Chylous ascites following radical nephrectomy: a case report

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Anti-CCP2 Antibodies: An Overview and Perspective of the Diagnostic Abilities of this Serological Marker for Early Rheumatoid Arthritis

The literature of the last 4 years confirms that the anti-CCP2 test is a very useful marker for the early and specific diagnosis of rheumatoid arthritis (RA). The anti-CCP2 test is very specific for RA (95–99%) and has sensitivity comparable to that of the rheumatoid factor (70–75%). The antibodies can be detected very early in the disease and can be used as an indicator for the progression and prognosis of RA. In this review, these interesting properties and some future possibilities of this diagnostic test are discussed

Association of IL4R single-nucleotide polymorphisms with rheumatoid nodules in African Americans with rheumatoid arthritis

Abstract Introduction To determine whether IL4R single-nucleotide polymorphisms (SNPs) rs1805010 (I50V) and rs1801275 (Q551R), which have been associated with disease severity in rheumatoid arthritis (RA) patients of European ancestry, relate to the presence of rheumatoid nodules and radiographic erosions in African Americans. Methods Two IL4R SNPs, rs1805010 and rs1801275, were genotyped in 749 patients from the Consortium for Longitudinal Evaluation of African-Americans with Early Rheumatoid Arthritis (CLEAR) registries. End points were rheumatoid nodules defined as present either by physical examination or by chest radiography and radiographic erosions (radiographs of hands/wrists and feet were scored using the modified Sharp/van der Heijde system). Statistical analyses were performed by using logistic regression modeling adjusted for confounding factors. Results Of the 749 patients with RA, 156 (20.8%) had rheumatoid nodules, with a mean age of 47.0 years, 84.6% female gender, and median disease duration of 1.9 years. Of the 461 patients with available radiographic data, 185 (40.1%) had erosions (score >0); their mean age was 46.7 years; 83.3% were women; and median disease duration was 1.5 years. Patients positive for HLA-DRB1 shared epitope (SE) and autoantibodies (rheumatoid factor (RF) or anti-cyclic citrullinated peptide (CCP)) had a higher risk of developing rheumatoid nodules in the presence of the AA and AG alleles of rs1801275 (odds ratio (OR)adj = 8.08 (95% confidence interval (CI): 1.60-40.89), P = 0.01 and ORadj = 2.97 (95% CI, 1.08 to 8.17), P = 0.04, respectively). Likewise, patients positive for the HLA-DRB1 SE and RF alone had a higher risk of developing rheumatoid nodules in presence of the AA and AG alleles of rs1801275 (ORadj = 8.45 (95% CI, 1.57 to 45.44), P = 0.01, and ORadj = 3.57 (95% CI, 1.18 to 10.76), P = 0.02, respectively) and in the presence of AA allele of rs1805010 (ORadj = 4.52 (95% CI, 1.20 to 17.03), P = 0.03). No significant association was found between IL4R and radiographic erosions or disease susceptibility, although our statistical power was limited by relatively small numbers of cases and controls. Conclusions We found that IL4R SNPs, rs1801275 and rs1805010, are associated with rheumatoid nodules in autoantibody-positive African-American RA patients with at least one HLA-DRB1 allele encoding the SE. These findings highlight the need for analysis of genetic factors associated with clinical RA phenotypes in different racial/ethnic populations

Looking through the 'window of opportunity': is there a new paradigm of podiatry care on the horizon in early rheumatoid arthritis?

