tbuckley/cabot-search huggingface dataset:
AB0137 Effects and Mechanisms of Upar Expression in Rheumatoid Arthritis Fibroblast-Like Synoviocytes
Authors: P. Yunfeng, L. Yan
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> uPAR is thought to promote the growth,metastasis and invasion of a variety of tumors. uPAR/uPA system is also found to be active in RA-FLS and associated with cell function. Thus, we suppose uPAR be closely related to disease progression of RA, but this kind of correlation is mediated by what mechanism, has not been reported. <h3>Objectives</h3> To observe the effects and mechanisms of urokinase-type plasminogen activator receptor (uPAR) expression in rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS). <h3>Methods</h3> Tissues were collected from RA patients with joint replacement surgery or arthroscopy and RA-FLS were obtained by tissue culture; Chemically synthesized small interference RNA (siRNA) specifically targeting uPAR gene was transfected into RA-FLS by cationic liposome; The interference efficiency of uPAR-siRNA on the production of uPAR mRNA and protein was determined by RT-qPCR and Western blotting respectly; The proliferative inhibition rate was examined by CCK8 assay; Flow cytometry was adopted to determine the change of cell cycle distribution; The migration of RA-FLS were examined by Transwell assay; Western blotting was performed to detect the influence of uPAR on PI3K/AKT signal pathway. <h3>Results</h3> Transfection of uPAR-siRNA significantly decreased the mRNA and protein expression of uPAR gene; The proliferative inhibition rate was obviously higher in the uPAR-siRNA group than the control groups (P&lt;0.05) after transfection for 48h (17.51±2.27)%, 72h (28.62±4.82)%, 96h (22.91±5.78)%. Flow cytometry assay showed accumulation of cells in the G0/G1 phase and the number of RA-FLS in the S and G2/M decreased; Transwell migration assay demonstrated the RA-FLS through the transwell membrane in uPAR-siRNA group (35±11) were lesser than the NC-siRNA group (136±19) &lt;0.05) and the blank control group (138±21) (P&lt;0.05). After transfected with uPAR-siRNA, the phosphorylation of PI3K/AKT/GSK3β decreased significantly. <h3>Conclusions</h3> uPAR may play a role in the regulation of proliferation,cell cycle and migration of RA-FLS through activation of PI3K/AKT/GSK3β signal pathway. <h3>References</h3> Serratì S, Margheri F, Chillà A,et al.Reduction of in vitro invasion and in vivo cartilage degradation in a SCID mouse model by loss of function of the fibrinolytic system of rheumatoid arthritis synovial fibroblasts [J]. Arthritis Rheum.2011,63(9):2584-94. doi: 10.1002/art.30439. Malla R, Gopinath S, Alapati K,et al Downregulation of uPAR and cathepsin B induces apoptosis via regulation of Bcl-2 and Bax and inhibition of the PI3K/Akt pathway in gliomas. PLoS One.2010 Oct 29;5(10):e13731. doi:10. 1371/journal. pone. 0013731. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5304
Abstract 5110: RNA helicase p68 is a new marker for breast cancer heterogeneity
Authors: Daojing Wang
Journal: Cancer Research (2011)

Abstract Two major challenges in diagnosis and therapy of breast cancer lie in its heterogeneity and drug resistance. RNA helicase p68 (DDX5) has been shown to be involved in all aspects of RNA metabolism and serves as a transcriptional co-regulator. However, its functional role in breast cancer remains elusive. We utilized an integrative biology approach strategy to further define the role of p68 in breast cancer. Specifically, we determined the expression pattern of p68 at both mRNA and protein levels for a panel of ∼50 breast cancer cell lines. We performed immunohistochemistry of p68 using tissue microarrays containing a total of over 200 cases of primary human malignant breast cancer (various grades and stages). We knocked down p68 in a panel of representative breast cancer cell lines (e.g., SKBR3 and MDA-MB-231) and investigated the functional consequences such as their proliferation and responses to Lapatinib after the p68 knockdown. Finally, we carried out SILAC-based proteomic profiling of these breast cancer cells after p68 knockdown and identified p68-targeted proteins and networks contributing to the drug responses. We found that p68 expression pattern is distinct among different subtypes of breast cancers. More aggressive basal subtypes have predominantly high p68 protein expression while low p68 expression is predominantly associated with the luminal subtype. Knockdown of p68 inhibits the proliferation of breast cancer cells and sensitizes them to cancer drugs such as Lapatinib. We demonstrated that p68 is a new marker for breast cancer heterogeneity in addition to ER, PR, and Her2. Importantly, we identified p68-regualted cytoskeletal reorganization as a new mechanism in controlling breast cancer proliferation and drug resistance. In summary, RNA helicase p68 may serve as a new marker for breast cancer heterogeneity, as a predictor for drug resistance, and as a target for a combinational therapy to circumvent drug resistance of aggressive tumors. 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 5110. doi:10.1158/1538-7445.AM2011-5110
