P Woo

Publications (78)337.51 Total impact

• Article: Effects of genetic variation on chromatin structure and the transcriptional machinery: analysis of the IL6 gene locus.

  A J P Smith, D Zheng, J Palmen, D X Pang, P Woo, S E Humphries
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  ABSTRACT: The presence of functional regulatory polymorphism at the interleukin 6 (IL6) locus is uncertain, with many conflicting in vitro findings. To examine the in vivo effect of the three putative functional IL6 promoter variants, -174G>C, -572G>C and -6331T>C, two complementary techniques, allele-specific chromatin immunoprecipitation and allele-specific formaldehyde-assisted isolation of regulatory elements, were carried out using unrelated lymphoblast cell lines of known genotype. There were no allele-specific effects for all three single-nucleotide polymorphisms (SNPs) under basal conditions. Upon IL-1β stimulation, however, allele-specific effects were seen for the -6331 allele, which showed both increased RNA polymerase II loading (56%, P=0.001) and increased open chromatin (59%, P=0.004) for the T allele, which is in line with previous reports of this SNP and the effects from acute inflammation. These studies highlight the importance of examining chromatin under different environmental conditions when studying the functionality of regulatory polymorphisms.
  Genes and immunity 08/2012; 13(7):583-6. · 4.22 Impact Factor
• Source

  Available from: Natasa Toplak

  Article: Prevalence of monogenic autoinflammatory diseases among Pediatric Rheumatology centers: the Eurofever PReS/PRINTO survey

  M Gattorno, J Frenkel, S Ozen, F De Benedetti, I Konè-Paut, N Neven, H Girschick, H Özdogan, C Wouters, P Woo, M Hofer, P Dolezalova, N Toplak, V Richard, A Martini, N Ruperto
  Pediatric Rheumatology 04/2012; 6:1-1. · 1.44 Impact Factor
• Article: Effectiveness of infliximab in the treatment of refractory juvenile dermatomyositis with calcinosis.

  P Riley, L J McCann, S M Maillard, P Woo, K J Murray, C A Pilkington
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  ABSTRACT: Some juvenile dermatomyositis (JDM) patients have a disease course which is refractory to multiple drug treatments. Prolonged disease activity is associated with increased mortality and morbidity. TNF-alpha has been identified in high levels in JDM patients who have a long disease course and calcinosis. We assessed the response of five refractory JDM patients to the anti-TNF-alpha monoclonal antibody, infliximab. For all five patients intravenous infliximab was initially given at a dose of 3 mg/kg. Further doses were then given at weeks 2, 6 and every 8 weeks thereafter. The dose and frequency were tailored in accordance with clinical response. Clinical and laboratory data were collected prospectively. We report results between 8 and 30 months after starting infliximab. Improvements were seen in all five patients as shown by positive changes in physician visual analogue scale (VAS), Childhood Myositis Assessment Score (CMAS), Childhood Health Assessment Questionnaire (CHAQ), joint range of movement and, in some, regression of calcinosis and skin signs. There were no major side effects observed with addition of infliximab to the therapeutic regime. Major clinical benefit was demonstrated after the initiation of infliximab in all five cases of refractory JDM.
  Rheumatology (Oxford, England) 07/2008; 47(6):877-80. · 4.24 Impact Factor
• Article: Comprehensive association study of genetic variants in the IL-1 gene family in systemic juvenile idiopathic arthritis.

