Potential risk factors associated with the use of cidofovir to treat benign human papillomavirus-related disease.

Background: Cidofovir is currently being used off-licence to treat different viral infections, such as benign low-risk human papillomavirus (HPV)-related recurrent respiratory papillomatosis (RRP). There are concerns over the safety of this practice as rat studies demonstrated a high malignant transformation rate. As yet, there are no clinical reports of cidofovir-induced malignant changes in humans.

Levels of 5' RNA tags in plasma and buffy coat from EDTA blood increase with time.

Background: For biological sample banking it is important to precisely document sample treatment prior to extraction and storage. A major variable is the interval between blood sampling and subsequent processing and storage. We have determined the relationship between this time interval and frequency of 5' transcript tags.

Molecular phenotypic descriptors of Dupuytren's disease defined using informatics analysis of the transcriptome.

Purpose: Dupuytren's disease (DD) is a fibroproliferative disorder of unknown etiopathogenesis, which may cause progressive, permanent contracture of digits. Previous studies provide compelling evidence that genetic alterations play an important role. Macroscopically affected areas demonstrate phenotypic differences between the two structurally distinct fibrotic elements in DD (ie, the nodule and the cord).

HLA class II haplotype and autoantibody associations in children with juvenile dermatomyositis and juvenile dermatomyositis-scleroderma overlap.

Objectives: To investigate a large cohort of children with juvenile dermatomyositis (JDM), and those with JDM-scleroderma (JDM-SSc) overlap, using detailed serological analysis, HLA class II genotyping and clinical characterization.

Methods: Children (114) with JDM were recruited, and clinical data collected, through the JDM National Registry and Repository (UK and Ireland). Sera were assayed for ANA using standard immunofluorescence techniques and specific antibodies characterized using ELISA, immunodiffusion and radioimmunoprecipitation.

Successful downstream application of the Paxgene Blood RNA system from small blood samples in paediatric patients for quantitative PCR analysis.

Background: The challenge of gene expression studies is to reliably quantify levels of transcripts, but this is hindered by a number of factors including sample availability, handling and storage. The PAXgene Blood RNA System includes a stabilizing additive in a plastic evacuated tube, but requires 2.5 mL blood, which makes routine implementation impractical for paediatric use.

Identification of new reference genes for the normalisation of canine osteoarthritic joint tissue transcripts from microarray data.

Background: Real-time reverse transcriptase quantitative polymerase chain reaction (real-time RT-qPCR) is the most accurate measure of gene expression in biological systems. The comparison of different samples requires the transformation of data through a process called normalisation. Reference or housekeeping genes are candidate genes which are selected on the basis of constitutive expression across samples, and allow the quantification of changes in gene expression.

Tumour necrosis factor-alpha single nucleotide polymorphisms are not independent of HLA class I in UK Caucasians with adult onset idiopathic inflammatory myopathies.

Objective: To investigate haplotype tagging single nucleotide polymorphisms (SNPs) in the tumour necrosis factor alpha (TNF-alpha) gene, in UK Caucasian idiopathic inflammatory myopathy (IIM) patients.

Methods: A cross-sectional, case-control study of four TNF-alpha SNPs was undertaken, comparing cases of polymyositis (PM) (n = 121), dermatomyositis (DM) (n = 109) and myositis overlapping with other connective tissue diseases (CTD-overlap) (n = 73) with normal subjects (n = 177). Subgroup analyses were undertaken after stratifying for myositis specific/associated antibodies.

Expression profiling of select cytokines in canine osteoarthritis tissues.

The objective of this study was to investigate the level of expression of five cytokines in four different articular tissues from the joints of dogs with and without osteoarthritis (OA). Articular tissues were harvested from the stifle (fat, cranial cruciate ligament, synovial membrane) or hip (articular cartilage) from eight dogs with OA secondary to cranial cruciate ligament disease (stifle) or hip dysplasia (hip), undergoing routine surgical treatment for the condition, and from five dogs euthanatized without orthopaedic disease. The mRNA transcript numbers for interleukin-1beta (IL-1beta), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10) and interleukin-17 (IL-17) were determined by quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR).

Expression stability of commonly used reference genes in canine articular connective tissues.

Background: The quantification of gene expression in tissue samples requires the use of reference genes to normalise transcript numbers between different samples. Reference gene stability may vary between different tissues, and between the same tissue in different disease states. We evaluated the stability of 9 reference genes commonly used in human gene expression studies.

Interferon-gamma and interleukin-4 gene polymorphisms in Caucasian idiopathic inflammatory myopathy patients in UK.

Objective: To determine whether interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) genes confer susceptibility for the idiopathic inflammatory myopathies (IIMs).

Methods: A large cross-sectional study of UK caucasian adults with polymyositis (PM, n = 101), dermatomyositis (DM, n = 94) and myositis overlapping with a connective tissue disease (myositis/CTD-overlap, n = 70) was completed. 177 ethnically matched controls were available for comparison.

Monocyte chemotactic protein-1 single nucleotide polymorphisms do not confer susceptibility for the development of adult onset polymyositis/dermatomyositis in UK Caucasians.