Consultant's suspension leads to Commons reprimand
Authors: J. Warden
Journal: BMJ (1995)

The case of a British doctor who was suspended on full pay for nearly 12 years at a cost of £600000 has led to demands by an all party committee of members of parliament for robust action by the NHS to prevent such delays happening again. The committee also wants disciplinary moves against those responsible. In its reprimand the Commons public accounts committee is not satisfied that the NHS Executive has taken appropriate action concerning disciplinary proceedings against medical staff and instructs it to do …
Hydatidiform Mole — A Cause of Clinical Hyperthyroidism
Authors: Jerome M. Hershman, H. Patrick Higgins
Journal: New England Journal of Medicine (1971)

Original Article from The New England Journal of Medicine — Hydatidiform Mole — A Cause of Clinical Hyperthyroidism — Report of Two Cases with Evidence That the Molar Tissue Secreted a Thyroid Stimulator
OP0204 Autophagy and Unfolded Protein Response: A Fine Balance that can Influence the Pathogenesis of Ankylosing Spondylitis and Inflammatory Bowel Disease
Authors: N. Haroon, G. Guggino, Z. Zhang, K. Yee, H. Abdullah, R. Alessandro, S. Raimondo, G. Triolo, F. Ciccia
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> We have shown an increase in the unfolded protein response (UPR) with decreased ERAP1 or ERAP2 function in an <i>in vitro</i> system. Similarly UPR has been demonstrated to correlate with onset of disease in the HLA-B27 rat model. UPR has been difficult to demonstrate in the gut of AS patients but autophagy is upregulated. ERAP2 is associated with both AS and inflammatory bowel disease (IBD). <h3>Objectives</h3> Here we explore the moderating effect of autophagy on UPR. Specifically we study the impact of suppressing autophagy on UPR. <h3>Methods</h3> Lamina Propria Mononuclear cells (LPMC) were isolated from terminal ileal biopsies of 10 AS patients. Autophagy was suppressed with 2 agents anisomycin and 3-MA. In parallel an in vitro system was established with C1R-B27 cells (B-lymphoblastoid cells with stable HLA-B27 expression) and the presence of autophagy in these cells were established with electron microscopy as well as by transfecting these cells with LC3-RFP followed by confocal microscopy. Autophagy was suppressed in C1R-B27 cells using 3-MA. In both LPMC and C1R B27 cells, suppression of autophagy was demonstrated by RT-PCR of appropriate markers. Changes in MHC-I free heavy chain (FHC) expression were tested by HC10 staining and flow cytometry. Changes in UPR following inhibition were tested by XBP1 splicing assay and RT-PCR for BiP, CHOP, PERK, GADD34 and PDIA6. <h3>Results</h3> Electron and confocal microscopy demonstrated autophagy in C1R-B27 cells. Autophagy was in a dynamic state in the C1R cells as demonstrated by changes with rapamycin a stimulator of autophagy. Significant suppression of autophagy was noted in both LPMCs and C1R-B27 cells. Following autophagy suppression there was a significant increase in FHC expression in both C1R cells and LPMCs. In parallel we demonstrated increase in UPR markers in both LPMCs and C1R cells. <h3>Conclusions</h3> The inability to demonstrate UPR in some in vivo studies could be due to compensation by autophagy. Autophagy and UPR regulate each other and perturbations of this fine balance can influence the pathogenesis of AS and IBD. <h3>Disclosure of Interest</h3> None declared
ECHOCARDIOGRAPHIC, DOPPLER AND MYOCARDIAL DEFORMATION VARIABLES DISTINGUISHING HYPERTROPHIC CARDIOMYOPATHY FROM ATHLETICALLY TRAINED HEARTS IN ADOLESCENTS
Authors: Govinda Paudel, Muhammad Qureshi, Megan M. O’Byrne, Jonathan Johnson, Benjamin Eidem, Rebecca K. Lindquist, Chelsea Reece, Angela R. Miller, Patrick O’Leary
Journal: Journal of the American College of Cardiology (2016)
Diagnostic Accuracy of EUS-FNA for Pancreatic tumors Smaller than 20mm
Authors: Kaneko Maki
Journal: Endoscopy (2011)

Background and Aim: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has been widely used as an examination method for histological diagnosis. However, it is sometimes difficult to obtain tissues from small lesion of pancreas. In this study, we assessed the diagnostic potency of EUS-FNA for pancreatic tumors smaller than 20mm.
