tbuckley/cabot-search huggingface dataset:
Abstract 3954: Changes in Subunit Composition of AMPK in the Developmental and Diseased Hearts
Authors: Maengjo Kim, Mei Shen, Soeun Ngoy, Ronglih Liao, Rong Tian
Journal: Circulation (2009)

AMP-activated protein kinase (AMPK) is a heterotrimeric complex composed of catalytic  α -subunit and regulatory  β - and  γ -subunits with multiple isoforms for each subunit. Recently, point mutations in the regulatory  γ 2-subunit have been shown to cause glycogen storage cardiomyopathy in humans suggesting an unique role of  γ 2-AMPK in the heart. Thus, knowledge of subunit composition of the AMPK will provide important insights into the understanding of the AMPK function in the intact heart, and will ultimately benefit the pharmacological targeting of AMPK. Using antibodies specific to each subunit isoform, we determined the protein expression pattern of AMPK subunit isoforms during cardiac development as well as during the progression of cardiac hypertrophy to failure in mouse and human hearts. In mouse developmental hearts, AMPK was highly expressed in the fetal stage and fell ~2-fold to adult expression level after birth. In hypertrophied and failing hearts, we found that the expression levels of  β -subunit shifted from  β 1 (2-fold down) to  β 2 (2–3 fold up) in both mice and humans. However, in failing mouse hearts the  γ 2-subunit increased by 2.5 fold while the human failing hearts switched to  γ 1 isoforms ( γ 1 8.8 fold up and  γ 2 5.7 fold down, p α 2-AMPK accounts for 78% of total AMPK activity with the  α 1-AMPK accounts for the remaining (22%) activity. In human hearts, however,  α 1 and  α 2 complexes each account for 50% of the total AMPK activity. These results demonstrate that isoform composition of AMPK subunit in the heart changes during both physiological and pathological conditions. There are significant differences in the isoform-specific activity of AMPK between mice and humans. These observations provide a basis for future development of organ-selective strategies for AMPK activation.
Characterization QAW039 and QAV680, two novel, potent and selective CRTh2 antagonists
Authors: Liz Willard, Zarin Brown, Charles Owen, Gerald Dubois
Journal: European Respiratory Journal (2014)

Introduction 

QAW039 is an oral, selective, competitive and reversible CRTh2 receptor antagonist. The present study aims to provide a detailed pharmacological characterisation of QAW039 and QAV680 (two potent and selective CRTh2 antagonists).

Methods 

Antagonist properties such as potency, selectivity and functional activity of QAW039 and QAV680 were characterized through various pharmacology assays [radio ligand binding, cAMP functional assay, eosinophil shape change (ESC) and Th2 cytokine production].

Results 

QAW039 and QAV680 are sub-nM antagonists at the human CRTh2 receptor with an affinity (Ki) of 4.7 and 29 nM respectively. Both compounds are highly selective for CRTh2 receptors, potent inhibitors of ESC, and effectively found to inhibit PGD2- induced IL-3 and IL-5 production from human peripheral blood Th2 cells (Table).

View this table:



Conclusion 

QAW039 showed superior potency compared to QAV680 with minimal drop off in whole blood eosinophil shape change assay compared to QAV680 (1.9 vs 15-fold). The efficacy of QAW039 is currently being evaluated clinically in moderate-to-severe asthma patients.
Controversies in Management: Should carotid endarterectomy be purchased? Treatment avoids much morbidity
Authors: R. N Baird
Journal: BMJ (1995)

These were those trusts that were deemed to have land and buildings surplus to their requirements and were expected to dispose ofthem.Accordingly, it is now apparent that trusts are actually subject to very tight monitoring and direction.This is effected through controls applied to the three traditional statements of account: the balance sheet; the income and expenditure account; and the funds flow statement.In addition, there exists the potential for a further tightening of the screw in that if a trust turns out to be particularly profitable-earning over and above the 6% return on capital employed-it can be required to pay dividends on its public dividend capital.The trust regime is a good illustration of how NHS accounting practice is increasingly following what has been common practice in the world of industry and commerce.It is probably the major item currently on the agenda of NHS financial management and it is, of course, an issue of financial accounting.
Weak link found between power lines and leukaemia
Authors: Zosia Kmietowicz
Journal: BMJ (2001)

The United Kingdom's national radiation watchdog has ruled out electricity power lines as a possible cause of cancer in adults but admits that a “weak association” exists with childhood leukaemia.

