tbuckley/cabot-search huggingface dataset:
AB0764 Improved public health may explain a decrease in the incidence of seropositive rheumatoid arthritis in the early middle-aged finnish population in northern savo
Authors: A. Kononoff, L. Arstila, P. Pussinen, H. Kautiainen, E. Savolainen, P. Elfving, H. Niinisalo, J. Rutanen, O. Marjoniemi, O. Kaipiainen-Seppänen
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Trends in the incidence of RA may reflect changes in the host-environment relationship. <h3>Objectives</h3> To assess the incidence of seropositive rheumatoid arthritis (RA) during 30 year period in Northern Savo Finland and to evaluate the role of dental health on the incidence. <h3>Methods</h3> The incidence of seropositive RA was evaluated on the basis of epidemiological data collected from the previous and current studies in Northern Savo area from years 1980, 1990, 2000 and 2010. Serum samples from 134 and 175 arthritis patients were collected in two studies on inflammatory joint diseases in 2000 and 2010, respectively. As markers of periodontal disease serum immunoglobulin A (IgA) and IgG –class antibodies against <i>Aggregatibacter actinomycetemcomitans</i> (Aa) and <i>Porphyromonas gingivalis</i> (Pg) were determined in various diagnostic categories. <h3>Results</h3> A total of 196 subjects suffered from seropositive RA that had started at the age of 16 or over in 1980, 1990, 2000 or 2010. The incidence rate ratio of seropositive RA decreased in the age group of 35-54 years and increased in the older age groups. The levels of Aa and Pg antibodies did not differ between the diagnostic categories. In 2010, 66.7 % of patients with seropositive RA and 26.7 % of patients with seronegative RA showed elevated levels of PgIgA antibodies, p=0.014. The age, gender and diagnosis adjusted levels of AaIgA, PgIgA, PgIgG antibodies between years 2000 and 2010 showed significant decrease, P=0.011, &lt;0.001, 0.011, respectively. In the age group of 35-54 years in all disease categories the decrease in PgIgA and PgIgG levels occurred only in women. <h3>Conclusions</h3> The declining trend for the incidence of seropositive RA occurred in the age-group of 35-54 years. Carriage of periodontal pathogens or a high prevalence of other infectious diseases may have influence on the risk of developing seropositive RA which could be reduced by public health measures. <h3>References</h3> Kaipiainen-Seppänen O, Kautiainen H. Declining trend in the incidence of rheumatoid factor-positive rheumatoid arthritis in Finland 1980-2000. J Rheumatol. 2006;33:2132-8. <h3>Disclosure of Interest</h3> None Declared
1367 NONCIRRHOTIC PORTAL HYPERTENSION (NCPH) IN HIV-INFECTED PATIENTS: A CASE CONTROL STUDY
Authors: N. Parikh, T. Kushner, V. Martel-Laferriere, K. Childs, D. Dronamraju, M.-L. Vachon, C. Taylor, K. Agarwal, T. Schiano, M.-I. Fiel, D. Dieterich
Journal: Journal of Hepatology (2012)
A Predominant Pelvic Gastrointestinal Stromal Tumor (GIST) Mass Observed on Tc-99m Red Blood Cell Gastrointestinal Bleeding Scintigraphy
Authors: Ravi Sood, Shang Ian Tee
Journal: Clinical Nuclear Medicine (2011)

A 51-year-old woman presented with recurrent bleeding per rectum. Her earlier endoscopies were negative. Tc-99m RBC GI bleeding scintigraphy was performed. It demonstrated an apparent hypervascular pelvic mass, and active small bowel bleeding. Based on scintigraphic finding of a predominant pelvic mass indicating tumor, CT of the abdomen and pelvis was performed for further gastrointestinal bleeding localization work up instead of an invasive angiography or endoscopy, which detected a small bowel tumor in the pelvis. A small bowel gastrointestinal stromal tumor was resected subsequently.
