tbuckley/cabot-search huggingface dataset:
Effect of Aggressive Blood Pressure Control on the Recurrence of Atrial Fibrillation After Catheter Ablation
Authors: Ratika Parkash, George A. Wells, John L. Sapp, Jeffrey S. Healey, Jean-Claude Tardif, Isabelle Greiss, Lena Rivard, Jean-Francois Roux, Lorne Gula, Isabelle Nault, Paul Novak, David Birnie, Andrew Ha, Stephen B. Wilton, Iqwal Mangat, Christopher Gray, Martin Gardner, Anthony S.L. Tang
Journal: Circulation (2017)

Background: Radiofrequency catheter ablation for atrial fibrillation has become an important therapy for AF; however, recurrence rates remain high. We proposed to determine whether aggressive blood pressure (BP) lowering prevents recurrent atrial fibrillation (AF) after catheter ablation in patients with AF and a high symptom burden. Methods: We randomly assigned 184 patients with AF and a BP &gt;130/80 mm Hg to aggressive BP (target &lt;120/80 mm Hg) or standard BP (target &lt;140/90 mm Hg) treatment before their scheduled AF catheter ablation. The primary outcome was symptomatic recurrence of AF/atrial tachycardia/atrial flutter lasting &gt;30 seconds, determined 3 months beyond catheter ablation by a blinded end-point evaluation. Results: The median follow-up was 14 months. At 6 months, the mean systolic BP was 123.2±13.2 mm Hg in the aggressive BP treatment group versus 135.4±15.7 mm Hg ( P &lt;0.001) in the standard treatment group. The primary outcome occurred in 106 patients, 54 (61.4%) in the aggressive BP treatment group compared with 52 (61.2%) in the standard treatment group (hazard ratio=0.94; 95% confidence interval, 0.65–1.38; P =0.763). In the prespecified subgroup analysis of the influence of age, patients ≥61 years of age had a lower primary outcome event rate with aggressive BP (hazard ratio=0.58; 95% confidence interval, 0.34–0.97; P =0.013). There was a higher rate of hypotension requiring medication adjustment in the aggressive BP group (26% versus 0%). Conclusions: In this study, this duration of aggressive BP treatment did not reduce atrial arrhythmia recurrence after catheter ablation for AF but resulted in more hypotension. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT00438113.
Abstract 19721: ATF6 is Required for ANP Secretion From the Heart
Authors: Erik A Blackwood, Jungkang Jin, Khalid Azizi, Adrian Arrieta, Donna Thuerauf, Christopher Glembotski
Journal: Circulation (2016)

Introduction: Atrial natriuretic peptide (ANP) is a potent depressor hormone synthesized and stored in the heart in secretory granules of atrial myocytes as a biologically inactive precursor, pro-A...
Abstract 11427: Calcium Mobilization From Endoplasmic Reticulum Involves Calmodulin-mediated NADPH Oxidase-derived Reactive Oxygen Species Production in Porcine Aortic Endothelial Cells
Authors: Keiichi Odagiri, Akio Hakamata, Hiroshi Watanabe
Journal: Circulation (2015)

