tbuckley/cabot-search huggingface dataset:
SAT0183 Autoantibodies for Several Antigens in Neutrophil Cytoplasm other than PR3 and MPO Promote Release of Nets from Neutrophils
Authors: Y. Komagata, S. Amonpatumrat, K. Sano, S. Kawashima, S. Kaname, Y. Arimura, A. Yamada
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Neutrophil extracellular traps (NETs) were first described as web-like structures that trap and neutralize microbes at sites of infection. NETs are comprised of chromatin components and neutrophil cytoplasmic proteins. Because these components of NETs might provide an immunogenic substrate for autoimmune responses during regular encounters with commensal and pathogenic microbes, it has been reported that NETs are involved in autoimmunity such as SLE or ANCA associated vasculitis (AAV). It has also been reported that autoantibodies themselves for important cytoplasmic auto-antigens of neutrophils such as MPO or PR3 induce NETs production. However, the role of other neutrophil cytoplasmic antigens for the production of NETs is unclear. <h3>Objectives</h3> Thus, we investigated how auto-antibodies for these antigens other than PR3 and MPO are involved in NETs productions by neutrophils. <h3>Methods</h3> Human peripheral blood neutrophils were obtained from healthy donors. Neutrophils were seed onto Polystyrene chamber slide system and incubated with PMA (control) or PMA plus several kinds of anti-neutrophil cytoplasmic antigens for 3 hours. Cells were fixed and stained with Hoechst 33342 and Sytox Green for DNA and anti-MPO antibody. The percentage NETs producing cells and the quantitation of nuclear decondensation were analyzed using Image J software. We distinguished cells that released NETs fiber from cells that just died of NETosis. <h3>Results</h3> Anti-MPO antibody strongly promoted both NETosis induction and release of NETs fiber. Although anti-PR3 antibody promoted NETosis induction, it did not increase the release of NETs fiber. Antibody for cathepsin G, found in the azunophil granule, also promoted NETosis induction only. There were some other antibodies, such as anti-lactoferrin and anti-neutrophil elastase, that promoted both NETosis and release of NETs fiber. <h3>Conclusions</h3> It has been thought that ANCAs directed against granule proteins of neutrophils are implicated in the pathogenesis of AAV, partly because ANCAs promote NETs production by neutrophils. We showed that not only anti-MPO and anti-PR3 but also antibodies for other neutrophil cytoplasmic antigens promote NETs production. The mechanism these antibodies for cytoplasmic protein induce NETosis and how important they are for the pathogenesis of AAV are to be elucidated. <h3>Disclosure of Interest</h3> None Declared
Abstract 932: Molecular characterization of transcription factors binding to the cancer-related interleukin-1 B gene polymorphisms
Authors: Nina Elisabeth Landvik, Aage Haugen, Shan Zienolddiny
Journal: Cancer Research (2010)