  C J W Stock, E M Ogilvie, J M Samuel, M Fife, C M Lewis, P Woo
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  ABSTRACT: Patients with systemic juvenile idiopathic arthritis (sJIA) have a characteristic daily spiking fever and elevated levels of inflammatory cytokines. Members of the interleukin-1 (IL-1) gene family have been implicated in various inflammatory and autoimmune diseases, and treatment with the IL-1 receptor antagonist, Anakinra, shows remarkable improvement in some patients. This work describes the most comprehensive investigation to date of the involvement of the IL-1 gene family in sJIA. A two-stage case-control association study was performed to investigate the two clusters of IL-1 family genes using a tagging single nucleotide polymorphism (SNP) approach. Genotyping data of 130 sJIA patients and 151 controls from stage 1 highlighted eight SNPs in the IL1 ligand cluster region and two SNPs in the IL1 receptor cluster region as showing a significant frequency difference between the populations. These 10 SNPs were typed in an additional 105 sJIA patients and 184 controls in stage 2. Meta-analysis of the genotypes from both stages showed that three IL1 ligand cluster SNPs (rs6712572, rs2071374 and rs1688075) and one IL1 receptor cluster SNP (rs12712122) show evidence of significant association with sJIA. These results indicate that there may be aberrant control of the activity of the IL-1 family in sJIA patients causing the increased susceptibility to the disease.
  Genes and immunity 07/2008; 9(4):349-57. · 4.22 Impact Factor
• Article: Identification of a novel regulatory region in the interleukin-6 gene promoter.

  J M Samuel, D Kelberman, A J P Smith, S E Humphries, P Woo
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  ABSTRACT: Interleukin-6 (IL6) is an important pleiotropic cytokine that is regulated at the transcriptional level. To date, most work on its regulation has focused on a 1.2kb region 5' from the start of transcription, similar to published reports on other cytokine genes. This report demonstrates for the first time that a cytokine gene can be regulated by cis-acting regions much further upstream than previously examined. Comparative genomic analysis showed that a 120 kb region contains blocks of sequence conservation between human and rodent genomes, and that a 15 kb region proximal to the start of transcription contains 10 highly homologous sequence blocks of between 100 and 250 bp. By means of a reporter gene assay, a novel transcriptionally active region located between -5307 and -5202 bp upstream from the start of transcription was identified. Electrophoretic mobility shift assays showed nuclear protein(s) binding to this region, thus raising the possibility that the regulatory activity shown by the reporter gene constructs may be mediated by these proteins. These results suggest that the regulation of IL6 expression involves a much larger upstream region than previously examined and the control of IL6 transcription is likely to be regulated by a complex mechanism of modular cis-regulatory elements.
  Cytokine 06/2008; 42(2):256-64. · 3.02 Impact Factor
• Article: EULAR/PReS endorsed consensus criteria for the classification of childhood vasculitides.

  S Ozen, N Ruperto, M J Dillon, A Bagga, K Barron, J C Davin, T Kawasaki, C Lindsley, R E Petty, A M Prieur, A Ravelli, P Woo
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  ABSTRACT: There has been a lack of appropriate classification criteria for vasculitis in children. To develop a widely accepted general classification for the vasculitides observed in children and specific and realistic classification criteria for common childhood vasculitides (Henoch-Schönlein purpura (HSP), Kawasaki disease (KD), childhood polyarteritis nodosa (PAN), Wegener's granulomatosis (WG), and Takayasu arteritis (TA)). The project was divided into two phases: (1) the Delphi technique was used to gather opinions from a wide spectrum of paediatric rheumatologists and nephrologists; (2) a consensus conference using nominal group technique was held. Ten international experts, all paediatricians, met for the consensus conference. Agreement of at least 80% of the participants was defined as consensus. Consensus was reached to base the general working classification for childhood vasculitides on vessel size. The small vessel disease was further subcategorised into "granulomatous" and "non-granulomatous." Final criteria were developed to classify a child as HSP, KD, childhood PAN, WG, or TA, with changes introduced based on paediatric experience. Mandatory criteria were suggested for all diseases except WG. It is hoped that the suggested criteria will be widely accepted around the world because of the reliable techniques used and the international and multispecialist composition of the expert group involved.
  Annals of the Rheumatic Diseases 08/2006; 65(7):936-41. · 8.73 Impact Factor
• Source

  Available from: Ivan Foeldvari

  Article: Juvenile localized scleroderma: clinical and epidemiological features in 750 children. An international study.

