tbuckley/cabot-search huggingface dataset:
Abstract 1025: Optimized DZNep exposure presensitizes pancreatic cancer cells to anticancer nucleoside analogues: potential clinical implications.
Authors: Sau Wai Hung, Hardik Mody, Sean Marrache, Yangzom D. Bhutia, Franklin Davis, Jong Hyun Cho, Shanta Dhar, Chung K. Chu, Rajgopal Govindarajan
Journal: Cancer Research (2013)

Abstract We evaluated the potential of a histone methylation reversal agent 3-deazaneplanocin A (DZNep) in improving the chemosensitivity of pancreatic cancer to nucleoside analogs (i.e., gemcitabine). DZNep brought delayed but selective cytotoxicity to pancreatic cancer cells without affecting normal human pancreatic ductal epithelial (HPDE) cells. Co-exposure of DZNep and gemcitabine induced cytotoxic additivity or synergism in both well- and poorly-differentiated pancreatic cell lines. In contrast, DZNep exerted antagonism with gemcitabine against HPDE cells with significant reduction in cytotoxicity compared with the gemcitabine-alone regimen. DZNep marginally depended on purine nucleoside transporters for its cytotoxicity, but the transport dependence was circumvented by acyl derivatization. Drug exposure studies revealed that a short priming with DZNep followed by gemcitabine treatment rather than co-treatment of both agents produced a maximal chemosensitization response in both gemcitabine-sensitive and gemcitabine-resistant pancreatic cancer cells. DZNep rapidly and reversibly decreased trimethylation of histone H3 lysine 27 but increased trimethylation of lysine 9 in an EZH2- and JMJD1A/2C-dependent manner, respectively. However, DZNep potentiation of nucleoside analog chemosensitization was found to be temporally coupled to trimethylation changes in lysine 27 and not lysine 9. Polymeric nanoparticles engineered to chronologically release DZNep followed by gemcitabine produced pronounced chemosensitization and dose-lowering effects. Together, our results identify that an optimized DZNep exposure can presensitize pancreatic cancer cells to anticancer nucleoside analogs and emphasize the promising clinical utilities of histone methylation reversal agents in future pancreatic cancer combination therapies. Citation Format: Sau Wai Hung, Hardik Mody, Sean Marrache, Yangzom D. Bhutia, Franklin Davis, Jong Hyun Cho, Shanta Dhar, Chung K. Chu, Rajgopal Govindarajan. Optimized DZNep exposure presensitizes pancreatic cancer cells to anticancer nucleoside analogues: potential clinical implications. [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 1025. doi:10.1158/1538-7445.AM2013-1025
Electrophysiological effects of disopyramide and quinidine on guinea pig atria and canine cardiac purkinje fibers. Dependence on underlying cholinergic tone.
Authors: M J Mirro, A M Watanabe, J C Bailey
Journal: Circulation Research (1980)

We studied the role of the anticholinergic properties of disopyramide and quinidine in mediating the electrophysiological effects of these agents on isolated cardiac tissue.In right atria, disopyramide, quinidine, and procainamide administered alone elicited negative chronotropic responses.However, after cholinergic stimulation with physostigmine (1 X 10" 6 M), disopyramide and quinidine produced a positive chronotropic response.Procainamide, when administered under the same conditions of increased cholinergic stimulation, elicited negative chronotropic responses similar to those observed when it was given alone.In Purkinje fibers, disopyramide, quinidine, and procainamide superfused alone for 5 minutes significantly prolonged action potential duration (APD).When administered to Purkinje fibers pretreated with isoproterenol (1 x 10"' M) plus acetylcholine (3 x 10~7 M), disopyramide and quinidine shortened APD.Atropine also shortened APD of fibers exposed to both isoproterenol and acetylcholine.In these experiments, isoproterenol consistently shortened APD, and acetylcholine consistently blunted these effects of isoproterenol.Thus, disopyramide and quinidine, alone, prolong APD, but when given in the setting of increased adrenergic-cholinergic stimulation, they shorten APD.Procainamide, when administered to Purkinje fibers pretreated with isoproterenol and acetylcholine, prolongs APD as when it is administered alone.These data demonstrate that disopyramide and quinidine exert important anticholinergic electrophysiologic effects on the atria and the ventricular conducting systems.These anticholinergic effects may contribute to the antiarrhythmic and arrhythmogenic properties of these compounds.
1295 THE INSULIN-LIKE GROWTH FACTOR 2 (IGF2) mRNA BINDING PROTEIN p62/IMP2–2 ACCELERATES STEATOSIS, INFLAMMATION AND FIBROSIS IN A DIETARY MODEL OF NON-ALCOHOLIC STEATOHEPATITIS (NASH)
Authors: Y. Simon, S.M. Kessler, N. Van Roijen, J. Haybaeck, A.K. Kiemer
Journal: Journal of Hepatology (2013)
Abstract LB-140: Menin-mediated regulation of pancreatic β-cell differentiation factors
Authors: Kerong Shi, Vaishali Parekh, Swarnava Roy, Sunita K. Agarwal
Journal: Cancer Research (2011)