CHARACTERIZATION OF ST-ELEVATION MYOCARDIAL INFARCTION ACROSS THE AGE SPECTRUM IN A LOW-INCOME URBAN COMMUNITY: CLINICAL FEATURES, ACUTE CARE, AND LONG-TERM OUTCOMES
Authors: Muhammad Shahid, Sanyog Shitole, Noel Kayo, Vankeepuram Srinivas, James Scheuer, Jorge Kizer
Journal: Journal of the American College of Cardiology (2015)
GALECTIN-3 LEVELS AND OUTCOMES IN PERIPARTUM CARDIOMYOPATHY: RESULTS FROM THE MULTICENTER IPAC INVESTIGATION
Authors: Kate Elizabeth Groh, Rami Alharethi, Gregory Ewald, Michael Givertz, G. Michael Felker, Jessica Pisarcik, Karen Hanley-Yanez, Indrani Halder, Charles McTiernan, Dennis McNamara
Journal: Journal of the American College of Cardiology (2016)
AB0037 CD4+CD25-GITR+regulatory T cells are expanded in the blood, display suppressive function and are inversely correlated with disease activity in patients with primary Sjögren’s syndrome
Authors: A. Alunno, G. Nocentini, E. Bartoloni, M.G. Petrillo, O. Bistoni, S. Ronchetti, G. Santoboni, V. Valentini, C. Riccardi, R. Gerli
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> In the last years, several molecules have been suggested as marker of human regulatory T cells (Treg), including GITR (glucocorticoid-induced TNFR-related gene), a specific marker of murine Treg cells. We recently provided evidence for a CD4<sup>+</sup>CD25<sup>-</sup>FoxP3<sup>+</sup> T-cell population that displays high surface levels of GITR and exerts in vitro suppressive activity in healthy subjects. <h3>Objectives</h3> Aim of the present study was to investigate phenotype and function of circulating CD4<sup>+</sup>CD25<sup>-</sup>GITR<sup>+</sup> cells in patients with primary Sjögren’s syndrome (pSS). <h3>Methods</h3> Thirty pSS patients and 30 normal controls (NC) were enrolled. Peripheral blood mononuclear cells (PBMCs) were separated by magnetic sorting and phenotypic characterization was performed by both flow cytometry and real-time PCR (FoxP3, CTLA-4, TGF-β). Functional assays were performed, by co-culturing magnetic sortedCFSE-stained effector T cells with the CD4<sup>+</sup>CD25<sup>-</sup>GITR<sup>+</sup> cell subset obtained from SS patients and HD. <h3>Results</h3> In pSS patients, circulating CD4<sup>+</sup>CD25<sup>-</sup>GITR<sup>+</sup> cells were expanded, whereas CD4<sup>+</sup>CD25<sup>high</sup>GITR<sup>+</sup> Treg cells were reduced. CD4<sup>+</sup>CD25<sup>-</sup>GITR<sup>+</sup> cells expressed Treg markers and displayed suppressive activity in vitro. In particular, similarly to in HD CD25-G+ cells, SS CD25<sup>-</sup>G<sup>+</sup> T cells inhibit autologous effector T cells proliferation, but to a lesser extent. We observed an inverse correlation between the percentage of circulating CD4<sup>+</sup>CD25<sup>-</sup>GITR<sup>+</sup> cells