College London Medical School, London, UK
Nat Rev Gastroenterol Hepatol 6:608-17. 2009..Surgical procedures should be contemplated only in an emergency setting because of the risk of decompensation of organs affected by amyloid deposition...
Perspectives in treatment of AL amyloidosisAshutosh D Wechalekar
National Amyloidosis Centre, Centre for Amyloidosis and Acute Phase Proteins, Department of Medicine, Royal Free and University College Medical School, London, UK
Br J Haematol 140:365-77. 2008..At the same time, various new specific anti-amyloid drugs have shown (in early phase studies or animal models) some very promising results. This review attempts to highlight the challenges, controversies and progress in AL amyloidosis...
Outcome in renal Al amyloidosis after chemotherapyJennifer H Pinney
National Amyloidosis Centre, Division of Medicine, University College London Medical School, Rowland Hill St, London NW3 2PF, United Kingdom
J Clin Oncol 29:674-81. 2011..The purpose of this study was to evaluate the effect of chemotherapy on clinical outcome among patients with renal AL amyloidosis...
Use of canakinumab in the cryopyrin-associated periodic syndromeHelen J Lachmann
University College London Medical School, London, United Kingdom
N Engl J Med 360:2416-25. 2009..The cryopyrin-associated periodic syndrome (CAPS) is a rare inherited inflammatory disease associated with overproduction of interleukin-1. Canakinumab is a human anti-interleukin-1beta monoclonal antibody...
Drug Insight: emerging therapies for amyloidosisJulian D Gillmore
National Amyloidosis Centre, Centre for Amyloidosis and Acute Phase Proteins, Royal Free and University College Medical School, London, UK
Nat Clin Pract Nephrol 2:263-70. 2006..Several exciting novel therapeutic strategies, reviewed in this article, are in development. These include interference with different stages of fibrillogenesis and enhancement of clearance of amyloid deposits...
The importance of complete screening for amyloid fibril type and systemic disease in patients with amyloidosis in the respiratory tractPallav L Shah
Department of Medicine, Royal Brompton Hospital, London, UK
Sarcoidosis Vasc Diffuse Lung Dis 19:134-42. 2002....
Systemic amyloidosisHelen J Lachmann
National Amyloidosis Centre, Department of Medicine, Royal Free and University College Medical School, Royal Free Campus, London NW3 2PF, UK
Curr Opin Pharmacol 6:214-20. 2006....
Proinflammatory effects of bacterial recombinant human C-reactive protein are caused by contamination with bacterial products, not by C-reactive protein itselfMark B Pepys
Centre for Amyloidosis and Acute Phase Proteins, Department of Medicine, Royal Free and University College Medical School, London, UK
Circ Res 97:e97-103. 2005....
Novel pharmacological strategies in amyloidosisHelen J Lachmann
National Amyloidosis Centre, Department of Medicine, Royal Free and University College Medical School, Royal Free Hospital, London, UK
Nephron Clin Pract 94:c85-8. 2003....
Developments in the scientific and clinical understanding of autoinflammatory disordersHelen J Lachmann
National Amyloidosis Centre and Centre for Acute Phase Proteins, Department of Medicine, University College London Medical School, Hampstead Campus, Rowland Hill Street, London NW32PF, UK
Arthritis Res Ther 11:212. 2009....
From scleredema to AL amyloidosis: disease progression or coincidence? Review of the literatureMagdalena Dziadzio
Centre for Rheumatology, Royal Free and University College Medical School, University College, Rowland Hill Street, London, NW 32PF, UK
Clin Rheumatol 25:3-15. 2006..We discuss the diagnosis of plasma cell dyscrasias and amyloidosis and their relevance in rheumatology practice...
Translocations of 14q32 and deletions of 13q14 are common chromosomal abnormalities in systemic amyloidosisChristine J Harrison
Department of Haematology, Royal Free and University College Medical School, London, UK
Br J Haematol 117:427-35. 2002..Ten patients (27% overall and 33% of those with systemic disease) showed del(13q). The gain or loss of IGH and CCND1 signals provided evidence of numerical chromosomal changes in three patients...
Eprodisate for the treatment of renal disease in AA amyloidosisLaura M Dember
Boston University School of Medicine, Boston, MA 02118, USA
N Engl J Med 356:2349-60. 2007....
