tbuckley/cabot-search huggingface dataset:
Abstract 17973: Chronic Fcγ Receptor II Stimulation by Immunization Leads to Dilated Cardiomyopathy
Authors: Lars R Herda, Carina Müller, Lars G Eckerle, Yvonne Reinke, Stephan B Felix
Journal: Circulation (2010)

Introduction:  Cardiotropic autoantibodies have been described in dilated cardiomyopathy (DCM). These antibodies can induce negative inotropic effects in cardiomyocytes by binding to the respective antigen via the Fab-part or by binding to Fcγ receptors. This study aimed to evaluate the role of activation by direct immunization against the Fcγ receptor II in the development of dilated cardiomyopathy.   Methods:  10 Lewis rats, age 4–6 weeks, were actively immunized by subcutaneous injection of an Fcγ receptor II peptide or vehicle and followed up by echocardiography. Isolated cardiomyocytes were cultured with IgG and Fcγ receptor II antibodies. Western blotting was performed to assess the phosphorylation status of Akt. Cellular contractility was measured in cardiomyocytes by field-stimulation using a video-imaging edge detector system.   Results:  In contrast to control animals, actively immunized rats developed an increased level of Fcγ receptor II-antibodies after one month (1320ng/ml vs.    Conclusions:  In this experimental setting, immunization against the Fcγ receptor II induces left ventricular dilatation and dysfunction. Activation of this receptor therefore seems to be involved in antibody-mediated DCM. Negative inotropy in this model might be mediated by reduced activation of AKT.
Abstract 187: Preshock Pause Intervals and Rearrest After Resuscitation from Out-of-Hospital Cardiac Arrest
Authors: Allison C Koller, David Salcido, James J Menegazzi
Journal: Circulation (2011)

Background: Loss of pulses after successful return of spontaneous circulation (ROSC) during resuscitation from out-of-hospital cardiac arrest (OHCA) is known as re-arrest (RA). Recent studies have provided estimates of the rate occurrence of re-arrest - as high as 38% -, but the causes and characteristics of RA are not yet fully understood. One plausible contributor to RA is the pre-shock pause (PSP) interval - the time interval between the last chest compression and a defibrillating shock - which has been shown to predict survival to hospital discharge. Objective: Measure the PSP time interval in cases of OHCA with and without RA in order to: a) provide an estimate of the PSP in cases with RA, and b) compare the PSP of cases with RA to cases without PSP. Methods: Case data for emergency medical services (EMS)-treated OHCA were obtained from the Pittsburgh site of the multi-center Resuscitation Outcomes Consortium (ROC) and were part of a previously identified dataset (n = 113) used to compare ECG characteristics of RA cases to those without RA. A subset of these cases was identified that received at least one shock during treatment by EMS. Time-coded impedance, compression force, compression depth, or audio recordings accompanying each ECG trace were used to calculate the PSP to the nearest second for each shock in each case. The PSP for shocks that followed ROSC without preceding compressions were calculated as the interval between loss of pulses and the shock. All other PSP were calculated as the difference between the time of the final pre-shock compression and shock delivery. The kruskal-wallis test was used to compare the medians of RA and no-RA PSP with an alpha level of 0.05. Results: Fifty-six cases were identified with at least 1 EMS-delivered defibrillating shock. Of these, 27 (48%) cases had at least one instance of RA. For a total of 159 shocks in both RA and no-RA groups, the median (IQR) PSP was 16s (12.75). The median (IQR) PSP for the RA group (n = 101) was 16s (14), while the median (IQR) PSP for the no-RA group (n = 58) was 14s (11). The median PSP of RA and no-RA groups were not significantly different (p = 0.15). Conclusion: The PSP for EMS-treated cases of OHCA with RA had a median duration of 16s. In this limited study, PSP were not different between groups with and without RA.
Abstract 3639: The Potent Angiogenic Factor Periostin Accelerates Degeneration and Sclerosis of the Cardiac Valve Complex
Authors: Daihiko Hakuno, Naritaka Kimura, Tokuhiro Kimura, Shinsuke Yuasa, Mitsushige Murata, Shinji Makino, Motoaki Sano, Yasunori Okada, Ryohei Yozu, Akira Kudo, Satoshi Ogawa, Keiichi Fukuda
Journal: Circulation (2008)