Emergence of Escherichia coli encoding Shiga toxin 2f in human Shiga toxin-producing E. coli (STEC) infections in the Netherlands, January 2008 to December 2011
Authors: I Friesema, K van der Zwaluw, T Schuurman, M Kooistra-Smid, E Franz, Y van Duynhoven, W van Pelt
Journal: Eurosurveillance (2014)

The Shiga toxins of Shiga toxin-producing Escherichia coli (STEC) can be divided into Shiga toxin 1 (Stx1) and Shiga toxin 2 (Stx2) with several sub-variants. Variant Stx2f is one of the latest described, but has been rarely associated with symptomatic human infections. In the enhanced STEC surveillance in the Netherlands, 198 STEC O157 cases and 351 STEC non-O157 cases, including 87 stx 2f STEC isolates, were reported between 2008 and 2011. Most stx 2f strains belonged to the serogroups O63:H6 (n=47, 54%), O113:H6 (n=12, 14%) and O125:H6 (n=12, 14%). Of the 87 stx 2f isolates, 84 (97%) harboured the E. coli attaching and effacing (eae) gene, but not the enterohaemorrhagic E. coli haemolysin (hly) gene. Stx 2f STEC infections show milder symptoms and a less severe clinical course than STEC O157 infections. Almost all infections with stx 2f (n=83, 95%) occurred between June and December, compared to 170/198 (86%) of STEC O157 and 173/264 (66%) of other STEC non-O157. Stx 2f STEC infections in the Netherlands are more common than anticipated, and form a distinct group within STEC with regard to virulence genes and the relatively mild disease.
Association of the polymorphisms CYP19 (TTTA)n in treatment response to hormone therapy based in aromatase inhibitors in breast cancer patients.
Authors: B Murillo-Ortiz, R Castillo-Valenzuela, S Martínez-Garza, A Moreno-Perez, A Silva, E Ruiz-García, H Astudillo-de la Vega
Journal: Cancer Research (2009)

Abstract Abstract #3033 Background &amp;#x2028; Case-control studies have reported inconsistent results concerning breast cancer risk and polymorphisms in genes that control endogenous estrogen biosynthesis. We report findings from the first study in Mexican women examining associations between female with breast cancer and polymorphisms CYP19 (TTTA repeated polymorphism).&amp;#x2028; Methods &amp;#x2028; We conducted a study among 180 healthy women and 70 women with breast cancer underwent hormone therapy with aromatase inhibitor. DNA and questionnaire data was obtained. Tandem repeated (TTTA)n polymorphism in CYP19 gene was determined by PCR followed by electrophoresis on denaturalizing acrilamide gel stained with silver nitrate. Differences were visualized with Gel-Doc BioRad. Estrone, estradiol and FSH levels were measured by RIA and IRMA. We used likelihood-based statistical methods to examine allelic associations.&amp;#x2028; Results:&amp;#x2028; 250 women (age 55 ± 12 years) were included. BMI was 30 ± 7.1 Kg/m2. We found a distribution of different CYP19 allele frequencies. In healthy women the allele frequencies with 6 (32.7 %) and 7 (21.6 %) tandem repetitions were the most frequent, in women with breast cancer the alleles with 6(29%) and 10(26%) tandem repeated were the most frequent. A relationship between hormonal levels and number of (TTTA) repeated was not found. Anastrozol reduced significantly estrona and estradiol. Surpriseling we found in a patients with 10 or more (TTTA)n repeated an association with a mayor tumoral activity (p=0.04).&amp;#x2028; Conclusion &amp;#x2028; This study indicates that status of CYP19 &amp;gt;10 TTTA repeated might be related to increased breast cancer risk and with the clinical response (aromatase inhibitor). Because of this is the first study to report an association between CYP19 &amp;gt;10 TTTA repeated and treatment hormonal response in breast cancer. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3033.