Introduction: Previous studies indicate that calcium/calmodulin (Ca 2+ /CaM) mediates the phosphorylation and activation of NADPH oxidase (NOX). In endothelial cells, elevation of intracellular Ca 2+ concentration ([Ca 2+ ] i ) level consists of two components, mobilization of Ca 2+ from intracellular stores and subsequent store-operated Ca 2+ entry (SOCE). However, little is known which component is required to regulate NOX-derived ROS production via Ca 2+ /CaM dependent pathway in endothelial cells. Hypothesis: We hypothesized that Ca 2+ mobilization from endoplasmic reticulum (ER), but not SOCE, is required to regulate NOX-derived ROS via Ca 2+ /CaM dependent pathway in porcine aortic endothelial cells (PAECs). Methods: We evaluated the association between Ca 2+ /CaM mediated NOX-derived ROS production and Ca 2+ mobilization from ER. We measured [Ca 2+ ] i by fura-2/AM a production of ROS by C-DCDHF-DA and in primary cultured PAECs with a fluorescence imaging and analysis system. Results: (1) In the presence of 1mM extracellular Ca 2+ ([Ca 2+ ] o ), BK induced a rapid increase [Ca 2+ ] i and followed by a sustained increase. However, in the absence of [Ca 2+ ] o (0mM with EGTA 1mM), BK caused only a small and transient increase [Ca 2+ ] i which was cause by Ca 2+ mobilization from ER. (2) BK (1μM) rapidly increased fluorescence intensity of C-DCDHF-DA compared with control. (150.2±51.3% and 107.2±5.6% of the baseline, respectively, p&lt;0.05). (3) BK-induced ROS production was inhibited by an inhibitor of NOX (VAS2870: 50μM) (125.5±9.9% of the baseline, respectively, p&lt;0.05). (4) When cells were exposed to BK with or without [Ca 2+ ] o , there was no difference in BK-induced ROS production. (5) In the absence of [Ca 2+ ] o , BK-induced ROS production is inhibited by an inhibitor of calmodulin (W-7: 100μM) (121.3±13.1% of the baseline, p&lt;0.05). Thapsigargin (an inhibitor of ER calcium ATPase: 1μM) and BAPTA/AM (100μM) eliminated BK-induced ROS production (110.0±5.1% and 115.7±9.5% of the baseline, respectively, p&lt;0.05 vs 1mM [Ca 2+ ] o ). Conclusions: The NOX-derived ROS production by BK is mediated via Ca 2+ /CaM dependent pathway. This was strictly regulated by Ca 2+ mobilization from ER.
Abstract 3068: Chronic alcohol exposure induces malignant transformation of pancreatic ductal epithelial cells and generates stem cell characteristics
Authors: We Yu, Yiming Ma, Sharmila Shankar, Rakesh K. Srivastava
Journal: Cancer Research (2018)

Abstract Findings from epidemiologic studies and research with experimental animal models provide insights into alcohol toxicity-related disease pathogeneses. Epidemiologic data indicate that heavy drinking is associated with high risk of pancreatic cancer. However the molecular mechanisms by which chronic ethanol exposure changes pathophysiology of human pancreatic ductal epithelial (HPNE) cells is not well understood. Cancer stem cells (CSCs) play significant role in cellular transformation, and their emergence is responsible for cancer initiation, progression and metastasis. SATB2 is required for normal mammalian development; however, it is not expressed in normal adult cells. Inappropriate activation of SATB2 gene may cause malignant cellular transformation. SATB2 regulates transcription of pluripotency maintaining factors which are required for sustaining the stem cells capacity for self-renewal. The main goal of the paper is to examine the molecular mechanisms by which chronic alcohol consumption induces cellular transformation of HPNE cells. To investigate the role of SATB2 at an early step of cell transformation, we utilized HPNE cells to generate progenitor cells either by chronic ethanol exposure or overexpression with SATB2. Our data demonstrate that chronic exposure of HPNE cells to ethanol induces cellular transformation by upregulating SATB2. Furthermore, during ethanol-induced cell transformation, cells gain the phenotype of progenitor cells / CSCs and express pluripotency maintaining factors and epithelial-mesenchymal transition (EMT) markers. Suppression of SATB2 expression in ethanol-transformed HPNE cells inhibits stemness and EMT. SATB2 is highly expressed in pancreatic cancer tissues derived from human and KrasG12D mice. In conclusion, chronic ethanol exposure may contribute in pancreatic carcinogenesis by inducing the expression of SATB2 gene. Citation Format: We Yu, Yiming Ma, Sharmila Shankar, Rakesh K. Srivastava. Chronic alcohol exposure induces malignant transformation of pancreatic ductal epithelial cells and generates stem cell characteristics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3068.
Abstract LB-011: Novel nano-formulation of paclitaxel for pancreatic cancer therapy
Authors: Bilal B. Hafeez, Andrew E. Massey, Vivek K. Kashyap, Mohammad Sikander, Advit Shetty, Mehdi Chaib, Hassan Mandil, Mohan Yallapu, Meena Jaggi, Subhash C. Chauhan
Journal: Cancer Research (2018)

