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Dive into the research topics where John Hamburger is active.

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Featured researches published by John Hamburger.


Arthritis & Rheumatism | 2001

Ectopic expression of the B cell-attracting chemokine BCA-1 (CXCL13) on endothelial cells and within lymphoid follicles contributes to the establishment of germinal center-like structures in Sjogren's syndrome

Nicole Amft; S. John Curnow; Dagmar Scheel-Toellner; Ash Devadas; Jane Oates; John Crocker; John Hamburger; John Ainsworth; John Mathews; Mike Salmon; Simon J. Bowman; Christopher D. Buckley

OBJECTIVE To test the hypothesis that the formation of ectopic germinal center (GC)-like structures in Sjögrens syndrome (SS) is associated with the ectopic expression of the constitutive lymphoid tissue-homing chemokines B cell-attracting chemokine 1 (BCA-1; or, CXCL13) and stromal cell-derived factor 1 (SDF-1; or, CXCL12). METHODS Immunohistochemical and immunofluorescence analysis was used to determine the expression of the constitutive chemokines BCA-1 (CXCL13) and SDF-1 (CXCL12) in salivary glands from 5 SS patients and 3 non-SS patients. In addition, the expression of their respective receptors (CXCR5 and CXCR4) was examined on infiltrating lymphocytes. Human tonsil was used as a positive control for secondary lymphoid tissue. RESULTS BCA-1 (CXCL13) was expressed within lymphoid aggregates in SS, which shared many structural features with GCs in tonsil. BCA-1 (CXCL13) was completely absent in control biopsy samples from patients who did not have SS. High levels of BCA-1 (CXCL13) were also found on endothelial cells in salivary glands from SS patients. Diseased SS tissue was infiltrated by CXCR5-expressing B cells which organized into GC-like clusters. In complete contrast, SDF-1 (CXCL12), a constitutive chemokine involved in leukocyte retention within lymphoid tissue, was expressed by epithelial cells in both diseased and control samples. The chemokine receptor for SDF-1, CXCR4, was expressed on T cells that accumulated in a periductal distribution in diseased tissue. CONCLUSION The ectopic expression of BCA-1 (CXCL13) on endothelial cells and within GC-like structures, together with the strong expression of SDF-1 (CXCL12) on ductal epithelial cells, is a unique feature of inflamed glands in SS. By creating a local microenvironment supportive of focal B cell aggregation and differentiation, with structural features that are remarkably similar to GCs, BCA-1 (CXCL13) and SDF-1 (CXCL12) may contribute to the excessive production of high-affinity, class-switched autoantibodies and to the high incidence of B cell lymphomas classically associated with SS.


Rheumatology | 2008

Patient-reported outcomes in primary Sjögren's syndrome: comparison of the long and short versions of the Profile of Fatigue and Discomfort—Sicca Symptoms Inventory

Simon Bowman; John Hamburger; Andrea Richards; Robert J Barry; Saaeha Rauz

OBJECTIVES The long-form 64-item Profile of Fatigue and Discomfort--Sicca Symptoms Inventory (PROFAD-SSI) questionnaire was developed as a patient-reported assessment tool for use in primary SS (PSS) and other rheumatic disorders. In this study, we assess whether the (shorter and more practical) 19-item PROFAD-SSI-SF (short form) gives similar results and whether a still briefer version using visual analogue scales (VASs) is feasible. METHODS Questionnaire surveys comprising the long and short versions of the PROFAD-SSI were mailed to 43 patients with PSS and 50 patients with RA, who were asked to complete these contemporaneously as well as repeating the process 1 month later. PSS patients also completed a series of VASs comprising fatigue and sicca domains of the SSI. RESULTS Surveys were returned from 35 PSS patients and 35 RA patients. All domains of the long- and short-form PROFAD-SSI showed strong correlations (Spearman rho between 0.779 and 0.996, P < 0.01). Factor analysis generally confirmed the previously validated domain structure with Cronbachs alpha = 0.99. The PROFAD-SF somatic fatigue domain correlated more strongly with a fatigue VAS than did the mental fatigue domain. The SSI-SF domain scores correlated with equivalent VAS scores. CONCLUSION The long- and short-form PROFAD-SSI questionnaires correlate closely suggesting that the PROFAD-SF is valid as an outcome tool. Preliminary data also suggest that an even briefer form with compression of the domains into single VAS is also feasible.