An advisory group of the National Radiological Protection Board has reviewed recent evidence that links exposure to magnetic fields and cancer risk in epidemiological studies from around the world.

Included in the analysis are findings from the UK childhood cancer study, the world's largest case-control study on the causes of childhood cancer, which could find no link. About half of all the studies that were reviewed, however, point to the possibility of a weak link with power lines.

The Advisory Group on Non-ionising Radiation, which is chaired by Sir Richard Doll from the Imperial Cancer Research Fund's Cancer Studies Unit, Oxford, concluded that any risk relates to relatively high exposure to power lines, which affects about 0.5% of UK homes.

ELF Electromagnetic Fields and the Risk of Cancer by the Advisory Group on Non-ionising Radiation is available from the NRPB, price £30 (tel 01235 822742).
CD4 Cross-Linking (CD4XL) Induces RAS Activation and Tumor Necrosis Factor-α Secretion in CD4+ T Cells
Authors: Seetha M. Lakshmi Tamma, Narendra Chirmule, Hirosuka Yagura, Naoki Oyaizu, Vaniambadi Kalyanaraman, Savita Pahwa
Journal: Blood (1997)
Foreign body; same clinic-different diagnosis
Authors: Aykut Eliçora, Serife Tuba Liman, Salih Topçu, Asli Gül Akgül, Seymur Salih Mehmetoglu, Tülay Hosten
Journal: European Respiratory Journal (2011)

Foreign body aspiration is a serious condition with risk of mortality. It happens at all ages but mostly at childhood. Chest x-ray can demonstrate the foreign body if it is radioopaque. But laterally and oblique chest graphies must seen for the exact diagnosis with its size and localization. We report two cases admitted with same symptoms indicate to foreign body but different final diagnosis.   Case 1:  A 1.5-year old child with Down syndrome was admitted to emergency clinic of our hospital with cough, wheezing and stridor. There was a history suitable for a foreign body aspiration and no any other significant history. Chest x-ray demonstrated an opasity similar to a foreign body. We performed a rigid bronchoscopy. There was no foreign body in his tracheobronchial system. Thereby esophagoscopy was performed under scopy. Again there was no foreign body although the image was suitable to a foreign body. In the postoperative period with a more detailed investigation it was understood that the radiological opasity was an endovasculary stent set up with angiography to carry on PDA for another cardiac disease treatment.   Case 2:  A 7-year old child was admitted to our hospital with persisting cough, wheezing and stridor. Clinical history and chest x-ray demonstrated a foreign body similar to the first case. Rigid bronchoscopy was performed and a metallic foreign body (pencil bow) is extracted from left main bronchus.  History takes a great role in diagnosis of foreign body aspiration. Radiological investigation must perform to all suspected cases. Although a chest x-ray demonstrate mostly atelectasis and hyperaeration at the affected side a normal graphy can not eliminate the foreign body. If the suspicion persists we must apply bronchoscopy.
Systematic Reviews: Obtaining data from randomised controlled trials: how much do we need for reliable and informative meta-analyses?
Authors: M J Clarke, L A Stewart
Journal: BMJ (1994)

Many randomised controlled trials compare treatments that will produce only moderate differences in outcome, but these differences can be clinically important. However, they are difficult to assess reliably and require a large amount of randomised evidence. This can be achieved through large prospective randomised trials which will accrue future patients, the meta-analysis of results from randomised trials involving patients from the past, or--ideally--both. The techniques require that all possible biases are minimised, and in meta-analyses this can best be achieved by ensuring that all of the randomised evidence--both trials and participants in those trials--is included. The meta-analysis of individual patient data has been described as the gold standard for this approach. It will remove many of the problems associated with relying solely on published data and some of the problems arising from a reliance on aggregate data, and will also add to the analyses that can be performed. Such projects, however, require considerable time and effort.
Batf3 maintains autoactivation of Irf8 for commitment of a CD8α+ conventional DC clonogenic progenitor
Authors: Gary E Grajales-Reyes, Arifumi Iwata, Jörn Albring, Xiaodi Wu, Roxane Tussiwand, Wumesh Kc, Nicole M Kretzer, Carlos G Briseño, Vivek Durai, Prachi Bagadia, Malay Haldar, Jörg Schönheit, Frank Rosenbauer, Theresa L Murphy, Kenneth M Murphy
Journal: Nature Immunology (2015)
Abstract 3428: Plaque Fibrous Cap Macrophage Density and the Peripheral White Cell Count Predict the Presence of Thin-cap Fibroatheroma: an Intravascular Optical Coherence Tomography Study
Authors: O C Raffel, Guillermo J Tearney, Denise A DeJoseph Gauthier, Elkan F Halpern, Brett E Bouma, Ik-Kyung Jang
Journal: Circulation (2006)

