tbuckley/cabot-search huggingface dataset:
OP0173 HLA-B27 and classification of enthesitis-related arthritis in an eight year follow up study of nordic patients with juvenile idiopathic arthritis
Authors: L. Berntson, K. Aalto, A. Fasth, T. Herlin, S. Nielsen, E. Nordal, S. Peltoniemi, M. Zak, M. Rygg
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The heterogeneity of juvenile idiopathic arthritis (JIA) is an important topic in research and in focus for our aim to find predictive signs in patients, guiding us in research and therapy. The cell-surface antigen HLA-B27 is well known to be associated with spondyloarthropathies and associated features. In children sacroiliitis often evolves after years of arthritis in peripheral joints, which complicates classification. In the current ILAR (Edmonton) classification HLA-B27 is an important disease descriptor. <h3>Objectives</h3> We wanted to investigate the associations of HLA-B27 on the clinical manifestation of JIA, during the first eight years of disease, in a study as close to population-based as possible. We also wanted to relate our findings to the ILAR classification. <h3>Methods</h3> We studied an incidence-based cohort of 440 patients collected prospectively in well-defined areas in Sweden, Norway, Finland, and Denmark. Clinical and serological data of the first eight years of disease were collected. <h3>Results</h3> HLA-B27 positive boys had significantly higher age at time of onset compared to HLA-B27 negative boys. This could not be found in girls. Signs of sacroiliitis were associated with HLA-B27 in boys but not in girls and girls with those signs were more seldom classified as enthesitis related arthritis (ERA) according to the ILAR criteria compared to boys. After a median of eight years of disease 16 girls and 33 boys were classified as ERA (11% of total cohort) and they were HLA-B27 positive in 72%. Occurrence of HLA-B27 was associated with a two times higher risk of not reaching remission off medication after eight years of disease. <h3>Conclusions</h3> In this prospectively collected cohort of Nordic patients with JIA, followed for a median of eight years we found significant differences between HLA-B27 positive boys and girls in signs of sacroiliitis and age distribution. Classification of ERA showed differences between genders and HLA-B27 was a negative predictor for achieving remission off medication after eight years of disease. <h3>Disclosure of Interest</h3> None Declared
Abstract 73: PELP1 is a novel reader of chromatin modifications: Implications in cancer progression
Authors: Ratna K. Vadlamudi, Monica Mann, Valerie A. Cortez
Journal: Cancer Research (2011)

Abstract Cancer is caused by abnormalities of the genome and epigenome including the frequently occurring epigenetic changes of histone modifications. Specifically, estrogen-induced breast carcinogenesis is characterized by alterations in histone modifications. Reader proteins that recognize these modifications facilitate modulation of genes and their resulting biological actions. In addition to regulation by several coregulators, estrogen receptor alpha (ERα) transcriptional activation or repression depends on the modulation of histone methylation at target promoters. The ERα coregulator PELP1 plays an important role in ERα signaling, is a proto-oncogene with aberrant expression in hormone-related cancers and a prognostic indicator of decreased survival in breast cancer patients. The molecular mechanisms by which PEPL1 promotes oncogenesis remain unknown; however, previous studies from our lab have shown that PELP1 interacts with histones and is a novel reader of chromatin modifications. To explore the PELP1 epigenetic interactome, we used a histone peptide array containing 384 unique combinations of histone modifications including methylation, phosphorylation, acetylation and citrullination. Our results show that PELP1 uniquely recognizes histones modified by arginine dimethylation, arginine citrullination and lysine