Objectives: Polymyositis (PM) and dermatomyositis (DM) form part of the idiopathic inflammatory myopathies (IIMs). The chemokine monocyte chemotactic protein-1 (MCP-1) is expressed at sites of the T cell inflammatory response in the IIMs. We thus investigate whether genetic markers in the MCP-1 gene confer disease susceptibility for the development of PM and DM.

ALK1 signalling analysis identifies angiogenesis related genes and reveals disparity between TGF-beta and constitutively active receptor induced gene expression.

Background: TGF-beta1 is an important angiogenic factor involved in the different aspects of angiogenesis and vessel maintenance. TGF-beta signalling is mediated by the TbetaRII/ALK5 receptor complex activating the Smad2/Smad3 pathway. In endothelial cells TGF-beta utilizes a second type I receptor, ALK1, activating the Smad1/Smad5 pathway.

In adult onset myositis, the presence of interstitial lung disease and myositis specific/associated antibodies are governed by HLA class II haplotype, rather than by myositis subtype.

The aim of this study was to investigate HLA class II associations in polymyositis (PM) and dermatomyositis (DM), and to determine how these associations influence clinical and serological differences. DNA samples were obtained from 225 UK Caucasian idiopathic inflammatory myopathy patients (PM = 117, DM = 108) and compared with 537 randomly selected UK Caucasian controls. All cases had also been assessed for the presence of related malignancy and interstitial lung disease (ILD), and a number of myositis-specific/myositis-associated antibodies (MSAs/MAAs).

MCP-1 gene haplotype association in biopsy proven giant cell arteritis.

Objective: Giant cell arteritis (GCA) is the most frequent vasculitis in European and North American countries. Increased expression of monocyte chemoattractant protein 1 (MCP-1) has been observed within the inflammatory infiltrates of blood vessels and serum of patients with GCA and in other autoimmune and inflammatory conditions. MCP-1 gene polymorphisms have been reported to contribute to susceptibility to several immune and inflammatory conditions.

Epistatic interactions between HLA-DRB1 and interleukin 4, but not interferon-gamma, increase susceptibility to giant cell arteritis.

Objective: To assess the roles of the interleukin 4 (IL-4) and interferon-g (IFN-g) gene polymorphisms in a series of patients with biopsy-proven giant cell arteritis (GCA).

Methods: Eighty-two patients with biopsy-proven GCA and 102 ethnically matched controls from the Lugo region (Northwest Spain) were studied. The following single nucleotide polymorphisms (SNP) were assessed: IL-4 (SNP1: rs2070874, SNP2: rs2227284, SNP3: rs2227282, SNP4: rs2243266, and SNP5: rs2243267) and IFN-g (SNP1: rs1861494, SNP2: rs1861493, and SNP3: rs2069718).

TNF autovaccination induces self anti-TNF antibodies and inhibits metastasis in a murine melanoma model.

TNF is a proinflammatory cytokine involved in the pathogenesis of chronic inflammatory diseases, but also in metastasis in certain types of cancer. In terms of therapy, TNF is targeted by anti-TNF neutralising monoclonal antibodies or soluble TNF receptors. Recently, a novel strategy based on the generation of self anti-TNF antibodies (TNF autovaccination) has been developed.

Polymorphisms in the mannose binding lectin (MBL) gene are not associated with radiographic erosions in rheumatoid or inflammatory polyarthritis.

Objective: To investigate the association between the mannose binding lectin gene (MBL) promoter and structural single nucleotide polymorphisms (SNP) with development of erosions in a primary care inception cohort of patients with inflammatory polyarthritis (IP).

Methods: DNA was available from 438 patients with IP and radiographic data were available for all patients at 5 years. Four SNP [MBL-550*C/G (H/L), MBL-221*G/C (Y/X), MBL codon 52*C/T, and MBL codon 54*G/A] mapping to the MBL gene were genotyped using primer extension techniques.

Polymorphisms in the tumour necrosis factor gene are not associated with severity of inflammatory polyarthritis.

Background: Tumour necrosis factor alpha (TNFalpha) is a powerful inflammatory mediator in rheumatoid and other types of inflammatory arthritis. Polymorphisms within the TNFalpha gene have previously been investigated to determine their role in the aetiopathogenesis of rheumatoid arthritis (RA), but it is unclear whether reported associations are with susceptibility to, or severity of, disease.

Objective: To examine the association between both individual TNFalpha single nucleotide polymorphisms (SNPs) and haplotypes with the development and severity of erosions by 5 years in patients with inflammatory polyarthritis (IP).

Validation of the interleukin-10 knockout mouse model of colitis: antitumour necrosis factor-antibodies suppress the progression of colitis.

Advances in understanding pathogenesis and developing new therapies are hastened by the use of effective animal models of disease. In inflammatory bowel disease, such as Crohn's disease, a variety of models have been used, including the IL-10 knockout mouse. However, in order to be truly valuable, the models need to respond to existing therapy in a way which resembles the human disease.