  F Zulian, B H Athreya, R Laxer, A M Nelson, S K Feitosa de Oliveira, M G Punaro, R Cuttica, G C Higgins, L W A Van Suijlekom-Smit, T L Moore, [......], L Lepore, C A Silva, C Machado, S M Garay, Y Uziel, G Martini, I Foeldvari, A Peserico, P Woo, J Harper
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  ABSTRACT: Juvenile localized scleroderma (JLS) includes a number of conditions often grouped together. With the long-term goal of developing uniform classification criteria, we studied the epidemiological, clinical and immunological features of children with JLS followed by paediatric rheumatology and dermatology centres. A large, multicentre, multinational study was conducted by collecting information on the demographics, family history, triggering environmental factors, clinical and laboratory features, and treatment of patients with JLS. Seven hundred and fifty patients with JLS from 70 centres were enrolled into the study. The disease duration at diagnosis was 18 months. Linear scleroderma (LS) was the most frequent subtype (65%), followed by plaque morphea (PM) (26%), generalized morphea (GM) (7%) and deep morphea (DM) (2%). As many as 15% of patients had a mixed subtype. Ninety-one patients (12%) had a positive family history for rheumatic or autoimmune diseases; 100 (13.3%) reported environmental events as possible trigger. ANA was positive in 42.3% of the patients, with a higher prevalence in the LS-DM subtype than in the PM-GM subtype. Scl70 was detected in the sera of 3% of the patients, anticentromere antibody in 2%, anti-double-stranded DNA in 4%, anti-cardiolipin antibody in 13% and rheumatoid factor in 16%. Methotrexate was the drug most frequently used, especially during the last 5 yr. This study represents the largest collection of patients with JLS ever reported. The insidious onset of the disease, the delay in diagnosis, the recognition of mixed subtype and the better definition of the other subtypes should influence our efforts in educating trainees and practitioners and help in developing a comprehensive classification system for this syndrome.
  Rheumatology 06/2006; 45(5):614-20. · 4.06 Impact Factor
• Article: PRINTO/PRES international website for families of children with rheumatic diseases: www.pediatric-rheumatology.printo.it.

  N Ruperto, P Garcia-Munitis, L Villa, M Pesce, A Aggarwal, A Fasth, T Avcin, S-C Bae, Z Balogh, C Li, [......], A-M Prieur, A-M Romicka, I Rumba, N Shafaie, G Susic, S Takei, Y Uziel, R Vesely, P Woo, A Martini
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  ABSTRACT: To prepare a website for families and health professionals containing up to date information about paediatric rheumatic diseases (PRD). Firstly, paediatric rheumatology centres and family self help associations were surveyed to characterise current clinical practice of physicians providing care for children with PRD, research activities, and training facilities of each centre. Secondly, international consensus was reached on the content of the website. Finally, the website was developed and the texts translated. The web page contains three main sections: (a) description for families of the characteristics of 15 PRD; (b) list of paediatric rheumatology centres; (c) contact information for family self help associations. A version for 45 countries in 52 languages (with another three in progress) is now available on the web. 291 surveys from 171 centres and 102 family associations were received from 42 countries. The median proportion of time spent in paediatric practice in the centres examined was 100%, with 70% of this time dedicated to paediatric rheumatology. 90% of the centres were willing to perform clinical trials in the future. The PRINTO/PRES website provides a well defined and competent set of information about PRD, with appropriate multiple translated versions and easy web navigational direction.
  Annals of the Rheumatic Diseases 08/2005; 64(7):1101-6. · 8.73 Impact Factor
• Article: Joint hypermobility syndrome in childhood. A not so benign multisystem disorder?