The Journal of Rheumatology | 2010

Estimating Indirect Costs in Primary Sjogren's Syndrome

Simon Bowman; Yvan St. Pierre; Nurhan Sutcliffe; David A. Isenberg; Fiona Goldblatt; Elizabeth Price; John Hamburger; Andrea Richards; Saaeha Rauz; Marian Regan; Shirley Rigby; Adrian Jones; Diarmuid Mulherin; Ann E. Clarke

Objective. To estimate the indirect costs associated with primary Sjögren’s syndrome (pSS) compared with rheumatoid arthritis (RA) and community controls. Methods. Data were obtained from 84 women patients with pSS as part of a study to develop a systemic activity measure, from 87 consecutive women patients with RA attending a hospital clinic, and from 96 women community controls on a general practice list. A modified economic component of the Stanford Health Assessment Questionnaire was used to assess lost productivity. Results. Using a conservative model, the estimated total annual indirect costs (95% CI) were £7677 (£5560, £9794) for pSS, £10,444 (£8206, £12,681) for RA, and £892 (£307, £1478) for controls. Using a model that maximizes the estimates, the equivalent figures were £13,502 (£9542, £17,463), £17,070 (£13,112, £21,028), and £3382 (£2187, £4578), respectively. These were all significantly greater at p < 0.001 for patient groups than for the control group. Conclusion. pSS is associated with significantly increased indirect costs equivalent to 69%–83% of that for patients with RA. This needs to be taken into account when evaluating the overall economic consequences of pSS.


Annals of the Rheumatic Diseases | 2000

Mast cells, extracellular matrix components, TGFβ isoforms and TGFβ receptor expression in labial salivary glands in systemic sclerosis

Gillian I. Mason; John Hamburger; John B. Matthews

OBJECTIVE To determine whether there was altered elaboration of non-collagenous extracellular matrix proteins or expression of TGFβ isoforms and their receptors in salivary glands of patients with systemic sclerosis (SSc) and Raynauds phenomenon (RP). Because of the possible role of mast cells in the early stages of SSc their presence was also investigated. METHODS Sections of normal labial salivary glands (n=10) and glands from patients with SSc (n=13) and RP (n=5) were stained immunohistochemically and using acid toluidine blue. RESULTS SSc glands contained more mast cells than control tissues (p<0.005) and similar numbers to those found in RP specimens. There were no differences in the pattern or amount of non-collagenous matrix proteins detected. Tenascin and elastin were predominantly found surrounding ducts whereas fibronectin had a more general distribution. TGFβ isoforms and receptors were expressed by glandular epithelium, fibroblasts, vascular endothelium and inflammatory cells. Cell counts showed no differences in expression of TGFβ1 or TGFβ receptors between groups. However, the percentage of TGFβ2 positive fibroblasts was significantly higher in SSc glands compared with controls (p<0.004). RP glands showed an intermediate level of expression. By contrast, a lower percentage of RP fibrolasts expressed TGFβ3 compared with controls with SSc glands showing an intermediate level of expression. CONCLUSIONS These results show that (a) there are no changes in glandular expression of tenascin, elastin and fibronectin in SSc and RP and (b) both conditions are associated with an increased salivary gland mast cell population and changes in expression of TGFβ2 and β3 isoforms by glandular fibroblasts.