We previously reported that chondromodulin-I (chm-I) is expressed in cardiac valves and maintains valvular function by preventing angiogenesis. Periostin has spliced isoform; it promotes embryonic valvulogenesis and left ventricular remodeling. However, its role in valvular heart disease (VHD) remains unknown. [Methods] (1) RT-PCR, quantitative PCR, Western blot, and immunostaining with periostin were performed in mouse and rat cardiac valves. (2) Human normal (n=8, 52.1 years in average) or degenerated (n=22, 63.0 years) cardiac valves were obtained from autopsied or surgical specimens with bicuspid, atheroscle-rotic, and rheumatic VHD. Immunostaining with periostin, chm-I, vWF, and VEGF and von Kossa stains was performed. (3) Tube formation assay and migration assay with a modified Boyden chamber using human endothelial cells were performed to investigate whether it had angiogenic or angioinhibitory activity. (4) Phenotype of wild type (WT) or periostin gene targeting (KO) mice fed with 4 months normal or high fat (HF) diet (n=6 each) was analyzed by 30 MHz echocardiography. [Results] (1) Periostin was specifically expressed at all cardiac valves and annuli from 10.5 dpc embryo to adult in the rodent heart. (2) RT-PCR revealed the shift from long to short periostin isoform after birth in mouse heart. (3) Periostin was observed at the subendothelial superficial layer, while chm-I was seen at the core layer of human normal cardiac valves, their expressions being mutually exclusive. (4) Interestingly, the periostin-positive area was markedly increased by 4-fold in the thickened degenerative valves, where the increased capillary density, VEGF expression, and calcium deposition was also observed. (5) Stimulation with recombinant periostin augmented the tube formation and increased the migrated cell number by 81% and 73%, respectively. (6) Echocardiography revealed that aortic valve thickness was increased, and the hyperechoic area in valve annuli suggesting calcification was significantly increased in WT+HF; it was reduced in KO+HF. The hyperechoic area in AV annulus: 0.38 / 0.88 / 0.61 mm 2  in WT / WT+HF / KO+HF. [Conclusions] Periostin is a potent angiogenic factor and markedly accelerates degeneration and sclerosis of the cardiac valve complex.
Abstract 13089: Serum Soluble ST2 as a Biomarker for Detecting Heart Failure with a Normal Ejection Fraction in Hypertensive Patients
Authors: Yi-Chih Wang, Chih-Chieh Yu, Fu-Chun Chiu, Juey-Jen Hwang, Ling-Ping Lai, Chia-Ti Tsai, Jiunn-Lee Lin
Journal: Circulation (2011)

Background. Serum soluble ST2 is a novel diagnostic and prognostic marker for patients (pts) with heart failure (HF) and left ventricular (LV) systolic dysfunction. However, its application to HF w...
Abstract 3674: Active Wnt Signaling in Cardiac Response to Injury
Authors: Martinus I Oerlemans, Marie-Jose Goumans, Hans Clevers, Pieter A Doevendans, Joost P Sluijter
Journal: Circulation (2009)

Objectives. After myocardial infarction (MI), injured myocardium is replaced by scar tissue leading to cardiac remodeling. Endogenous repair in vivo via activation of resident cardiac progenitor ce...
Breaks without bruises
Authors: D. Eastwood
Journal: BMJ (1998)

Papers p (p 1117) 

