tbuckley/cabot-search huggingface dataset:
Ionic Remodeling of Cardiac Purkinje Cells by Congestive Heart Failure
Authors: Wei Han, Denis Chartier, Danshi Li, Stanley Nattel
Journal: Circulation (2001)

Background Cardiac Purkinje cells (PCs) are important for the generation of triggered arrhythmias, particularly in association with abnormal repolarization. The effects of congestive heart failure (CHF) on the ionic properties of PCs are unknown. Methods and Results PCs were isolated from false tendons of control dogs and dogs with ventricular tachypacing-induced CHF. CHF PCs were hypertrophied (capacitance, mean±SEM, 149±4 pF, n=130; versus 128±3 pF, n=150, control; P &lt;0.001). Transient outward current density was reduced in CHF PCs without change in voltage dependence or kinetics. CHF also reduced inward-rectifier current density, with no change in form of the current-voltage relationship. Densities of L- and T-type calcium, rapid and slow delayed rectifier, and Na + -Ca 2+ exchange currents were unaltered by CHF, but L-type calcium current inactivation was slowed at positive potentials. Purkinje fiber action potentials from CHF dogs showed decreased phase 1 amplitudes and elevated plateau voltages and demonstrated twice as much prolongation on exposure to the rapid delayed rectifier blocker E-4031 as control Purkinje fibers. Conclusions CHF causes remodeling of important K + and Ca 2+ currents in cardiac PCs, decreasing repolarization reserve and causing an exaggerated repolarization delay in response to a class III drug. These results have important potential implications regarding ventricular arrhythmogenesis, particularly related to triggered activity in PCs, in patients with CHF.
New susceptibility locus for coronary artery disease on chromosome 3q22.3
Authors: Jeanette Erdmann, Anika Großhennig, Peter S Braund, Inke R König, Christian Hengstenberg, Alistair S Hall, Patrick Linsel-Nitschke, Sekar Kathiresan, Ben Wright, David-Alexandre Trégouët, Francois Cambien, Petra Bruse, Zouhair Aherrahrou, Arnika K Wagner, Klaus Stark, Stephen M Schwartz, Veikko Salomaa, Roberto Elosua, Olle Melander, Benjamin F Voight, Christopher J O'Donnell, Leena Peltonen, David S Siscovick, David Altshuler, Piera Angelica Merlini, Flora Peyvandi, Luisa Bernardinelli, Diego Ardissino, Arne Schillert, Stefan Blankenberg, Tanja Zeller, Philipp Wild, Daniel F Schwarz, Laurence Tiret, Claire Perret, Stefan Schreiber, Nour Eddine El Mokhtari, Arne Schäfer, Winfried März, Wilfried Renner, Peter Bugert, Harald Klüter, Jürgen Schrezenmeir, Diana Rubin, Stephen G Ball, Anthony J Balmforth, H-Erich Wichmann, Thomas Meitinger, Marcus Fischer, Christa Meisinger, Jens Baumert, Annette Peters, Willem H Ouwehand, Panos Deloukas, John R Thompson, Andreas Ziegler, Nilesh J Samani, Heribert Schunkert
Journal: Nature Genetics (2009)
Retinoblastoma Tumor Suppressor Gene Expression Determines the Response to Sequential Flavopiridol and Doxorubicin Treatment in Small-Cell Lung Carcinoma
Authors: Tulin Budak-Alpdogan, Bobin Chen, Anjali Warrier, Daniel J. Medina, Dirk Moore, Joseph R. Bertino
Journal: Clinical Cancer Research (2009)