Over the past decade there have been significant advances in the clinical understanding and care of rheumatoid arthritis (RA). Major paradigm changes include earlier disease detection and introduction of therapy, and 'tight control' of follow-up driven by regular measurement of disease activity parameters. The advent of tumour necrosis factor (TNF) inhibitors and other biologic therapies have further revolutionised care. Low disease state and remission with prevention of joint damage and irreversible disability are achievable therapeutic goals. Consequently new opportunities exist for all health professionals to contribute towards these advances. For podiatrists relevant issues range from greater awareness of current concepts including early referral guidelines through to the application of specialist skills to manage localised, residual disease activity and associated functional impairments. Here we describe a new paradigm of podiatry care in early RA. This is driven by current evidence that indicates that even in low disease activity states destruction of foot joints may be progressive and associated with accumulating disability. The paradigm parallels the medical model comprising early detection, targeted therapy, a new concept of tight control of foot arthritis, and disease monitoring

An Induced Mutation in Tomato eIF4E Leads to Immunity to Two Potyviruses

BACKGROUND: The characterization of natural recessive resistance genes and Arabidopsis virus-resistant mutants have implicated translation initiation factors of the eIF4E and eIF4G families as susceptibility factors required for virus infection and resistance function. METHODOLOGY/PRINCIPAL FINDINGS: To investigate further the role of translation initiation factors in virus resistance we set up a TILLING platform in tomato, cloned genes encoding for translation initiation factors eIF4E and eIF4G and screened for induced mutations that lead to virus resistance. A splicing mutant of the eukaryotic translation initiation factor, S.l_eIF4E1 G1485A, was identified and characterized with respect to cap binding activity and resistance spectrum. Molecular analysis of the transcript of the mutant form showed that both the second and the third exons were miss-spliced, leading to a truncated mRNA. The resulting truncated eIF4E1 protein is also impaired in cap-binding activity. The mutant line had no growth defect, likely because of functional redundancy with others eIF4E isoforms. When infected with different potyviruses, the mutant line was immune to two strains of Potato virus Y and Pepper mottle virus and susceptible to Tobacco each virus. CONCLUSIONS/SIGNIFICANCE: Mutation analysis of translation initiation factors shows that translation initiation factors of the eIF4E family are determinants of plant susceptibility to RNA viruses and viruses have adopted strategies to use different isoforms. This work also demonstrates the effectiveness of TILLING as a reverse genetics tool to improve crop species. We have also developed a complete tool that can be used for both forward and reverse genetics in tomato, for both basic science and crop improvement. By opening it to the community, we hope to fulfill the expectations of both crop breeders and scientists who are using tomato as their model of study

IL-17A Expression Is Localised to Both Mononuclear and Polymorphonuclear Synovial Cell Infiltrates

This study examines the expression of IL-17A-secreting cells within the inflamed synovium and the relationship to in vivo joint hypoxia measurements.IL-17A expression was quantified in synovial tissue (ST), serum and synovial fluid (SF) by immunohistochemistry and MSD-plex assays. IL-6 SF and serum levels were measured by MSD-plex assays. Dual immunofluorescence for IL-17A was quantified in ST CD15+ cells (neutrophils), Tryptase+ (mast cells) and CD4+ (T cells). Synovial tissue oxygen (tpO(2)) levels were measured under direct visualisation at arthroscopy. Synovial infiltration was assessed using immunohistochemistry for cell specific markers. Peripheral blood mononuclear and polymorphonuclear cells were isolated and exposed to normoxic or 3% hypoxic conditions. IL-17A and IL-6 were quantified as above in culture supernatants.IL-17A expression was localised to mononuclear and polymorphonuclear (PMN) cells in inflamed ST. Dual immunoflourescent staining co-localised IL-17A expression with CD15+ neutrophils Tryptase+ mast cells and CD4+T cells. % IL-17A positivity was highest on CD15+ neutrophils, followed by mast cells and then CD4+T-cells. The number of IL-17A-secreting PMN cells significantly correlated with sublining CD68 expression (r = 0.618, p<0.01). IL-17A SF levels correlated with IL-6 SF levels (r = 0.675, p<0.01). Patients categorized according to tp0(2)< or >20 mmHg, showed those with low tp0(2)<20 mmHg had significantly higher IL-17A+ mononuclear cells with no difference observed for PMNs. Exposure of mononuclear and polymorphonuclear cells to 3% hypoxia, significantly induced IL-6 in mononuclear cells, but had no effect on IL-17A expression in mononuclear and polymorphonuclear cells.This study demonstrates IL-17A expression is localised to several immune cell subtypes within the inflamed synovial tissue, further supporting the concept that IL-17A is a key mediator in inflammatory arthritis. The association of hypoxia with Il-17A expression appears to be indirect, probably through hypoxia-induced pro-inflammatory pathways and leukocyte influx within the joint microenvironment