Investigative Ophthalmology & Visual Science | 2016

Conjunctival Neutrophils Predict Progressive Scarring in Ocular Mucous Membrane Pemphigoid

Geraint P. Williams; Peter Nightingale; Sue Southworth; Alastair K. Denniston; Paul J. Tomlins; Stephen J. Turner; John Hamburger; Simon Bowman; S. John Curnow; Saaeha Rauz

Purpose Ocular mucous membrane pemphigoid (OcMMP) is a rare autoimmune disorder resulting in progressive conjunctival fibrosis and ocular surface failure leading to sight loss in up to 50%. This study was designed to optimize an ocular surface sampling technique for identification of novel biomarkers associated with disease activity and/or progressive fibrosis. Methods Fifty-seven patients with OcMMP underwent detailed examination of conjunctival inflammation and fibrosis using fornix depth measurement. Ocular surface impression cytology (OSIC) to sample superior bulbar conjunctiva combined with flow cytometry (OSIC-flow) profiled infiltrating leukocytes. Profiles were compared with healthy controls (HC) and disease controls (primary Sjögrens syndrome, pSS). Thirty-five OcMMP patients were followed every 3 months for 12 months. Results Overall neutrophils were elevated in OcMMP eyes when compared to pSS or HC (109 [18%] neutrophils/impression [NPI]; 2 [0.2%]; 6 [0.8%], respectively [P < 0.0001]) and in OcMMP patients with no visible inflammation when compared with HC (44.3 [7.9%]; 5.8 [0.8%]; P < 0.05). At 12 months follow-up, 53% of OcMMP eyes progressed, and this was associated with baseline conjunctival neutrophilia (P = 0.004). As a potential biomarker, a value of 44 NPI had sensitivity, specificity, and positive predictive values of 75%, 70%, and 73%, respectively. Notably, eyes with no visible inflammation and raised conjunctival neutrophils were more likely to progress and have a greater degree of conjunctival shrinkage compared to those without raised neutrophils. Conclusions These data suggest that OSIC-flow cytometric analyses may facilitate repeated patient sampling. Neutrophils may act as a biomarker for monitoring disease activity, progressive fibrosis, and response to therapy in OcMMP even when the eye appears clinically uninflamed.


Journal of Biomedical Materials Research Part A | 2012

Architectural characterization of organotypic cultures of H400 and primary rat keratinocytes

Erum Khan; Richard M. Shelton; Paul R. Cooper; John Hamburger; Gabriel Landini

Organotypic epithelial structures can be cultured using primary or immortalized keratinocytes. However, there has been little detailed quantitative histological characterization of such cultures in comparison with normal mucosal architecture. The aim of this study is to identify morphological markers of tissue architecture that can be used to monitor tissue structure, maturation, and differentiation and to enable quantitative comparison of organotypic cultures (OCs) with normal oral mucosa. OCs of oral keratinocytes [immortalized H400 or primary rat keratinocytes (PRKs)] were generated using the three scaffolds of de-epidermalized dermis (DED), polyethylene terephthalate (PET), and collagen gels for up to 14 days. Cultures and normal epithelium were analyzed immunohistochemically and by using the semi-quantitative reverse transcriptase polymerase chain reaction (sq-RT-PCR) for E-cadherin, desmoglein-3, plakophilin, involucrin, cytokeratins-1, -5, -6, -10, -13, and Ki67. The epithelial thickness of OCs was measured in stained sections using image processing. Histological analysis revealed that air-liquid interface (ALI) cultures generated stratified organotypic epithelial structures by 14-days. The final thickness of these cultures as well as the degree of maturation/stratification (including stratum corneum formation) varied significantly depending on the scaffold used. For certain scaffolds, the immunohistochemical profiles obtained recapitulated those of normal oral epithelium indicating comparable in vitro differentiation and proliferation. In conclusion, quantitative microscopy approaches enabled unbiased architectural characterization of OCs. The scaffold materials used in the present study (DED, collagen type-I and PET) differentially influenced cell behavior in OCs of oral epithelia. H400 and PRK OCs on DED at the ALI demonstrated similar characteristics in terms of gene expression and protein distribution to the normal tissue architecture.