Everyone knows what constitutes a bruise, and most people understand what a fracture is. The Shorter Oxford English Dictionary defines a bruise as “a breaking, a breach, an injury to the body causing discolouration but not laceration,” and Stedman's Medical Dictionary simply describes a fracture as “a break.” As both bruises and fractures are concerned with breaks, it would be logical to assume that they invariably occur together. Colloquially, orthopaedic surgeons describe a fracture as “a soft tissue injury complicated by a break in the bone.” However, the reason this definition arose was because, all too often, the intimate link between the bone and its soft tissue surrounds was forgotten as the soft tissue injury, while undoubtedly present, was not visible to the naked eye. Bruising is thus …
Abstract 13944: Incomplete Revascularization in Patients With Acute Myocardial Infarction Who Underwent Percutaneous Coronary Intervention Predicts Heart Failure During One-Year Clinical Follow-Up
Authors: Min Chul Kim, Youngkeun Ahn, Myung Ho Jeong, Jong Hyun Kim, Shung Chull Chae, Young Jo Kim, Seung Ho Hur, In Whan Seong, Taek Jong Hong, Myeong Chan Cho, Chong Jin Kim, Ki Bae Seung, Yang Soo Jang, Seung Woon Rha, Jang Ho Bae, Seung Jung Park
Journal: Circulation (2010)

Introduction:  There has been controversy that total revascularization in patients with acute myocardial infarction (AMI) has efficacy in preventing heart failure.   Hypothesis:  We investigated the clinical outcomes of incomplete revascularization in patients with AMI who had remnant critical coronary stenosis.   Methods:  A total of 1,899 patients with AMI who had not heart failure and underwent percutaneous coronary intervention (PCI) in a nationwide prospective Korea AMI Registry (KAMIR) from November 2005 to January 2008 were divided into two groups by a presence of remnant critical coronary stenosis (≥70% diameter stenosis in three epicardial arteries). Group I had one or more remnant lesions (n=696, 73.1% male, 62.4±11.6 years) and group II did not have any remnant lesions (n=1203, 77.2% male, 59.1±11.8 years). All patients were evaluated by baseline and follow-up 2-dimensional echocardiography to determine ejection fraction (EF) during follow-up periods (mean 207.6±81.9 days). End-points were new symptomatic heart failure (NYHA class ≥2) with EF less than 40%, death or re-MI, and re-PCI during one-year clinical follow-up.   Results:  Group I had more atherosclerotic risk factors and showed higher admission creatinine level (≥1.3 mg/dL). During PCI, drug-eluting stents were more implanted in group I (94.3% vs. 91.5%, p = 0.029) and more peri-procedural cardiogenic shock was developed in group I. End-points occurred in 327 patients (17.3%) during one-year follow-up. In multi-variate analysis, remnant coronary lesion was an independent predictor of new heart failure (hazard ratio [HR] 1.68, 95% confidence interval [CI] 1.03 to 2.82, p = 0.037) and re-PCI (HR 1.94, 95% CI 1.47 to 2.57, p    Conclusions:  We should consider more aggressive revascularization strategy in patients with AMI to prevent development of new heart failure.
Abstract 15147: Increased ER Stress is a Fundamental Mechanism for Impairment of Cardioprotective Signaling in Type 2 Diabetes
Authors: Hidemichi Kouzu, Takahito Itoh, Takayuki Miki, Masaya Tanno, Toshiyuki Yano, Tatsuya Sato, Akifumi Takada, Daisuke Sunaga, Tetsuji Miura
Journal: Circulation (2010)

Background: Recently, we found two mechanisms that impair cardioprotective signaling in a rat model of obese type 2 diabetes (T2DM), OLETF: up-regulation of calcineurin activity and increased ER st...
Abstract 1712: The P2Y <sub>12</sub> Antagonist Cangrelor and the GP IIb/IIIa Blocker Abciximab Reduce Platelet-Mediated Myocardial Injury After Ischemia and Reperfusion
Authors: Jose A Barrabes, Javier Inserte, Maribel Mirabet, Adoracion Quiroga, Victor Hernando, Jaume Figueras, David Garcia-Dorado
Journal: Circulation (2008)