Abstract Pancreatic cancer (PanCa) is one of the leading causes of cancer-related mortality in the United States due to very limited therapeutic options. Thus, there is an urgent need to develop novel therapeutic strategies for the management of this disease. Paclitaxel (PTX), a natural product derived from the Pacific Yew tree, is an agent typically used in combination therapy for PanCa. Currently, PTX nanoparticles (Abraxane®) along with gemcitabine are in use for the treatment of advanced PanCa. Herein, we have generated and characterized a novel nano-formulation of PTX comprised of PLGA core, stabilized with polyvinyl alcohol (PVA) and coated with poly-L-lysine (PLL). Dynamic light scattering (DLS) characterization indicated that the average particle size of this formulation was approximately 160 nm, and exhibited Zeta potentials of ~ -6.02 mV in 10% serum, along with an outstanding PL loading efficiency. We also evaluated the uptake mechanism of PPNPs in PanCa cells using different endocytosis inhibitors (Genistein, amiloride, nocodazole, chlorpromazine, and methyl beta cyclodextrin). Our results demonstrated that PPNPs were taken up mainly by lipid raft mediated endocytosis pathway in an energy-dependent manner. Next, we evaluated its therapeutic efficacy and underlying molecular mechanisms in human PanCa cells (HPAF-II, Panc1, and MiaPaCa-2) by performing various in vitro experiments. We first performed MTS and colony formation assays to determine the effects of free PTX and PPNPs on growth of PanCa cells. In this experiment, cells were treated with various concentrations of free PTX or abraxane, or PPNPs (2.5-160 nM) for 48 hrs. As a result, the PPNPs formulation showed more therapeutic effect over free abraxane as determined by decrease in cell proliferation and enhanced apoptosis induction in PanCa cells. PPNPs also showed a significant (P&amp;lt;0.01) inhibition in colony formation compared to free PTX. Moreover, PPNPs showed a superior inhibition of the invasive and migratory potential of HPAF-II and Panc1 as determined by commercially available kits (Invitrogen). PPNPs more effectively inhibited expression of GLI-1 and SHH as determined by qPCR and Western blot analysis. In conclusion, our findings suggest that PPNPs formulation has more anti-cancer potential than free PTX/Abraxane against PanCa and could be a novel therapeutic modality for the treatment of PanCa. Citation Format: Bilal B. Hafeez, Andrew E. Massey, Vivek K. Kashyap, Mohammad Sikander, Advit Shetty, Mehdi Chaib, Hassan Mandil, Mohan Yallapu, Meena Jaggi, Subhash C. Chauhan. Novel nano-formulation of paclitaxel for pancreatic cancer therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-011.
Anticoagulant Therapy with Dicumarol Maintained during Major Surgery
Authors: Stenmüllertz, Olestorm
Journal: Circulation (1954)

Most postoperative thromboses are probably initiated before or during surgical interventions and most of the fatal embolisms occur during the early postoperative period. As a complete prophylaxis, Dicumarol therapy was begun before, and maintained at an effective level during and after, major surgical interventions in 11 patients with a marked thromboembolic predisposition. No excessive hemorrhage, thromboembolic incidents or other unusual complications were encountered. The precautions necessary for a safe performance of the procedure are described.
Abstract 15990: Elderly Lack Fundamental Knowledge of CPR and Mobile Phone Use With Importance for Effective Dispatcher Assisted CPR Performance
Authors: PhilipCaap, Mette ANebsbjerg, Stinne ERasmussen, Lise QKrogh, KatrineBjørnshave, KristianKrogh, Jonas APovlsen, BoLøfgren
Journal: Circulation (2016)

