tbuckley/cabot-search huggingface dataset:
Abstract 1432: Cardiomyocyte Myostatin Contributes to Skeletal Muscle Wasting in Heart Failure
Authors: Joerg Heineke, Mannix Auger-Messier, Michelle Sargent, Allen York, Stephen Welle, Jeffery D Molkentin
Journal: Circulation (2008)

Introduction: Skeletal muscle wasting during heart failure constitutes a major therapeutic challenge. The TGFβ superfamily member myostatin is a negative regulator of skeletal muscle growth. For example, elimination of myostatin (MSTN) in adult mice through an inducible Cre/lox recombination strategy has been shown to increase skeletal muscle mass by about 25%. Previous studies identified skeletal muscle and to a lesser extent cardiac and fat tissue as the source of MSTN production in the body. MSTN is produced as a precursor protein, which has been suggested to constitute the main reservoir of the protein in skeletal muscle. In mouse serum, however, MSTN is abundantly present in its mature form, which consists of the C-terminal fragment of the precursor protein. Results: We detected high levels of the mature MSTN protein (MM) in the mouse myocardium by western blotting. Interestingly, MM was significantly upregulated in the myocardium of mice subjected to long-term myocardial pressure overload (TAC, 12 weeks; protein levels: sham 100±22% vs. TAC 218±18%, p&lt;0.01). In contrast, MM was barely detectable in mouse skeletal muscle. Immunhistochemical staining confirmed enhanced cardiomyocyte MSTN production after TAC. To determine the impact of cardiomyocyte MSTN on skeletal muscle growth during heart failure, we crossed cardiomyocyte specific Nkx2.5-Cre mice with mice in which the MSTN exon3 was flanked by loxp sites to eliminate expression of mature MSTN selectively in cardiomyocytes (CKO mice). While CKO mice did not have significant changes in skeletal muscle mass after a sham operation (e.g. quadriceps, normalized to tibia length: sham control 111±3.8 g/cm vs. sham CKO 106±4.3 g/cm), a 16% increase in skeletal muscle mass was observed in CKO mice after longterm TAC (quadriceps: TAC control 100±3.3 g/cm vs. TAC CKO 116±5.3 g/cm, p&lt;0.05). In line with these results, mice with cardiomyocyte specific overexpression of MSTN (MSTN-Tg) showed a reduction in skeletal muscle mass (quadriceps: control 91±2.5 g/cm vs. MSTN-Tg 82±1.5 g/cm, p&lt;0.05). Conclusion: Myocardial MSTN contributes to the development of skeletal muscle wasting in heart failure, most likely through an endocrine mechanism involving its secretion into the circulatory system.
Abstract 15921: Prevalence of Suboptimal Non-High-Density Lipoprotein Cholesterol Levels in US Adults With Hypertriglyceridemia: The National Health and Nutrition Examination Survey 2003-2010
Authors: Peter P Toth, Charles Doyle, Karin M Henriksson
Journal: Circulation (2013)

Introduction: Non-high-density lipoprotein cholesterol (non-HDL-C) is recommended as a secondary target for patients with hypertriglyceridemia in the National Cholesterol Education Program Adult Tr...
In vitro cytotoxicity of ABT-751, a novel tubulin inhibitor, in pediatric solid tumor cell lines
Authors: Holly J. Meany, Elizabeth Fox, Anne E. Hagey, Frank Balis
Journal: Cancer Research (2006)

