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1.  Characterisation of a dendritic cell subset in synovial tissue which strongly expresses Jak/STAT transcription factors from patients with rheumatoid arthritis 
Annals of the Rheumatic Diseases  2007;66(8):992-999.
Objectives
To characterise the phenotype of the putative dendritic cells strongly expressing Jak3 and STAT4, which have been previously identified in the synovial tissue of patients with active rheumatoid arthritis (RA).
Methods
Synovial biopsy specimens were obtained at arthroscopy from 30 patients with active RA (42 synovial biopsies). Immunohistological analysis was performed using monoclonal antibodies to detect dendritic cell subsets, including activation markers and cytokines relevant to dendritic cell function. Co‐localisation of cell surface markers and cytokines was assessed primarily using sequential sections, with results confirmed by dual immunohistochemistry and immunofluorescence with confocal microscopy.
Results
The dendritic cells identified in RA synovial tissue that strongly express Jak3 also strongly express STAT4 and STAT 6 and are correlated with the presence of serum rheumatoid factor. These cells are not confined to a single dendritic cell subset, with cells having phenotypes consistent with both myeloid‐ and plasmacytoid‐type dendritic cells. The activation status of these dendritic cells suggests that they are maturing or mature dendritic cells. These dendritic cells produce IL12 as well as interferon α and γ.
Conclusions
The close correlation of these dendritic cells with the presence of serum rheumatoid factor, a prognostic factor for worse disease outcome, and the strong expression by these cells of components of the Jak/STAT transcription factor pathway suggest a potential therapeutic target for the treatment of RA.
doi:10.1136/ard.2006.060822
PMCID: PMC1954703  PMID: 17223651
rheumatoid arthritis; myeloid dendritic cells; plasmacytoid dendritic cells; IL12; interferon alpha; interferon gamma
2.  Changes in synovial tissue Jak‐STAT expression in rheumatoid arthritis in response to successful DMARD treatment 
Annals of the Rheumatic Diseases  2006;65(12):1558-1564.
Background
Modulation of Jak‐STAT signalling may provide an effective therapeutic strategy in inflammatory arthritis (IA).
Objective
To examine the effect of successful disease‐modifying antirheumatic drug (DMARD) treatment on the expression of Jak‐STAT in a cohort of patients with active rheumatoid arthritis.
Methods
Synovial tissue biopsy specimens from 16 patients with active rheumatoid arthritis, taken before and after initiation of DMARD treatment, were examined for the presence of janus kinase (Jak)3, signal transducer and activator of transcription (STAT)1, STAT4 and STAT6 expression using immunohistochemistry.
Results
Successful treatment with DMARDs results in reduction in STAT1 expression in the lining, and STAT1 and STAT6 in the sublining of rheumatoid arthritis synovial tissue. Although the overall expression of STAT4 and Jak3 was not significantly altered by DMARD treatment, there was a significant reduction in the expression of the STAT4 and Jak3 bright cells, thought to be an activated dendritic cell subpopulation.
Conclusion
Results show that Jak3, STAT1, STAT4 expression and STAT6 sublining expression decrease in response to successful treatment of rheumatoid arthritis with standard DMARDs. Therefore, altering the expression of these pathways may represent an alternative treatment option, either through promoting up‐regulation of inhibitory pathways, or suppressing inflammatory paths.
doi:10.1136/ard.2005.050385
PMCID: PMC1798468  PMID: 16760256
3.  Expression of Jak3, STAT1, STAT4, and STAT6 in inflammatory arthritis: unique Jak3 and STAT4 expression in dendritic cells in seropositive rheumatoid arthritis 
Annals of the Rheumatic Diseases  2005;65(2):149-156.
Background
Modulation of Jak‐STAT signalling may provide an effective therapeutic strategy in inflammatory arthritis.
Objective
To document Jak‐STAT expression in a cohort of patients with active rheumatoid arthritis (RA), spondyloarthritis (SpA), and osteoarthritis (OA) and compare these subsets with normal synovial tissue.
Methods
Synovial tissue biopsy specimens from patients with RA, OA, and SpA and histologically normal tissue (n = 10 in each arthritis group) were examined for the presence of Jak3, STAT1, STAT4, and STAT6 expression using immunohistochemistry. Phenotyping was performed using immunohistochemistry and immunofluorescence. Clinical and serological characteristics of patients with RA expressing Jak3‐STAT4 were assessed.
Results
STAT1, STAT4, and Jak3 protein expression was generally increased in inflammatory arthritis. In contrast, STAT6 expression was relatively heterogeneous. A subpopulation of CD1a positive dendritic cells unique to seropositive patients with RA was detected. These cells showed intense protein expression for Jak3, STAT4, and STAT6.