Introduction: Early bystander cardiopulmonary resuscitation (CPR) improves survival after cardiac arrest. The most likely bystander to initiate CPR is an elderly layperson. Dispatcher assisted CPR (DA-CPR) is known to increase the rate of bystander CPR, and may be important for the elderly population in their effort to perform CPR. Multiple factors including activation of phone speaker function are important for the performance of high quality DA-CPR. The aim was to examine the knowledge on factors important to effective DA-CPR, including the use of mobile phones. Methods: A structured questionnaire containing on CPR guidelines and the use of mobile phone was distributed to laypersons over the age of 65. Responders were recruited during a 4-month period in 2014 among members of leisure clubs for seniors in Denmark. The responders’ mobile phones were identified and examined for phone speaker function. Results: The overall 124 elderly laypersons were invited to participate and 99 (response rate: 82%) questi...
Genetic and epigenetic evolution as a contributor to WT1-mutant leukemogenesis
Authors: Elodie Pronier, Robert L. Bowman, Jihae Ahn, Jacob Glass, Cyriac Kandoth, Tiffany R. Merlinsky, Justin T. Whitfield, Benjamin H. Durham, Antoine Gruet, Amritha Varshini Hanasoge Somasundara, Raajit Rampal, Ari Melnick, Richard P. Koche, Barry S. Taylor, Ross L. Levine
Journal: Blood (2018)
Abstract 16630: Clinical Predictors of Intraatrial Reentrant Arrhythmias in Adults With Congenital Heart Disease
Authors: PabloÁvila, José MaríaOliver, PastoraGallego, AnaGonzález-García, María JoséRodríguez-Puras, JoséRuíz-Cantador, AnaCampos, RafaelPeinado, RaquelPrieto, FernandoSarnago, RaquelYotti, FranciscoFernández-Avilés
Journal: Circulation (2016)

Background: Intraatrial reentrant tachycardias (IART) are a significant source of morbidity and mortality in adults with congenital heart disease (CHD). The aim of this study was to evaluate the incidence and clinical predictors of IART in a cohort of patients with CHD. Methods: We conducted a retrospective analysis of 3,311 adults (median age at entry 22.6 years, 50.6% males) with CHD (49% simple, 39% moderate and 12% complex) followed-up in a tertiary center for 37,607 person-years. Predictors of IART were identified by multivariate logistic regression. An external validation was performed in a second cohort of 1,432 patients. ROC curves were used to assess the discriminative ability of model obtained. Survival curves were constructed by Kaplan-Meier method. Results: Overall, 153 (4.6%) patients presented IART. Risk factors independently related to IART are presented in the Table. The model obtained showed excellent discrimination power (area under the ROC [AUC] curve 0.807, p<0.001) (Figure, panel A) a...
Abstract 19185: Upregulation of DJ-1 Protein after Prolonged Ischemia in a Murine Model for Myocardial Ischemia and Reperfusion
Authors: TamasSeres, JelenaKlawitter, UweChristians, TobiasEckle
Journal: Circulation (2014)