dimethylation. Phosphorylation of residues adjacent to a methyl modification affects the ability of PELP1 to recognize histone methylation. Using various deletions of PELP1 peptides, we have found that PELP1 acts as a module for recognition of a specific histone modification through the carboxyl-terminal glutamic acid rich region. Reporter gene assays showed that PELP1 functionally interacts with arginine methyltransferases including CARM1 and PRMT6, both shown to be dysregulated in human cancers, and synergistically enhances ERα-transactivation. Chromatin immunoprecipitation assays revealed that PELP1 has the potential to alter histone H3 arginine methylation status at ERα target gene promoters. The critical role of PELP1 status in modulating arginine methylation status was also observed through in vivo studies which show PELP1 knockdown results in decreased tumorigenesis and arginine dimethylation. Our findings suggest that PELP1 is a reader of histone methyl modifications and deregulation may have implications on tumor proliferation via epigenetic alterations at ERα target promoters. Targeting these epigenetic alterations through inhibition of PELP1 and the arginine methyltransferases could be a promising cancer therapeutic. This study was funded by NIH grant CA095681. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 73. doi:10.1158/1538-7445.AM2011-73
FRI0374 Factors associated with poor control of urate levels under urate lowering therapy: A cross sectional study of 1689 gouty patients
Authors: P. Richette, G. Errieau, R.-M. Flipo
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> In real life, urate levels are not maintained below the target of 6 mg/dL in a substantial proportion of gouty patients receiving urate-lowering therapy (ULT). <h3>Objectives</h3> To search for factors associated with poor control of serum urate levels (sUA) in a large population of gouty patients receiving ULT. <h3>Methods</h3> This is a cross-sectional multicentre study. Demographic, clinical data and recent (&lt;1year) sUA levels were collected from 2444 gouty patients by 857 general practitioners and 92 rheumatologists from November 2010 to May 2011. Of these, 1689 patients were receiving ULT. Uni and multivariate logistic regression were used to search determinants for sUA level &gt;6mg/dL. <h3>Results</h3> 76% of the 1689 patients (mean age 64±12 years; men 85%) under ULT (xanthine oxidase inhibitors 96.6%) had urate levels above the recommended sUA target of 6mg/dL. Univariate analysis showed that patients with sUA levels above 6 mg/dl were older (p=0.003), consumed more sweetened soft drinks (&gt;1 serving a day, p=0.02) and alcohol (≥30g/day, p=0.0001), had a higher waist circumference (p=0.02), and a shorter disease duration (p=0.01). These determinants persisted in multivariate logistic regression analysis after adjustment for potential confounders: sweetened soft drinks consumption (OR=1.55, 95%CI=0.99-2.43, p=0.05), alcohol consumption (OR=1.39, 95%CI=1.08-1.78, p=0.01), higher waist circumference (OR=1.38, 95%CI=1.01-1.88, p=0.04) and a shorter disease duration (less than 5 years) (OR=1.11, 95%CI=1.02-1.22, p=0.02). <h3>Conclusions</h3> This study shows that a large proportion of gouty patients receiving ULT are not adequately treated. Sweetened soft drinks and alcohol consumption, waist circumference and short disease duration are associated with a poor urate levels control. Reinforcement of lifestyle interventions and dietary modifications may improve adequate control of sUA in patients suffering from chronic gout and receiving ULT. <h3>Disclosure of Interest</h3> None Declared
FATAL BLEEDING, CASE-FATALITY RATE OF MAJOR BLEEDING AND ALL-CAUSE MORTALITY IN PATIENTS TAKING TARGET-SPECIFIC ORAL ANTICOAGULANT, A META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS
Authors: Chatree Chai-Adisaksopha, Christopher Hillis, Tetsuya Isayama, Mark Crowther
Journal: Journal of the American College of Cardiology (2015)
Mitoxantrone and the new drug approval process.