Small-cell lung cancers (SCLC) are defective in many regulatory mechanisms that control cell cycle progression, i.e., functional retinoblastoma protein (pRb). Flavopiridol inhibits proliferation and induces apoptosis in SCLC cell lines. We hypothesized that the sequence flavopiridol followed by doxorubicin would be synergistic in pRb-deficient SCLC cells.A H69 pRb-deficient SCLC cell line, H865, with functional pRb and H865 pRb small interfering RNA (siRNA) knockdown cells were used for in vitro and in vivo experiments. The in vivo efficiencies of various sequential combinations were tested using nude/nude athymic mice and human SCLC xenograft models.Flavopiridol then doxorubicin sequential treatment was synergistic in the pRB-negative H69 cell line. By knocking down pRb with specific siRNA, H865 clones with complete pRb knockdown became sensitive to flavopiridol and doxorubicin combinations. pRb-deficient SCLC cell lines were highly sensitive to flavopiridol-induced apoptosis. pRb-positive H865 cells arrested in G0-G1 with flavopiridol exposure, whereas doxorubicin and all flavopiridol/doxorubicin combinations caused a G2-M block. In contrast, pRb-negative SCLC cells did not arrest in G0-G1 with flavopiridol exposure. Flavopiridol treatment alone did not have an in vivo antitumor effect, but sequential flavopiridol followed by doxorubicin treatment provided tumor growth control and a survival advantage in Rb-negative xenograft models, compared with the other sequential treatments.Flavopiridol and doxorubicin sequential treatment induces potent in vitro and in vivo synergism in pRb-negative SCLC cells and should be clinically tested in tumors lacking functional pRB.
Real-Time Magnetic Resonance Imaging–Guided Endovascular Recanalization of Chronic Total Arterial Occlusion in a Swine Model
Authors: Amish N. Raval, Parag V. Karmarkar, Michael A. Guttman, Cengizhan Ozturk, Smita Sampath, Ranil DeSilva, Ronnier J. Aviles, Minnan Xu, Victor J. Wright, William H. Schenke, Ozgur Kocaturk, Alexander J. Dick, Venkatesh K. Raman, Ergin Atalar, Elliot R. McVeigh, Robert J. Lederman
Journal: Circulation (2006)

Endovascular recanalization (guidewire traversal) of peripheral artery chronic total occlusion (CTO) can be challenging. X-ray angiography resolves CTO poorly. Virtually "blind" device advancement during x-ray-guided interventions can lead to procedure failure, perforation, and hemorrhage. Alternatively, MRI may delineate the artery within the occluded segment to enhance procedural safety and success. We hypothesized that real-time MRI (rtMRI)-guided CTO recanalization can be accomplished in an animal model.
Abstract SY36-03: How aneuploidy drives tumorigenesis
Authors: Teresa Davoli, Wei Xu, Peter Park, Stephen J. Elledge
Journal: Cancer Research (2014)

Abstract Aneuploidy has been recognized as a hallmark of cancer for over 100 years, yet no general theory to explain the recurring patterns of aneuploidy in cancer has emerged. Here we describe the development of Tumor Suppressor and Oncogene (TUSON) Explorer, a computational method that analyzes the patterns of mutational signatures in tumors and predicts the likelihood that any individual gene functions as a tumor suppressor (TSG) or oncogene (OG). By analyzing &amp;gt;8200 tumor-normal pairs we provide statistical evidence suggesting many more genes possess cancer driver properties than anticipated, forming a continuum of oncogenic potential. Integrating our driver predictions with information on somatic copy number alterations, we find that the distribution and the potency of TSGs (STOP genes), OGs and essential genes (GO genes) on chromosomes can predict the complex patterns of aneuploidy and copy number variation characteristic of cancer genomes. We propose that the cancer genome is shaped through a process of cumulative haploinsufficiency and triplosensitivity. Citation Format: Teresa Davoli, Wei Xu, Peter Park, Stephen J. Elledge. How aneuploidy drives tumorigenesis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr SY36-03. doi:10.1158/1538-7445.AM2014-SY36-03
A longitudinal PRINTO study on growth and puberty in juvenile systemic lupus erythematosus
Authors: Marite Rygg, Angela Pistorio, Angelo Ravelli, Mohamad Maghnie, Natascia Di Iorgi, Brigitte Bader-Meunier, Carlos Da Silva, Rosa Roldan-Molina, Judith Barash, Cristina Dracou, Sylvie Gandon Laloum, Katerina Jarosova, Chantal Job Deslandre, Isabelle Koné-Paut, Franco Garofalo, Joseph Press, Claudia Sengler, Tsivia Tauber, Alberto Martini, Nicolino Ruperto
Journal: Annals of the Rheumatic Diseases (2011)