4351  ABT-751 is an orally bioavailable sulfonamide that is not a substrate for P-glycoprotein and which binds the colchicine binding site of β-tubulin to inhibit tubulin polymerization. A phase I trial in children with refractory solid tumors suggests selective activity in neuroblastoma. The ABT-751 steady state plasma concentration is 11 μM in children at the maximum tolerated dose. We assessed the in vitrocytotoxicity of ABT-751 and vincristine (VCR), a vinca alkaloid tubulin inhibitor, and evaluated their effect on tubulin polymerization in eight pediatric tumor cell lines, including neuroblastoma (SKNAS, SKNDZ, KCNR), Ewing’s sarcoma (LD, TC-71), osteosarcoma (HOS), medulloblastoma (Daoy), and rhabdomyosarcoma (RD). 5–10,000 cells/well were incubated for 24 hours then exposed to vehicle, ABT-751 (0.1–100 μM) or VCR (0.1–1000 nM) for 72 hours. Cell survival was measured with the standard sulforhodamine B (SRB) assay and with the ACEA RT-CES, which continuously monitors changes in electrical impedance of adherent cells over time. Cell survival, which is expressed as percent of vehicle control, was plotted as a function of drug concentration. IC50’s were estimated from the cell survival curves. Tubulin polymerization was assessed before and after drug exposure by western blots using antibodies specific for post-translational modifications that occur during tubulin polymerization/depolymerization. The ABT-751 IC50 was 0.7–2.3 μM and 0.8–6.0 μM in neuroblastoma and non-neuroblastoma cell lines, respectively. The VCR IC50 was 1.6 –5.7 nM and 1.6–6.6 nM in neuroblastoma and non-neuroblastoma cells lines, respectively. The difference between the ABT-751 IC50 in neuroblastoma and other solid tumor cell lines was not significant (P = 0.14). No significant difference was observed between IC50’s determined using the SRB assay and ACEA RT-CES method (P = 0.2). Following ABT-751 or VCR exposure, polymerized tubulin was decreased in a concentration dependent manner in all cell lines. IC50’s generated using the ACEA RT CES cell survival assay were similar to results from the standard SRB assay. ABT-751 is cytotoxic at concentrations that are tolerable in children. Although not statistically significant, a trend of increased activity of ABT-751 against neuroblastoma cell lines as compared to the activity exhibited in other pediatric solid tumor cell lines was observed. Dose-dependent effects on tubulin polymerization were observed in pediatric solid tumor cell lines and may serve as a surrogate marker.
Abstract 13153: Fasudil and Vardenafil Improve Myocardial Function and Attenuate Fibrosis in Experimental Diabetic Mellitus
Authors: Syed Ameenuddin, Brenda K Huntley, Elise A Oehler, Horng H Chen
Journal: Circulation (2010)

Introduction: Cardiovascular complications are the leading cause of morbidity and mortality in diabetic patients. Fasudil, a Rho-kinase inhibitor, and Vardenafil, a PDE-5 inhibitor, are promising t...
Abstract P218: Extremely Elevated HDL-Cholesterol Levels Are Independently Associated With Lower Carotid Intima-Media Thickness: Data From the ELSA-Brasil
Authors: Antonio G Laurinavicius, Itamar S Santos, Raul D Santos, Isabela M Bonsenor, Paulo A Lotufo
Journal: Circulation (2015)

Introduction:  HDL-cholesterol (HDL-c) is a strong, traditional negative cardiovascular (CV) risk factor. However, some reports suggest that extremely elevated HDL-c, i.e. hyperalphalipoproteinemia (HALP), may mark dysfunctional HDL particles, paradoxically conferring increased CV risk. Moreover, therapies aimed to increase HDL-c levels through CETP inhibition failed to demonstrate CV risk reduction despite substantial increase in HDL-c. Carotid Intima-Media Thickness (cIMT) is a reliable surrogate for atherosclerotic disease, validated for CV risk assessment. We studied cIMT among individuals with HALP.   Hypothesis:  We assessed the hypothesis that HALP is independently associated with lower cIMT when compared with HDL-c levels on usual normal range.   Methods:  The Brazilian Longitudinal Study for Adult Health (ELSA-Brasil) enrolled 15,105 subjects aged 35-74 years between 2008-10 for long-term follow-up, which included IMT measurements in both common carotid arteries and assessment of lipid profile. Two groups were considered for the present analysis: those with “normal” HDL-c levels (HDL-c 40-50mg/dL for men; 50-60mg/dL for women) and those with HALP (HDL-c ≥90mg/dL for both men and women). We assessed and compared the cardiometabolic profile of both populations and its association with cIMT. We used multiple linear regression to study the association between HALP and cIMT.   Results:  Overall, 3,372 individuals with “normal” HDL-c levels (mean 49.6 ± 5.7mg/dL) and 272 with HALP (mean 101.2 ± 10mg/dL) were considered. Subjects with HALP were older (54.6±9.5 vs 51.5±9 y, p   Conclusion:  HALP is independently associated with lower cIMT and seems to confer additional CV protection when compared with HDL-c levels on the usual normal range. These findings do not support the identification of HALP as a proatherogenic phenotype.
P0682 : Preclinical characterization of AL-335, a potent uridine based nucleoside polymerase inhibitor for the treatment of chronic hepatitis C
Authors: H. Tan, K. Shaw, A. Jekel, J. Deval, Z. Jin, A. Fung, Y. Tam, L.M. Blatt, S.M. Chanda, G. Wang, M. Prhavc, V. Serebryany, Q. Zhang, J.A. Symons, L. Beigelman, D.B. Smith
Journal: Journal of Hepatology (2015)
Abstract 2877: A Combined Cell Therapy and In Situ Tissue Engineering Approach for Myocardial Repair
Authors: Manhal Habib, Keren Shapira, Oren Caspi, Gil Arbel, Amira Gepstein, Dror Seliktar, Lior Gepstein
Journal: Circulation (2008)