Annals of the Rheumatic Diseases | 2015

THU0544 Auditing the Impact of the Application of the Proposed New 2014 International Criteria for Behçet's Disease

D. Mitton; T. Blake; David Carruthers; E. Damato; A. Denniston; A. Poveda-Gallego; John Hamburger; Philip I. Murray; S. Powell; Andrea Richards; V. Sewell; D. Situnayake

Background As there is no diagnostic test for Behçets Disease (BD), multidisciplinary assessment remains the gold standard for diagnosis In 2014, an international team from 27 countries (not including the UK), described the New International Criteria for Behçets disease. The Criteria were judged capable of “performing with good discriminatory potential (Sensitivity 94.8%, ISG 85%, specificity 90.5%, ISG 96%) regardless of country” and were felt to be “intuitive and easy to use in a wide variety of settings” [1]. The authors suggessted a role for for mass screening and identification of possible BD Objectives To assess the performance of the proposed new international criteria for Behcets Disease in a UK setting. Methods The following information was captured from the cohort: Patient demographics Frequency distribution of clinical characteristics of BD for patients with clinically confirmed BD, incomplete BD and a rejected diagnosis of BD. The proposed 2014 ICBD criteria were compared with the ISG 1990 in comparison to the gold standard multidisciplinary assessment at the Birmingham National Centre. Results There were 80 females and 39 males. 16 cases were clinically diagnosed following multidisciplinary review but failed to meet ISG 1990 criteria. All of these met the ICBD 2014 criteria. 12 cases were ISG+ but BD was not confirmed clinically (including 3 clinically rejected BD diagnosis). This increased to 14 cases for the ICBD 2014 criteria (including 5 clinically rejected BD diagnosis) Conclusions As expected the proposed ICBD 2014 criteria were more sensitive at picking up cases than ISG 1990 using the multidisciplinary assessment process as the gold standard Specificity was less than expected for both criteria, as in our hands some clinical features were not always judged either to be attributable to a possible BD diagnosis or confidently ascertained, though time and future follow up may improve performance. A more detailed expert gynaecology assessment has now been factored into service design Those patients with “Incomplete BD” form an interesting subgroup which may warrant more detailed examination e.g. those patients who present with posterior uveitis consistent with BD but fail to fulfil the classification criteria. Routine use of pathergy testing may enhance performance. ICBD may serve as a useful screening tool but in our hands in a mainly UK population (62% white British) may over diagnose BD Patients referred to the National Behçets Centres. Our three national centres represent an ideal setting to extend our study. References International Team for the Revision of the International Criteria for Behçets Disease (ITR-ICBD). The International Criteria for Behçets Disease (ICBD): a collaborative study of 27 countries on the sensitivity and specificity of the new criteria. J Eur Acad Dermatol Venereol 2014;28:338-47. Disclosure of Interest None declared


Rheumatology | 2007

Sjögren's Systemic Clinical Activity Index (SCAI)—a systemic disease activity measure for use in clinical trials in primary Sjögren's syndrome

Simon Bowman; N. Sutcliffe; D. A. Isenberg; Fiona Goldblatt; M. Adler; E. Price; A. Canavan; John Hamburger; Andrea Richards; Saaeha Rauz; M. Regan; K. Gadsby; S. Rigby; A. Jones; R. Mathew; D. Mulherin; A. Stevenson; P. Nightingale


Hepatology | 1994

Distribution of pyruvate dehydrogenase dihydrolipoamide acetyltransferase (PDC-E2) and another mitochondrial marker in salivary gland and biliary epithelium from patients with primary biliary cirrhosis.

Ruth Joplin; Gerald D. Johnson; John B. Matthews; John Hamburger; J. Gordon Lindsay; Stefan G. Hubscher; Alastair J. Strain; James Neuberger


Sexually Transmitted Infections | 2000

The significance of oral health in HIV disease

Iain L. C. Chapple; John Hamburger

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Simon Bowman

University Hospitals Birmingham NHS Foundation Trust

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Saaeha Rauz

University of Birmingham

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S. John Curnow

University of Birmingham

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