Abstract Pancreatic endocrine tumors occur sporadically or in familial multiple tumor syndromes such as MEN1 (Multiple Endocrine Neoplasia type 1). Biallelic loss/inactivation of the MEN1 tumor suppressor gene is only found in 20–30% of sporadic pancreatic endocrine tumors. Therefore, identification of other molecular and genetic causes of pancreatic endocrine tumorigenesis is an area of intense investigation. Because MEN1 is the main gene reported so far that affects pancreatic endocrine tumors, analyzing downstream effects of menin (MEN1 gene encoded protein) could uncover other candidate genes and pathways responsible for pancreatic endocrine tumorigenesis. During the process of endocrine pancreas development, a cascade of transcription factors under tight sequential- and temporal-regulated expression ensures normal organogenesis. Alteration of such developmental and differentiation factors could potentially lead to tumorigenesis. To study cellular transformation related to menin loss in the pancreatic β-cell, we used the mouse pancreatic β-cell line MIN6 as a model system. RNA and protein were isolated from MIN6 cells after menin knockdown or after menin over-expression as well as from their respective controls. Twelve transcription factors associated with β-cell differentiation were analyzed using QRT-PCR and western blot: Hlxb9, Hnf3β, Isl-1, MafA, MafB, NeuroD1, Ngn3, Nkx2.2, Nkx6.1, Pax4, Pax6, and Pdx1. Three different sources of menin siRNAs and four different transfection reagents were tested in time course knockdown experiments. Significant menin knockdown in MIN6 cells was observed with 74.3% ± 15.03% (n=6) knockdown efficiency at 72 hours post-transfection. For transient menin over-expression in MIN6 cells, the transfection efficiency was close to 60% (based on GFP plasmid transfection). Endogenous expression of all factors, except Ngn3, was detectable in MIN6 cells. None of the eleven transcription factors showed significantly altered RNA expression upon menin knockdown or upon menin over-expression. Western blot analyses showed 4–5 factors that were up-regulated upon menin knockdown, and down-regulated upon menin over-expression. Evolutionarily conserved promoter regions of Hlxb9, Isl-1, Nkx6.1, or Pax4 were not regulated upon menin knockdown or upon menin over-expression. These data indicate that menin could regulate some β-cell differentiation factors in a post-transcriptional manner. Mechanism of menin-mediated post-transcriptional regulation and downstream consequences on β-cell transformation and tumorigenesis is under investigation. 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-140. doi:10.1158/1538-7445.AM2011-LB-140
A rare complication of endoloop-assisted polypectomy: adhesion of snare and endoloop
Authors: Alexander Tischer, Theresia Schober, Margret Karner, Stephan Moser, Michael Schleicher, Michael Gschwantler
Journal: Endoscopy (2016)