Cell replacement and tissue engineering strategies are emerging as novel therapeutic paradigms for myocardial repair. Here we tested the hypothesis that a combined in situ tissue engineering and cell delivery strategy utilizing transplantable hydrogel-embedded cardiomyocytes [either neonatal rat ventricular cardiomyocytes (NRVCMs) or human embryonic stem cell-derived cardiomyocytes (hESC-CMs)] will improve functional performance in the rat infarction model. Methods and results : A novel liquid biodegradable PEGylated fibrinogen was developed, which was proved to be compatible with cardiomyocyte survival and maturation in vitro . Photopolymerization using UV beam results in a rapid liquid to hydrogel transformation. Animals were randomized to injection of saline, NRVCMs alone, the biopolymer alone, or the combined delivery of the biopolymer and the NRVCMs. Histological studies demonstrated the presence of the hydrogel-embedded cardiomyocytes within the scar tissue. The biopolymer was fully absorbed one month following delivery. Echocardiography revealed typical post-infarction remodeling in the control group (saline injection) as manifested by the deterioration of ejection fraction (EF) by 28±3% (from 43±2% at post-injury baseline to 30±2% at 4 weeks). Injection of the biopolymer or NRVCMs alone prevented this remodeling process (39±2% to 39±2% and 43±3% to 43±2% respectively; p&lt;0.05 when compared to controls). Co-injection of the biopolymer and NRVCMs resulted in the best functional outcome with EF improving by 22±8% from 40±4% to 48±4% (p&lt;0.05 when compared to the saline or biopolymer groups and p=0.07 when compared to NRVCM group). Finally, initial studies also demonstrated a favorable effect following the co-injection of the biopolymer together with hESC-CMs (from a baseline value of 45±1% to 47±1%). Similar improvements in all groups were also noted for other remodeling parameters (LV diastolic area and wall motion score) Conclusions: We describe a novel injectable in-situ-forming hydrogel that functions as an efficient cardiomyocyte carrier for both NRVCM and hESC-CMs and acts synergistically with the grafted cells to prevent the unfavorable post-infarction cardiac remodeling and improve ventricular function in rats.
Abstract 17834: Incident Cardioversion is Associated with Reduced Mortality among Older Adults with Atrial Fibrillation: Insights from the AFFIRM Trial
Authors: Brita Roy, Ravi V Desai, Susan J Zieman, Mustafa I Ahmed, Gregg C Fonarow, Wilbert S Aronow, Ali Ahmed
Journal: Circulation (2010)