An Israeli Arab patient with a de novo TNFRSF1A mutation causing tumor necrosis factor receptor-associated periodic syndromeEbun Aganna
MRCPI: Barts and the London, Queen Mary's School of Medicine and Dentistry, University of London, UK
Arthritis Rheum 46:245-9. 2002..These findings demonstrate the need to include TRAPS in the differential diagnosis of recurrent fevers in this population...
Interleukin-1-receptor antagonist in the Muckle-Wells syndromePhilip N Hawkins
N Engl J Med 348:2583-4. 2003
Structural and folding dynamic properties of the T70N variant of human lysozymeGennaro Esposito
Dipartimento di Scienze e Tecnologie Biomediche, Universita di Udine, 33100 Udine, Italy
J Biol Chem 278:25910-8. 2003..This is the opposite of the conformational variation shown by the amyloidogenic variant D67H, but it accounts for the reduced stability and catalytic performance of T70N...
Hereditary amyloidosis with progressive peripheral neuropathy associated with apolipoprotein AI Gly26Arg: outcome of hepatorenal transplantationAdam G Testro
Department of Gastroenterology and Hepatology, Austin Health, Melbourne, Australia
Liver Transpl 13:1028-31. 2007....
Cardiac transplantation for amyloid heart disease: the United Kingdom experienceSimon W Dubrey
The Imperial College School of Medicine, National Heart and Lung Institute, London, United Kingdom
J Heart Lung Transplant 23:1142-53. 2004..In contrast, the 5-year survival after TX for non-AL amyloid, combined as necessary with liver or kidney TX, was similar to that after TX in general...
Diagnostic performance of 123I-labeled serum amyloid P component scintigraphy in patients with amyloidosisBouke P C Hazenberg
Department of Rheumatology, University Medical Centre, Groningen, The Netherlands
Am J Med 119:355.e15-24. 2006..To assess the diagnostic accuracy and additional information provided by 123I-labeled serum amyloid P component (SAP) scintigraphy in patients with systemic and localized amyloidosis...
Neonatal-onset multisystem inflammatory disease responsive to interleukin-1beta inhibitionRaphaela Goldbach-Mansky
National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
N Engl J Med 355:581-92. 2006..Many patients have mutations in the cold-induced autoinflammatory syndrome 1 (CIAS1) gene, encoding cryopyrin, a protein that regulates inflammation...
Use of anakinra (Kineret) in the treatment of familial cold autoinflammatory syndrome with a 16-month follow-upJ Barrie Ross
Division of Dermatology and Department of Medicine, Dalhousie University, Halifax, NS, Canada
J Cutan Med Surg 12:8-16. 2008..Anakinra (Kineret) is known to block IL-1 receptor and in the few patients with FCAS in whom it has been used, it has been shown to provide relief for this lifelong disability...
NALP3 forms an IL-1beta-processing inflammasome with increased activity in Muckle-Wells autoinflammatory disorderLaetitia Agostini
Department of Biochemistry, University of Lausanne, Chemin des Boveresses 155, CH 1066 Epalinges, Switzerland
Immunity 20:319-25. 2004..Macrophages from Muckle-Wells patients spontaneously secrete active IL-1beta. Increased inflammasome activity is therefore likely to be the molecular basis of the symptoms associated with NALP3-dependent autoinflammatory disorders...
Liver transplantation in transthyretin-related familial amyloid polyneuropathyArie J Stangou
Institute of Liver Studies and Liver Transplant Services, King s College Hospital, Denmark Hill, London SE5 9RS, UK
Curr Opin Neurol 17:615-20. 2004....
Quantitative high-resolution microradiographic imaging of amyloid deposits in a novel murine model of AA amyloidosisJonathan S Wall
Human Immunology and Cancer Program, Department of Medicine, University of Tennessee Graduate School of Medicine, Knoxville, 37920, USA
Amyloid 12:149-56. 2005....
The significance of paired MEFV mutations in individuals without symptoms of familial Mediterranean feverMehmet Tunca
Eur J Hum Genet 10:786-9. 2002..MEFV genotyping results must be interpreted with due caution, and follow-up of apparently asymptomatic subjects with paired mutations is advisable...
