tbuckley/cabot-search huggingface dataset:
Abstract 3718: MMP-12 Inhibitor Reduces Severity of ANGII-induced Aortic Abdominal Aneurysms in apoE−/− Mice
Authors: Dawn A Savio, Anita R Halpern, Yuchuan Wu, Wei Li, Joseph Sypek, Elaine M Quinet
Journal: Circulation (2008)

Abdominal aortic aneurysm (AAA) is an inflammatory disorder characterized by local connective tissue degradation, macrophage recruitment and infiltration leading to aortic dilation and rupture. Aneurysms of the abdominal aorta represent a significant cardiovascular risk for which inflammation plays an integral role in the defined pathology. Genetic ablation of metalloprotease-12 (MMP-12) eliminates metalloelastase activity and attenuates aneurysm formation in apoE−/− mice. In the current study, a selective MMP-12 inhibitor, WAY-644 was evaluated in the well-established murine model of ANGII-induced aneurysm formation. This inhibitor displays activity for murine MMP-12, IC50 = 6.3 nM by FRET analysis, with low crossreactivity for other MMPs (exception MMP-8), and has established in vivo efficacy in inflammation models. Coadministration of WAY-644 to hyperlipidemic apoE−/− mice during ANGII infusion (1.44 mg/kg) for 28d alters the severity of AngII-induced AAAs as measured by changes in abdominal aortic wet weights and typical AAA classification. As expected, plasma MMP-12 protease activity measured by FRET analysis was inhibited. RNA profiling of abdominal aortic aneurysm tissue characterizes ANGII-induced AAA expansion driven by macrophage infiltration, destructive MMP production and attenuation by MMP-12 inhibition. The transcription of a subset of proinflammatory genes activated with ANGII treatment was repressed by the inhibitor. These genes include quantitative markers of macrophage accumulation in the vessel wall, CD68, MCP1/CCL2, CCR2, MMP-12, and Csf1. Associated reductions in gene markers for inflammation and oxidative stress, ie., heme oxidase (HO), nitric oxide synthase (nos2), Ikbkb, and Stat3 also correlate with MMP-12 antagonism. These changes occur in the absence of lipid changes (TC or TG), or quantitative changes in aortic arch lesions in the ANGII-infused animals. The findings support a mechanism whereby MMP-12 metalloelastase inactivation reduces macrophage recruitment to aneurysmal lesion sites, to lessen activated-macrophage expression of proinflammatory cytokines that figure prominently in vascular wall destruction and the pathogenesis of AAAs.
Abstract P97: Standardized Post Resuscitation Care including Therapeutic Hypothermia for Patients with Non-VF Arrests
Authors: Oystein Tomte, Tomas Draegni, Dag Jacobsen, Arild Mangschau, Kjetil Sunde
Journal: Circulation (2008)

Introduction: Whether therapeutic hypothermia (TH) improves survival after out-of-hospital cardiac arrest (OHCA) with initial asystole (AS) or pulseless electrical activity (PEA) is still controversial. At our hospital, revived OHCA patients follow the same standardized post resuscitation care protocol, if active treatment is desired. This includes TH, irrespectively of initial rhythm. Thus, we wanted to report the outcome for our OHCA patients of non-VF origin. Methods: Since September 2003 all OHCA patients admitted to our hospital have been registered in a database. All patients with initial AS or PEA admitted to the Intensive Care Unit (ICU), or ward, between September 2003 and July 2007 were included. Favorable outcome is defined as a Cerebral Performance Category (CPC) of 1–2. Results: Altogether 58 patients, all comatose, with a median age of 55 (range 19 –90 years), were registered. Cardiac etiology was present in 24 patients (41%), half of which had a myocardial infarction. Among the 34 patients (59%) with non-cardiac etiology, 15 were intoxications (44%), seven had asphyxia after respiratory failure (21%), five had suffered a cerebral event (15%), three drowned (9%), one had a pulmonary embolism (3%), and three causes remained unidentified. Overall, 37 patients (67%) were treated with TH; 16 (43%) received external cooling (Arctic Sun, Medivance), 13 (35%) endovascular cooling (Coolgard, Alsius Corporation) and eight (22%) other external cooling, all methods combined with initial ice cold fluids/ice packs. Median time in ICU was three days (range 0 –19 days). Eleven patients (19%) were discharged alive from hospital (cardiac etiology in four, 36%). Nine patients (16%) had a favorable outcome, and two patients (3%) had CPC 3. Conclusion: After implementation of standardized post resuscitation care including TH, we found a 16% favorable survival among those admitted after non-VF OHCA, demonstrating a survival potential also for these patients.
Multiple Myeloma with IGH-Involving del(14q): Report of 34 Cases.
Authors: Iwona Wlodarska, Fiona M. Ross, Lisa J. Russell, Helena Pospisilova, Laura Chiecchio, Marie-Astrid Van Caillie, GianPaolo Dagrada, Christiane De Wolf-Peeters, Christine J. Harrison, Pascale De Paepe, Peter Vandenberghe, Lucienne Michaux
Journal: Blood (2007)
Abstract 1072: Myocardial and Microvascular Stunning in Apical Ballooning Syndrome
Authors: Alberto R De Caterina, Angelo Porfidia, Simona Giubilato, Francesca Marzo, Maurizio Pieroni, Antonio G Rebuzzi, Filippo Crea, Leonarda Galiuto
Journal: Circulation (2008)