To obtain longitudinal data on growth/puberty in a large-scale, multi-national prospective cohort of juvenile systemic lupus erythematosus (SLE).Data from 331/557 (59.4%) patients ≤18 years old with juvenile SLE in active phase, with anthropometric data available at four follow-up visits, were studied.There was a significant reduction in parent-adjusted height z score with time in females and males (p<0.0001), with a significant gender difference (p<0.0001) and with male height being most affected. Median body mass index z score peaked at 6 months and was still significantly above baseline after 26 months (p<0.01), with no gender difference. Standardised height reduction was inversely related to age at onset. Females with onset age <12 years had a median parent-adjusted height z score of -0.87 with no catch-up growth. At the end of the study, growth failure was seen in 14.7% of the females and 24.5% of the males. Height deflection (less than -0.25/year) was found in 20.7% of the females and 45.5% of the males. Delayed pubertal onset was seen in 15.3% and 24% of the females and males, respectively, and delayed/absent menarche was seen in 21.9%, while 36.1% of the females and 44% of the males had some degree of delayed pubertal development. Growth failure baseline determinants were previous growth failure (OR: 56.6), age at first visit ≤13.4 years (OR: 4.2) and cumulative steroid dose >426 mg/kg (OR: 3.6).The children at risk of having a negative effect on height and pubertal development are prepubertal and peripubertal children treated with >400 mg/kg cumulative dose of corticosteroids.
Aire-dependent production of XCL1 mediates medullary accumulation of thymic dendritic cells and contributes to regulatory T cell development
Authors: Yu Lei, Adiratna Mat Ripen, Naozumi Ishimaru, Izumi Ohigashi, Takashi Nagasawa, Lukas T. Jeker, Michael R. Bösl, Georg A. Holländer, Yoshio Hayashi, Rene de Waal Malefyt, Takeshi Nitta, Yousuke Takahama
Journal: The Journal of Experimental Medicine (2011)

Dendritic cells (DCs) in the thymus (tDCs) are predominantly accumulated in the medulla and contribute to the establishment of self-tolerance. However, how the medullary accumulation of tDCs is regulated and involved in self-tolerance is unclear. We show that the chemokine receptor XCR1 is expressed by tDCs, whereas medullary thymic epithelial cells (mTECs) express the ligand XCL1. XCL1-deficient mice are defective in the medullary accumulation of tDCs and the thymic generation of naturally occurring regulatory T cells (nT reg cells). Thymocytes from XCL1-deficient mice elicit dacryoadenitis in nude mice. mTEC expression of XCL1, tDC medullary accumulation, and nT reg cell generation are diminished in Aire-deficient mice. These results indicate that the XCL1-mediated medullary accumulation of tDCs contributes to nT reg cell development and is regulated by Aire.
Programmed death ligand-1 expression in adrenocortical carcinoma: an exploratory biomarker study
Authors: André P Fay, Sabina Signoretti, Marcella Callea, Gabriela H Telό, Rana R McKay, Jiaxi Song, Ingrid Carvo, Megan E Lampron, Marina D Kaymakcalan, Carlos E Poli-de-Figueiredo, Joaquim Bellmunt, F Stephen Hodi, Gordon J Freeman, Aymen Elfiky, Toni K Choueiri
Journal: Journal for ImmunoTherapy of Cancer (2015)