Endoloop-assisted polypectomy may minimize the risk of bleeding after endoscopic resection of large pedunculated colorectal adenomas [1] [2] [3]. To the best of our knowledge, this is the first report of a rare complication of this technique caused by adhesion of the snare and endoloop.
THE ASSOCIATION OF REGIONAL INFLAMMATION OF THE AORTA ASSESSED BY 18F-FLUORODEOXYGLUCOSE POSITRON EMISSION TOMOGRAPHY WITH SYSTEMIC INFLAMMATORY AND ECHOCARDIOGRAPHIC INDICES IN MARFAN SYNDROME
Authors: Styliani V. Brili, Evangelos Oikonomou, Nikoletta Pianou, Alexios Antonopoulos, Emmanouil Athanasiadis, Alexandros Georgakopoulos, Gerasimos Siasos, George Spyroy, Pavlos Kafouris, Iosif Cutajar, Constantinos Anagnostopoulos, Dimitris Tousoulis
Journal: Journal of the American College of Cardiology (2016)
SAT0059 Baseline Interleukin-17A PREDICT Treatment Response to TOCILIZUMAB and Disease-Modifying Antirheumatic Drugs Therapy
Authors: S.J. Lee, M.J. Yoon, S.H. Joo, W. Park, S.H. Park, S.C. Shim, H.J. Baek, D.-H. Yoo, H.A. Kim, S.K. Lee, Y.J. Lee, Y.E. Park, H.-S. Cha, I.A. Choi, E.Y. Lee, E.B. Lee, Y.W. Song
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Tocilizumab (TCZ) has been developed and investigated in several clinical trials for efficacy and adverse events in RA patients. But it remains to be investigated which biomarkers have early predictive values. <h3>Objectives</h3> To investigate predictive cytokines of TCZ therapy in rheumatoid arthritis (RA) patients with an inadequate response to disease-modifying antirheumatic drugs (DMARDs). <h3>Methods</h3> We collected sera as part of CWP-TCZ301, a 24-week, randomized, double–blinded trial of TCZ in RA patients with an inadequate response to DMARDs. Serum levels of cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-17A, IL-21 and IL-23 were determined by luminex multiplex analysis at baseline and after treatment (4, 12 and 24 weeks). IL-6 and soluble IL-6 receptor (sIL-6R) were measured by ELISA. Therapeutic response was evaluated by American College of Rheumatology 20% improvement (ACR20) in the TCZ group (n=47) and placebo group (n=48) after 24 weeks. <h3>Results</h3> Early withdrawal patients from the study were excluded in the evaluation. In TCZ group (n=40), 29 patients were ACR20 responders and 11 patients were non-responders after 24 weeks of treatment. Baseline serum levels of IL-17A were significantly lower in responders than in non-responders (<i>p</i> &lt;0.05). However IL-17A level did not significantly change during TCZ treatment irrespective of ACR20 response. Levels of IL-21 and IL-23 were not significantly different at baseline in responders and non-responders. However, they were significantly decreased at 12 and 24 weeks in responders (all <i>p</i> &lt;0.005), but not in the non-responders. In the placebo group (n=43), 8 patients were ACR20 responders and 35 patients were non-responders after 24 weeks of treatment. Baseline serum levels of IL-17A and IL-21 in ACR20 responders were significantly lower than in non-responders (p&lt;0.001 and p=0.001, respectively). But they did not significantly change during DMARDs treatment, irrespective of ACR20 response. Multivariable logistic regression analysis showed that lower baseline IL-17A patients had increased the odds ratio of being a responder after TCZ (OR 7.364) as well as placebo (OR 9.333) treatment. <h3>Conclusions</h3> Baseline serum level of IL-17A could be used to predict response of TCZ and DMARDs therapy in RA patients. <h3>References</h3> Zhou L, Ivanov, II, Spolski R, Min R, Shenderov K, Egawa T, et al. IL-6 programs T(H)-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways. Nat Immunol 2007;8(9):967-74. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5095
Sphingolipids Implicated in Programmed Cell Death
Authors: J. Bowersox
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article Sphingolipids Implicated in Programmed Cell Death Get access John Bowersox John Bowersox Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 9, 5 May 1993, Pages 696–697, https://doi.org/10.1093/jnci/85.9.696 Published: 05 May 1993
Abstract 2644: Advanced nanoparticles with anticancer and MRI function for liver cancer in rats and rabbits
Authors: Soon-Sun Hong, Jin-Hee Maeng, Ju-Hee Lee, Myung-Joo Choi, Hyunseung Lee, Kyung Hee Jung, Jeong-Sang Lee
Journal: Cancer Research (2010)