  N Adib, K Davies, R Grahame, P Woo, K J Murray
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  ABSTRACT: Joint hypermobility (JH) or "ligamentous laxity" is felt to be an underlying risk factor for many types of musculoskeletal presentation in paediatrics, and joint hypermobility syndrome (JHS) describes such disorders where symptoms become chronic, often more generalized and associated with functional impairment. Clinical features are felt to have much in common with more severe disorders, including Ehlers-Danlos syndrome (EDS), osteogenesis imperfecta and Marfan syndrome, although this has not been formally studied in children. We defined the clinical characteristics of all patients with joint hypermobility-related presentations seen from 1999 to 2002 in a tertiary referral paediatric rheumatology unit. Patients were identified and recruited from paediatric rheumatology clinic and ward, and a dedicated paediatric rheumatology hypermobility clinic at Great Ormond Street Hospital. Data were collected retrospectively on the patients from the paediatric rheumatology clinics (1999-2002) and prospectively on patients seen in the hypermobility clinic (2000-2002). Specifically, historical details of developmental milestones, musculoskeletal or soft tissue diagnoses and symptoms, and significant past medical history were recorded. Examination features sought included measurements of joint and soft tissue laxity, and associated conditions such as scoliosis, dysmorphic features, cardiac murmurs and eye problems. One hundred and twenty-five children (64 females) were included on whom sufficient clinical data could be identified and who had clinical problems ascribed to JH present for longer than 3 months. Sixty-four were from the paediatric rheumatology clinic and 61 from the hypermobility clinic. No differences were found in any of the measures between the two populations and results are presented in a combined fashion. Three-quarters of referrals came from paediatricians and general practitioners but in only 10% was hypermobility recognized as a possible cause of joint complaint. The average age at onset of symptoms was 6.2 yr and age at diagnosis 9.0 yr, indicating a 2- to 3-yr delay in diagnosis. The major presenting complaint was arthralgia in 74%, abnormal gait in 10%, apparent joint deformity in 10% and back pain in 6%. Mean age at first walking was 15.0 months; 48% were considered "clumsy" and 36% as having poor coordination in early childhood. Twelve per cent had "clicky" hips at birth and 4% actual congenital dislocatable hip. Urinary tract infections were present in 13 and 6% of the female and male cases, respectively. Thirteen and 14%, respectively, had speech and learning difficulties diagnosed. A history of recurrent joint sprains was seen in 20% and actual subluxation/dislocation of joints in 10%. Forty per cent had experienced problems with handwriting tasks, 48% had major limitations of school-based physical education activities, 67% other physical activities and 41% had missed significant periods of schooling because of symptoms. Forty-three per cent described a history of easy bruising. Examination revealed that 94% scored > or =4/9 on the Beighton scale for generalized hypermobility, with knees (92%), elbows (87%), wrists (82%), hand metacarpophalangeal joints (79%), and ankles (75%) being most frequently involved. JHS is poorly recognized in children with a long delay in the time to diagnosis. Although there is a referral bias towards joint symptoms, a surprisingly large proportion is associated with significant neuromuscular and motor development problems. Our patients with JHS also show many overlap features with genetic disorders such as EDS and Marfan syndrome. The delay in diagnosis results in poor control of pain and disruption of normal home life, schooling and physical activities. Knowledge of the diagnosis and simple interventions are likely to be highly effective in reducing the morbidity and cost to the health and social services.
  Rheumatology 07/2005; 44(6):744-50. · 4.06 Impact Factor
• Article: Novel IL-6 haplotypes and disease association.

  M S Fife, E M Ogilvie, D Kelberman, J Samuel, A Gutierrez, S E Humphries, P Woo
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  ABSTRACT: Interleukin-6 (IL-6) is a pleiotropic cytokine crucial in both adaptive and innate immunity. Numerous genetic studies have shown association with variants of this gene in a multitude of diseases and phenotypes. Most tests of association have focused on a limited set of promoter polymorphisms, in particular, the -174G>C; however, there are many inconsistencies within and between these studies. We propose that there is a more complex regulatory haplotype extending further upstream of the previously characterised promoter region which will provide a more detailed view of the effect of variation on lL-6 regulation. We have exploited two additional single nucleotide polymorphisms (SNPs) in IL-6 that, when examined as a haplotype with existing markers, show an increased level of association with systemic onset juvenile arthritis in a family-based study. This suggests that the haplotype effect may be more functionally relevant to the disease.
  Genes and Immunity 06/2005; 6(4):367-70. · 3.87 Impact Factor
• Article: Isolated inflammatory coxitis associated with protrusio acetabuli: a new form of juvenile idiopathic arthritis?

