tbuckley/cabot-search huggingface dataset:
AB1117 Epidemiology and course of uveitis in children in a pediatric rheumatology clinic of universidade federal do rio de janeiro
Authors: B.R. Bica, A.B. Vargas, C.C. Valentim, F.W. Castro, J. Fragoso, J. Serra, C.C. Figueiredo, M.N.L. Azevedo
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Uveitis is a common manifestation of rheumatic diseases with a broad spectrum of clinical presentation. It can be acute or chronic, affect any part of the uveal tract, can occur before or after the diagnosis of the associated rheumatic condition and can progress with severe complications. In Juvenile Idiopathic Arthritis (JIA) it tipically involves the anterior chamber, is frequently oligosymptomathic and carries a high rate of complications. <h3>Objectives</h3> Analyze the course and the development of uveitis associated with rheumatic diseases in outpatients of the Rheumatic Clinic of Hospital Universitário Clementino Fraga Filho (HUCFF) at Universidade Federal do Rio de Janeiro between 2000 and 2010. <h3>Methods</h3> We conducted a retrospective study based on review of medical records of 37 patients in the Rheumatology Clinic of the HUCFF. The selected patients had a previous diagnosis of uveitis and were enrolled to our service between 2000 and 2010. <h3>Results</h3> Twenty-six patients (70,3%) presented with a rheumatic disease, while 11 (29,7%) patients had isolated uveits. The most frequent diagnosis was JIA (56,8%), followed by idiopathic uveitis (29,7%) and the spondyloarthritis was diagnosed in 8,1%. In most cases, the uveitis presented in the course of the underlying disease (56,8%), as it was the involvement of the anterior chamber of the eye (70,3%). Of these 37 patients, there were a total of 57 affected eyes and 92% had a chronic presentation. The presence of antinuclear antibodies (ANA) was associated with higher frequency of uveitis and most patients with positive ANA developed complications (65%). The most frequent complications were cataract (30.2%) and posterior synechiae (13.2%). All patients who were on biological therapy presented some complication, what could be explained by the greater severity of uveitis in patients who require the use of these medications. <h3>Conclusions</h3> Juvenile idiopathic arthritis-related uveitis accounts for the majority of identifiable causes of childhood onset uveitis. The characteristics of uveitis associated with rheumatic diseases observed in this study were similar to those found by other authors. The rate and spectrum of vision threatening complications of pediatric uveitis are significant and the authors emphasize the importance of regular eye evaluation in rheumatic diseases. <h3>Disclosure of Interest</h3> None Declared
Mechanisms of SLUG-Induced Drug Resistance Development in Breast Cancer Cells.
Authors: M. Mittal, K. Singh, G. Chaudhuri
Journal: Cancer Research (2009)

Abstract Down regulation of vitamin D receptor and over-expression of cyclin D1 are often associated with breast cancers. Depending upon the genetic context of the breast cancer cells, these alterations also often lead to development of resistance of the breast cancer cells against drugs like vitamin D3, all-trans retinoic acid and tamoxifen. We report here that the metastasis promoter protein SLUG indirectly induces the elevation of cyclin D1 levels in human breast cancer cells by repressing vitamin D3 receptor (VDR) and ubiquitin conjugating enzyme UbE2D3 genes. SLUG over-expression repressed the mRNA and protein levels of VDR and UbE2D3 in SLUG-negative human breast cells whereas knockdown of SLUG in the SLUG-expressing human breast cells had the reverse effect. SLUG also E2-box-dependently inhibited the activity of VDR and UbE2D3 gene promoters. CtBP1 and HDAC1 are co-recruited at the VDR and UbE2D3 gene promoters with SLUG, further indicating that SLUG represses this gene through chromatin remodeling. Knockdown of UbE2D3 or VDR in the SLUG-negative human breast cells elevated the levels of cyclin D1 as well as the rates of proliferation/invasiveness of these cells. While SLUG over expression has no effect on tamoxifen-resistance of ER-negative breast cancer cells, it significantly decreases tamoxifen-sensitivity of ER-positive breast cancer cells. On the other hand, knockdown of VDR gene expression by SLUG increased the resistance of both ER-positive and ER-negative breast cancer cells to 1, 25(OH)2D3 and all-trans retinoic acid. Our data thus suggest that SLUG not only promotes metastatic development of breast cancer cells, but also conspire to the development of resistance of these cells against several anti-cancer compounds. Supported by the DOD-CDMRP IDEA Grant# W81XWH-06-1-0466 and the Susan G. Komen Breast Cancer Foundation grant# BCTR0707627 to GC. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1128.
Abstract 1738: Multiparametric approaches to evaluate mitochondrial toxicity, oxidative stress and apoptosis in drug discovery studies.
Authors: Katherine Gillis, Julie Clor, Kimvan Tran, Asima Khan, Kamala Tyagarajan
Journal: Cancer Research (2013)