Apical Ballooning Syndrome (ABS) is characterized by chest pain, ST segment elevation at ECG, normal coronary arteries and transient left ventricular (LV) apical a-dyskinesia that typically recovers within a few weeks. Limited and conflicting data about microvascular flow pattern in ABS exist so far. Eight consecutive patients (all women, 72±14 years) presenting with ABS were evaluated by Myocardial Contrast Echocardiography (MCE) at rest, during adenosine test and at 1 month follow-up. Myocardial dysfunction was assessed by Wall Motion Score Index (WMSI) and endocardial length of contractile dysfunction defect (CDD), while myocardial perfusion by Contrast Score Index (CSI) and endocardial length of perfusion defect (PD). MCE study was performed during the infusion of contrast medium (Sonovue, Bracco) at rest and at peak of 90 seconds-infusion of adenosine (140 μg/Kg/min) to elicit coronary microvascular response. LV perfusion defect was present in apical dysfunctional myocardium in all patients. Compared to resting condition, during adenosine WMSI decreased from 1.90±0.29 to 1.72±0.32 (p&lt;.01) and CDD from 40.3±15.5% to 33.2±15.3% of LV endocardial length (p&lt;.001). Similarly, during adenosine test, CSI decreased from 1.55±0.21 to 1.36±0.16, (p&lt;.01) and PD from 23.8±8.6% to 18.6±6.5% of LV endocardial length (p&lt;.05). At follow-up, both myocardial and microvascular dysfunction reverted to normal. Our early results indicate that ABS is characterized by a condition of regional myocardial and microvascular dysfunction partially reversible during adenosine infusion and entirely reversible at 1-month follow-up. These observations suggest that myocardial stunning associated with microvascular stunning could represent a common pathophysiologic pattern in ABS.
Serum B-Cell Maturation Antigen Is a Novel Prognostic Indicator for Multiple Myeloma Patients and Correlates with Clinical Status and Survival
Authors: Michael Ghermezi, Suzie Vardanyan, Nika Manik Harutyunyan, Jillian Gottlieb, Ariana Berenson, Claudia Andreu-Vieyra, Eric Sanchez, Regina A. Swift, James R. Berenson
Journal: Blood (2014)
Abstract 20069: Serum-Free Culture Conditions Support Human Cardiac Stem Cell Outgrowth
Authors: Seth Mount, Nesma Etoubashi, Darryl R Davis
Journal: Circulation (2014)

Introduction: Autologous cardiac stem cell (CSC) therapies represent an emerging treatment option for patients with congestive heart failure. Unfortunately, straightforward translation to the clinic is limited by traditional culture conditions that are supplemented by ill-defined or xenobiotic components such as fetal bovine serum. As such, overcoming these barriers is the next critical step in developing next generation CSC therapies for clinical use. Methods/Results: Transition of CSC culture methods to serum-free, xeno-free culture conditions demonstrated negligible effects on the overall numbers of cells cultured with equivalent cardiac (c-Kit+; 7.8±0.2 %, p=0.34) and mesenchymal (CD90+; 32±7 %, p=0.57) progenitor content as compared to standard culture conditions. Flow cytometry morphometry demonstrated that serum free cells provide a smaller, more homogeneous cell product. Exposure to hypoxic stress conditions demonstrated equivalent secretion of SDF-1α, SCF, HGF, and VEGF-A with reduced production of the pro-inflammatory cytokine IL-6 from serum-free cells (7±2 fold less; p=0.005). Despite differences in cytokine production, conditioned media from serum-free CSCs promoted similar new vessel formation (37±5 vs. 41±7 % of positive control within a HUVEC tube formation assay; p=0.69) and circulating stem cell recruitment (39±9 vs. 47±12% of the positive control within a transwell assay, p=0.64) when compared to media conditioned by standard cultures. Storage of cell suspensions at 4°C had negligible effects on 12 hour viability (95.3±1.6%, p=0.50), suggesting a shelf life sufficient for transport between institutions. Finally, injection of CSCs through a clinically approved coronary artery perfusion catheter did not alter cell viability (99.2±1.7 % after delivery, p=0.77) while ensuring successful product delivery to the peri-infarct zone. Conclusions: Transitioning CSCs to clinically acceptable protocols provides a more uniform cell product ready for clinical delivery. These findings represent the first published evidence that altered serum-free xeno-free culture conditions can provide a superior CSC cell product with the potential for ready translation to clinical use.
Demonstration of Kaposi's Sarcoma-Associated Herpes Virus Cyclin D Homolog in Cutaneous Kaposi's Sarcoma by Colorimetric In Situ Hybridization Using a Catalyzed Signal Amplification System
Authors: Jon A. Reed, Roland G. Nador, David Spaulding, Yoichi Tani, Ethel Cesarman, Daniel M. Knowles
Journal: Blood (1998)
Adenoviral and Retroviral Transduction of the Thymidine Kinase PET Reporter Gene in Mesenchymal Stem Cells: Effect on Functional Parameters and Length of Expression
Authors: Véronique Roelants, Jean-Louis Vanoverschelde, Carole de Meester, Xavier Havaux, Antonio Tabilio, Sanjiv S. Gambhir, Mauro Di Ianni, Luc Bertrand
Journal: Circulation (2008)
Abstract 3486: Minimally Elevated Cardiac Troponin T Independently Predicts Death in Apparently Healthy Adults: Results from the Rancho Bernardo Study
Authors: Lori B Daniels, