tbuckley/cabot-search huggingface dataset:
AB0380 The Inhibition of Tumor Necrosis Factor-Alpha (TNFA) Reduce Plasmatic Reactive Oxygen Metabolites (ROM) of Rheumatoid Arthritis (RA) Patients
Authors: F. Cacciapaglia, M.G. Anelli, D. Rizzo, E. Morelli, C. Rotondo, A. Rinaldi, M. Covelli, F. Iannone, G. Lapadula
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Accumulating evidences indicate that chronic inflammation and oxidative stress play a key role in the early and accelerated atherosclerosis seen in patients with RA (1). Tumor necrosis factor-alpha (TNFa) overproduction is thought to be the main contributor to increased ROS release in patients with RA (2). TNFa inhibitors are effective treatments in the management of RA but the effects of these drugs on the heart and vessels is under investigation (3,4). <h3>Objectives</h3> The aim of this study was to assess the circulating levels of reactive oxygen metabolites (ROMs) during anti-TNFa treatment in RA. <h3>Methods</h3> Forty patients with RA (36 female; age 53±13yrs) treated with different TNFa inhibitors were analyzed for 52 weeks. The oxidant status was determined from plasmatic samples taken before, 24 and 52 weeks after anti-TNFa treatment, by assessing hydroperoxides levels using a Diacron automated method (d-ROMs test), which has proved to be clinically useful as an oxidative stress marker (5). <h3>Results</h3> Mean ROMs levels before TNFa-inhibitors were 33.2±10 mg H2O2/dL while after 24 and 52 weeks of treatment they were 29.5±7 and 29.3±9 mg H2O2/dL, respectively (P&lt;0.05). Twenty-two (55%) RA patients with active disease had high d-ROM level (&gt;32 mg H2O2/dL). After 24 and 52 weeks of anti-TNFa treatment 50% of patients reached remission/low disease status (DAS-28CRP&lt;3.2) and all these patients had low d-ROM levels (&lt;27 mg H2O2/dL). <h3>Conclusions</h3> Our result demonstrate that good disease control with anti-TNFa agents is able to reduce oxidative stress in RA patients. <h3>References</h3> Shoenfeld Y. et al. Circulation 2005;112:3337-47. Szekanecz Z. et al. Ann N Y Acad Sci 2007;1108:349-58. Cacciapaglia F. et al. Autoimmun Rev 2011;10(10):631-5. Kageyama Y. et al. Clin Exp Rheumatol. 2008;26(1):73-80. Vassalle C. et al. J Atheroscler Thromb 2012;19(8):712-7. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2556
Controversies in management: Should methionine be added to every paracetamol tablet? (Yes: but perhaps only in developing countries)
Authors: E. P Krenzelok
Journal: BMJ (1997)

The paracetamol era began in 1886 when it was recognised that acetanilide had analgesic and antipyretic properties.1 What went unrecognised for years was that acetanilide's therapeutic properties were secondary to paracetamol. The toxicity of acetanilide's other metabolite, aniline, was unacceptable, and various derivatives were synthesised to find a suitable alternative with analgesic and antipyretic properties. Phenacetin was soon recognised as a viable alternative, and paracetamol was first used for medicinal purposes in 1893.1 However, it did not become popular until 1949.1 In 1995 paracetamol sales in the United States were roughly $965m (personal communication, IMS America, Plymouth Meeting, PA 19462-1048).

To paraphrase the Swiss philosopher and physician Paracelsus: only the dose differentiates a poison from a remedy. Paracetamol is not an exception to this rule. At therapeutic doses paracetamol is relatively benign, but when it is ingested in excessive amounts endogenous hepatic glutathione is depleted and the toxic metabolite of paracetamol ( N -acetyl- p -benzoquinoneimine) binds covalently with hepatocytes causing cellular death and hepatic necrosis.2 In 1991-5 paracetamol exposure was the most common incident reported to American …
SP0114 Innate lymphoid cells and their interaction with stroma in tertiary lymphoid tissue formation
Authors: S.A. Luther
Journal: Annals of the Rheumatic Diseases (2013)