  N Adib, K L Owers, J D Witt, C M Owens, P Woo, K J Murray
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  ABSTRACT: Isolated hip disease in the context of chronic childhood inflammatory arthritis is uncommon. This paper reports 14 children who presented to the rheumatology and orthopaedic departments of our hospitals with severe hip symptoms, and who continued to have primarily hip disease throughout their clinical course. Our aim was to characterize and present the relevant demographic, clinical, investigational, treatment and outcome data from the above cohort. All paediatric cases with the diagnosis of protrusio acetabuli, Otto pelvis or idiopathic chondrolysis who were seen in the past 15 yr at Great Ormond Hospital and Middlesex Hospital in London were identified and their case notes were searched retrospectively for relevant information. In 11 cases, the disease progressed to involve no joints other than the contralateral hip. None were considered to have a specific subtype of juvenile idiopathic arthritis (JIA) and all tested were negative for HLA-B27. Elevation of serum inflammatory markers was variable. Protrusio acetabuli was the predominant radiological feature. There were definite inflammatory changes on the gadolinium-enhanced magnetic resonance imaging study in all patients who had this procedure performed (seven cases). Microbiological investigations were all consistently negative. Severe hip disease resulted in considerable ongoing symptoms and disability. Six cases were treated with disease-modifying anti-rheumatic drugs. Total hip replacement has been required in four patients to date, with major functional improvement. These cases represent severe and disabling primary hip disease with considerable clinical and investigational inflammatory features. Such a mode of presentation has not been described previously in the context of childhood chronic inflammatory arthritides, and may represent a separate oligoarthritis subtype of JIA.
  Rheumatology 03/2005; 44(2):219-26. · 4.06 Impact Factor
• Source

  Available from: oxfordjournals.org

  Article: Anti-BiP antibody levels in juvenile idiopathic arthritis (JIA).

  M D Bodman-Smith, M F Fife, H Wythe, V M Corrigal, G S Panayi, L R Wedderburn, P Woo
  Rheumatology 11/2004; 43(10):1305-6. · 4.06 Impact Factor
• Article: The use of the British Isles Lupus Assessment Group (BILAG) index as a valid tool in assessing disease activity in childhood-onset systemic lupus erythematosus.

  S D Marks, C Pilkington, P Woo, M J Dillon
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  ABSTRACT: The British Isles Lupus Assessment Group (BILAG) index is a standardized systemic lupus erythematosus (SLE) disease activity assessment. The main aim of this study was to correlate the BILAG index with laboratory measures of disease activity in childhood-onset SLE with and without biopsy-proven lupus nephritis. Prospective observational comparison study of the BILAG index in 21 SLE patients under 18 yr of age over a 12-month period in a tertiary referral paediatric outpatient clinic. Eleven patients with lupus non-nephritis and 10 patients with lupus nephritis were reviewed. The lupus nephritis patients had significantly (P<0.001) more admissions over a similar time interval since diagnosis. The renal BILAG disease activity scores were significantly greater (P = 0.013) in the lupus nephritis group (range 1-9, median 3.0, compared with 0-3 and 1.0 in the lupus non-nephritis group). The total BILAG scores and patient visual analogue scores (VAS) were higher in the lupus nephritis groups, unlike the lower physician VAS, but these differences were not statistically significant compared with other laboratory indices of disease activity. The BILAG index is a useful tool in monitoring disease activity in children and adolescents with SLE. The data collected for the BILAG index can be used serially and effectively by different clinicians over time to enable recording of disease status at sequential assessments. The lower patient VAS in the lupus non-nephritis group was not significant and may reflect the patients' own perception of lethargy at times of increased disease activity.
  Rheumatology 09/2004; 43(9):1186-9. · 4.06 Impact Factor
• Article: Quantitative assessment of MRI T2 relaxation time of thigh muscles in juvenile dermatomyositis.