Authors: M D Abeloff
Journal: Journal of Clinical Oncology (1989)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1989.7.5.551 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 2651575 Mitoxantrone and the new drug approval process. M D AbeloffxM D AbeloffSearch for articles by this author https://doi.org/10.1200/JCO.1989.7.5.551 First Page PDF © 1989 by American Society of Clinical Oncology
P785 PROJECTED HEALTH AND ECONOMIC IMPACT OF HEPATITIS C ON THE UNITED STATES VETERANS ADMINISTRATION HEALTH SYSTEM FROM 2014 TO 2024
Authors: D.B. Rein, J.S. Wittenborn, D.K. Liffmann, J.C. Hasche, J.M. Borton, J.R. Kramer, Z. Duan, H.B. El-Serag
Journal: Journal of Hepatology (2014)
SAT0325 Neurological Mechanisms of Chronic Pain in Knee Osteoarthritis
Authors: E. Turovskaya, L. Alekseeva
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> It is now known that OA pain is a complex interaction between many different pain mechanisms. A subset of adults with chronic, symptomatic knee OA may therefore, have neuropathic mechanisms contributing to their pain experience. <h3>Objectives</h3> We evaluate pathogenetic mechanisms involved in the initiation of pain in OA, to measure the prevalence of neuropathic pain and NP(neuropathic) symptoms among adults with this condition and additionally to detect somatosensory deficit <h3>Methods</h3> Patients were 39 women aged from 45-65 years with chronic knee pain (the duration of painat least during the last 3 months) and OA severity II-III grade by Kellgren-Lawrence. Two main types of pain: nociceptive and neuropathic pain were revealed with the help of clinical (rheumatologic and neurological) examinations and neuropathic pain scales (Paindetect and DN4). The patients were asked about duration of knee symptoms and knee OA, knee OA severity (WOMAC), and pain intensity. We used the prevalence of anxiety and depressive disorders in population with OA, examined the interrelationships between severity of pain and emotional disturbances by Hospital Anxiety and Depression scale. The level of knee destruction was assessed with radiography using the Kellgren-Lawrence grading scale and US examination and rheumatologic examination. <h3>Results</h3> Patients were categorized into two groups according to the results of neuropathic questionnaire DN4: patients with DN4 score&gt;4, having a neuropathic pain(NP) features and patients with DN4 score&lt;4, who had no evident neuropathic pain. According to DN4 score patients, who used NP descriptors composed 28%(n=11). No significant differences between groups were seen in age, the character of pain, duration of knee OA, quantity of impacted knee joints, body index, quality of life, radiographic and US severity of knee OA. But the presence of NP features was correlated with higher pain intensity assessed, WOMAC and significantly correlated with higher level of anxiety. In clinical studies, compared to controls, patients with NP features had more diffuse hyperalgesia to mechanical stimuli, no other somatosensory defects were found. <h3>Conclusions</h3> The results indicated that people with chronic OA can experience pain due to both nociceptive and neuropathic mechanisms to varying degrees, so OA can be associated with a mixture of pain mechanisms. The likely neuropathic mechanism in OA is central sensitization, that may be the reason for the often observed discreapancy between joint damage (radiological joint changes) and clinical pain intensity. So treatment should also target central nervous system structures. <h3>Disclosure of Interest</h3> None Declared
Abstract 3383: Expression and role of BORIS/CTCFL in human cancer stem cells
Authors: Jean Benhattar, Loredana Alberti
Journal: Cancer Research (2012)

Abstract The existence of CSCs, a small population that drives the tumors development, progression, metastasis and drug resistance, could explain the failure of several anti-cancer therapy. The discovery of the genes responsible for the CSCs phenotype would point out to the development of new target for the cancer therapy. To date, many tumor markers have been identified but almost none of them are specific to target the CSCs population. The cancer testis gene BORIS/CTCFL was shown to be exclusively expressed in germ cells in normal tissues and was involved in epigenetic reprogramming. BORIS is slightly activated in a wide variety of tumors. It is not clear if this expression is due to basal expression in almost all tumor cells or rather to the expression in a restricted population of cells, as in the CSC. To date, there is no validated antibody against BORIS. Therefore, to analyze BORIS expression in vivo, we developed a molecular beacon (MB) imaging technology to detect BORIS mRNA gene expression. BORIS MB binds to its specific target and produced fluorescence signal at 37°C in vitro, as well as in vivo in the cells expressing high level of BORIS mRNA. BORIS was found to be expressed only in