<h3>Background</h3> Adrenocortical carcinoma (ACC) is a rare tumor in which prognostic factors are still not well established. Programmed Death Ligand-1 (PD-L1) expression in ACC and its association with clinico-pathological features and survival outcomes are unknown. <h3>Methods</h3> Formalin-fixed paraffin-embedded (FFPE) specimens were obtained from 28 patients with ACC. PD-L1 expression was evaluated by immunohistochemistry (IHC) in both tumor cell membrane and tumor infiltrating mononuclear cells (TIMC). PD-L1 positivity on tumor cells was defined as ≥5% tumor cell membrane staining. TIMC were evaluated by IHC using a CD45 monoclonal antibody. For PD-L1 expression in TIMC, a combined score based on the extent of infiltrates and percentage of positive cells was developed. Any score greater that zero was considered PD-L1 positive. Baseline clinico-pathological characteristics and follow up data were retrospectively collected. Comparisons between PD-L1 expression and clinico-pathological features were evaluated using unpaired t-test and Fisher's exact test. Kaplan-Meier method and log-rank test were used to assess association between PD-L1 expression and 5-year overall survival (OS). <h3>Results</h3> Among 28 patients with surgically treated ACC, 3 (10.7%) were considered PD-L1 positive on tumor cell membrane. On the other hand, PD-L1 expression in TIMC was performed in 27 specimens and PD-L1 positive staining was observed in 19 (70.4%) patients. PD-L1 positivity in either tumor cell membrane or TIMC was not significantly associated with higher stage at diagnosis, higher tumor grade, excessive hormone secretion, or OS. <h3>Conclusions</h3> PD-L1 expression can exist in ACC in both tumor cell membrane and TIMC with no relationship to clinico-pathologic parameters or survival.
Effects of Tadalafil Treatment on Erectile Function Recovery Following Bilateral Nerve-sparing Radical Prostatectomy: A Randomised Placebo-controlled Study (REACTT)
Authors: Francesco Montorsi, Gerald Brock, Jens-Uwe Stolzenburg, John Mulhall, Ignacio Moncada, Hitendra R.H. Patel, Daniel Chevallier, Kazimierz Krajka, Carsten Henneges, Ruth Dickson, Hartwig Büttner
Journal: European Urology (2013)
Will a Healthy Lifestyle Help Prevent Alzheimer's Disease?
Authors: Sandra K. Pope, Valorie M. Shue, Cornelia Beck
Journal: Annual Review of Public Health (2003)

Alzheimer's disease (AD) appears to resemble other chronic diseases, whereby a myriad of interconnected factors, including those associated with lifestyle, are involved in disease development. In this paper, we examine accepted and proposed risk factors for AD and explore health behaviors, including diet, exercise, prevention of injury, and cognitive stimulation, that may help prevent AD. Adherence to a healthy lifestyle may directly protect against AD or may prevent diseases associated with AD, such as vascular disease and diabetes. A healthy lifestyle to prevent AD may be important throughout life rather than after disease manifestation and may be particularly relevant if other factors, such as genetic predisposition, also increase risk of AD. If changes in lifestyle can help prevent AD by reducing modifiable risk factors, this knowledge can aid individuals who wish to take action to protect themselves and their families from the disease.
Cholesteryl Ester Synthesis in Normal and Atherosclerotic Aortas of Rabbits and Rhesus Monkeys
Authors: Peter I. Brecher, Aram V. Chobanian
Journal: Circulation Research (1974)