Abstract Drug discovery and toxicity studies require access to methods and technologies that can provide comprehensive evaluation of the types of cellular impacts caused by anti-cancer compounds. In particular, there is growing emphasis on the study of mitochondrial toxicity at an early phase of compound evaluation and its relations to multiple cell death processes that include apoptotic cell death, caspase-independent death and autophagic processes. The study of oxidative stress and its relation to cell death pathways also provides insights into mechanism of cellular stress. In this study we have used multiparametric assays that correlate changes in mitochondria with different cell health parameters using plate-based microcapillary cytometry on guava easyCyte platforms. Compound screening studies were performed on Jurkats (suspension) and HeLa adherent cell lines using an array of over 80 compounds to study inter-relationships between mitochondrial perturbations and different cell health parameters. Compounds were evaluated for mitochondrial depolarization and relationship to apoptosis and cell death; mitochondrial perturbations with regard to caspase levels were also evaluated; and the parallel connection between mitochondrial superoxide stress and apoptosis was also studied. Our studies identified several hit compounds, examples of which included compounds like gambogic acid, thimerosal, camtothecin, antimycin A, staurosporine, celastrol and juglone which caused significant mitochondrial perturbation and apoptosis. In addition, compounds such as antimycin A and staurosporine caused significant oxidative stress. Simplified and rapid screening assays that provide information on multiple parameters of cellular stress and apoptosis can greatly benefit the identification of hit compounds and provide a more comprehensive understanding of the mechanism of compound toxicity. Citation Format: Katherine Gillis, Julie Clor, Kimvan Tran, Asima Khan, Kamala Tyagarajan. Multiparametric approaches to evaluate mitochondrial toxicity, oxidative stress and apoptosis in drug discovery studies. [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 1738. doi:10.1158/1538-7445.AM2013-1738
Abstract ADV14: One advocate's journey: I went from fighting for my life to now fighting for others.
Authors: Kristen Keesen
Journal: Cancer Research (2013)

Abstract Kristin Keesen, 45 year old colorectal cancer survivor from Colorado, describes her personal journey with colorectal cancer, and how she became inspired to work with Fight Colorectal Cancer to help others. Fight Colorectal Cancer demands a cure for colon and rectal cancer. We educate and support patients, push for changes in policy that will increase and improve research, and empower survivors to raise their voices against the status quo. Fight Colorectal Cancer believes that a cure means accessible, accurate population-based screening, and personalized treatment. To that end, we connect with people touched by colorectal cancer, provide information to help them cope with their current situation and then, if they choose, empower them to raise their voices and training advocates around the country. Fight Colorectal Cancer and our advocates educate lawmakers and regulators, pushing them for better policies. Our research advocates serve on research committees and help focus on meaningful outcomes. They also collaborate with a variety of prestigious academic institution on research projects. In 2013, our One Million Strong initiative will help our advocates engage the general public by asking them to take the pledge to get screened if appropriate, and spread the word without screening. Our programs include: - Research Advocacy Training and Support (RATS): training lay advocates to participate effectively in the research process. - Patient Information Services: providing information in multiple channels. - Lisa Fund: career development funding for young researchers performing translational research relevant to patients with metastatic colorectal cancer. Our seminal effort is Call-on-Congress, our annual advocacy training and lobbying event which is based on our regulatory and legislative priorities. Citation Format: Kristen Keesen. One advocate's journey: I went from fighting for my life to now fighting for others. [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 ADV14. doi:10.1158/1538-7445.AM2013-ADV14
AB0166 The Levels of Soluble CD163 in Patients with Ankylosing Spondylitis
Authors: M. Tošovský, P. Bradna, C. Andrýs, K. Andrýsová, E. Čermáková, T. Soukup, K. Kubínová, J. Krejsek
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Innate immune cells play an important role in pathogenesis of spondylarthropathies (SpA) since the increased infiltration of macrophages, especially CD163+, has been proven in synovitis tissue in these patients. <h3>Objectives</h3> To evaluate the levels of soluble CD163 (sCD163) in patients with ankylosing spondylitis in comparison with patients treated for degenerative spinal disease. <h3>Methods</h3> Levels of sCD163 were measured by enzyme-linked immunosorbent assay in patients with established ankylosing spondylitis according to modified New York criteria (n=55) and were compared with control group - patients treated for degeneratve spinal disease (n=20). Furthermore, we compared the levels of sCD163 in patients with ankylosing spondylitis treated (n=21) and not treated (n=34) with tumor necrosis factor alpha inhibitors. <h3>Results</h3> The levels of soluble CD163 were significantly increased in group of patients with ankylosing spondylitis as compared with the control group (mean ± SEM 1670,8±91,6 ng/ml vs. 1131,5±80,3 ng/ml, <i>p=</i>0,0013). No significant difference was found between levels of soluble CD163 in patients treated and not treated with tumor necrosis factor alpha inhibitors (mean ± SEM 1805,2±184,8 ng/ml vs. 1587,8±94,4 ng/ml respectively, <i>p</i>=0,52). <h3>Conclusions</h3> Our finding shows, that CD163+ cells may play role in pathogenesis of spondylarthorpathies, particularly ankylosing spondylitis, and soluble CD163 may be applicable biomarker in this disorder. <h3>Acknowledgements</h3> Supported by MH CZ –DRO (UHHK, 00179906) <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4464
Abstract 3024: Elucidation of WNT signaling pathway players “sFRP-1” and “TCF7L2” as novel potential biomarkers of triple negative breast cancer
Authors: Carolin Huelsewig, Martin Goette, Christof Bernemann, Christian Ruckert, Marie-Kristin von Wahlde, Olaf Buchweitz, Ludwig Kiesel, Lajos Pusztai, Cornelia Liedtke
Journal: Cancer Research (2012)