Background: A rhythm control strategy has not been shown to improve long-term outcomes in atrial fibrillation (AF), possibly due to detrimental effects of antiarrhythmic medications. Aging is assoc...
Abstract 1812: The Chromosome 9p21.3 Coronary Artery Disease Risk Locus is Associated with Altered Cardiac Gene Expression in Individuals without Overt Cardiac Abnormality
Authors: Anna Pilbrow, John Pearson, Les McNoe, Mik Black, Christine Moravec, Wendy Sweet, Wilson Tang, Richard Troughton, Mark Richards, Vicky Cameron
Journal: Circulation (2008)
Abstract 3494: Short Duration Hypertension is Associated with the Development of Substrate for Atrial Fibrillation
Authors: Dennis H Lau, Lorraine Mackenzie, Darren J Kelly, Michael Worthington, Arumuga Rajendram, Yuan Zhang, Mohan Rao, James Edwards, Prashanthan Sanders
Journal: Circulation (2008)

Hypertension is frequently complicated by the development of atrial fibrillation (AF). However, the mechanisms of this link are poorly understood. Whether short duration hypertension results in atr...
Abstract 3808: AAV-9 Micro-Dystrophin Gene Therapy Halts Heart Disease Progression in Symptomatic Dystrophic Mice
Authors: Brian P Bostick, Yongping Yue, Yi Lai, Chun Long, Dejia Li, Dongsheng Duan
Journal: Circulation (2008)

Duchenne muscular dystrophy (DMD) is a fatal genetic disease caused by mutations in the dystrophin gene. Lack of dystrophin causes muscle wasting that eventually leads to premature death from respi...
Influences of practice characteristics on prescribing in practices
Authors: S. J Roberts
Journal: BMJ (1996)

sources outside the systematic review, such as relevant cohort studies.' Senn's concerns arise from what he calls the principle of "label invariance."We agree that many analyses of data from clinical trials are unaffected by which group is called the treated group and which the control group.The distinction does, however, need to be made in analyses of underlying risk, when this term usually refers to the risk in the placebo, control, standard, or reference treatment group.In a withdrawal trial the "standard treatment" group would comprise those patients receiving the active treatment, because then the question of interest is whether the effect of withdrawing this treatment is the same for patients who are at different levels of risk while they are receiving it.In a trial comparing two active treatments, A and B, the definition of underlying risk would depend on the precise question being addressed, which might be the effect of changing from A to B given the risk associated with A or, alternatively, the effect of changing from B to A given the risk associated with B.
Abstract 3641: Consistent Improvement of Regional Perfusion and Function Following Selective Pressure-Regulated Retroinfusion of Ad HIF-1{alpha}/VP 16 in a Percutaneous Pig Model of Chronic Ischemia
Authors: Rabea Hinkel, Maria Fydanaki, Chiraz El-Aouni, Michael Thormann, Hans-Christof Held, Christian Kupatt, Peter Boekstegers
Journal: Circulation (2008)
Abstract 1418: Receptor For Advanced-glycation End Products Inhibits Myocardin Function And Induces Msx2-dependent Osteoblastic Differentiation Of Vascular Smooth Muscle Cells
Authors: Toshihiro Suga, Tatsuya Iso, Takehisa Shimizu, Toru Tanaka, Shoichi Yamagishi, Masashi Arai, Tutomu Imaizumi, Masahiko Kurabayashi
Journal: Circulation (2007)