Ectopic or tertiary lymphoid tissues (TLTs) are frequently associated with sites of chronic inflammation and are thought to contribute to pathological responses. They typically contain various hematopoietic cell types including antigen-presenting dendritic cells, but also vessels (high endothelial venules and lymphatic vessels) as well as fibroblastic cell types (follicular dendritic cells and fibroblastic reticular cells) reminiscent of lymph nodes (LN) and Peyer’s patches (PP). Similar to these lymphoid organs, expression of homeostatic chemokines (CXCL13, CCL21, CCL19) and cytokines (IL-7, TNFα, LTαβ) can be often observed. Therefore it has been proposed that TLT formation may recapitulate the embryonic process of LN/PP development where a subset of innate lymphoid cells called lymphoid tissue inducer (LTi) cells interact with fibroblastic organizer cells to setup the structure which will be colonized later by lymphocytes. In contrast to LN/PP development, however, TLT formation can start anytime, at virtually any anatomical site in the adult body and is typically driven by antigen and inflammatory signals. In my lecture I plan to discuss our current understanding of the fibroblastic cell populations and the LTi-equivalents which may serve as drivers of the acute inflammation and of the transition to chronic inflammation. A better understanding of the cells and molecules involved in this process may open new avenues for therapeutic intervention aimed at resolving sites of chronic immune response. <h3>Disclosure of Interest</h3> None Declared
Non-Insulin-Dependent Diabetes Mellitus — A Genetically Programmed Failure of the Beta Cell to Compensate for Insulin Resistance
Authors: Kenneth S. Polonsky, Jeppe Sturis, Graeme I. Bell
Journal: New England Journal of Medicine (1996)

Non-insulin-dependent diabetes mellitus (NIDDM), the commonest form of diabetes, affects approximately 5 percent of the population of the United States. Although the pathophysiology of this condition has not been fully characterized and the nature of the primary defect is controversial, the results of recent studies provide insights into its basic causes. Here, we review these studies and suggest how insulin resistance and genetically programmed pancreatic beta-cell dysfunction may interact in susceptible persons to cause diabetes.Insulin ResistanceInsulin resistance is a diminished ability of insulin to exert its biologic action across a broad range of concentrations. Unless persons with insulin . . .
ABDOMINAL AORTIC ANEURYSM IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION: ITS PREVALENCE AND RISK FACTORS IN PROSPECTIVE STUDY
Authors: Yu Horiuchi, Shuzou Tanimoto, Kentaro Yasuhara, Tatsuyuki Sato, Nahoko Kato, Koichi Furui, Masaya Shinohara, Mika Watanabe, Masahiko Asami, Noriko Shiokawa, Osamu Wada, Jiro Aoki, Eiichi Tooda, Hiroyoshi Nakajima, Kazuhiro Hara, Kengo Tanabe
Journal: Journal of the American College of Cardiology (2015)
Clamping of the Umbilical Cord
Authors: Anthony E. Colozzi
Journal: New England Journal of Medicine (1954)

IT is difficult to assay the various methods of umbilical-cord clamping. Every physician employs a different technic and usually establishes a pattern that he carries out routinely in his obstetric work. At times this pattern is influenced by the equipment, the nursing situation, hospital policy in care of the newborn and various emergencies arising in the mother or the infant. Thus, in some cases, the infant is placed on the mother's abdomen while the physician attends to a bleeding episiotomy, or on a small delivery table beneath the level of the mother, with consequent delay in cord clamping. It has . . .
Late News: National Cancer Act Hailed at Kennedy Hearing
Authors: C. Vanchieri
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article Late News: National Cancer Act Hailed at Kennedy Hearing Get access Cori Vanchieri Cori Vanchieri Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 10, 15 May 1991, Page 681, https://doi.org/10.1093/jnci/83.10.681 Published: 15 May 1991
ACS Survey Finds 9% Of Cancer Patients Use Questionable Treatments
Authors: E. Taylor
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article ACS Survey Finds 9% Of Cancer Patients Use Questionable Treatments Get access Ellen Taylor Ellen Taylor Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 13, 1 July 1992, Pages 1002–1003, https://doi.org/10.1093/jnci/84.13.1002 Published: 01 July 1992
Abstract 4275: PLA2 activities in human epithelial ovarian cancer ascites
Authors: Yan Xu, Qingchun Cai, Zhenwen Zhao, Caryl J. Antalis, Libo Yan, Ali H. Hamed, Frederick B. Stehman, Jeanne M. Schilder, Giuseppe Del Priore
Journal: Cancer Research (2012)