Prognostic significance of the null genotype of glutathione S-transferase-T1 in patients with acute myeloid leukemia: increased early death after chemotherapy
Authors: T Naoe, Y Tagawa, H Kiyoi, Y Kodera, S Miyawaki, N Asou, K Kuriyama, S Kusumoto, C Shimazaki, K Saito, H Akiyama, T Motoji, M Nishimura, K Shinagawa, R Ueda, H Saito, R Ohno
Journal: Leukemia (2002)
Abstract A18: Molecular mechanisms of nuclear receptor-dependent chromosomal translocations
Authors: Liuqing Yang
Journal: Cancer Research (2009)

Abstract Chromosomal translocations are a hallmark of leukemia/lymphoma and also appear widespread in solid tumors, but the underlying molecular basis has remained elusive. By establishing a cellular model to dissect specific and inducible translocations in the absence of proliferative selection, we report an androgen receptor (AR)-dependent pathway for tumor translocation events in prostate cancer cells. This pathway is initiated by binding of liganded AR to specific intronic sites that triggers intra- and inter-chromosomal interactions that place translocation sites in close spatial proximity, and local architectural alterations that permit serial recruitment of an enzymatic machinery, including Activation-Induced Cytidine Deaminase (AID) induced by liganded AR and genotoxic stress. Strikingly, this process is enhanced by the expression of the ORF2 endonuclease from LINE-1 repeats, caused by diminished PIWIL1 and increased AID, generating staggered double-strand breaks (DSBs) at intronic AR binding sites that result in tumor translocation by components of the Non-Homologous Ending Joining (NHEJ) mechanism. Together, these findings reveal specific architectural/enzymatic mechanisms underlying well-defined chromosomal translocations observed in tumors, which may function in many types of tumors and in other biological and pathological processes. Citation Information: Cancer Res 2009;69(23 Suppl):A18.
AB0759 A direct comparison of web-based and real-life ultrasound assessments of rheumatoid arthritis hands involving the same ultrasonographers
Authors: V. Vlad, M. Micu, L. Varzaru, M. Bojinca, M. Milicescu, F. Berghea, D. Predeteanu, R. Ionescu
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Ultrasound(US) is intensely tested for becoming a real outcome measure in Rheumatoid Arthritis (RA) and to be used in clinical trials. The method has proven good reliability in recent over-the-web exercises (LUMINA Study –results not published yet) offering simmilar results with published real-life exercises (1). However no direct comparison between over-the-net and real life exercises with the same rheumatologists involved was done so far. <h3>Objectives</h3> To test inter and intraobserver agreement of US grading on RA patients in two settings (over-the-web and real-life) with the same assessors involved in both settings. <h3>Methods</h3> 4 patients suffering from active RA (clinically swollen hands) were selected from our database, after having given their consent to participate in the study. For each patient we selected 100 joint sites to be examined - carpal, MCPs 2-5, PIPs 2-5 (both dorsal and volar, bilaterally), extensor compartments 2,4, and 6, and flexor tendons 2-5 (total 400 scans for all patients). In the real-life exercise, 5 rheumatologists with different experience (but more than 5 years of US practice each) from different rheumatology clinics took turn in scanning patients on 2 US machines (Essaote MyLab 25 and Essaote MyLab 70) for 6-7 hours, during the same day. The joints were graded with semiquantitative scale (0,1,2,3) and tendons with binar scale (0/1). In the over-the-web exercise, from each investigator's recorded movies, 20 movies were selected and resent to them by internet (on youtube channel) for the second grading. Values of agreement of 0–0.20 were considered poor, &gt;0.20–0.40 fair, &gt;0.40–0.60 moderate, &gt;0.60–0.80 good and &gt;0.80–1 excellent Statistical analyses were performed using SPSS 16.0. <h3>Results</h3> For web-based exercise, interobserver agreement coeficient was 0.774 and 0.786 (in two different exercises 7 days apart). For real-life-exercise the results have been