Abstract Background: Triple negative breast cancer (TNBC) is characterized by an unfavorable prognosis. While patients do not benefit from endocrine or Her2 targeted therapies except chemotherapy, there is an increased propability of response to taxane-/anthracycline-containing therapy compared to other breast cancers. However, molecular determinants of chemotherapy sensitivity for patients with TNBC specifically remain largely unknown. The WNT signaling cascade has been shown to play an important role in breast cancer pathogenesis. Material and Methods: Differentially expressed genes in triple negative (TN) vs. non-TN breast cancers of patients treated with neoadjuvant taxane-/anthracycline-containing chemotherapy were identified and validated in an independent AffymetrixU133A gene chip dataset. Genes were tested for correlation with relapse-free survival, response to neoadjuvant chemotherapy and Ki67 expression. The effects of siRNA mediated knockdown in the TNBC and non-TNBC cell lines on proliferation, chemo sensitivity invasion competency and gene expression of target genes via quantitative real-time PCR were analyzed. Results: sFRP-1 (secreted frizzled related protein 1) and TCF7L2 (transcription factor-7 like 2) were identified as significantly over expressed genes in TNBC vs. non-TNBC and validated in an independent dataset. While sFRP-1 expression was not associated with relapse-free survival in TNBC, it was significantly correlated with a pCR. Importantly, no correlation to Ki67 expression could be demonstrated. While mRNA knockdown of sFRP-1 in MDA-MB 468 was associated with an increased resistance to paclitaxel, doxorubicin and cisplatin, target gene expression analysis suggest sFRP-1 as a biphasic modulator in breast tissue. TCF7L2 knockdown analysis in the TN cell line MDA MB 231 as well as the non-TN lines MCF7 and SKBR-3 shows an increased cell invasiveness of up to 200 %. Conclusion: We suggest sFRP-1 as predictive biomarker and potential mediator of sensitivity to taxane-, anthracycline and platinum-containing chemotherapy in TNBC in vitro referring to its biphasic WNT modulation. Furthermore TCF7L2 is suggested as a prognostic biomarker in vitro breast cancer cell lines including TN and non-TN cell lines. Our results provide proof of principle that high-throughput gene expression analysis may be exploited as a means to derive at a biological / translational hypothesis that may be supported by basic science. 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 3024. doi:1538-7445.AM2012-3024
The interaction of social class and other factors in the etiology of schizophrenia
Authors: M L Kohn
Journal: American Journal of Psychiatry (1976)