and the EULAR Sjögren’s syndrome disease activity index (ESSDAI) (p&lt;0.05). Immunofluorescence studies of minor salivary glands in pSS to identify CD4<sup>+</sup>CD25<sup>-</sup>GITR<sup>+</sup> cells are currently ongoing. <h3>Conclusions</h3> pSS patients display an expansion of CD4<sup>+</sup>CD25<sup>-</sup>GITR<sup>+</sup> Treg subset which is functionally suppressive. Moreover, the CD4<sup>+</sup>CD25<sup>-</sup>GITR<sup>+</sup> Treg subset is lower in active pSS as compared to inactive pSS, leading to the hypothesis that a strong inflammatory response, reflecting higher disease activity, could determine an imbalance of this cell subset. <h3>References</h3> Bianchini R et al. Eur J Immunol 2011;41:2269 Gerli R et al. Autoimmunity Rev 2009;8:426 <h3>Disclosure of Interest</h3> None Declared
923 INTERACTION BETWEEN RS12979860 POLYMORHISM OF IL28B GENE WITH BASELINE PREDICTIVE FACTORS OF RESPONSE TO TREATMENT IN PATIENTS WITH HEPATITIS C
Authors: A. Rojas, M. Maraver, L. Rojas, J. Ampuero, R. Sola, R. Moreno-Otero, R. Andrade, M. Diago, J. Salmeron, L. Rodrigo, J. García-Samaniego, J.L. Calleja, J.A. Pons, C. Cano, M. Millan, R. Millan, M. Romero-Gomez
Journal: Journal of Hepatology (2012)
Case 19-1991
Authors: Timothy R. Wu, Eugene J. Mark
Journal: New England Journal of Medicine (1991)

Presentation of CaseAn 80-year-old woman was admitted to the hospital because of increasing dyspnea, a cough, and an abnormal x-ray film of the chest.The patient was in a stable state of health until 10 months earlier, when stiffness and aching developed in proximal muscles; a diagnosis of polymyalgia rheumatica was made, and prednisone was begun, with prompt improvement and a decrease in the erythrocyte sedimentation rate. The patient required daily doses of insulin when the dose of prednisone was in excess of 20 mg daily. Six weeks before admission the dose of prednisone was reduced from 20 mg . . .
Severe Lung Injury after Exposure to Chloramine Gas from Household Cleaners
Authors: David A. Tanen, Kimberlie A. Graeme, Robert Raschke
Journal: New England Journal of Medicine (1999)

To the Editor: The inhalation of the noxious fumes associated with the mixing of household cleaners can lead to pulmonary irritation and pneumonitis. Household ammonia (3 to 10 percent aqueous NH3) and bleach (5 percent NaOCl) are two of the most common cleaning agents. Combining them releases chloramine gas, which is a combination of monochloramines (NH2Cl) and dichloramines (NHCl2). When inhaled, chloramines react with the moisture of the respiratory tract to release ammonia (NH3), hydrochloric acid (HCl), and oxygen free radicals. Typically, exposures to low concentrations of chloramines produce only mild respiratory . . .