quite simmilar with an interobserver agreement coeficient of 0.680. In both cases the agreement was better for joints than for tendons (simmilar with very recent published studies -1). Intraobserver agreement was between 0.707 and 0.856 (web-based). We analysed various sub-groups:joints, tendons, joint different recesses. <h3>Conclusions</h3> This study demonstrates simmilar results of over-the-web and real-life US grading of hand joints in RA patients opening the possibility of using internet in large colaborative trials involving US. <h3>References</h3> Esperanza Naredo et al on behalf of the OMERACT Ultrasound Task Force- Reliability of a consensus-based ultrasound score for tenosynovitis in rheumatoid arthritis, AnnRheumDis 2012;0:1-7 Shrout PE, Fleiss JL. Intraclass correlations: uses in assessing rater reliability. Psychol Bull.1979;86:420–428. <h3>Disclosure of Interest</h3> None Declared
OP0252 Modulation of pro-inflammatory response of monocytes by glucocorticoids
Authors: K.J. Barczyk, Y. Fleischer, J. Ehrchen, J. Roth
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Active resolution of inflammation is a previously unrecognized process essential for tissue homeostasis<sup>1</sup>. Monocytes and macrophages are the central component of the immune system critical not only for initiation and maintenance of the immune response but also for the resolution of inflammation. Glucocorticoids (GC) are still the most widely used anti-inflammatory agents acting on many targets in a cell-specific manner, including monocytes and macrophages<sup>2</sup>. We previously demonstrated that the treatment of monocytes with GC does not suppress monocytes functions, but rather induces specific differentiation of cells with anti-inflammatory phenotype<sup>3,4</sup>. Nevertheless the mechanism of GC action on monocytes during inflammation is currently not well defined. <h3>Objectives</h3> The aim of our studies was to investigate the effects of GC on pro-inflammatory monocytes. <h3>Methods</h3> GC-, LPS- and GC-LPS-induced gene expression patterns in monocytes were analysed by microarray technology. The results were independently confirmed by real-time PCR. Protein expression and activation was analysed by Western Blot and Flow Cytometry. Monocyte functions pivotal for innate immunity – migration, chemotaxis, phagocytosis, killing, oxidative burst – were assessed. <h3>Results</h3> As expected, treatment of LPS-stimulated monocytes with GC resulted in inhibited expression of many of pro-inflammatory factors. Nevertheless, many of them have not been described to be regulated by GC in monocytes so far. Surprisingly, we have found that GC-LPS treatment of monocytes led also to synergistical up-regulation of many genes, which are not induced by GC or LPS alone. Moreover, we observed additive effects of GC and LPS on expression of many anti-inflammatory genes which was much more pronounced compared to monocytes stimulated with GC alone. Analysis of specific functions of monocytes have shown that GC-LPS treatment inhibited specifically monocyte adherence, but enhanced spontaneous migration, chemotaxis, phagocytosis and killing of pathogens, and engulfment of apoptotic cells as well as the ability to produce anti-inflammatory lipid mediators. <h3>Conclusions</h3> Our results demonstrate that GC do not simply suppress LPS-mediated activation of monocytes, but rather induce their re-programming toward a specific anti-inflammatory phenotype involved in resolution of inflammation. Interestingly, this anti-inflammatory phenotype is not associated with reduced but rather with enhanced anti-microbial activity. Unravelling specific GC-actions on monocytes may thus define novel pathways allowing anti-inflammatory therapy without enhanced risk for severe infections. <h3>References</h3> Serhan et al. FASEB J. 2007, 21:325-332. Buttgereit et al. Arthritis Rheum. 2004, 50:3408-3417. Ehrchen et al. Blood 2007, 109:1265-1274. Barczyk et al. Blood 2010, 116: 446-455. <h3>Disclosure of Interest</h3> None Declared
Abstract 443: PKC epsilon is activated by ionizing radiation in a reactive nitrogen species dependent manner in tumor endothelial cells.