Abstract Pulmonary inflammation together with chemical exposure may potentiate the carcinogenic process, underlining the importance of inflammation in cancer development. Interleukin-1beta (IL-1β) encoded by the IL1B gene, has been associated with chronic inflammation and plays an important role in lung inflammatory diseases, including COPD and lung cancer. Elevated levels of IL-1β will greatly enhance the intensity of the inflammatory response. There are large inter-individual differences in IL1B gene expression, which may be explained genetically by presence of single-nucleotide polymorphisms (SNPs) scattered throughout the regulatory region (rSNPs) of the gene. These rSNPs may affect IL1B expression by changing the binding affinity of transcription factors or creating novel transcription binding sites. Our studies have shown that several polymorphisms located in the promoter and the enhancer regions of the IL1B gene may affect risk of non-small cell lung cancer. Notably, rSNPs at −3893 G, −1464 G, −511 C and −31 T position formed a specific haplotype (GGCT) with near complete linkage disequilibrium in lung cancer patients, but not in controls where the risk haplotype (GGCT) was present in 65% of cases compared with 36% of controls. The risk haplotype was correlated with significantly higher IL1B mRNA levels in the lung of lung cancer patients. Particularly, we found that the T to C SNP at the −31 position which is located close to the transcription start site of the gene resulted in binding of different transcription factors to the C and T variants. We have further characterized the specific transcription factors binding to the −31 SNP. In DNA-protein interaction studies using Electrophoretic Mobility Shift Assay (EMSA) and human lung epithelial cells we found evidence that the transcription factor Ying Yang 1 (YY1) bound preferentially to the C SNP. The binding of YY1 to the C SNP was further confirmed using Chromatin Immunoprecipitation (ChIP) assay in human lung epithelial cells. In summary, we have characterized transcription factors that may interact differentially with base changes in the SNPs and thereby may explain the biological effects of the SNPs in modifying the risk to cancer (supported by the Norwegian Cancer Society). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 932.
OP0182 Drug Free Remission After One Year of Treatment in Patients with Early Rheumatoid Arthritis: Also Possible for ACPA Positive Patients?
Authors: K. V. C. Wevers-De Boer, L. Heimans, K. Visser, A. Schouffoer, M. van Oosterhout, H. van Groenendaal, I. Speyer, T. Huizinga, C. Allaart
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> In rheumatoid arthritis (RA) remission is a realistic treatment goal. Is tapering medication to drug free remission (DFR) possible for all patients? <h3>Objectives</h3> To assess which patients with early (rheumatoid) arthritis achieve DFR after one year (DFR<sub>1year</sub>) of early remission induction therapy. <h3>Methods</h3> By protocol of the IMPROVED study, patients who achieved remission (DAS&lt;1.6) after 4 months (early remission, n=375) of combination therapy with methotrexate 25 mg/wk and a tapered high dose of prednisone (60 mg/day tapered in 7 weeks to 7.5 mg/day, continued up to 4 months) had to taper stepwise and finally discontinue these drugs as long as remission was maintained. Characteristics of patients achieving and not achieving DFR1year were compared and predictors of DFR were identified using logistic regression. Follow up data of 16 months were included to investigate in how many patients DFR1year was sustained for 4 more months. <h3>Results</h3> 119 patients (32%) achieved DFR<sub>1year</sub>, while 245 (65%) flared and restarted medication over time. Eleven patients had insufficient data. Of patients in DFR<sub>1year</sub>, 51 (28%) at baseline fulfilled the 1987 and 2010 classification criteria for RA, 34 (35%) only fulfilled the 2010 criteria and 20 (35%) patients had UA and fulfilled neither criteria (p=0.4). In 77 (65%) DFR<sub>1year</sub> was sustained up to 16 months. Patients in DFR<sub>1year</sub> were more often rheumatoid factor (RF) negative than patients not achieving DFR<sub>1year,</sub> (50% versus 62%, p=0.04). There were no differences in baseline DAS (2.9 (0.9) versus 3.1 (0.8), p=0.12), symptom duration (16 (8-29) versus 17 (9-32), p=0.52) or ACPA positivity (56% versus 61% respectively, p=0.27). Univariable predictors were positive RF (OR 95%CI 0.6 (0.4-0.99)) and high baseline tender joint count (TJC) (OR 95%CI 0.9 (0.9-1.0). Baseline DAS, positive ACPA, age, male sex, being classified as RA according to the 2010 ACR/EULAR criteria or short symptom duration were not predictive for DFR<sub>1year</sub>. The only independent predictor was RF negativity (OR 95%CI 0.6 (0.4-0.97, adjusted for baseline TJC)<sub>.</sub> <h3>Conclusions</h3> Of 375 early (rheumatoid) arthritis patients who achieved remission after 4 months of initial combination therapy with methotrexate and prednisone, 32% maintained in remission despite having tapered and discontinued all drugs at 1 year. DFR was sustained up to 16 months in 65% of these. With this treatment strategy, presence of ACPA appears not to preclude drug discontinuation, but patients with positive RF achieved DFR after 1 year somewhat less often than RF negative patients. <h3>Disclosure of Interest</h3> None Declared
INCIDENCE OF VENTRICULAR ARRHYTHMIAS AFTER CARDIAC RESYNCHRONIZATION DEFIBRILLATOR THERAPY IN PATIENTS WITH RIGHT VENTRICULAR PACING VERSUS INTRINSIC QRS WIDENING
Authors: Bhupendar Tayal, Antonia Delgado Montero, Akiko Goda, Stephanie Holt, Samir Saba, David Schwartzman, Peter Søgaard, John Gorcsan
Journal: Journal of the American College of Cardiology (2015)
Abstract 282: PAI-2 promotes astrocyte differentiation from glial precursor cells via enhancing STAT3 signaling
Authors: Zaibo Li, Chris Proschel, Mark Noble
Journal: Cancer Research (2011)