Abstract Ascites production is characteristic of late stage human epithelial ovarian cancer (EOC) and it correlates with tumor spread clinically. However, the role of this microenvironment in cancer cells and the mechanisms by which ascites promotes tumor development are not well understood. In recent years, phospholipase A2 (PLA2) enzymes have been identified as cancer therapeutic targets focusing mainly on secreted PLA2s (sPLA2s). In this work, we optimized and validated the quantitative analytic methods to measure PLA2 activities in human EOC ascites and tissues. We found, for the first time, that both cytosolic PLA2 (cPLA2) and calcium-independent PLA2 (iPLA2), but not sPLA2 and autotaxin (ATX), activities (not their expression levels) in human EOC tissues and ascites (the tumor microenvironment) were significantly elevated. In addition, while cell-free (S1) and vesicle-free (S4) human EOC ascites had potent promoting activities in proliferation, migration, and invasion of human EOC cells, the PLA2 activities were involved and account for a significant portion of these activities. Moreover, in vivo studies demonstrated that methyl arachidonyl fluorophosphonate (MAFP, a dual inhibitor of cPLA2 and iPLA2), was highly effective in inhibiting EOC tumorigenesis/metastasis in xenograft models, supporting PLA2 activities as new targets for EOC. LPA, an enzymatic product of ATX and PLA2 enzymes, mediates a significant part of the cellular effects of ascites as evidenced by 1) LPA is produced in cell-free ascites; 2) LPA production and their sensitivities to inhibitors correlate well with the cellular effects in ascites; and 3) the cellular activities were sensitive to LPAR inhibitor and siRNA against LPARs. While cPLA2 and iPLA2 are cytosolic enzymes, our findings indicate that they are associated with cell- and microvesicle-free ascites. In summary, our work implies the potential marker and therapeutic values of PLA2 activity in ovarian cancer. 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 4275. doi:1538-7445.AM2012-4275
ASSOCIATION OF ANEMIA WTH OUTCOMES IN PATIENTS UNDERGOING PERCUTANEOUS PERIPHERAL VASCULAR DISEASE INTERVENTION: INSIGHTS FROM THE BMC2 VIC (BLUE CROSS BLUE SHIELD OF MICHIGAN CARDIOVASCULAR CONSORTIUM VASCULAR INTERVENTIONS COLLABORATIVE) REGISTRY
Authors: Nikhil Ambulgekar, Scott F. Grey, Howard Rosman, Hussein Othman, Thomas Davis, Timothy Nypaver, Peter Henke, Theodore Schreiber, Thomas LaLonde, Hitinder Gurm, Rajendra Mehta, Paul Grossman
Journal: Journal of the American College of Cardiology (2016)
A new approach to authorship: A call for change from Nigeria
Authors: Bawo O James
Journal: Journal of the Royal Society of Medicine (2012)

In Nigeria the pressure for academicians to publish or perish is intense. Limited resources mean scholars have to include heads of departments who made no contributions to scholarly work as co-authors. Researchers are compelled to do this in order to continue to secure grants, and an ‘enabling’ environment to do research. I do not see how author contributions help since we cannot state, for example, that ‘author ABC only gave permission for the study to be undertaken’. A change is needed, urgently.
Abstract 1890: Superoxide modulates tumor cell survival in response to hypoxia and metabolic stress: role of p53 status.
Authors: Valery Chavez-Perez, Mary Strasberg-Rieber, Manuel Rieber
Journal: Cancer Research (2013)