Conclusion
CD1a positive dendritic cells intensely express Jak3, STAT4, and STAT6 in seropositive RA tissue and may be an alternative marker for dendritic cells in their early stages of activation as well as providing a tool for identifying RA at the level of the synovium. Jak3 inhibition may be a potential therapeutic target to prevent dendritic cell maturation in RA. STAT1 expression is increased in inflammatory arthritis, suggesting that its pro‐apoptotic and anti‐inflammatory effects cannot effectively counteract inflammation. STAT6 expression is heterogeneous in synovium, suggesting a possible homoeostatic role in addition to any anti‐inflammatory effects.
doi:10.1136/ard.2005.037929
PMCID: PMC1798020  PMID: 16096332
dendritic cells; rheumatoid arthritis; transcription factors
4.  Upper gastrointestinal Kaposi's sarcoma in patients positive for HIV antibody without cutaneous disease 
Six patients with antibodies to the human immunodeficiency virus (HIV) and with persistent gastrointestinal symptoms of HIV infection but without cutaneous lesions of Kaposi's sarcoma underwent endoscopy. Four also underwent barium meal examination. In all six cases small lesions were seen in the stomach at endoscopy, and histological examination of biopsy specimens taken from the lesions confirmed the diagnosis of Kaposi's sarcoma. The barium meal examinations were reported as normal in three patients and showed oesophageal candidiasis in the fourth.
These findings suggest that Kaposi's sarcoma of the upper gastrointestinal tract is common in patients positive for HIV antibody, even those without cutaneous lesions. Endoscopy, with biopsy of suspicious lesions, is necessary to make the diagnosis and is recommended in all HIV antibody positive patients with persistent upper gastrointestinal symptoms.
Images
PMCID: PMC2544701  PMID: 3122968
5.  Incidence and significance of faecal hydroxystearic acid in alimentary disease 
Gut  1974;15(8):614-621.
Three-day faecal collections were obtained from 87 patients with a variety of gastroenterological diagnoses and 12 control subjects while consuming normal diets. Faecal weight, total fatty acids, and the proportion of hydroxystearic (OHSA) acid were measured. All patients had some easily detectable hydroxystearic acid. It was found that in general the percentage of OHSA in the faecal fatty acids increased with increasing fat output. Thus most patients excreting less than 20 g of fat per day had less than 5% OHSA while those with greater steatorrhoea had levels of 6 to 23%. Exceptions were patients with mild steatorrhoea with ileal disease, ileal resections, or small intestinal bacterial colonization, who had more than 5% OHSA whilst patients with colonic resection had much lower levels of OHSA than otherwise found. It is impossible to determine whether OHSA had a specific cathartic action from this study since the data implicated total fatty acids to the same extent.
PMCID: PMC1413027  PMID: 4418840
6.  Medical and Social Screening of Patients aged 70 to 72 by an Urban General Practice Health Team 
British Medical Journal  1974;2(5910):108-111.
A medico-social survey of 259 elderly patients aged 70-72 was carried out by three doctors, a health visitor and a nurse in an urban general practice. Seven hundred and ninety diseases or disabilities were identified—an average of 3·2 per patient—of which 20·5% were unknown to the doctors. Using a simple check list for symptom inquiry, the health visitor or nurse missed very little of the physical or psychological disease. In some respects their symptom inquiry was more revealing than that of the doctors but they had difficulty in eliciting evidence of malnutrition, masked depression, and incipient dementia. Initial health screening of the elderly for unreported disease in general practice can easily be done by a health visitor with training in geriatric problems and the recognition of psychiatric illness.
Initial health screening can also be done by a nurse with community-nursing experience but she will require additional training in the techniques of social assessment. The doctor must examine those patients found to be suffering from alerting symptoms. A general practice of three or four doctors requires one health visitor for routine work and one additional health visitor or nurse for screening of the elderly. Unreported disease in the elderly indicates failure to make contact and failure to ask the right questions. Unknown disease may be due to inadequate records.
PMCID: PMC1610712  PMID: 4274813
8.  Chronic Liver Disease and Mitochondrial Antibodies: A Family Study 
British Medical Journal  1972;1(5793):146-148.
Two sisters had primary biliary disease and associated autoimmune thyroiditis with high titres of mitochondrial and other autoantibodies. Their deceased mother possibly suffered from similar disorders. In the same family two brothers had multiple autoimmune reactions, including mitochondrial antibodies, but liver function tests gave normal results. Ten other close relatives were investigated. Australia antigen was not found in the proband or her relatives.
PMCID: PMC1787106  PMID: 5007841
9.  Idiopathic retroperitoneal fibrosis--is serum alkaline phosphatase a marker of disease activity? 
Postgraduate Medical Journal  1988;64(749):239-241.
Two patients are presented in whom extensive investigations were carried out to determine the cause of a raised serum alkaline phosphatase. Idiopathic retroperitoneal fibrosis was diagnosed in both cases and the serum alkaline phosphatase returned to normal following treatment with corticosteroids and coincident with resolution of the patients' symptoms.
Images
PMCID: PMC2428837  PMID: 3174545
10.  Percutaneous cholangiography in the management of biliary stricture. 
Gut  1966;7(2):164-174.
Images
PMCID: PMC1552335  PMID: 5932894

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