The Future of Rheumatoid Arthritis and Hand Surgery - Combining Evolutionary Pharmacology and Surgical Technique

Rheumatoid arthritis is a systemic autoimmune disease of uncertain aetiology, which is characterized primarily by synovial inflammation with secondary skeletal destructions

Functional characterisation of the osteoarthritis genetic risk residing at ALDH1A2 identifies rs12915901 as a key target variant

To identify the functional single nucleotide polymorphisms (SNPs) and mechanisms conferring increased hand osteoarthritis (OA) risk at the ALDH1A2 locus, which is a retinoic acid (RA) regulatory gene.Tissues from 247 knee, hip or hand OA patients who had undergone joint surgery were included. RNA-sequencing was used to investigate differential expression of ALDH1A2 and other RA signalling pathway genes in cartilage. ALDH1A2 expression in multiple joint tissues was quantified by qPCR. Allelic expression imbalance (AEI) was measured by pyrosequencing. The consequences of ALDH1A2 depletion by RNAi were assessed in primary human chondrocytes. In silico and in vitro analyses were used to pinpoint which among 62 highly correlated SNPs could account for the association at the locus.We observed ALDH1A2 expression across multiple joint tissues, including osteochondral tissue from the hand. The expression of ALDH1A2 and of several RA signalling genes was different in diseased versus non-diseased cartilage, with ALDH1A2 showing lower levels in OA samples. Experimental ALDH1A2 depletion impacted upon a number of chondrogenic markers, including SOX9. In addition, reduced expression of the OA risk-conferring allele was witnessed in a number of joint tissues, with the strongest effect in cartilage. The intronic SNP rs12915901 recapitulated the AEI observed in patient tissues, while the ETS transcription factors were identified as potential mediators of this effect.The ALDH1A2 locus seems to increase hand OA risk through decreased expression of ALDH1A2 in joint tissues depending on rs12915901, a mechanism that can now be targeted to modulate OA risk. This article is protected by copyright. All rights reserved

Functional characterisation of the osteoarthritis genetic risk residing at ALDH1A2 identifies rs12915901 as a key target variant

To identify the functional single nucleotide polymorphisms (SNPs) and mechanisms conferring increased hand osteoarthritis (OA) risk at the ALDH1A2 locus, which is a retinoic acid (RA) regulatory gene.Tissues from 247 knee, hip or hand OA patients who had undergone joint surgery were included. RNA-sequencing was used to investigate differential expression of ALDH1A2 and other RA signalling pathway genes in cartilage. ALDH1A2 expression in multiple joint tissues was quantified by qPCR. Allelic expression imbalance (AEI) was measured by pyrosequencing. The consequences of ALDH1A2 depletion by RNAi were assessed in primary human chondrocytes. In silico and in vitro analyses were used to pinpoint which among 62 highly correlated SNPs could account for the association at the locus.We observed ALDH1A2 expression across multiple joint tissues, including osteochondral tissue from the hand. The expression of ALDH1A2 and of several RA signalling genes was different in diseased versus non-diseased cartilage, with ALDH1A2 showing lower levels in OA samples. Experimental ALDH1A2 depletion impacted upon a number of chondrogenic markers, including SOX9. In addition, reduced expression of the OA risk-conferring allele was witnessed in a number of joint tissues, with the strongest effect in cartilage. The intronic SNP rs12915901 recapitulated the AEI observed in patient tissues, while the ETS transcription factors were identified as potential mediators of this effect.The ALDH1A2 locus seems to increase hand OA risk through decreased expression of ALDH1A2 in joint tissues depending on rs12915901, a mechanism that can now be targeted to modulate OA risk. This article is protected by copyright. All rights reserved