Abstract Regulation of the generation of astrocytes and oligodendrocytes is a key process in the development of normal central nervous system (CNS) and glial tumors including oligodendrocytoma, astrocytoma and glioblastoma. Glial cell differentiation occurs in two sequentially generated glial progenitor cells, the glial-restricted precursor (GRP) cells and the oligodendrocyte-type-2 astrocyte (O-2A) progenitor cells. The molecular mechanisms of cell generation in these precursor cells are only incompletely understood. In this study, PAI-2 (Plasminogen Activator inhibitor-2) was identified to be upregulated during glial cell differentiation. Ectopic expression of PAI-2 induced GRP cells to differentiate into astrocytes and inhibited their proliferation. In contrast, suppression of endogenous PAI-2 by small interfering RNA in GRP cells promoted cell proliferation and inhibited their ability to differentiate into astrocytes. More interestingly, we observed a higher Rb protein level and a correlated lower E2F1 transcriptional activity during glial differentiation due to increased PAI-2 protein level. In consistent with these findings, ectopic expression of PAI-2 indeed stabilized Rb protein. We also found that PAI-2 upregulated GFAP expression in glial progenitor cells, an antigenic marker for astrocytes. Astrocytogenesis is controlled by two different signaling, the IL-6, LIF or CNTF-induced STAT3 pathway and the BMP-4-induced SMAD1 pathway. Interestingly, PAI-2 significantly enhanced CNTF, LIF or IL-6-induced GFAP expression as illustrated by both reporter assay and immunostaining, but not BMP4-induced GFAP expression. Furthermore, We demonstrated that PAI-2 could enhance CNTF-induced STAT3 phosphorylation and the complex formation between STAT3 and p300. It has also been reported that Rb could enhance the transcriptional activity of several transcription factors via enhancing p300/CBP activity by releasing them from some inhibitory transcriptional repressors such as EID1 (E1A-like inhibitor of differentiation). Indeed, suppression of Rb by small interfering RNA or overexpression of EID1 abrogated PAI-2's effect on STAT3 activity. Also, suppression of endogenous EID1 by small interfering RNA could further enhance PAI-2's effect. Finally, we illustrated Glial precursor cells from PAI-2 knockout mice are less responsive to CNTF and IL-6 than wild-type cells. Based on these data, we concluded that PAI-2 promotes glial progenitor cells to differentiate into astrocytes via stabilizing Rb, which can abrogate EID's inhibitory effect, and then enhancing STAT3 transcriptional activity induced by CNTF or IL-6. 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 282. doi:10.1158/1538-7445.AM2011-282
ANTI-THYMOCYTE GLOBULIN PROTECTS AGAINST ISCHEMIA REPERFUSION INJURY IN THE IMMEDIATE POST HEART TRANSPLANT PERIOD
Authors: Parham Zarrini, Tamar Aintablian, Michelle Kittleson, David Chang, Dael Geft, Lawrence Czer, Jon Kobashigawa
Journal: Journal of the American College of Cardiology (2016)
DILATACION NEUMÁTICA DE LAS ESTENOSIS BENIGNAS DEL TRACTO DIGESTIVO SUPERIOR. RESULTADOS EN LA ÚLTIMA DÉCADA
Authors: L Vaquero Ayala, M García Alvarado, J Espinel Díez, R Díez Rodríguez
Journal: Endoscopy (2011)

Introducción: La dilatación endoscópica es el método de elección de las estenosis esofágicas benignas.
Septic Emboli Visualized with Leukocyte Scintigraphy
Authors: ROBERT K. MYERS, ALAN SIEGEL
Journal: Clinical Nuclear Medicine (2002)

From the Department of Radiology, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire Received for publication December 12, 2001. Revision accepted February 26, 2002. Reprint requests: Alan Siegel, Department of Radiology, Dartmouth Hitchcock Medical Center, One Medical Center Drive, Lebanon, New Hampshire 03756. E-mail: [email protected]
ACUTE CORONARY SYNDROME IN ACTIVE HEMATOLOGICAL MALIGNANCIES: A COHORT STUDY OF 5,300 PATIENTS
Authors: Jae Yoon Park, Mohammed Al-Hijji, Abdallah El Sabbagh, Kebede H. Begna, Thomas M. Habermann, Thomas E. Witzig, Amir Lerman, Joerg Herrmann
Journal: Journal of the American College of Cardiology (2016)
Ga-67 in Castleman’s Disease
Authors: Jean-Louis Alberini, Philippe Blanche, Florence Tenenbaum, Annabelle Merlat-Guitard, Jean-Yves Devaux, Francois Dreyfus, Didier Sicard, Bruno Richard
Journal: Clinical Nuclear Medicine (2003)