Abstract Recently drug delivery systems are focusing on the improvement of efficacy, the reduction of side effect, and diagnostics. In the current research, we developed a novel polymeric nanoparticle (YCC) with anticancer effect as well as magnetic resonance (MR) imaging, which encapsulate doxorubicin and superparamagnetic iron oxide (Fe3O4) with the size of 86.4 nm. The efficacy of the nanoparticles was evaluated in hepatocellular carcinoma (HCC) rats induced by the treatment of diethylnitrosamine for 13 weeks as well as in rabbit model with VX2 carcinoma in the liver, comparing with free doxorubicin (FD) and a commercial liposome drug DOXIL®. Each formula was administered intravenously at a dose of 2 mg/kg as doxorubicin three times with 5 day intervals, and anticancer efficacy of YCC were confirmed by MRI (T2) and hematoxylin-eosin (H&amp;E) staining. The tumor size using MRI and the change of body weight were monitored for 10 days after the last administration of each formula. On the end of the study (Day 20th), all the formulas containing doxorubicin suppressed the tumor growth compared with the saline-treated group (control). Especially the relative tumor volume of YCC group was decreased three and four fold compared with the FD and DOXIL® group, respectively. Nevertheless, the loss of body weight as a side effect in YCC group was lower than FD or DOXIL® group. The results from Perls staining and transmission electron microscopy (TEM) confirmed that YCC was distributed in the liver, especially in tumor region rather than non-tumor region. In rabbit model with VX2 carcinoma in the liver, the relative tumor volume in YCC group was decreased two and four fold compared with the FD and DOXIL® group, respectively, as a result of MRI and tissue staining. Like in rat model, the loss of body weight as a side effect in YCC group was lower than FD or DOXIL® group. In both rat and rabbit model, YCC showed the MRI sensitivity comparable to a conventional MRI contrast agent (Resovist®) even in its lower iron content. In the immunohistochemical analysis, YCC group showed the lower expression of CD34 and Ki-67, markers of angiogenesis and cell proliferation, respectively, while apoptotic cells were significantly rich in the YCC group in terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Taken together, a novel nanoparticle YCC had anticancer efficacy better than conventional doxorubicin formulas (free doxorubicin and DOXIL®) with the function of MR imaging in rat and rabbit model with carcinoma in the liver. It was considered to a good candidate for the treatment of liver cancer monitoring the progress of the cancer using MRI. 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 2644.
Sixty seconds on . . . the digital NHS
Authors: Nigel Hawkes
Journal: BMJ (2016)

Wrong already. The NHS will be paperless by 2020, says Jeremy Hunt, health secretary for England. Printing anything is so 1980s.

Well, yes. In 2013 he said that the NHS would be paperless by 2018. The timetable’s been refined.

It’s very difficult. Don’t forget the National Programme for Information Technology, …
RISK OF HEART FAILURE AND ADVERSE CARDIOVASCULAR OUTCOMES WITH DIPEPTIDYL PEPTIDASE-4 INHIBITORS IN TYPE 2 DIABETIC PATIENTS: A META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS
Authors: Amartya Kundu, Partha Sardar, Sreeparna Ghosh, Saurav Chatterjee, Theo Meyer
Journal: Journal of the American College of Cardiology (2016)
SP0160 CAS: A Primary Care Cohort
Authors: G. Peat
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> 90% of contacts with formal healthcare services take place in primary care and osteoarthritis is the most common, disabling long-term condition seen in this setting. In this presentation the value of observational cohort studies of osteoarthritis in primary care will be critically examined using illustrative findings from a series of cohort studies undertaken in the past decade - the Clinical Assessment Studies (CAS). Of central concern is the ability to generate practice-relevant evidence consistent with the defining functions of primary care: notably, generalist, person-focussed care; the management of undifferentiated illness at first contact; and the provision of care across the lifecourse, typically at a high volume and low cost. These functions have major implications for early diagnosis and prognosis and for understanding osteoarthritis in the context of multimorbidity. The presentation concludes by looking at the prospects for routine primary care data to support meaningful observational cohort research. <h3>Disclosure of Interest</h3> None Declared
HYPOXEMIA RESULTING FROM RIGHT-TO-LEFT SHUNT THROUGH A PATENT FORAMEN OVALE WITH NORMAL PULMONARY ARTERY PRESSURES SECONDARY TO RIGHT VENTRICULAR DIASTOLIC DYSFUNCTION AND PULMONIC VALVE REGURGITATION
Authors: Varun Maheshwari, Stacy Fisher, Sunjay Kaushal
Journal: Journal of the American College of Cardiology (2016)
THU0210 Impact of Components of the Metabolic Syndrome on Knee Osteoarthritis Progression in the SEKOIA Study
Authors: F. Eymard, M. Edwards, C. Parsons, C. Cooper, F. Petit Dop, J.Y. Reginster, O. Bruyere, P. Richette, X. Chevalier
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Recent studies have suggested that components of the metabolic syndrome might be involved in the pathophysiology of knee osteoarthritis (OA). However, their impact on joint space narrowing in patients with established knee OA is unknown. <h3>Objectives</h3> We investigated the impact of each component of the metabolic syndrome on annual and 3-year joint space narrowing of medial tibiofemoral compartment. <h3>Methods</h3> 559 men and women aged over 50 years with symptomatic knee OA (K&amp;L 2-3) were recruited to the placebo arm of the SEKOIA study (98 centres; 18 countries). The presence or absence of type 2 diabetes, hypertension, and hyperlipidaemia was determined at baseline interview. Height and weight were measured and BMI calculated. Minimal medial tibiofemoral joint space on plain radiographs of the knee was assessed by two independent readers at baseline and then yearly for up to 3 years. <h3>Results</h3> The mean (SD) age of participants was 62.8 (7.5) years. A total of 43.8% had a BMI&gt;30, 6.6% had type 2 diabetes, 45.1% hypertension and 27.6% hyperlipidaemia. Those with type 2 diabetes had significantly higher joint space loss over the duration of the study than those without (0.63 and 0.35mm respectively; p=0.015). This relationship also held true for the assessment of annual joint space reduction (p=0.01). No evidence of an association was found between the remaining components of the metabolic syndrome (obesity, hypertension and hyperlipidaemia) and the joint space narrowing per year (p=0.99, p=0.49 and p=0.77 respectively) or over study duration (p=0.50, p=0.20 and p=0.28 respectively). The relationship between type 2 diabetes and both annual and 3-year joint space loss remained statistically significant after adjustment for BMI (p=0.011 and p=0.027 respectively). When sexes were examined separately, type 2 diabetes was a significant predictor of joint space loss in men but not women. <h3>Conclusions</h3> Type 2 diabetes was a predictor of the rate of joint space narrowing in individuals with established knee OA. No such relationships were found for obesity, hypertension, and hyperlipidaemia. Further studies are required to replicate these findings and to explore a biological explanation. <h3>Disclosure of Interest</h3> : F. Eymard: None declared, M. Edwards: None declared, C. Parsons: None declared, C. Cooper Consultant for: Servier, F. Petit Dop Employee of: Servier, J. Y. Reginster Grant/research support: Servier, Consultant for: Servier, O. Bruyere Consultant for: Servier, P. Richette: None declared, X. Chevalier Consultant for: Servier <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2433
Action-oriented predictive processing and the neuroeconomics of sub-cognitive reward
Authors: Don Ross
Journal: Behavioral and Brain Sciences (2013)