  S M Maillard, R Jones, C Owens, C Pilkington, P Woo, L R Wedderburn, K J Murray
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  ABSTRACT: The aim of the study was to examine the validity and reliability of a quantifiable measure of inflammation using magnetic resonance imaging (MRI) in children with juvenile dermatomyositis (JDM). Children with active JDM, inactive JDM and healthy children received detailed assessments of recognized measures of muscle inflammation including muscle strength (manual muscle testing and myometry) and function (Childhood Myositis Assessment Scale, Childhood Health Assessment Questionnaire), the muscle enzymes lactate dehydrogenase (LDH) and creatine kinase (CK) and T2-weighted MRI scans of the thigh muscles, and these values were correlated with each other. Ten children with active JDM, 10 with inactive JDM and 20 healthy children completed the study. There was no significant difference in ages between the three groups. The MRI T2 relaxation times were significantly increased in active JDM compared with inactive JDM and healthy children (P = 0.05), indicating a detectable increase in inflammation within the muscles. There were also good correlations between the MRI scores and the measures of muscle strength and function; however, there was no correlation between the MRI and muscle enzymes. The MRI T2 relaxation time can be used as a quantitative measure of muscle inflammation and it has good correlations with other measures of disease activity.
  Rheumatology 06/2004; 43(5):603-8. · 4.06 Impact Factor
• Article: Intravenous cyclophosphamide pulse therapy in juvenile dermatomyositis. A review of efficacy and safety.

  P Riley, S M Maillard, L R Wedderburn, P Woo, K J Murray, C A Pilkington
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  ABSTRACT: To assess the efficacy and safety of intravenous cyclophosphamide (CYP) used in severe and refractory juvenile dermatomyositis (JDM). Retrospective case note review of the outcome of 12 patients. Assessment at 6 months of therapy in 10 of the 12 patients showed a significant improvement in muscle function as assessed by the Childhood Myositis Assessment Scale (CMAS) (P = 0.012), muscle strength (P = 0.008), global extramuscular disease score (P = 0.008), skin disease severity (P = 0.015) and lactate dehydrogenase (P = 0.028). There were reductions in creatine kinase, alanine aminotransferase, prednisolone dose and ESR, but these did not reach statistical significance. Clinical improvement was maintained after CYP until the most recent follow-up (between 6 months and 7 yr) and no severe side-effects were seen. Reversible complications included lymphopenia, herpes zoster infections and alopecia. The median cumulative dose was 4.6 g/m(2) (range 3-9 g/m(2)). The available evidence suggests that, at the doses required, risks of malignancy, infertility and gonadal failure are low. Two patients with severe treatment-resistant disease died after one dose of CYP, both of whom were ventilated prior to commencement of CYP and were thought to have died as a result of their severe disease process, and too early for clinical benefit to be obtained from the drug. In this cohort of children with severe and refractory JDM, CYP appeared to have provided major clinical benefit with no evidence of serious toxicity in the short term.
  Rheumatology 05/2004; 43(4):491-6. · 4.06 Impact Factor
• Article: Synovial dendritic cells in juvenile idiopathic arthritis (JIA) express receptor activator of NF-kappaB (RANK).