ALBERINI, JEAN-LOUIS M.D.*; BLANCHE, PHILIPPE M.D.†; TENENBAUM, FLORENCE M.D.*; MERLAT-GUITARD, ANNABELLE M.D.‡; DEVAUX, JEAN- YVES M.D., Ph.D.*; DREYFUS, FRANÇOIS‡; SICARD, DIDIER M.D., Ph.D.†; RICHARD, BRUNO M.D., Ph.D.* Author Information
Case 37-2006
Authors: Daniel C. Chung, Michael M. Maher, William C. Faquin
Journal: New England Journal of Medicine (2006)

A 19-year-old woman was evaluated in the gastroenterology clinic because of intermittent painless rectal bleeding and chronic iron-deficiency anemia. Eight months earlier, a papillary thyroid carcinoma had been treated with total thyroidectomy and administration of radioactive iodine (iodine-131). A diagnostic procedure was performed.
Abstract LB-416: Evaluation of phase 3 multicenter clinical data of receptor targeted (CD206) Tc99m-tilmanocept for sentinel node evaluation (ILM) in breast cancer and melanoma
Authors: Vernon K. Sondak, Anne M. Wallace
Journal: Cancer Research (2011)

Abstract Background: Sentinel lymph node (SLN) mapping is widely used for staging clinically node-negative breast cancer and melanoma. [99mTc]tilmanocept is a new receptor-targeted (CD206) radiopharmaceutical designed for SLN mapping. The purpose of this review is to report the results of the Phase 3 clinical data designed to assess the concordance of [99mTc]tilmanocept with vital blue dye, considered the standard for identifying sentinel lymph nodes in these two malignancies. Methods: The Phase 3 program was a multicenter, prospective, open label, evaluation of [99mTc]tilmanocept in patientswith clinically localized melanoma or breast cancer. Within the Intent-to-treat population, [99mTc]tilmanocept and vital blue dye were administered to patients and standard SLN mapping was performed, during which all identified radioactive and/or blue-stained lymph nodes were excised and histologically examined. The primary endpoint was concordance of [99mTc]tilmanocept with vital blue dye. The patient concordance rate was defined as the percentage of patients for whom all nodes detected by blue dye were also detected by [99mTc]tilmanocept. Results: At least one blue-stained lymph node was exhibited by 91% patients and 98.0% had at least one “hot” node. The concordance of [99mTc]tilmanocept with vital blue dye was statistically significant with ∼98% concordant. Of the melanoma patients, ∼97% were concordant; and within the breast cancer patients, ∼99% were concordant. In contrast, vital blue dye had a concordance rate with [99mTc]tilmanocept of &amp;lt;55%. No severe adverse events were related to the administration of [99mTc]tilmanocept. Conclusions: [99mTc]Tilmanocept was well tolerated and effectively identifies sentinel nodes with a statistically significant degree of concordance to blue dye in either breast cancer or melanoma surgery. Additional outcomes will be presented. (Also refer to ClinicalTrials.gov, key word, tilmanocept) 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 LB-416. doi:10.1158/1538-7445.AM2011-LB-416
Abstract 3628: The forced interaction of α4 integrin and CD44 by the novel peptide HYD1 may be a determinant of HYD1-induced cell death in multiple myeloma
Authors: Anthony W. Gebhard, Michael F. Emmons, Raul F. Argilagos, Mark McLaughlin, John Koomen, Anne E. Cress, Lori A. Hazlehurst
Journal: Cancer Research (2011)

Abstract Our laboratory has previously shown that treatment with the novel d-amino acid peptide HYD1 (kikmviswkg) induces necrotic cell death in multiple myeloma (MM) cell lines. Furthermore, we have implicated the adhesion receptor VLA-4 as being involved in this process via shRNA silencing strategies. However, reducing α4 integrin only demonstrated partial protection indicating that other components of the HYD1 binding complex may be required for cell death. Thus, in the present study, we investigated the possible role of other adhesion molecules and/or complexes that may contribute to HYD1-induced cell death. Using an unbiased approach, we performed a total membrane pull-down with biotin conjugated HYD1 and NeutrAvidin beads on NCI-H929 MM cells. Samples were then loaded on an SDS-PAGE gel and analyzed by Mass Spectrometry. Data were then mined with the Scaffold 3 proteome software to determine pertinent hits. The adhesion receptor CD44 was determined to have the most peptide match hits and was confirmed as a valid hit via Western Blot analysis. Preliminary data using ELISA based binding studies with biotin-HYD1 as bait shows that recombinant CD44 directly binds to biotin-HYD1 in a concentration dependent manner. In order to identify complexes involved in HYD1-induced cell death, membrane immunoprecipitation assays were performed using CD44 and α4 integrin mAbs in both the presence and absence of HYD1. While Western Blot analysis confirmed basal levels of complex interactions between α4 integrin and CD44, the complex was significantly enhanced in the presence of HYD1. These data not only indicate a possible role of CD44 in HYD1-induced cell death, but also the ability of HYD1 to induce interactions among adhesion molecules and complexes. Further studies, including CD44shRNA targeting strategies, as well as looking at other adhesion molecules will be needed in order to confirm the role of individual cell surface receptors identified in the biotin-HYD1 complex in mediating HYD1 induced cell death. 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 3628. doi:10.1158/1538-7445.AM2011-3628
Medical Staff Training Program for Assessment of Chemoradiotherapy-Induced Oral Mucositis in Head and Neck Cancer
Authors: T. Yurikusa, T. Yokota, T. Kubo, M. Sawamura, H. Tachibana, T. Konishi, S. Zenda, M. Taguri, M. Sato, Y. Ota
Journal: Annals of Oncology (2013)
Abstract 1247: ARHI downregulates PI3K and Ras-MAP signaling and induces autophagy by promoting integrin and EGFR membrane protein degradation
Authors: Zhen Lu, Warren S.L. Liao, Maojie Yang, Fengqin Gao, Robert C. Bast
Journal: Cancer Research (2012)