Epidemiological evidence clearly indicates an especially high rate of schizophrenia at the lowest social class levels of urban populations. The author suggests that this relationship between class and schizophrenia exists because the conditions of life experienced by people of lower social class position foster conceptions of social reality that are so limited and rigid as to impair their ability to deal resourcefully with the problematic and the stressful. Such impairment does not in itself result in schizophrenia; however, in conjunction with genetic vulnerability and great stress, it could be disabling.
3-Year Outcomes in High-Risk Patients Who Underwent Surgical or Transcatheter Aortic Valve Replacement
Authors: G. Michael Deeb, Michael J. Reardon, Stan Chetcuti, Himanshu J. Patel, P. Michael Grossman, Steven J. Yakubov, Neal S. Kleiman, Joseph S. Coselli, Thomas G. Gleason, Joon Sup Lee, James B. Hermiller, John Heiser, William Merhi, George L. Zorn, Peter Tadros, Newell Robinson, George Petrossian, G. Chad Hughes, J. Kevin Harrison, Brijeshwar Maini, Mubashir Mumtaz, John Conte, Jon Resar, Vicken Aharonian, Thomas Pfeffer, Jae K. Oh, Hongyan Qiao, David H. Adams, Jeffrey J. Popma
Journal: Journal of the American College of Cardiology (2016)
Quantification of minimal residual disease in patients with e1a2 BCR-ABL-positive acute lymphoblastic leukemia using a real-time RT-PCR assay
Authors: H Yokota, NH Tsuno, Y Tanaka, T Fukui, K Kitamura, H Hirai, K Osumi, N Itou, H Satoh, M Okabe, K Nakahara
Journal: Leukemia (2002)
Phase I/II Study of Amrubicin Combined with Nedaplatin (CDGP) in Untreated Non-Small-Cell Lung Cancer
Authors: D. Ogawara, Y. Nakamura, M. Fukuda, K. Nakatomi, S. Doi, H. Nakano, K. Motoshima, H. Senjyu, T. Iida, S. Kohno
Journal: Annals of Oncology (2013)
Production of High-Potency Concentrates of Antihemophilic Globulin in a Closed-Bag System
Authors: Judith Graham Pool, Angela E. Shannon
Journal: New England Journal of Medicine (1965)

REPLACEMENT therapy of classic hemophilia in this country is still handicapped by the low potency and high price of therapeutic materials. In this disease severely affected patients have less than 1 per cent of the mean normal circulating level of antihemophilic globulin (AHG, factor VIII). To stop various types of hemorrhage, minimum levels of 10 to 35 per cent must be achieved and maintained for one to twelve days. When one considers that frozen plasma has on the average 65 per cent of the antihemophilic globulin in the mean fresh sample, and when one further realizes that the half-life of . . .
S114 Simvastatin improves neutrophil migratory targeting in COPD:<i>in vitro</i>studies supporting Statin use as a potential adjuvant therapy
Authors: CS Sadhra, T Purvis, GM Walton, JA Stockley, RA Stockley, E Sapey
Journal: Thorax (2013)