Objective: Platelets activated during experimental acute myocardial infarction (AMI) contribute to myocardial injury. We aimed to investigate whether platelets from patients with AMI increase myocardial damage after transient ischemia in isolated rat hearts and the modification of this effect by the P2Y 12 receptor antagonist cangrelor and the GPIIb/IIIa receptor blocker abciximab. Methods: Platelets were obtained from 9 AMI patients (7 thrombolyzed, all on aspirin) within 24 h after symptom onset. Incubation with 100 μM cangrelor or 50 μg/ml abciximab resulted, respectively, in 78 ± 4 and 90 ± 2% inhibition of aggregation (optical aggregometry). Isolated rat hearts (four simultaneous experiments per patient) were subjected to 40 min of global ischemia and 60 min of reperfusion. Hearts received no additional intervention (Control) or were infused during the 5 min prior to ischemia with platelets (22.5x10 6 /min), either untreated or treated with cangrelor or abciximab. Results: P-selectin expression (flow cytometry) in isolated platelets before infusion was 31 ± 3% (P = NS between groups). Platelets augmented myocardial injury, as demonstrated by worse left ventricular developed pressure (LVDevP), higher left ventricular enddiastolic pressure (LVEDP) and coronary resistance, and greater LDH release and infarct size (TTC staining), and both cangrelor and abciximab greatly attenuated these effects (Table ). Conclusions: Activated platelets from patients with AMI increase myocardial injury after ischemia and reperfusion, and cangrelor and abciximab attenuate this effect. The results support the notion that very early antiplatelet treatment may increase myocardial salvage by direct effects on the microcirculation in these patients.
Abstract P163: Immediate Extracorporeal Cardiopulmonary Resuscitation Can Provide Better Neurological Outcomes In Patients With Out-of-hospital Cardiac Arrest
Authors: Mamoru Hase, Nobuaki Kokubu, Hidemichi Kouzu, Satoshi Nara, Shinya Shimoshige, Satoshi Yuda, Akiyoshi Hashimoto, Kazufumi Tsuchihashi, Tetsuji Miura, Yasufumi Asai, Kazuaki Shimamoto
Journal: Circulation (2009)

OBJECTIVES: The purpose of this study was to evaluate the clinical effects of extracorporeal cardiopulmonary resuscitation (ECPR) for the out-of-hospital cardiac arrest (OHCA) patients having diffi...
IMiDs® Immunomodulatory Agents Regulate Interferon-Stimulated Genes through Cereblon-Mediated Aiolos Destruction in Multiple Myeloma (MM) Cells: Identification of a Novel Mechanism of Action and Pathway for Resistance
Authors: Courtney G. Havens, Chad Bjorklund, Jian Kang, Maria Ortiz, Celia Fontanillo, Michael Amatangelo, Ling Lu, Paola E. Neri, Antonia Lopez-Girona, Nizar J. Bahlis, Anjan Thakurta, Mathew Trotter, Anita K. Gandhi, Anke Klippel, Rajesh Chopra
Journal: Blood (2014)
Abstract 3445: Notch1 Represses Bmp-Dependent Aortic Valve Calcification in a Cell-Autonomous Manner
Authors: Vishal Nigam, Deepak Srivastava
Journal: Circulation (2008)

Calcific aortic stenosis is the third leading cause of adult heart disease and the most common form of acquired valvular disease in developed countries. However, the molecular pathways leading to calcification are poorly understood. We recently reported two families in which heterozygous mutations in NOTCH1 that resulted in premature stop codons caused bicuspid aortic valve and severe calcification of the aortic valve. Notch1 is a part of a highly conserved signaling pathway involved in cell fate decisions, cell differentiation, and cardiac valve formation. We found that mice heterozygous-null for Notch1 had over four-fold more aortic valve calcification compared to age and sex matched littermates (p&lt;0.03). To determine what cell type is involved in the Notch1 related calcification, Notch1+/− bone-marrow was transplanted into wild-type mice. Six months after transplant, there was no difference in the amount of aortic valve calcification between the recipients of Notch1+/− bone-marrow versus recipients of control bone-marrow. In contrast, cultured sheep aortic valve interstitial cells (AVICs) treated with a chemical inhibitor of Notch signaling developed over five-fold more calcification (p&lt;0.03). We found that expression of Bmp2, which has been implicated in human aortic valve disease, was 3-fold higher in aortic valve leaflets of Notch1+/− mice compared to wild type littermates (p&lt;0.02). Furthermore, AVICs treated with the Notch inhibitor had increased Bmp2 protein levels and siRNA-mediated knock-down of Bmp2 expression in the AVICs blocked the calcification process induced by Notch inhibition. These findings suggest that Notch1 signaling within aortic valve cells is required for repression of Bmp2-dependent calcification pathways and may provide novel approaches to inhibit the progression of calcific aortic stenosis.
Abstract 2831: Endomyocardial-to-Epimyocardial Blood Flow Ratio Distinguishes Severity of Coronary Artery Disease: A Perfusion CMR Study
Authors: Amit R Patel, Patrick F Antkowiak, Kiran R Nandalur, Vishal Arora, Christopher M Kramer, Frederick H Epstein
Journal: Circulation (2008)