Abstract Clark expresses reservations about Friston's reductive interpretation of action-oriented predictive processing (AOPP) models of cognition, but he doesn't link these reservations to specific alternatives. Neuroeconomic models of sub-cognitive reward valuation, which, like AOPP, integrate attention with action based on prediction error, are such an alternative. They interpret reward valuation as an input to neocortical processing instead of reducing it.
Hyponatremia, Convulsions, Respiratory Arrest, and Permanent Brain Damage after Elective Surgery in Healthy Women
Authors: Allen I. Arieff
Journal: New England Journal of Medicine (1986)

Severe hyponatremia developed after elective surgery in 15 previously healthy women who subsequently either died or had permanent brain damage. The mean age was 41 years (range, 22 to 66), and the preoperative serum sodium level was 138 mmol per liter. All the patients recovered from anesthesia, but about 49 hours after surgery, when the average plasma sodium level was 108 mmol per liter, grand mal seizures, followed by respiratory arrest requiring intubation, developed in all 15. At that time, the urinary sodium level and the osmolality averaged 68 mmol per liter and 501 mOsm per kilogram, suggesting inappropriate secretion of antidiuretic hormone. In 10 of 15 patients, an acute cerebral vascular disorder was suspected, leading to a delay in treatment and multiple diagnostic studies, including CT scanning, cerebral angiography, and open-brain biopsies. The net postoperative fluid retention was 7.5 liters, and when correction of the serum sodium level was initiated, the rate of correction was less than 0.7 mmol per liter per hour. Histologic studies of the brain in five patients were not diagnostic, and no patient had any evidence of central pontine myelinolysis on the basis of autopsy, brain biopsy, or CT scanning. Seven patients recovered from coma after the serum sodium level was increased to 131 mmol per liter, but coma recurred two to six days later and ended in either death or a persistent vegetative state. Overall, 27 percent of the patients died, 13 percent had limb paralysis, and 60 percent were left in a persistent vegetative state.
A Specific Congenital Brain Defect (Arhinencephaly) in 13–15 Trisomy
Authors: James Q. Miller, Ernest H. Picard, Mustafa K. Alkan, Susan Warner, Park S. Gerald
Journal: New England Journal of Medicine (1963)

IT is now recognized that specific clinical syndromes ■ may be associated with certain human chromosome defects. One such chromosome abnormality is known as 13–15 trisomy, which is characterized by the presence of an extra chromosome of the 13–15, or, group.1 , 2 It has been d-cribed3 , 12 in males and females, Negroes and Cau sians. The following findings have been noted in most cases of 13–15 trisomy: cleft palate; harelip; eye defects; polydactyly; cardiac malformations; and the neurologic signs of mental retardation, seizures and probable deafness.A Caucasian male infant, who was studied at the Children's Hospital Medical Center, had 13–15 trisomy . . .