Authors: Asim Alam, Chris Rabender, Ross Mikkelsen
Journal: Cancer Research (2013)

Abstract PKCε is activated by ionizing radiation in a reactive nitrogen species dependent manner in tumor endothelial cells. Ionizing radiation (IR) has been shown to increase angiogenic markers and migration in endothelial cells involving reactive oxygen/nitrogen species and eNOS, but the exact mechanism is poorly understood. This activation of endothelial cells can increase angiogenesis post radiation and confer cytoprotection to tumor cells. Thus targeting this IR induced activation of endothelial cells should increase therapeutic efficacy of radiation therapy. Protein Kinase C Epsilon is a molecule that has been shown to be important in cancer cell motility, proliferation, hormone sensitivity and angiogenesis. PKCε activates downstream pathways involved in tumorigenicity such as Akt and Stat3. PKCε has also been shown to be nitrated in response to NO donors and inflammatory conditions in cardiac myocytes. During inflammation, hypoxia and irradiation, levels of reactive nitrogen species are elevated due to uncoupling of Nitric Oxide Synthase (NOS). NOS can be recoupled with tetrahydrobiopterin precursor (sepiapterin) which decreases RNS/ROS in cells. We have shown in 2H11 cells (mouse tumor endothelial cells) that PKCε levels are increased due to exposure to clinically relevant doses of ionizing radiation or levels of NO found in chronic inflammatory conditions. Also in these cells PKCε is nitrated in response to reactive nitrogen species which leads to its activation and activation of Stat3 and Akt. Using sepiapterin, we have shown decreased levels of PKCε, Stat3 and Akt. We have also blocked ionizing radiation induced migration in vitro in 2H11 cells using sepiapterin and a PKCε inhibitor. We hope to show that PKCε is nitrated at specific residue(s) after ionizing radiation and activates tumor endothelial cells to promote the survival of the tumor. We believe sepiapterin with ionizing radiation therapy will result in increase cytotoxicity in a spontaneous mouse model of lung cancer, by decreasing endothelial activation, migration, proliferation and angiogenesis. Citation Format: Asim Alam, Chris Rabender, Ross Mikkelsen. PKC epsilon is activated by ionizing radiation in a reactive nitrogen species dependent manner in tumor endothelial cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 443. doi:10.1158/1538-7445.AM2013-443 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
AB1058 Time to resolution of tophi with urate lowering agents: A literature analysis of randomized trials:
Authors: M. Becker, R. Yood, F. Perez-Ruiz, N. Dalbeth
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The tophus is a pathognomonic feature of chronic gout and may cause disability and joint damage. Accordingly, OMERACT has endorsed tophus measurement as a key domain in clinical trials of chronic gout. The approval of febuxostat (FEB) in 2009 and pegloticase (PGL) in 2010 has been accompanied by publications describing clinical trials of urate-lowering therapies (ULTs). These trials also provide detailed data, not previously available, on change in tophus burden in response to treatment in defined gout populations. <h3>Objectives</h3> We compared tophus resolution in published clinical trials of ULTs that included such measurements. <h3>Methods</h3> A PubMed search using the terms "gout" and "tophi OR tophus" was performed with the following limits applied: clinical trial, humans, and English. The 15 articles retrieved were evaluated for appropriateness and used to identify additional publications/abstracts. Six trials met the analysis criteria. <h3>Results</h3> <h3>Conclusions</h3> Clinical trials of ULTs have not used consistent methods or timepoints to evaluate tophus response. Nevertheless, pegloticase treatment results in more robust