Side Population cells (Hoechst negative cells) in different tumor cell lines (HeLa, HT29, Raji, MB-MDA-231). Our data indicates that BORIS-positive cells are present at low frequency (0.01% is the estimated frequency) in tumor cell lines. Quantitative RT-PCR analysis revealed a significantly higher expression level of BORIS in SP sorted cells (10-20 fold) compared to that from non-SP cells, similar resultswere obtained in colon spheres (40 fold) compared to adherent cells. This result indicates that BORIS is overexpressed in CSCs enriched population of tumor cells. To define the potential role of BORIS in CSCs, we performed shRNA knockdown experiments in several tumor cell lines. We found that BORIS mRNA inhibition could allow decreasing cancer cell survival in studied tumor cell lines, supporting the hypothesis that BORIS could be critical for the survival and self-renewal of tumors. In conclusion, our study provides evidence that BORIS/CTCFL is a promising marker of CSCs that could also play a critical role in the maintenance of self-renewal capacity of the tumor initiating cells and as a consequence, of tumor survival. Therefore, due to its restricted expression in normal tissues and its reexpression in a wide variety of tumors, BORIS/CTCFL could become a good target for cancer therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3383. doi:1538-7445.AM2012-3383
Alpha-immunotherapy compared to gamma-radiation, cold antibody, and chemotherapy in B-CLL in vitro: Correlation with clinical chemosensitivity
Authors: Fritz Offner, Kl Vandenbulcke, F Devos, Ann Janssens, Jan Philippé, Guido Slegers, Hubert Thierens, T Nikula, C Apostolides, W Janssens, Rudi Dierckx
Journal: Blood (2002)
SAT0297 Non-Invasive Assessment of Silent Liver Fibrosis in Patients with Systemic Sclerosis
Authors: A. Vacca, A. Civolani, A. Devigus, L. Fadda, A. Floris, G. Porru, P. Garau, V. Ibba, M. Piga, O. Sorbello, L. Demelia, A. Mathieu
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Although up to 90% of patients systemic sclerosis (SSc) have been estimated to have gastrointestinal involvement, liver disease (without any cause other than SSc itself) has been reported only rarely in this disease. Liver biopsy is considered the gold standard for an accurate assessment of liver fibrosis. However, it is an invasive and expensive tool, so there has been increasing interest in non-invasive assessment evaluation of liver stiffness (LS) by transient elastography (TE) which have been recently demonstrated to be useful for the diagnosis of various grades of fibrosis in the course of chronic liver diseases. <h3>Objectives</h3> To evaluate the presence of liver fibrosis in a series of SSc patients, without any functional sign of liver disease and any cause other than SSc itself, and to identify any possible associations with demographic data, disease duration and disease phenotype. <h3>Methods</h3> Thirty-nine SSc patients (33 females and 6 males) without liver diseases, mean age 63.4±13.2 years, disease duration 10.5±8,67 years, and a sex- and age-matched control group, were consecutively studied. LS was evaluated using TE (Fibroscan; Echosens, Paris, France) and measured in kPa. We adopted 5.3 kPa as the cutoff for abnormal LS values. <h3>Results</h3> Seventeen (43.5%) SSc patients had abnormal LS values when patients were classified into two groups according to the cutoff (group A &lt;5.3 kPa, group B &gt;5.3 kPa); the median LS value was 4 kPa in group A and 7.1 kPa in group B. There were no significant differences between the two groups in disease duration, demographics, laboratory variables or disease characteristics. Among medications, a significant difference for patients on endothelin receptor antagonist therapy was seen in group B (P=0.02). <h3>Conclusions</h3> TE suggested, in a non-invasive fashion, liver fibrosis in 43.5% of our SSc patients, as a result of a primary hepatic involvement. LS measurement could be suggested for checking silent liver fibrosis in SSc, even in absence of abnormal liver function serological tests. However, further studies are required to investigate whether treatment regimens can influence the progression of liver fibrosis, or if they should be modified when abnormal LS values are identified. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3523
OP0141 No Signs for Direct Bone Formation or Endochondral Ossification at the Entheses in Facet Joints from Ankylosing Spondylitis Patients
Authors: J. Bleil, U. Syrbe, R. Maier, J. Sieper, H. Appel