SP0163 Innate and Adaptive Immune Responses in Angioproliferative Pah
Authors: N. Voelkel
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> Severe angioproliferative PAH still today remains refractory to treatment, and PAH associated with scleroderma has a particularly dismal prognosis.A close link between idiopathic PAH and complex immune disorders has been recognized for decades and cells of the innate (macrophages, mast cells) and adaptive (T cells, B cells and dendritic cells) are present in and around the pulmonary vascular lesions; there are lymph follicles in close proximity to the lung vessel lesions. New animal models of severe PAH have recently improved our understanding of this link. In mice activated T lymphocytes appear to be involved in the muscularization of pulmonary arterioles and T cell deficient athymic rats treated with the VEGF receptor inhibitor Sugen 5416 (Su) develop lethal angioobliterative PAH that is rescued by transplantation of regulatory T cells. In human PAH high blood levels of IL-1 and IL-6 predict a shorter survival, there is a reduction of circulating T reg cell numbers and endothelial cell (EC) apoptosis, as in scleroderma. May be the initiating pathobiologically important event. Lung small vessel EC apoptosis may be triggered by high shear stress, impaired VEGF signaling, anti –endothelial cell antibodies and leukotriene B4 (LTB4). Hypoxia may, via HIF-1α and NFkappaB cause and amplify inflammation, alter the immune response and stimulate VEGF-dependent EC proliferation. The growth of apoptosis-resistant vascular cells may be driven and maintained by precursor/stem cells. Macrophage-derived LTB4 plays an important role in the athymic Su rat model of severe PAH and perhaps in patients with scleroderma-associated severe PAH who have elevated blood levels of the EC apoptosis – inducing LTB4. In conclusion: both elements of the innate and adaptive immune system participate in the pathobiology of severe angioobliterative PAH. Specific treatments targeting critically important signaling nodes of inflammatory pathways need to be developed and tested. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6270
THU0425 Cigarette Smoking and Disease Activity in Rheumatoid Arthritis Patients: Results from Ontario Best Practice Research Initiative (OBRI)
Authors: B. Jacob, G. Tomilionson, P. Akahavan, C. Bombardier
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Smoking has been shown to be a significant risk factor for developing rheumatoid arthritis; however its impact on disease activity has conflicting evidence. <h3>Objectives</h3> The objective of this study was to assess the effect of smoking on disease activity in rheumatoid arthritis (RA) patients. <h3>Methods</h3> Data from the Ontario Best Practices Research Initiative (OBRI), a clinical registry of RA patients followed in routine care, were examined. All patients whose smoking status was reported at baseline were included in the study. Patients were divided into three groups based on their smoking status: Never, Past and Current smokers. The demographic, clinical laboratory and therapeutic features were compared according to their smoking habits. Physician reported disease activity measures such as tender joint counts (TJC), swollen joint counts (SJC), disease activity score 28 joints (DAS28), clinical disease activity index (CDAI) and patient reported disease activity score of rheumatoid arthritis disease activity index (RADAI) were considered as the outcomes. Differences between the groups were compared using chi-square test for categorical parameters, or analysis of variance (ANOVA) for continuous parameters. Multivariable analysis was performed for each outcome to assess the impact of smoking on disease activity when adjusted for potential confounders including patient demographics and rheumatoid factor (RF). When there was an overall difference in an outcome according to smoking status, Tukey-adjusted pair wise comparisons were made between groups. <h3>Results</h3> A total of 2,090 patients with a mean (SD) age 57.3 (12.9) years were included in the study and 77% were females. There were 343 (16.4%) current smokers (men-22.1% and women-14.8%), 812 (38.9%) past smokers (men-50.5% and women 35.5%) and 935 (44.7%) never smokers (men-27.4% and women-49.7%) in the cohort. A significantly higher proportion of RF positives were found in current smokers (76.7%) compared to past (70.9%) and never smokers (64.5%), p=0.0003. More DMARDS and less biologics were used at baseline in smokers; however it was not statistically significant. Current cigarette smokers found to have significantly higher mean TJC (7.4 vs. 6.3, p&lt;0.001), SJC (7.1 VS. 6.4, p&lt;0.001), CDAI (24.3 vs. 21.5, p&lt;0.001), and RADAI (4.5 vs. 3.7, p&lt;0.001) than non-smokers, after adjusting for patient sex, age and RF. There was no difference in DAS28 scores between the groups. <h3>Conclusions</h3> Smokers have worse disease activity outcomes than non-smokers among RA patients, after adjusting for measured confounders. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3765
Women's Health and the Environment in the 21st Century
Authors: Kenneth Olden, Retha R. Newbold
Journal: Environmental Health Perspectives (2000)

For many years, the National Institute of Environmental Health Sciences has been a leader in studying the role of environmental factors in the causation of diseases that are particularly prevalent or unique to women. As we enter the next millennium, we face exciting new possibilities in broadening our understanding of how the environment impacts women's health. Sophisticated new technology and scientific information are now available to help us more precisely define environmental contributions to disease. Moreover, further development of our information base in environmental health sciences will usher in a new era of informed preventive care for women of all ages. The hallmark of this new era will be our ability to finally address the etiology and prevention of disease, rather than simply focusing on treatment and management of human illness.