Abstract Background: Cancer cells from solid tumors become metabolically stressed, when nutrients are insufficient within poorly vascularized regions. Metabolic stress resulting from severe deprivation of glucose and serum-derived growth factors can promote cell death, partly through excessive reactive oxygen species (ROS) production. As possible sources of oxidative stress, NADPH oxidases (NOX) are centrally involved in the control of the malignant state: activated NOX enzymes use NADPH as an electron donor to reduce molecular oxygen generating superoxide anion radical (O2•−), which can act extracellularly as an autocrine/paracrine regulator or intracellularly as a signaling messenger in a variety of mammalian cells. Excessive superoxide can be dismutated to H2O2. by superoxide dismutases (SOD). Objectives: To investigate whether chemical inhibition of NOX or removal of extracellular superoxide by exogenous SOD influences tumor cell survival depending on p53 status or metabolic stress. Experimental: Genetically-matched human melanoma cells with unequal p53 mutational status were exposed to glucose or serum starvation under normoxia, physical hypoxia and/or chemical hypoxia .Differential cell survival was assesed by live-dead fluorometric assays or crystal violet staining. Mechanisms influencing response to glucose limitation were studied by specific immune blotting. Results: Lower cell proliferation under normoxia in 1 % serum was attenuated by chemically or enzymatically decreasing superoxide or by exposing them to hypoxia. Diphenylene iodonium preferentially restored the metabolic activity of mutant p53 cells in 1 % serum, whereas SOD acted preferentially on wt p53 cells under comparable conditions. Apoptosis-associated PARP cleavage under normoxia in 2.5 mM glucose and 5 % dialyzed serum was counteracted by SOD only in wt p53 cells. Cell death induced by CoCl2 preconditioning in the absence of physical hypoxia was preferential for mut p53 C8161 melanoma and reversed by SOD. Conclusions: Our results support a cytotoxic role for Nox-mediated free radical production in cancer cell death under metabolic stress, and suggests that p53 mutation increases superoxide-mediated toxicity during limitation of intracellular glucose and/ serum-derived growth factors. Citation Format: Valery Chavez-Perez, Mary Strasberg-Rieber, Manuel Rieber. Superoxide modulates tumor cell survival in response to hypoxia and metabolic stress: role of p53 status. [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 1890. doi:10.1158/1538-7445.AM2013-1890
Abstract SY08-02: Markers of caspase activation in cells and serum
Authors: James A. Wells
Journal: Cancer Research (2011)

Abstract The final and hoped for outcome for treatment with cancer drugs is selective apoptosis of cancer cells. However, despite the low response rates to cancer drugs patients do not discover this until months after treatment has begun. Apoptosis is rapid process which is often induced within 24 hours of drug treatment. The hallmark of apoptosis is the activation of caspases, cysteine proteases that are specific for cleaving target proteins after aspartic acid. We have developed a novel proteomics technology that allows us to tag and enrich for caspase-cleaved proteins during apoptosis (Mahrus et al (2008) Cell, 134, 866-876. “Global Sequencing of Proteolytic Cleavage Sites in Apoptosis by Specific Labeling of Protein N Termini”). We have been characterizing the apoptotic products of caspase cleavage in a variety of cell lines and in human serum with the view that this information can be used to monitor apoptosis during cancer drug treatment. These and other studies in a variety of cancer cell lines showed that upwards of 1000 proteins are cleaved by caspases during apoptosis. However, in any given cell line we find there are fewer than 500 targets because of differences in expression patterns between cell types. Thus, while many targets are in common from one cell line to another, many are unique. We have developed single-reaction monitoring (SRM) methods to identify these products in serum. We are beginning to identify specific apoptotic products in leukemia patients treated with various cancer drugs. These studies and the prospects for using these as apoptotic markers to assist in cancer drug treatment will be discussed. 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 SY08-02. doi:10.1158/1538-7445.AM2011-SY08-02
P359Inhibition of phosphoinositide 3-kinase gamma protects against chemotherapy-induced heart failure
Authors: M Li, A Ghigo, J Cimino, I Franco, F Morello, E Hirsch
Journal: Cardiovascular Research (2014)

Purpose: Phosphoinositide 3-kinase γ (PI3Kγ) signaling is pivotal in the regulation of myocardial contractility and remodeling. We demonstrated previously that inhibition of PI3Kγ lipid kinase activity limits cardiac inflammation and improves contractile function in pressure overload-induced heart failure. Here we intend to investigate whether PI3Kγ inhibition is beneficial in chemotherapy-induced cardiomyopathy.
Impact of universal two-dose vaccination on varicella epidemiology in Navarre, Spain, 2006 to 2012
Authors: M García Cenoz, J Castilla, J Chamorro, I Martínez-Baz, V Martínez-Artola, F Irisarri, M Arriazu, C Ezpeleta, A Barricarte
Journal: Eurosurveillance (2013)