The formation of cholesteryl ester in aortic tissue was studied using subcellular fractions from normal and atherosclerotic rabbit and rhesus monkey aortas. The properties of two enzyme systems capable of esterifying 1- 14 C-oleic acid into cholesteryl ester in vitro were investigated, and increased activity was demonstrated for both systems as a result of cholesterol feeding. Microsomal preparations were used to study the ATP, CoA-dependent esterification which involves two enzymes, fatty acyl CoA synthetase and fatty acyl CoA: cholesterol acyltransferase. The properties of both enzymes were investigated, and an increase of about fourfold in activity of the acryltransfrease was demonstrated in aortic microsomes as a result of cholesterol feeding for 3-6 months. Esterification of oleic acid into cholesteryl ester by aortic high-speed supernatant fractions at an acidic pH was also observed; the enzyme system involved did not require cofactors, and its activity greatly increased as a result of cholesterol feeding. Similar increases in the activity of both esterifying enzyme systems were found when normal and atherosclerotic rhesus monkey aortic fractions were compared. p -Chlorophenoxyisobutyrate (CPIB) and 2-methyl-2-[ p -(1, 2, 3, 4-tetrahydro-l-naphthyl)-phenoxy]propionic acid (TPIA) produced inhibition of both cholesterol-esterifying enzyme systems. TPIA was a more effective inhibitor than CPIB on both enzyme systems by at least an order of magnitude. These studies suggest that increased intracellular synthesis of cholesteryl ester by aortic tissue may contribute to its accumulation in atherosclerosis.
Core Components of Cardiac Rehabilitation/Secondary Prevention Programs: 2007 Update
Authors: Gary J. Balady, Mark A. Williams, Philip A. Ades, Vera Bittner, Patricia Comoss, JoAnne M. Foody, Barry Franklin, Bonnie Sanderson, Douglas Southard
Journal: Circulation (2007)

The American Heart Association and the American Association of Cardiovascular and Pulmonary Rehabilitation recognize that all cardiac rehabilitation/secondary prevention programs should contain specific core components that aim to optimize cardiovascular risk reduction, foster healthy behaviors and compliance to these behaviors, reduce disability, and promote an active lifestyle for patients with cardiovascular disease. This update to the previous statement presents current information on the evaluation, interventions, and expected outcomes in each of the core components of cardiac rehabilitation/secondary prevention programs, in agreement with the 2006 update of the American Heart Association/American College of Cardiology Secondary Prevention Guidelines, including baseline patient assessment, nutritional counseling, risk factor management (lipids, blood pressure, weight, diabetes mellitus, and smoking), psychosocial interventions, and physical activity counseling and exercise training.
DNA Microarrays Are Predictive of Cancer Prognosis: A Re-evaluation
Authors: Xiaohui Fan, Leming Shi, Hong Fang, Yiyu Cheng, Roger Perkins, Weida Tong
Journal: Clinical Cancer Research (2010)

The reliability of microarray-based cancer prognosis is questioned by Michiels et al. They reanalyzed seven studies published in the prominent journals as successful stories of microarray-based cancer prognosis and concluded that the originally reported assessments are over optimistic. We set to investigate the reality of microarrays for predicting cancer prognosis by using the same data sets with commonly accepted data analysis approaches.Michiels et al.'s analysis protocol used a correlation-based feature selection method, split sample validation, and a nearest-centroid rule classifier. We examined their results through systematically replacing their analysis approaches with other commonly used methods as a parameter study. In addition, we applied a widely accepted permutation test in conjunction with 5-fold cross-validation to verify Michiels et al.'s findings.The stability of signature genes is likely obtained when a fold change-based feature selection method is applied. When cross-validation procedures are used to replace Michiels et al.'s split sample validation, only one of the seven studies yielded uninformative classifiers. The permutation test reveals that the confidence interval based on the split sample used in the Michiels et al.'s review is not a rigorous and robust approach to assess the validity of a classifier.We concluded that the use of DNA microarrays for cancer prognosis can be demonstrated. We also stressed that caution should be exercised when a general conclusion is withdrawn based on a single statistical practice without alternative validation, which can leave a false impression and pessimistic perspective for emerging biomarker methodologies to advance cancer research.
Cutaneous inflammatory cell infiltrate in chronic idiopathic urticaria: Comparison of patients with and without anti-FcϵRI or anti-IgE autoantibodies
Authors: Ruth A. Sabroe, Eric Poon, Guy E. Orchard, David Lane, David M. Francis, Robert M. Barr, Martin M. Black, Anne Kobza Black, Malcolm W. Greaves
Journal: Journal of Allergy and Clinical Immunology (1999)
Angiotensin II-forming pathways in normal and failing human hearts.
Authors: H Urata, B Healy, R W Stewart, F M Bumpus, A Husain
Journal: Circulation Research (1990)