Background: Histopathological data suggest most acute coronary events occur due to disruption of inflamed thin-cap fibroatheroma (TCFA). White blood cells (WBC) are important mediators of inflammat...
Abstract 2871: Saddle-Shaped Annuloplasty Reduces Mitral Leaflet Stress: A Real-Time 3D Echocardiographic Study
Authors: Aaron S Blom, Chun Xu, Liam P Ryan, Benjamin Jackson, Landi M Parish, Thomas J Eperjesi, Joseph H Gorman, Robert C Gorman
Journal: Circulation (2008)

Objectives: High leaflet and chordal stresses contribute to recurrent mitral regurgitation after repair procedures. We hypothesized that a saddle-shaped annuloplasty ring would reduce leaflet stress compared to a similarly sized flat annuloplasty ring. To test this hypothesis we used a novel 3D echocardiographically-based finite element modeling (FEM) technique for quantifying regional mitral valve stress. Methods: Real-time 3D echocardiography was performed in 8 sheep before and after placement of either a 30mm flat annuloplasty (n=4) or a 30mm saddle-shaped annuloplasty. Full-volume data sets of the MV were obtained using an IE33 platform(Philips Medical Systems, Andover, Massachusetts) and exported to Cardio-View (Tomtec Imaging Systems, Munich, Germany) for image analysis. Individual leaflet data were then interpolated using Matlab (The Mathworks, Natick, Massachusetts). Triangulated leaflet surfaces were extracted and the data imported into a commercial finite element program (ABAQUS/Explicit 6.3, HKS Inc. Pawtucket, RI) to quantify regional stress distributions in all segments (P1, P2, P3 and A1, A2, A3) of the MV. Results: Peak anterior and posterior leaflet stresses after flat annuloplasty placement were 0.20±0.001MPa and 21±0.02MPa. Peak anterior and posterior leaflet stress after saddle-shaped annuloplasty placement was 0.19±0.02MPa and 13±0.01MPa (p&lt;0.05 for the posterior leaflet stresses) Conclusions: Saddle-shaped annuloplasty design results in greater stress reduction in the posterior leaflet than standard flat annuloplasty rings and may, therefore, result in more durable repairs. This research has received full or partial funding support from the American Heart Association, AHA Great Rivers Affiliate (Delaware, Kentucky, Ohio, Pennsylvania &amp; West Virginia).
Effect of all-trans retinoic acid on procoagulant and fibrinolytic activities of cultured blast cells from patients with acute promyelocytic leukemia
Authors: V De Stefano, L Teofili, S Sica, S Mastrangelo, A Di Mario, S Rutella, P Salutari, C Rumi, G d'Onofrio, G Leone
Journal: Blood (1995)
Gadolinium-Induced Fibrosis
Authors: Derrick J. Todd, Jonathan Kay
Journal: Annual Review of Medicine (2016)

Gadolinium-based contrast agents (GBCAs), once believed to be safe for patients with renal disease, have been strongly associated with nephrogenic systemic fibrosis (NSF), a severe systemic fibrosing disorder that predominantly afflicts individuals with advanced renal dysfunction. We provide a historical perspective on the appearance and disappearance of NSF, including its initial recognition as a discrete clinical entity, its association with GBCA exposure, and the data supporting a causative relationship between GBCA exposure and NSF. On the basis of this body of evidence, we propose that the name gadolinium-induced fibrosis (GIF) more accurately reflects the totality of knowledge regarding this disease. Use of high-risk GBCAs, such as formulated gadodiamide, should be avoided in patients with renal disease. Restriction of GBCA use in this population has almost completely eradicated new cases of this debilitating condition. Emerging antifibrotic therapies may be useful for patients who suffer from GIF.
Cytogenetic-Specific Heterogeneity in the Kinetics of Minimal Residual Disease (MRD) Clearance in Childhood Acute Lymphoblastic Leukaemia (ALL).
Authors: Anthony V. Moorman, Sue M. Richards, Jerry P. Hancock, Chris D. Mitchell, Ajay J. Vora, Christine J. Harrison, Nick J. Goulden
Journal: Blood (2007)
Abstract 3712: A Randomized Placebo-Controlled Trial of a Conjugate Nicotine Vaccine (NicVAX®) in Smokers Who Want to Quit: 12 Month Results
Authors: Stephen I Rennard, Douglas E Jorenby, David Gonzales, Nancy A Rigotti, Arjen de Vos, Enoch B Bortey, Roxanne Akhavain, Dorothy K Hatsukami
Journal: Circulation (2007)