Abstract Autophagy selectively degrades cellular proteins, protein aggregates and organelles, providing energy in a nutrient-deprived environment. We have reported that autophagy can be induced by re-expression of ARHI (DIRAS3), a maternally imprinted Ras-related tumor suppressor gene that is down regulated in more than 60% of ovarian cancers. Whereas prolonged expression of ARHI in cultured cells induces autophagic cell death, ARHI expression in xenografts sustains dormant cancer cell survival for weeks. When ARHI levels were reduced in dormant cells, xenografts grew rapidly. Inhibition of ARHI-induced autophagy with chloroquine dramatically reduces regrowth of xenografts, suggesting that autophagy contributes to the survival of dormant cells. Re-expression of ARHI inhibits both PI3K and Ras-MAPK signaling. Growth factors (VEGF, IL-8, IGF) and ECM components (fibronectin) found in the cancer microenvironment can rescue ovarian cancer cells from ARHI-induced autophagic cell death in culture, associated with partial reversal of ARHI-mediated inhibition of PI3K signaling. Consequently, we have hypothesized that autophagy together with growth factors and ECM in the microenvironment are all required to maintain dormancy, where autophagy provides energy for xenografts and survival factors prevent autophagic death by partially reversing inhibition of PI3K-AKT signaling. The mechanism by which ARHI regulates PI3K and Ras-MAPK signaling has not been fully elucidated. Here, we show that re-expression of ARHI in SKOv3 ovarian cancer cells inhibits expression of integrin β1 and EGFR. ARHI expression enhanced EGF-mediated receptor endocytosis and colocalization of EGFR with Rab11 and Rab7, markers for multivesicular endosomes and lysosomes, respectively. Our results suggest that ARHI enhances membrane receptor turnover, in part, by facilitating the internalization and association of membrane receptors with vesicular trafficking proteins targeted for degradation in the lysosome. ARHI-mediated downregulation of membrane receptors reduces both PI3K-AKT and Ras-MAPK signaling, ultimately contributing to the inhibition of tumor growth. 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 1247. doi:1538-7445.AM2012-1247
Universities will be rewarded for backing forensic science research, MPs hear
Authors: A. O'Dowd
Journal: BMJ (2011)

Universities will be financially rewarded for investing in research in forensic science, MPs have been told. The move is an attempt to bolster research in the area despite the closure of the Forensic Science Service early next year.

The government announced in December 2010 that the Forensic Science Service—the government owned company that analyses crime scene evidence for police forces and government agencies in England and Wales—will close by March 2012. As the service is wound down the government will transfer its work to private companies (which already carry out 40% of forensic work), and some forensic work is already being carried out by police forces themselves.

The House of Commons Science and Technology Committee was holding an evidence session for an inquiry to examine the government’s response to the committee’s previous inquiry held earlier this year into the closure of the Forensic Science Service.

In the report from the earlier inquiry, …
956 BILIARY ANTI-NEUTROPHIL CYTOPLASMIC ANTIBODIES ARE ASSOCIATED WITH DISEASE SEVERITY IN PRIMARY SCLEROSING CHOLANGITIS
Authors: H. Lenzen, T.J. Weismueller, A.A. Negm, H. Poos, J. Wedemeyer, M.P. Manns, T.O. Lankisch
Journal: Journal of Hepatology (2012)