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The mechanisms leading to new bone formation and ankylosis in zygapophyseal joints of patients with ankylosing spondylitis (AS) are not well understood. Despite the hypothesis that the enthesis is the primary disease localization in SpA [1], immunohistochemical analysis of bone and cartilage metabolism in the entheses of diarthrodial joints like facet joints have not been performed yet. <h3>Objectives</h3> Immunohistochemistry, using different markers indicating anabolic and catabolic processes within cartilage and bone, was performed in order to detect possible entheseal new cartilage and bone formation in facet joints of patients with AS. <h3>Methods</h3> An immunohistochemical analysis of beta-Catenin, Dickkopf-1 (DKK-1), Sclerostin, SRY(sex determining region Y)-box 9 (Sox9), runt-related transcription factor 2 (Runx2), matrix metalloproteinase 3 (MMP3), matrix metalloproteinase 13 (MMP13), collagen type 10 (COL10), bone morphogenetic protein 2 and 7 (BMP-2 and BMP-7) and Osteocalcin (OC) was performed. Facet joints from 10 patients with AS, 11 with osteoarthritis (OA) and 10 controls (CO, autopsies without spinal diseases) were analyzed at the enthesial sites. <h3>Results</h3> A significantly higher expression of intracellular ß-catenin (p=0.6985), DKK-1 (p=0.9476), Sclerostin (p=0.9468), BMP-7 (p=0.5545), COL10 (p=0.7039), MMP3 (CO&gt;AS p=0.0020) or OC (p=0.1740) in patients with AS in comparison to controls was not observed at enthesial sites. Only the frequency of Runx2 (p=0.0006) and MMP13 (p=0.0378) expressing cells at the entheses was significantly higher in AS than in controls, while Sox9 (AS vs. CO p=0.0097; AS vs. OA p=0.0045) and BMP-2 (AS vs. CO p=0.0016; AS vs. OA p=0.0021) were expressed even less in AS. All markers were significantly (MMP13 p=0.0017; OC p=0.0003; Sox9 p=0.0045; Sclerostin p=0.0180; DKK-1 p=0.0183; BMP-2 p=0.0021) or at least slightly (Runx2 p=0.1568; MMP3 p=0.3222; ß-catenin p=0.0615; BMP-7 p=0.2512; COL10 p=0.3560) lower expressed in AS compared to OA. <h3>Conclusions</h3> The analysis for parameters of endochondral ossification (like the hypertrophy markers Runx2, COL10 and MMP13) or of the wnt pathway (ß-catenin, DKK-1 and Sclerostin) revealed the absence of further signs for direct bone formation or endochondral ossification at the entheses in AS facet joints. <h3>References</h3> McGonagle D, Gibbon W, Emery P. Classification of inflammatory arthritis by enthesitis. Lancet. 1998 Oct 3; 352(9134):1137-1140. <h3>Disclosure of Interest</h3> J. Bleil: None Declared, U. Syrbe: None Declared, R. Maier: None Declared, J. Sieper Consultant for: Roche and Sanofi, H. Appel: None Declared
SP0006 Visualising Crystals: DECT and More
Authors: B. Manger
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> The first human to see monosodium urate (MSU) crystals in his newly invented microscope was the Dutch researcher Antoni van Leeuwenhoek in 1679. Since then, the gold standard to establish the diagnosis of gout arthritis is the detection of these crystals, phagocytosed by leukocytes contained in the synovial fluid of an inflamed joint. However, various obstacles may interfere with arthrocentesis individual cases: (i) Gout patients frequently carry a high cardiovascular risk and are on anticoagulant therapy or they do not consent to an invasive procedure due to the extreme pain level of their condition. (ii) In addition, diffuse soft tissue swelling without clearly detectable effusion can make it difficult to yield sufficient material to establish diagnosis. To overcome these problems, the EULAR evidence based recommendations for gout state that "for typical presentations of gout (such as recurrent podagra with hyperuricaemia) a clinical diagnosis alone is reasonably accurate but not definitive without crystal confirmation". Musculoskeletal ultrasound has the potential to support the non-invasive diagnosis of gouty arthritis. Sonography can detect free-floating MSU crystals in synovial fluid ("snow storm appearance") or subclinical tophus deposits. The most specific ultrasonographic finding, however, is the double contour sign, representing MSU deposits on the surface of hyaline cartilage (e. g. of femoral condyles or metatarsal heads). Recently, yet another diagnostic method has been described, which allows non-invasive identification of sodium urate crystals deposits in the periarticular tissues. Dual energy computed tomography (DECT) is an imaging method, which uses X-ray beams of two different energies to differentiate solid sodium urate deposits from connective tissues and from calcium containing structures by their absorption properties. Several clinical studies could clearly demonstrate that DECT does not only reliably detect clinically overt tophi, but also detects subclinical urate deposition at periarticular or peritendinous sites in gout patients. Therefore, DECT may not only be a very helpful imaging method for tophus assessment and follow-up in clinical trials and during urate lowering therapy in patients with the established diagnosis of chronic gout. It may also be valuable as differential diagnostic tool in patients with "unclassified" acute or relapsing arthritides, when aspiration of synovial fluid is not possible or not successful. <h3>Disclosure of Interest</h3> None Declared