and rapid resolution of tophi compared to treatment with febuxostat or allopurinol. <h3>References</h3> Wallace et al. Arth Rheum 1977;20:895-900. <h3>Disclosure of Interest</h3> M. Becker Grant/Research support from: Savient, Takeda, Consultant for: Savient, Takeda, Ardea, BioCryst, Regeneron, URL/Mutual/Metabolex/Chugai, R. Yood Grant/Research support from: Savient, Takeda, F. Perez-Ruiz Consultant for: Ardea, Menarini, Novartis, Savient, Speakers Bureau: Ardea, Menarini, Novartis, Savient, N. Dalbeth Grant/Research support from: Fonterra, Consultant for: Takeda, Ardea, Novartis, Abbott, Roche
FRI0001 IL-17 producing-DN T cells are expanded in the blood, infiltrate salivary glands and are resistant to corticosteroids in sjÖgren’s syndrome
Authors: A. Alunno, O. Bistoni, E. Bartoloni, S. Caterbi, B. Bigerna, A. Tabarrini, R. Mannucci, D. Beghelli, B. Falini, R. Gerli
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The discovery of IL-17-producing CD4<sup>+</sup> T helper (Th17) cells challenged the long-standing paradigm of Th1/Th2 cell immune response and shed some light on the pathogenic mechanisms of systemic autoimmune disorders. IL-17 in a pro-inflammatory cytokine which mediates target organs damage during the disease. To note, it has been recently observed that asmall CD3<sup>+</sup> T-cell population, that lacks of both CD4 and CD8 molecules, defined as double negative (DN), is expanded in the peripheral blood of patients with systemic lupus erythematosus, produces IL-17 and accumulates in the kidney during lupus nephritis. <h3>Objectives</h3> Since IL-17 production is enhanced in salivary gland infiltrates of patients with primary Sjögren’s syndrome (SS), we aimed to investigate whether DN T cells may be involved in the pathogenesis of salivary gland damage <h3>Methods</h3> Thirty patients with SS and 16 normal controls (NC) were enrolled. CFSE-stained PBMCs were cultured in anti-CD3-coated plates in presence or absence of dexamethasone (Dex) at different concentrations. Phenotypic characterization was performed by flow cytometry in freshly isolated cells and after culture using anti-CD3, CD4, αβ-TCR, γδ-TCR, RORγt, IL-17 antibodies and respective isotypes. SS minor salivary glands (MSG) were processed for immunofluorescence staining. <h3>Results</h3> Total circulating DN T cells were increased in SS compared to NC. This was due to an increase of both αβ-TCR<sup>+</sup> and γδ-TCR<sup>+</sup> cells. NC and SS freshly isolated DN T cells express RORγt and produce consistent amounts of IL-17. Notably, DN T cells were found in the SS-MSG infiltrate. αβ-TCR<sup>+</sup>, but not γδ-TCR<sup>+</sup>, DN T-cell expansion in SS was dependent on disease activity according to the EULAR Sjögren’s syndrome disease activity index (ESSDAI). Dex was able to down-regulate IL-17 in vitro production in NC and SS CD4<sup>+</sup> cells and in NC DN T cells, but not in DN T cells from SS samples. <h3>Conclusions</h3> DN T cells are expanded in SS PB, produce IL-17 and infiltrate SS MSG. The expansion is dependent on disease activity. In SS, conventional Th17 cells are inhibited by Dex, but DN T cells appear to be resistant to this effect. The recognition of a pathogenic T-cell subset, that appears to be in vivo activated and not sensitive to CS, in an autoimmune disorder such as SS may represent an intriguing finding with potential therapeutic implications of great interest. <h3>References</h3> Crispin C et al. J Immunol 2008;181:8761 Nguyen CQ et al. Arthritis Rheum 2008;58:734 <h3>Disclosure of Interest</h3> None Declared
869 ADDITION OF FLUVASTATIN TO STANDARD OF CARE TREATMENT DOES NOT IMPROVE SUSTAINED VIROLOGICAL RESPONSE IN CHRONIC HEPATITIS C GENOTYPE 3 PATIENTS
Authors: T. Selic Kurincic, G. Lesnicar, M. Poljak, J. Meglic Volkar, M. Rajter, J. Prah, Z. Baklan, M. Maticic
Journal: Journal of Hepatology (2013)