Transmission of systemic transthyretin amyloidosis by means of domino liver transplantationArie J Stangou
N Engl J Med 352:2356. 2005
Amyloidosis, not myelomaHugh J B Goodman
Br J Haematol 129:158-9; author reply 159-60. 2005
Hereditary amyloidosis in early childhood associated with a novel insertion-deletion (indel) in the fibrinogen Aalpha chain geneHee Gyung Kang
Department of Pediatrics, Seoul National University Medical School, Clinical Research Institute, Seoul National University Hospital, Seoul, Korea
Kidney Int 68:1994-8. 2005..The disease is potentially curable by combined hepatorenal transplantation...
Rapid and complete resolution of proteinuria due to renal amyloidosis in a patient with rheumatoid arthritis treated with infliximabOri Elkayam
Department of Rheumatology, Tel Aviv Sourasky Medical Center, 6 Weizman Street, Tel Aviv 64239, Israel
Arthritis Rheum 46:2571-3. 2002..This response was accompanied by resolution of the proteinuria and stabilization of the amyloid deposits as seen on serial (123)I-labeled serum amyloid P scintigraphy...
The role of PBSCT in treatment of AL amyloidosis is far from settledHugh J B Goodman
Blood 104:2991; author reply 2992-4. 2004
Familial amyloidotic polyneuropathy with severe renal involvement in association with transthyretin Gly47Glu in Dutch, British and American-Finnish familiesElizabeth B Haagsma
Department of Gastroenterology and Hepatology, University Hospital Groningen, Hanzeplein 1, P.O. Box 30.001, 9700 RB Groningen, The Netherlands
Amyloid 11:44-9. 2004..These observations support early intervention with orthotopic liver transplantation in patients with FAP associated with TTR Gly47Glu...
Hereditary auto-inflammatory disorders and biologicsLeigh D Church
Academic Unit of Musculoskeletal Disease, Leeds Institute of Molecular Medicine, Epidemiology and Cancer Research, University of Leeds, Leeds, UK
Springer Semin Immunopathol 27:494-508. 2006....
Amyloidosis and primary biliary cirrhosis, Rodriguez-Luna et alHugh J B Goodman
Dig Dis Sci 51:1133. 2006
Acute renal failure and nephrotic range proteinuria due to amyloidosis in an HIV-infected patientKirk M Chan-Tack
Institute of Human Virology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA
Am J Med Sci 332:364-7. 2006..Clinical diagnosis, based on CD4 count, viral load, and degree of proteinuria, may not predict the pathological diagnosis in HIV-positive patients...
Diagnostic performance of amyloid A protein quantification in fat tissue of patients with clinical AA amyloidosisBouke P C Hazenberg
Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands
Amyloid 14:133-40. 2007..Amyloid A protein quantification in fat tissue is a new immunochemical method for detecting AA amyloidosis, a rare but serious disease. The objective was to assess diagnostic performance in clinical AA amyloidosis...
Definition of organ involvement and treatment response in immunoglobulin light chain amyloidosis (AL): a consensus opinion from the 10th International Symposium on Amyloid and Amyloidosis, Tours, France, 18-22 April 2004Morie A Gertz
Dysproteinemia Clinic, Mayo Clinic, Rochester, Minnesota 55905, USA
Am J Hematol 79:319-28. 2005..We report criteria that centers can now use to define organ involvement and uniform response criteria for reporting outcomes in patients with light-chain AL...
Phenotype, genotype, and sustained response to anakinra in 22 patients with autoinflammatory disease associated with CIAS-1/NALP3 mutationsKieron S Leslie
Department of Dermatology, University of California, San Francisco, USA
Arch Dermatol 142:1591-7. 2006..To characterize the multisystem chronic inflammatory phenotype, dermatopathologic features, and response to therapy with interleukin 1 receptor antagonist (anakinra) in patients with mutations in the CIAS-1/NALP3 gene...
Evaluation and management of the cardiac amyloidosisJoseph B Selvanayagam
Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom
J Am Coll Cardiol 50:2101-10. 2007..Recent studies also indicate promising strategies to stabilize the native structures of amyloidogenic proteins; inhibit fibril formation; and disrupt established deposits using antibodies, synthetic peptides, and small-molecule drugs...