Introduction: Upregulation of cardiac DJ-1 protein might be a cardio-protective mechanism under conditions of ischemia or ischemia and reperfusion by regulating mitogen activated protein (MAP) kinases or inducing enzymes for detoxification and glutathione metabolism. We recently observed that significantly elevated DJ-1 protein expression was associated with decreased expression of phosphatase and tensin homolog (PTEN) and increased phosphorylation of the cell protective kinase AKT (protein kinase B) in human heart tissue samples from patients with chronic ischemic cardiomyopathy. Hypothesis: The expression of DJ-1 protein and its interaction with PTEN and AKT during ischemia or ischemia and reperfusion in a murine heart model might play a cardio-protective role. Methods: The level of DJ-1 was analyzed from the area at risk after 30 or 60-minute ischemia or 30-minute ischemia with 30 or 60 minutes of reperfusion using C57BL/6J mice (n=3). The changes in DJ-1 expression were correlated with the expression ...
Abstract 18542: Genetic Ablation of miR-33 Attenuates Inflammation and Reduces Abdominal Aortic Aneurysm Formation
Authors: Tetsushi Nakao, Takahiro Horie, Osamu Baba, Masataka Nishiga, Tomohiro Nishino, Hitoo Nishi, Masayasu Izuhara, Shunsuke Usami, Noriko Nakaseki, Satoshi Koyama, Yuya Ide, Takeshi Kimura, Koh Ono
Journal: Circulation (2016)

Introduction: Abdominal aortic aneurysm (AAA) pathogenesis is characterized by inflammation and matrix degradation, part of which are observed in atherosclerosis. Despite statins are only clinicall...
Abstract 647: Identification of novel and known hotspot variants in African Americans with colorectal cancer
Authors: Hassan Brim, Payaam Tavakoli, Mohammad Reza Daremipouran, Babak Shokrani, Edward Lee, Mehdi Nouraie, Adeinko O. Laiyemo, Hassan Ashktorab
Journal: Cancer Research (2018)

Abstract Background: The recent introduction of the cancer hotspot panel can help enhance targeted cancer therapy, but requires further refinement to identify which genes have significant clinical value for the population of interest. We aim to determine such genes by identifying somatic alterations in the 48 cancer gene panel in African Americans. Methods: Tumor matched normal tissues (n=16) from African American colorectal cancer patients were analyzed using a 48 hotspot cancer panel by Ion Torrent sequencing. Variants of the genes found in TruSeq Amplicon - Cancer Panel (TSACP) were identified and validated. The type of variant was determined using bioinformatic pipelines including Ensembl's Variant Effect Predictor. The genes with relevant clinical value were determined based on frequency of somatic variants and results from previous studies. Results: Somatic variants were detected in 39/48 (82%) genes. Of the 39 genes, the 7 with the most clinical value were selected for further analysis. Overall, 46 novel and known hotspot somatic variants were determined in the following 7 genes: KRAS (7/46 [15%]), NRAS (2/46 [4%]), MLH1 (1/46 [2%]), PIK3CA (8/46 [18%]), SMAD4 (6/46 [13%]), RET (9/46 [20%]), and TP53 (13/46 [28%]). Of the KRAS variants, 57% (4/7) were found in codons 12 and 13 while the other 43% (3/7) were found in codons 117 and 146. Out of the 46 somatic variants, 30% (14/46) were in hotspot regions. Of the KRAS hotspot variants, 100% (4/4) were in codons 12 and 13. The 2 NRAS variants were in codons 59 and 61. Lastly, the 9 genes without variants in our population are CDKN2A, SMARCB1, AKT1, ALK, FGFR2, IDH2, CSF1R, HNF1A and MPL. Conclusion: We have identified novel and known hotspot somatic variants in African Americans with colorectal lesions. Patients with significant hotspot variants, primarily missense alterations, had a worse prognosis. As a result, cancer gene panel hotspot profile should be taken into consideration when treating African American CRC patients. Citation Format: Hassan Brim, Payaam Tavakoli, Mohammad Reza Daremipouran, Babak Shokrani, Edward Lee, Mehdi Nouraie, Adeinko O. Laiyemo, Hassan Ashktorab. Identification of novel and known hotspot variants in African Americans with colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 647.
Totally Cloth-Covered Prostheses
Authors: Roberthodam, Albertstarr, Donraible, Herbertgriswold
Journal: Circulation (1970)