Reduced preload and afterload to the heart are important effects of angiotensin converting enzyme (ACE) inhibitors in the treatment of congestive heart failure. However, since angiotensin II (Ang II) directly increases the strength of myocardial contraction, suppression of Ang II formation by ACE inhibitors could potentially reduce the beneficial effects of Ang II on the failing heart. To study how ACE inhibition suppresses cardiac Ang II formation in man, we characterized ACE-dependent and ACE-independent Ang II-forming pathways in eight normal and 24 failing human hearts obtained at cardiac transplantation. Ang II-forming activity in left ventricular (LV) membrane preparations was assessed by measuring the conversion of [125I]angiotensin I (Ang I) to [125I]Ang II. LV [125I]Ang II-forming activity in normal hearts (35.5 +/- 2.7 fmol/min/mg, n = 8) was not different from that in hearts from patients with ischemic cardiomyopathy (25.5 +/- 2.9 fmol/min/mg, n = 9) and was 48% lower (p less than 0.001) in hearts from patients with idiopathic cardiomyopathy (18.5 +/- 1.9 fmol/min/mg, n = 15).(ABSTRACT TRUNCATED AT 250 WORDS)
Pulmonary toxicity of recombinant interleukin-2 plus lymphokine-activated killer cell therapy
Authors: F Villani, M Galimberti, M Rizzi, R Manzi
Journal: European Respiratory Journal (1993)

The aim of the present investigation was to evaluate lung toxicity in 15 patients affected by metastatic melanoma of different sites, and treated with recombinant interleukin-2 (rIL-2) plus lymphokine-activated killer (LAK) cells The treatment regimen included a first and a second course of rIL-2, separated by four consecutive daily leukaphereses. Autologous LAK cells were reinfused during the second course. Lung function was monitored before and after each rIL-2 administration. In the 12 patients who could be followed until completion of the therapy, spirometric parameters and transfer factor of the lungs for carbon monoxide (TLCO) decreased significantly during the first rIL-2 course, remained stable during leukapheresis, and declined significantly further during the second rIL-2 course. In the second phase, chest radiography documented some degree of pulmonary oedema, ranging from interstitial oedema to frank pulmonary oedema. A significant dose-dependent correlation was found between the cumulative rIL-2 dose and the decline in TLCO in the first course of therapy. Moreover, patients who developed symptomatic respiratory insufficiency (World Health Organisation grade III or IV) during the second course of therapy received a higher number of LAK cells than those who did not. The data support the hypothesis that LAK cells have an additional toxic effect on the lung.
Physical activity is independently related to aerobic capacity in cystic fibrosis
Authors: H. Hebestreit, S. Kieser, S. Rüdiger, T. Schenk, S. Junge, A. Hebestreit, M. Ballmann, H-G. Posselt, S. Kriemler
Journal: European Respiratory Journal (2006)

It is unclear whether a relationship between physical activity (PA) and maximal oxygen uptake (V'(O2,max)) exists in cystic fibrosis (CF) and, if so, whether the relationship reflects a direct effect or is mediated by the effects of confounding variables, such as pulmonary or muscle function. The objective of the present study was to determine the relationship between PA and V'(O2,max) in CF while adjusting for possible influences of confounding factors. In total, 36 female and 35 male patients with CF from Germany and Switzerland (aged 12-40 yrs, forced expiratory volume in one second (FEV1) 25-107% predicted) were studied. A Wingate test was employed to measure muscle power. PA was monitored for 7 days and expressed in two ways: 1) average daily accelerometer count (ADAC) and 2) time spent in moderate-to-vigorous PA (MVPA). V'(O2,max) was determined during an incremental cycle exercise test to volitional fatigue. PA was positively related to V'(O2,max). In a multiple linear regression analysis, height, sex, FEV1, muscle power and ADAC (additionally explained variance 2.5%) or time spent in MVPA (additionally explained variance 3.7%) were identified as independent predictors of V'(O2,max). In conclusion, high levels of physical activity in addition to good muscular and pulmonary functions are associated with a high aerobic capacity in cystic fibrosis.