<h3>Introduction</h3> Statin use in COPD is associated with a reduction in all cause mortality, with greatest reductions seen in patients with the highest inflammatory burden. However, the mechanism for these effects is poorly understood, as statin treatment has not been found to lower systemic inflammation and <i><i>in vitro</i></i>studies of cellular effects use concentrations that exceed the therapeutic range. Neutrophils are key effector cells in COPD, and correlate with disease severity and inflammation. Recent <i>in vitro</i> studies have shown neutrophil migratory accuracy to be reduced in COPD. This is thought to contribute to the destruction of lung parenchyma and the poor responses seen in infective exacerbations. We aimed to characterise neutrophil migration in COPD and assess whether physiologically relevant concentrations of simvastatin altered neutrophil migration. <h3>Methods</h3> Neutrophils were isolated from COPD patients and healthy smoking age-matched controls (age &gt; 60yrs, n = 13 per group) and incubated with 1nM - 1μM Simvastatin or with a carrier control before migratory dynamics were assessed towards IL8 and fMLP using time-lapse photography. Data is expressed as means with standard deviation in parentheses. <h3>Results</h3> COPD neutrophils displayed reduced chemotaxis (directional speed of migration) and reduced chemotactic accuracy (Chemotactic Index - a vector analysis of migratory tracks) compared to cells from healthy age-matched controls (HC) in the presence of IL-8 and f-MLP, replicating previous work. For example, Chemotactic Index: IL8; HC, 0.42CU (0.03), COPD 0.22CU (0.05), p = 0.002: fMLP; HC, 0.34CU (0.05), COPD, 0.18CU (0.03) p = 0.014). Treatment with Simvastatin significantly improved the chemotactic ability of COPD neutrophils in a dose response with greatest improvement seen at the highest concentration (e.g. Chemotaxis to IL8, Carrier control 0.8um/min (0.2), 1nM Simvastatin 1.3um/min (0.2), p = 0.04; 1uM Simvastatin 1.4um/min (0.2), p = 0.004). A similar improvement was seen in Chemotactic Accuracy (e.g. Chemotactic Index to fMLP, Carrier control 0.17CU (0.03), 1nM Simvastatin 0.26CU (0.02), p = 0.018; 1uM Simvastatin 0.31CU (0.03), p = 0.002). <h3>Conclusions</h3> Migratory accuracy of circulating neutrophils is reduced in COPD patients compared with healthy, smoking, age-matched controls but can be restored by treatment with therapeutic concentrations of Simvastatin <i><i>in vitro</i></i>. Our data suggest statin therapy might be an adjuvant intervention in COPD, modulating neutrophil responses.
IMPACT OF PROTON PUMP INHIBITOR USE ON THE COMPARATIVE SAFETY AND EFFECTIVENESS OF PRASUGREL VERSUS CLOPIDOGREL: INSIGHTS FROM TRANSLATE-ACS
Authors: Larry R. Jackson, Eric Peterson, Lisa McCoy, Christine Ju, Marjorie Zettler, Brian Baker, John Messenger, Douglas Faries, Mark Effron, David Cohen, Tracy Wang
Journal: Journal of the American College of Cardiology (2015)
Refinement of the Positive Predictive Value of Gallbladder Nonvisualization After Morphine Administration for Acute Cholecystitis Based on the Temporal Pattern of Common Bile Duct Activity
Authors: CHUN K. KIM, MIJIN YUN, JEUNG-KEUN LIM, XIAOJIN LIN, BORYS R. KRYNYCKYI, JOSEF MACHAC
Journal: Clinical Nuclear Medicine (2000)

The authors previously reported two major patterns in the time–activity curve of the common hepatic bile duct (BD) after morphine administration in patients with gallbladder nonvisualization. The first pattern consists of a gradual increase in BD activity (of variable duration) occurring during a simultaneous decrease in liver parenchymal activity (BD↑), representing the physiologic effects of morphine administration. The second pattern consists of a continuous decrease in BD activity that parallels the activity in the liver parenchyma (BD↓), representing lower or no physiologic effects of morphine administration. The authors hypothesize that gallbladder nonvisualization associated with a continuous decrease in BD activity after morphine administration will have a lower positive predictive value (PPV) for acute cholecystitis than gallbladder nonvisualization associated with an increase in BD activity. Methods Thirty-six patients who had morphine-augmented cholescintigraphy were divided into two groups: 19 with BD↑ after morphine administration and 17 with BD↓. Results Of the 36 patients, 22 had acute cholecystitis. The positive predictive value (PPV) of gallbladder nonvisualization was 61%. All of the remaining 14 had chronic cholecystitis. Of 19 patients with BD↑, 15 had acute cholecystitis (PPV = 79%), whereas only 7 of 17 patients with BD↑ (PPV = 41%) had acute cholecystitis (P = 0.023 by the one-tailed and 0.038 by the two-tailed Fisher exact tests). Conclusions Gallbladder nonvisualization after morphine administration with the pattern of BD↓ is not as reliable (intermediate probability in this series) for the diagnosis of acute cholecystitis as is nonvisualization of the gallbladder in patients with a pattern of BD↑ (high probability).
The Heart of the Matter
Authors: Laura Tarter, Jinoos Yazdany, Brian Moyers, Christopher Barnett, Gurpreet Dhaliwal
Journal: New England Journal of Medicine (2013)

A 22-year-old woman presented to the emergency department with a history of cough, progressive shortness of breath, subjective fevers, and malaise. On the day of admission, she was unable to walk more than one city block without rest. She noted new swelling in both legs.
FREQUENCY AND EFFECTS OF EMOTIONAL AND PHYSICAL STRESSORS IN PATIENTS WITH SPONTANEOUS CORONARY ARTERY DISSECTION
Authors: Sina Alipour, Andrew Starovoytov, Milad Heydari-Kamjani, Brady Robinson, Patrick Daniele, Min Gao, Karin Humphries, G.B. John Mancini, Jacqueline Saw
Journal: Journal of the American College of Cardiology (2016)