As an activator of diverse signaling pathways in the vascular cells, receptor for advanced-glycation end products (RAGE) has been related to atherosclerosis initiation and progression in the patients with diabetes and chronic renal failure (CRF). However, little is known about the efects of RAGE activation on the differentiation program of vascular smooth muscle cells (VSMC). We first examined effects of RAGE on expression of myosin heavy chain (MHC), a definitive VSMC marker. RT-PCR analyses showed that expression of MHC was diminished in VSMC transduced with adenovirus expressing RAGE. A RAGE ligand HMGB1, but not another ligand AGE2, enhanced RAGE-dependent MHC repression. Activation of HMGB1-RAGE pathway induced the endogenous RAGE expression, suggesting positive feedback loop in atherosclerotic lesion. In mesenchymal 10T1/2 cells, HMGB1-RAGE inhibited an induction of MHC gene expression by myocardin, a potent positive regulator of VSMC differentiation. We next examined the effects of RAGE on osteogenic conversion of VSMC by monitoring the expression and activity of alkaline phosphatase (ALP). RT-PCR analysis showed that expression of ALP was up-regulated in VSMC when RAGE was overexpressed by adenovirus. The degree of the ALP induction was dependent on the concentration of fetal bovine serum, suggesting that fetal bovine serum contains RAGE ligands. The induction of ALP was accompanied by ALP activity and an inducible expression of osteogenic transcription factors, Msx2 and Runx2 as well as an increase in osteopontin and bone morphogenic protein 2 (BMP2) expression. We further found that addition of BMP2 and RAGE synergistically enhanced expression of ALP mRNA and ALP activity. Immunohistochemistry revealed that RAGE antigen is present in calcified atherosclerotic plaque in a distribution overlapping with osteoblastic markers and calcium deposition detected by Kossa staining in human carotid artery. These findings suggest that RAGE induction in VSMC contributes to the development of calcifying atherosclerotic plaque characterizing the diabetes- and CRF-associated vascular lesion by repressing myocardin-induced VSMC differentiation and inducing Msx2-dependent osteogenic differentiation.
Abstract 19753: First in Man Experience with Left Ventricular Reconstruction in Patients with Systolic Heart Failure Using a Novel Approach of Biopolymer Hydrogel Implantation
Authors: Beatrice Retzlaff, Bernhard Voss, Albrecht Will, Rudiger Lange, Robert Bauernschmitt
Journal: Circulation (2010)

Background: The prevention or reversal of left ventricular (LV) remodeling by means of wall stress reduction is an important target in the treatment of heart failure (HF). We previously demonstrate...
Abstract 18111: Significance of Delayed Gadolinium Enhancement Cardiac Magnetic Resonance in Patients with Brugada Syndrome
Authors: Masato Murakami, Satoshi Nagase, Hiroshi Morita, Kazufumi Nakamura, Kunihisa Kohno, Kengo F Kusano, Hidetaka Suenaga, Hiroshi Ito, Tohru Ohe, Shigeru Saito
Journal: Circulation (2011)

Introduction- Gadlinium-enhanced Cardiac magnetic resonance (CMR) is a useful diagnostic tool for evaluating myocardial abnormality in several diseases. However, the prevalence of delyed Gadlinium enhancement (DGE) in CMR has not been yet reported in patients with Brugada syndrome (BrS). Methods- Seventy consecutive patients with BrS who underwent Gadlinium-enhanced CMR were evaluated in this study. All patients underwent echocardiography and signal-averaged electrocardiography (SAECG). Forty six patients underwent both ventriculography and electrophysiologic study, and 26 patients received mutation analysis of SCN5A. Results- DGE was found in five patients (7.1 %). All patients with DGE were symptomatic. Early repolarization (ER) in inferolateral leads was significantly highly detected in patients with DGE than without DGE (80.0% vs 16.9%, P&lt;0.01). Late potentials examined with SAECG were present in all patients with DGE and in 42 of 65 patients without DGE (64.6%). The value of RMS40 evaluated with SAECG was significantly smaller in patients with DGE than in patients without DGE (p&lt;0.0001). CMR, echocardiography, and both ventriculography failed to show apparent abnormalities of chamber dimensions and wall motion in any patients. In electrophysiologic study, VF was induced with programmed ventricular stimulation in four of five patients with DGE (80.0%) and in 21 of 41 patients without DGE (51.2%). Mutation analysis revealed that DGE was present in one patient with SCN5A mutation and in 2 patients without SCN5A mutation. Conclusions- This is the first report that CMR with DGE can identify abnormal myocardium which is undetectable with other methods in some cases with BrS. Depolarization abnormality is prominent in BrS patients with DGE. Because the positive predictive value of DGE is high, CMR with DGE might be a useful tool for evaluating high risk patient with BrS.
Abstract 18201: PPAR-{delta} Augments the Interaction Between Platelets and Late EPCs via EDG-2 Signaling Pathway, Leading to Vascular Regeneration
Authors: Jung-Kyu Han, Joo-Yun Won, Jee-Hoon Kang, Jae-Won Lee, Hyun-Jai Cho, Kyung-Woo Park, Hyun-Jae Kang, Byung-Hee Oh, Young-Bae Park, Hyo-Soo Kim
Journal: Circulation (2011)