Background: Ischemia propagates as a wave front from the endocardial (ENDO) to the epicardial (EPI) surface. Normally, myocardial blood flow (MBF) is higher in the ENDO than EPI. We hypothesized that the ENDO/EPI ratio could differentiate the severity of coronary stenoses in a clinical patient population. Methods: Perfusion CMR was performed in 29 patients within 30 days of x-ray angiography and quantitative coronary analysis. During adenosine infusion and at rest, dual boluses of Gd-DTPA were infused (4ml/s) to quantify arterial input function (0.0075mM/kg) and tissue perfusion (0.075mM/kg) in 3 short axis slices using hybrid gradient echo/echo planar imaging. ENDO and EPI MBF for rest and stress were estimated by determining the peak amplitude of the impulse response derived from Fermi function deconvolution. Stress and rest ENDO/EPI ratios were calculated and then corrected (corr) for rate-pressure product (RPP) using the formula ENDO/EPI * (SBP*HR*10 −4 ). Results: Coronary stenosis (CS) &gt;50% was present in 23 of 29 patients. Hypertension, diabetes, and dyslipidemia were present in 23, 9, and 26 patients, respectively. Stress corrENDO/EPI (mean±SE) was inversely related to CS (CS&lt;50% = 1.356 ± 0.030, CS 50–70% = 1.266 ± 0.029, and CS&gt;70% = 1.149 ± 0.039; p&lt;0.05) (Figure ). The relationship persisted after exclusion of the 56 segments with a myocardial scar (p&lt;0.05). No relationship existed between CS and rest ENDO/EPI, rest corrENDO/EPI, or uncorrected stress ENDO/EPI. Conclusions: Stress corrENDO/EPI is inversely related to the severity of CS. Quantitative stress endo/epi ratios can distinguish intermediate from severe stenoses in patients with known or suspected CS.
Abstract 19842: Laparoscopic Gastric Bypass Surgery and Adjustable Gastric Banding Significantly Improves Cardiometabolic Disease Risk Among Morbidly Obese Multiethnic Adolescents
Authors: Nestor de la Cruz-Munoz, Gabriela Lopez-Mitnik, Kristopher Arheart, Alan Livingstone, Erick Frono, Tracie Miller, Steven E Lipshultz, Sarah E Messiah
Journal: Circulation (2010)

Background: Extreme obesity and the associated co-morbidities continue to be major health issues in the United States and disproportionally affect ethnic minority adolescents. Surgical intervention...
Abstract 291: Association of Single Nucleotide Polymorphisms in Inflammatory Candidate Genes with Circulating Inflammatory Biomarker Concentrations: The Framingham Heart Study
Authors: Renate Schnabel, Kathryn L Lunetta, Martin G Larson, Josée Dupuis, John F Keaney, Izabella Lipinska, Diddahally R Govindaraju, Joel N Hirschhorn, Sekar Kathiresan, James B Meigs, Douglas S Lee, Christopher J O’Donnell, Christopher Newton-Cheh, Ming-Huei Chen, Zhenming Zhao, Jian Rong, Patrice Sutherland, Ramachandran S Vasan, Emelia J Benjamin
Journal: Circulation (2007)