This report deals with our experience with totally cloth-covered prostheses over a 28-month period from April, 1967 to August, 1969. During this interval 223 patients were treated with an operative mortality of 11%. The earliest model cloth-covered prosthesis proved in some instances to have an excessively large transprosthetic gradient.8,9 The introduction of the composite seat design, however, has resulted in a prosthesis with very favorable hydraulic characteristics, as shown by late postoperative catheterization studies. Early follow-up data indicate that the composite seat style prostheses have a favorably low rate of thromboembolic complications. In 88 patients receiving this style valve, there have been no early emboli and only one late embolus, despite the fact that a portion of the group are not taking anticoagulants. We stress, however, that these still represent short-term observations and must stand the test of time. Until the results of the double-blind study are completed, we continue to rec...
Abstract 16055: A Decrease in Na/K ATPase Function Occurs before Changes to Calcium Handling in a Guinea-Pig Model of Progressive Heart Failure
Authors: Hung-Yen Ke, Thomas P Collins, Christina Rowlands, Kenneth T MacLeod
Journal: Circulation (2012)

Although the underlying cellular mechanisms of heart failure are gradually being better understood, the changes to these mechanisms during the progression of hypertrophy toward heart failure have n...
CD40 Ligand Mediates Inflammation Independently of CD40 by Interaction With Mac-1
Authors: AndreasZirlik, ChristophMaier, NorbertGerdes, LindseyMacFarlane, JulianaSoosairajah, UdoBavendiek, IngoAhrens, SandraErnst, NicoleBassler, AnnaMissiou, ZsofiaPatko, MasanoriAikawa, UweSchönbeck, ChristophBode, PeterLibby, KarlheinzPeter
Journal: Circulation (2007)

Background— Strong evidence supports a role for CD40 ligand (CD40L) as marker and mediator of inflammatory diseases such as atherosclerosis. Despite extensive characterization of CD40, the classic receptor of CD40L, its role in immune defense against inflammatory diseases remains uncertain. The present study aimed to characterize the contribution of CD40 signaling to atherogenesis. Methods and Results— Surprisingly, mice deficient in both CD40 and the low-density lipoprotein receptor did not develop smaller lesions in the aortic arch, root, and thoracoabdominal aorta compared with mice deficient only in the low-density lipoprotein receptor that consumed an atherogenic diet for 8 and 16 weeks. By flow cytometry, radioactive binding assays, and immunoprecipitation, we demonstrate that CD40L interacts with the integrin Mac-1, which results in Mac-1–dependent adhesion and migration of inflammatory cells as well as myeloperoxidase release in vitro. Furthermore, mice deficient in CD40L show significantly reduce...
Caveolin-1 Expression Is Critical for Vascular Endothelial Growth Factor–Induced Ischemic Hindlimb Collateralization and Nitric Oxide–Mediated Angiogenesis
Authors: PierreSonveaux, PhilippeMartinive, JulieDeWever, ZuzanaBatova, GéraldineDaneau, MichelPelat, PhilippeGhisdal, VincentGrégoire, ChantalDessy, Jean-LucBalligand, OlivierFeron
Journal: Circulation Research (2004)

Nitric oxide (NO) is a powerful angiogenic mediator acting downstream of vascular endothelial growth factor (VEGF). Both the endothelial NO synthase (eNOS) and the VEGFR-2 receptor colocalize in caveolae. Because the structural protein of these signaling platforms, caveolin, also represses eNOS activity, changes in its abundance are likely to influence the angiogenic process in various ways. In this study, we used mice deficient for the caveolin-1 gene (Cav−/−) to examine the impact of caveolae suppression in a model of adaptive angiogenesis obtained after femoral artery resection. Evaluation of the ischemic tissue perfusion and histochemical analyses revealed that contrary to Cav+/+ mice, Cav−/− mice failed to recover a functional vasculature and actually lost part of the ligated limbs, thereby recapitulating the effects of the NOS inhibitor l-NAME administered to operated Cav+/+ mice. We also isolated endothelial cells (ECs) from Cav−/− aorta and showed that on VEGF stimulation, NO production and endoth...