Background: Cigarette smoking triples the risk of dying from heart disease among middle-aged men and women. A nicotine vaccine (NicVAX®) has been developed to produce nicotine-specific antibodies as a means of reducing entry of nicotine into the brain as an aid to smoking cessation. Objective: To assess 12-month safety, efficacy and immunogenicity of NicVAX in smokers who want to quit. Method: Randomized, double-blinded, placebo-controlled multicenter clinical trial with 2 dose levels of NicVAX (200μg &amp; 400μg) and 2 schedules. Generally healthy adults who smoked ≥ 15 cigarettes/day were recruited. Subjects were randomized 2:1, active:placebo, at 9 sites in the US. The primary endpoint was self reported continuous abstinence for weeks 19 – 26 confirmed by expired CO levels of ≤ 8 ppm. Secondary endpoints include point prevalence abstinence at 12 months. Results: 301 subjects (52% female) with a mean age of 48, smoking on average 24 cigarettes/day were enrolled. A pre-defined analysis of antibody levels for subjects receiving NicVAX were reviewed and divided into low and high responder groups, with the top 30 th percentile representing the high responder group. Analysis for the primary endpoint demonstrated that 15/61 (24.6%) of subjects having the highest antibody titers achieved an 8 week period of continuous abstinence between weeks 19 –26, compared to 13/100 (13.0%) for the subjects who received placebo (p=0.04). In contrast, the quit rate for those subjects that did not achieve a high antibody titer was not significantly different from placebo (14/140, 10%). There was a significant relationship between anti-nicotine antibody levels and continuous abstinence from smoking (p=0.0001). NicVAX was well-tolerated and showed no differences in adverse events or in local/systemic reactions between placebo and each active vaccine group. Conclusion: Proof-of-concept has been established by the strong correlation of high antibody titers with smoking abstinence. Interim data (6 months post vaccination) demonstrate that generating antibodies to nicotine may be a useful approach for aiding smoking cessation. This study will be completed in Sept 2007. Immunogenicity, sustained smoking cessation and relapse rates at 12 months after vaccination will be presented.
Genetic variability of wild-type measles viruses, circulating in the Russian Federation during the implementation of the National Measles Elimination Program, 2003–2007
Authors: S.V. Shulga, P.A. Rota, J.R. Kremer, M.A. Naumova, C.P. Muller, N.T. Tikhonova, E.N. Lopareva, T.A. Mamaeva, O.V. Tsvirkun, M.N. Mulders, G.Y. Lipskaya, A.G. Gerasimova
Journal: Clinical Microbiology and Infection (2009)
Advances in oncologic imaging
Authors: Oguz Akin, Sandra B. Brennan, D. David Dershaw, Michelle S. Ginsberg, Marc J. Gollub, Heiko Schöder, David M. Panicek, Hedvig Hricak
Journal: CA A Cancer Journal for Clinicians (2012)

Imaging has become a pivotal component throughout a patient's encounter with cancer, from initial disease detection and characterization through treatment response assessment and posttreatment follow-up. Recent progress in imaging technology has presented new opportunities for improving clinical care. This article provides updates on the latest approaches to imaging of 5 common cancers: breast, lung, prostate, and colorectal cancers, and lymphoma.
Abstract 2445: Comparison of Atrial Fibrillation Ablation Strategies for Paroxysmal patients presenting to the Electrophysiology Laboratory In atrial fibrillation
Authors: Luigi Di Biase, Claude S. Elayi, Chi Keong Ching, Richard Hongo, Steven Hao, Salwa Beheiry, Chia-Tung Wu, Dimpi Patel, Mohamed Kanj, Atul Verma, Oussama M. Wazni, Luciana Armaganijan, Kai Sonnie, Mohammed Kanj, Gemma Pelargonio, Antonio Dello Russo, Michela Casella, Pietro Santarelli, Domenico Potenza, Casa sollievo della Sofferenza, Raimondo Massaro, Casa Sollievo della Sofferenza, Jennifer E. Cummings, Walid I. Saliba, Yaariv Khaykin, Mauricio Arruda, Andrea Natale
Journal: Circulation (2007)