In 2007 in Navarre, Spain, universal varicella vaccination with two doses of Varivax was introduced in the childhood immunisation schedule for children aged 15 months and three years. This study describes changes in the epidemiology of varicella in the period 2006 to 2012 and evaluates vaccination effectiveness using epidemiological surveillance data. The incidence of varicella in children aged 0 to 14 years decreased by 98.1%, from 50.1 cases per 1,000 inhabitants in 2006, to 1.0 per 1,000 in 2012. Children aged one to eight years were the vaccinated cohorts, and their incidence of varicella decreased by 98.5% (p&lt;0.0001). In unvaccinated age groups, important reductions were also achieved between 2006 and 2012: 90.5% (p&lt;0.0001) in infants under one year of age, and 89.4% (p&lt;0.0001) in children aged nine years. In the period 2006 to 2012, the hospital admissions rate for varicella or its complications decreased by 89.0%, and in 2012, there was only one admission of a newborn with neonatal varicella. Vaccine effectiveness for at least one dose was 96.8% (95% confidence interval: 96.3-97.2%). Universal vaccination with two doses has reduced varicella circulation to minimum levels within five years and has proved highly effective.
Stat Bite: Cancer Rates for U.S. Whites, 1973-1991
Authors: S. S. Devesa
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article Stat Bite: Cancer Rates for U.S. Whites, 1973–1991 Get access Susan S. Devesa, Ph.D. Susan S. Devesa, Ph.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 3, February 1995, Page 168, https://doi.org/10.1093/jnci/87.3.168 Published: 01 February 1995
227 MAGNETIC RESONANCE ELASTOGRAPHY (MRE) CAN DISCRIMINATE NORMAL VS. ABNORMAL LIVER BIOPSY IN CANDIDATES FOR LIVE LIVER DONATION
Authors: J.F. Gallegos-Orozco, A.M. Silva, Y.-H. Chang, M.J. Batheja, K.L. Hansen, L.-H. Dora, G. De Petris, E.J. Carey, B.A. Aqel, T.J. Byrne, D.D. Douglas, D.C. Mulligan, J. Rakela, A. Silva, H.E. Vargas
Journal: Journal of Hepatology (2012)
Abstract 2720: Glycosylation of Mucins Expressed in Pancreatic Adenocarcinoma
Authors: Neeley Remmers, Christy Rothermund-Franklin, Thomas Caffrey, Michael A. Hollingsworth
Journal: Cancer Research (2010)

Abstract Glycosylation of mucins expressed by pancreatic adenocarcinoma There were an estimated 42,470 new cases and 35,240 deaths due to pancreatic adenocarcinoma (PA) for 2009, ranking PA as the third leading cause of cancer related death. Virtually all long term survivors are diagnosed early but only 7% are detected in the early stages of disease thus highlighting the need for an early diagnostic test. CA19-9, the only current clinical serum-based assay used to monitor PA, detects an oligosaccharide blood group antigen Sialyl Lewisa (sLeA) with the structure (Neu5Acα2-3Galβ1-3[Fucα1-4]GlcNAc), which can be present on glycolipids or as an O-linked oligosaccharide on glycoproteins, and is expressed at relatively low levels on the surfaces of normal epithelial cells. The full spectrum of proteins on which the CA19-9 epitope is expressed has never been defined. CA19-9 is differentially expressed on mucins, which are extensively glycosylated. The CA19-9 test lacks high specificity for PA, as CA19-9 is commonly elevated in patients with benign chronic pancreatitis and other malignant diseases. Different epithelial tissues and cell types produce distinct combinations of mucin-type core proteins, and the expression patterns of these are generally altered during different disease processes including malignant transformation. Mucin expression is deregulated in cancer, which results in aberrant expression and glycosylation of mucin core proteins. We employed immunohistochemistry and immunofluorescence to show the unique mucin and glycosylation patterns seen in tissue specimens from patients diagnosed with PA. Deglycosylation of samples immunoprecipitated from cancer cell lines and pancreatic cancer patient tissue specimens was used to enable detection of mucin core proteins. Immunoaffinity chromatography was used to isolate CA19-9 from patient ascites and serum samples and mass spectrometry was used to analyze the core proteins. Results show that pancreatic cancers expressing the mucin core proteins MUC1, MUC4 and MUC5AC carry the CA19-9 epitope. Preliminary results suggest that a strategy to detect the CA19-9 tumor antigen and its cognate mucin core protein(s) will improve the performance characteristics of this assay. 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 2720.
CLINICAL OUTCOMES IN CANCER PATIENTS TREATED WITH CHEST RADIATION AND CORONARY ARTERY BYPASS GRAFT SURGERY OR PERCUTANEOUS CORONARY INTERVENTION
Authors: Erin Fender, Jackson Liang, Terence T. Sio, John Stulak, Joshua Slusser, Ryan Lennon, Abhiram Prasad, Jonathan B. Ashman, Robert Miller, Gurpreet Sandu
Journal: Journal of the American College of Cardiology (2016)