BACKGROUND EDG (endothelial differentiation gene)-2 is a membrane receptor for LPA (lysophosphatidic acid) which is the major lysophospholipid growth factor generated by platelet activation. We foc...
Abstract 16152: The Mustard Operation for Transposition of the Great Arteries: Challenges During Adulthood
Authors: Jerry Stortenbeker, Edward J Hickey, Yaroslavna Nosikova, Candice Silversides, Erwin Oechslin, William G Williams, Glen S Van Arsdell
Journal: Circulation (2011)

Background  Survivors of the Mustard operation have largely transitioned to adulthood, yet their prognosis is uncertain.   Methods  We investigated all 205 patients who underwent Mustard operation for d-TGA (1963-1991) and transitioned to our adult services. Outcomes were analyzed by parametric competing risks and repeated measures analysis of ECGs (2776), echos (1363), cardiopulmonary tests (321) and MRIs (288).   Results  Attrition was constant (~1%/year); 20 years after transitioning to adulthood 79% were alive with a systemic RV circulation. Only 8 underwent transplantation. Intact ventricular septum was associated with improved late survival during adulthood (85% versus 69%, P=.05). The systemic RV gradually dilated over time (figure). This was associated with progressive decline in qualitative contractility (P   Conclusions  Gradual deteriorations in RV and tricuspid performance account for a high incidence of congestive heart failure in adults surviving Mustard operation. Nevertheless, very late survival is impressive, transplantation is rare and tricuspid or baffle interventions are infrequent. Inexorable RV dilatation will pose future management dilemmas.
Pregnancy-Related Hypertensive Disorders Are The Major Risk Factor For TRALI In Patients With Severe Post-Partum Hemorrhage
Authors: Luciana Teofili, Maria Bianchi, Bruno A. Zanfini, Stefano Catarci, Rossella Sicuranza, Serena Spartano, Gaetano Draisci, Gina Zini
Journal: Blood (2013)
Abstract 3468: Perioperative Betablockers Reduce Cardiovascular events in Patients Undergoing High Risk Non-cardiac Surgery-A Meta-analysis
Authors: Nandana Mapakshi, Paari D Swaminathan, Vamsi Kodumuri, Sandeep Bhargava, Namratha Reddy, Sandeep Khosla
Journal: Circulation (2007)

Introduction: ACC/AHA 2006 guidelines recommend perioperative beta blockers(BB) for high risk cardiac patients (class IIa), intermediate and low cardiac risk patients (class IIb) undergoing non-cardiac surgery. Meta-analysis of trials on perioperative blockers up to April 2003 found insufficient evidence for reduction of major cardiovascular events. We analysed the current evidence on effects of perioperative beta-blockers in patients not on BB and undergoing non-cardiac surgery. Materials and Methods: We did a literature search for randomized placebo controlled clinical trials of perioperative beta blockers in patients undergoing high risk non-cardiac surgery. End points were 30 day total mortality, cardiovascular mortality, perioperative cardiovascular outcomes, non-fatal MI, unstable angina, ventricular tachycardia, congestive heart failure, non-fatal stroke,non-fatal cardiac arrest,hypotension, bradycardia, bronchospasm. Data was extracted on an intention-to-treat basis. Heterogeneity of the studies was analyzed by Cochran’s Q statistics. The Mantel-Haenszel fixed-effect model was used to calculate combined relative risks for outcomes. Results: 24 studies with 3454 patients were included. Perioperative BB showed statistically significant benefit in reducing perioperative cardiovascular events and non-fatal MI and a nominally statistically significant benefit for cardiovascular mortality. The other end points were not significantly different between the two treatment groups. The results are summarized in the table below. Conclusion: Perioperative beta blockers reduce cardiovascular events and their use is recommended in all patients without contraindications and undergoing non-cardiac surgery.