BACKGROUND : Whether different ablation strategies affect paroxysmal atrial fibrillation (AF) termination mode and long term cure is unclear. We compared the effect of different ablation strategies on the AF termination and long term success in patients with parox-AF presenting to the electrophysiology laboratory in AF. METHODS : One hundred and three (103) consecutive patients with parox-AF scheduled for AF ablation presenting in the lab in AF were selected for this study. The patients were randomized to PVAI only (35 pts) versus bi-atrial ablation of the complex fractionated atrial electrograms (CFAE defragmentation) including the coronary sinus (34 pts) versus CFAE followed by PVAI (34 pts) Modes of AF termination were: conversion to SR, organization into AT or persistence of AF requiring cardioversion following ablation. RESULTS are summarized below: There was no significant difference between the groups in term of sex, age, AF duration, LA size and EF. Follow up after a single procedure with AAD is summarized below CONCLUSION : Defragmentation alone had the smallest impact on both acute AF termination and one year follow-up cure rate. No difference in terms of acute and chronic success was seen between PVAI alone and PVAI asoociated with defragmentation. This suggests that PV isolation is critical to cure AF in paroxysmal AF and that adjunctive strategies have minimal impact on cure rate and should not be considered in all patients.
Incidence and risk factors of EBV related post transplant lymphoproliferative diseases in paediatric liver transplant recipients treated with tacrolimus.
Authors: Etienne Sokal, Claire Beguin, Raymond Reding, Monique Bodéus, Pierre Wallemacq, Jean-Bernard Otte, H Antunes, Jd. Degoyet, M. Janssen, Jean-Paul Buts
Journal: Hepatology (1997)
Pro-adrenomedullin, procalcitonin and CRP levels to predict bacterial pneumonia in patients admitted to emergency room
Authors: Alicia Lacoma, Cristina Prat, Pere Tudela, Montse Giménez, Aida Ramirez, Josep Maria Mòdol, Jose Dominguez, Vicente Ausina
Journal: European Respiratory Journal (2011)

Objectives:  To assess if MR-proADM, PCT and CRP levels can distinguish bacterial pneumonia from other kind of lower respiratory tract infections (LRTI).   Methods:  Patients with fever and respiratory symptoms that were admitted in emergency room (ER) and from whom blood cultures were drawn. After retrospective analysis, patients were classified as: pneumonia (n=85), chronic obstructive pulmonary disease (COPD) exacerbation (n=25) and bronchial infection (n=52). Four patients were admitted to ICU and 9 died.   Results:  PCT showed significantly higher levels in pneumonia when comparing with COPD exacerbation (p=0.003) and bronchial infection (p=0.002). CRP only showed significantly higher levels when comparing pneumonia group vs bronchial infection (p=0.002). Finally, MR-proADM showed statistical higher levels when comparing pneumonia group with COPD exacerbation (p=0.014) and bronchial infection (p=0.006). PCT and MR-proADM showed significantly higher levels in cases of definite bacterial diagnosis in comparison to other cases (pneumonia of probable bacterial or unknown origin, COPD exacerbations and bronchial infections) (p=0.017 and p=0.004). PCT and MR-proADM are significantly higher in patients admitted to ICU (p=0.011 and p=0.001). Regarding mortality, no significant differences were found.   Conclusions:  PCT and MR-proADM show significantly higher levels in pneumonia in comparison to other lower respiratory tract infections.  PCT and MR-proADM levels are increased in confirmed bacterial infections.  Biomarkers measurement can be helpful for the management of patients admitted in ER with clinical symptoms of respiratory tract infection.
Should we essentially ignore the role of stimuli in a general account of operant selection?
Authors: Rick A. Bevins
Journal: Behavioral and Brain Sciences (2001)

The selectionist account of behavior is actually a focused discussion of operant selection. To this end, the authors essentially exclude stimuli from their analysis. This exclusion is inconsistent with the importance placed on environmental interaction in their general account. Further, this exclusion limits the generality of their account by missing important sources of stimulus-elicited behavior (e.g., classical conditioning).