  H Varsani, A Patel, Y van Kooyk, P Woo, L R Wedderburn
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  ABSTRACT: To analyse the expression of receptor activator of NF-kappaB (RANK) and RANK ligand (RANKL) in the joints of children with juvenile idiopathic arthritis (JIA), to characterize the phenotype of RANK(+) cells and to test the hypothesis that some RANK(+) cells are of the dendritic type. Paired samples of peripheral blood mononuclear cells (PBMC) and synovial fluid mononuclear cells (SFMC) from children with oligoarticular (n=14) or polyarticular (n=4) JIA and PBMC from 10 control subjects were studied for expression of RANK, RANKL and dendritic cell-specific ICAM (intercellular adhesion molecule)-grabbing non-integrin (DC-SIGN) by the reverse transcriptase-polymerase chain reaction and three-colour flow cytometry. Expression of DC-SIGN and RANK was followed after 1 week of culture with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 4 (IL-4). mRNA for RANK was detected in both adherent cells and T cells from PBMC and SFMC of patients with JIA and in control PBMC, while mRNA for RANKL was detectable in the T-cell fraction from JIA patients but not in that from controls. By flow cytometry, a large number of RANK(+) cells were detected in the joint; these cells had the phenotype HLA-DR(hi)CD86(hi) CD11c(+) and expressed low levels of DC-SIGN. There is increased expression of RANKL and RANK in the juvenile arthritic joint. RANK is expressed on a population of cells with features of dendritic cells. RANK/RANKL interactions may contribute to the survival of inflammatory cells within the joint, as well as to erosions and osteoporosis in juvenile arthritis.
  Rheumatology 05/2003; 42(4):583-90. · 4.06 Impact Factor
• Article: Transcriptional regulation of serum amyloid A1 gene expression in human aortic smooth muscle cells involves CCAAT/enhancer binding proteins (C/EBP) and is distinct from HepG2 cells.

  Y Kumon, T Suehiro, D J Faulkes, T Hosakawa, Y Ikeda, P Woo, J D Sipe, K Hashimoto
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  ABSTRACT: Regulation of acute-phase serum amyloid A (A-SAA) synthesis by proinflammatory cytokines and steroid hormones in human aortic smooth muscle cells (HASMCs) is distinct from that in HepG2 cells. To study the cis- and trans-activating promoter element involved in the SAA1 gene expression by HASMCs and HepG2 cells, we constructed plasmid vectors for luciferase reporter gene assay with varying lengths of SAA1 upstream regulatory region (up to 1431 bp), and examined their response to proinflammatory cytokines and/or steroid hormones. The corresponding vectors with the SAA4 upstream regulatory region served as controls. The presence of proposed transcriptional regulatory factors binding to these regions was confirmed immunohistochemically. The sequences of 1478 and 1836 bp of the SAA1 and SAA4 5'-flanking regions were determined, respectively. SAA1 promoter transcription in cultured HASMCs was upregulated not by proinflammatory cytokines, but rather by glucocorticoids. This differed from HepG2 cells, in which SAA1 promoter transcription was upregulated synergistically by proinflammatory cytokines and glucocorticoids. The promoter activity of a series of truncated SAA1 promoter constructs measured using the reporter gene assay showed that the 5'-region from -252 to -175, containing a consensus site for CCAAT/enhancer binding proteins alpha,beta (C/EBPalpha,beta), was essential for SAA1 induction in HASMCs. In HepG2 cells, the 5'-region from -119 to -79, containing a nuclear factor kappa-B (NFkappaB) consensus sequence, was essential for the induction. The functional significance of the C/EBP site as indicated by the immunohistochemical result was that in HASMCs anti-C/EBPbeta reactivity was shifted from the cytoplasm to the nuclei. We have, therefore, demonstrated that the region containing the C/EBPalpha,beta consensus binding site between the bases -252 and -175 is important for the glucocorticoid-induced SAA1 gene expression in HASMCs but not in HepG2 cells.
  Scandinavian Journal of Immunology 12/2002; 56(5):504-11. · 2.23 Impact Factor
• Article: Juvenile-onset localized scleroderma activity detection by infrared thermography.