Background : Chronic subclinical inflammation is a prominent feature of atherosclerotic disease. The genetic background for this pro-inflammatory state is not well-established. Circulating biomarker concentrations have become attractive candidates to measure disease activity and prognosis. Methods : We examined 2356 single-nucleotide polymorphisms (SNPs) in 235 inflammatory pathway genes in association with 11 circulating inflammatory biomarkers in about 1800 Framingham Offspring cohort participants [CD40 ligand, CRP, intercellular adhesion molecule-1, interleukin-6 (IL6), urinary isoprostanes, monocyte chemoattractant protein-1 (MCP1), myeloperoxidase, P-selectin, tumor necrosis factor alpha, tumor necrosis factor receptor-2, fibrinogen]. We created residuals of log transformed biomarker concentrations adjusting for 16 potential confounders. Only SNPs with call rate ≥0.98 and HWE p&gt;0.01, which had at least 5 minor allele carriers entered analyses. False discovery rate (FDR) and q-value methods were applied. Results : We observed similar results with FDR and q-value methods. A total of 45 associations were significant at a cutoff q value of 0.25. The top SNPs were observed in the SELP gene in association with P-selectin concentrations (rs6136 [nonsynonymous], p= 5.17*10 −39 , rs3753305 [intronic], p= 6.17*10 −9 ) and the ICAM1 gene in relation to ICAM-1 concentrations (rs1799969 [coding-nonsynonymous], p= 1.32*10 −8 ). Lowest p-values for trans-acting SNPs were observed for APCS (rs1374486 [function unknown], p= 1.01*10 −7 , and rs6695377 [function unknown], p= 1.85*10 −7 ) with MCP-1 concentrations and for IL6R (rs8192284 [coding-nonsynonimous,intronic], p= 3.36*10 −5 ) with IL6 concentrations. In addition, we could replicate reported findings for rs1799969, and rs5498 in the ICAM-1 gene in relation to ICAM-1 concentrations as well as associations of SNPs rs2857654, rs1024611, and rs2857657 in the CCL-2 gene with MCP-1 concentrations. Conclusions : The results of this candidate gene approach support the relevance of genetic variation for circulating inflammatory biomarker traits. Some former findings were confirmed and novel potential candidates are reported. Our findings merit replication in other cohorts.
Abstract 58: Locating AEDs in an Urban City: A Geospatial View
Authors: Raina Merchant, Heather M Griffis, Alison C Leung, Kirkland N Lozada, Olivia B Saynisch, Jeremy M Asch, Frances S Shofer, Larry M Starr, John C Hershey, Shawndra Hill, Graham Nichol, David A Asch, Lance B Becker
Journal: Circulation (2012)

Background: Survival from out-of-hospital cardiac arrest (OHCA) is poor and varies by geography. Variability in AED locations may be a contributing factor, but this is understudied. As publically accessible AEDs are more likely to be in commercial rather than residential areas, we sought to determine AED density in a large urban city relative to population and employment demographics. Methods: This was a retrospective analysis of MyHeartMap, a prospective cohort of AEDs in Philadelphia County. Geographic and population characteristics were obtained from US census and Local Employment Dynamics (LED) data by zipcode. Census characteristics included number of residents, percent of residents with a high school degree or above, median household income, and percent of African Americans. LED characteristics included total number of jobs reported, percent of jobs requiring a high school degree or above, percent of jobs with an annual income above $40,000, and percent of African Americans in jobs. Multivariate regression models using a Poisson distribution related the distribution of AEDs to population and employment characteristics using commercially available geographical information systems (GIS) software (ArcGIS Redlands CA) Results: AED locations (n=1295) and density per zip code (range 2-179) varied across the city. Population and employment characteristics were significantly related to the number of AEDs per zipcode (p&lt;0.001) [R-square=0.38 and 0.74, respectively]. The incident rate ratio (IRR) for AED density was higher in zipcodes with higher-education (1.10, p&lt;.01) and lower in zipcodes with more African American residents (0.99, p&lt;.01). Regarding employment characteristics, the IRR for AEDs was higher in zipcodes with jobs requiring a higher education (1.03, p&lt;.01) and jobs with higher income (1.04, p&lt;.01) and lower in zipcodes with more African American employees (0.99, p&lt;.01). Conclusions: Significantly fewer AEDs were located in areas with lower socioeconomic status. Employment characteristics better explained this variation across zipcodes. A more thorough study of this variability is important as optimizing the placement of AEDs in public areas may help to increase OHCA survival.