  G Martini, K J Murray, K J Howell, J Harper, D Atherton, P Woo, F Zulian, C M Black
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  ABSTRACT: The aim of this study was to define the clinical utility of infrared thermography in disease activity detection in localized scleroderma (LS). We retrospectively reviewed 130 thermal images of 40 children with LS and calculated the sensitivity and specificity of thermography, comparing clinical descriptions of the lesions and contemporary thermographs. The reproducibility of thermography was calculated by using the weighted kappa coefficient to determine the level of agreement between two clinicians who reviewed the thermographs independently. The sensitivity of thermography was 92% and specificity was 68%. Full concordance between the two clinicians was observed in 91% of lesions, with a kappa score of 0.82, implying very high reproducibility of this technique. Our results demonstrate that thermography is a promising diagnostic tool when associated with clinical examination in discriminating disease activity, as long as it is applied to lesions without severe atrophy of the skin and subcutaneous fat. Further evaluation is needed to determine whether thermography can predict the future progression of lesions.
  Rheumatology 11/2002; 41(10):1178-82. · 4.06 Impact Factor
• Article: Divergence in the degree of clonal expansions in inflammatory T cell subpopulations mirrors HLA-associated risk alleles in genetically and clinically distinct subtypes of childhood arthritis.

  L R Wedderburn, A Patel, H Varsani, P Woo
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  ABSTRACT: Clinically distinct forms of childhood arthritis are associated with different risk alleles of polymorphic loci within the MHC, which code for the antigen-presenting class I or class II molecules. We have compared the TCR diversity of synovial T cells from children with enthesitis-related (HLA-B27(+)) arthritis and oligoarticular arthritis (with class II MHC risk allele associations) in parallel with peripheral blood T cells from each child, using a high-resolution heteroduplex TCR analysis. We demonstrate that multiple clonal T cell expansions are present and persistent within the joint in both groups, but that there is disease-specific divergence in the dominant T cell subset containing these expansions. Thus, the largest clonotypes within the inflamed joints of children with class II-associated arthritis are within the CD4(+) synovial T cell population, while the dominant clones from children with enthesitis-related arthritis (associated with a class I allele) are within the CD8(+) synovial T cell population. These data provide powerful data to support the concept that recognition of MHC-peptide complexes by T cells plays a role in the pathogenesis of juvenile arthritis.
  International Immunology 01/2002; 13(12):1541-50. · 3.41 Impact Factor
• Source

  Available from: nih.gov

  Article: Macrophage activation syndrome: a potentially fatal complication of rheumatic disorders.

  S Sawhney, P Woo, K J Murray
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  ABSTRACT: To review the precipitating events, clinical features, treatment, and outcome of macrophage activation syndrome (MAS). Retrospective review of cases of MAS from a prospectively collected database of children with rheumatic diseases from 1980 to 2000. Nine patients (eight girls) were considered to have evidence of MAS. The primary diagnosis was systemic onset juvenile idiopathic arthritis in seven, enthesitis related arthritis in one, and chronic infantile neurological cutaneous articular syndrome in one. Mean age of onset was 5.7 years, and duration prior to MAS, 4.2 years. No medication was identified as a trigger. Eight had infections prior to MAS; specific infectious agents were identified in four. High grade fever, new onset hepatosplenomegaly, and lymphadenopathy were common clinical features. Platelet counts fell dramatically, from an average of 346 to 99 x 10(9)/l. Mean erythrocyte sedimentation rate (in three patients) fell from 115 to 28 mm/h. Eight had abnormal liver function during the disease course, and six had coagulopathy. Bone marrow examination supported the diagnosis with definite haemophagocytosis in four of seven. All received high dose steroids (eight intravenous, one oral), five cyclosporin, two cyclophosphamide, and one antithymocyte globulin. Two of three patients with significant renal impairment died. MAS is a rare and potentially fatal complication of childhood rheumatic disorders. Most of our patients were female, and most cases were preceded by infection. Bone marrow studies support the diagnosis. Deranged renal function may be a poor prognostic sign. Aggressive early therapy is essential.
  Archives of Disease in Childhood 12/2001; 85(5):421-6. · 2.88 Impact Factor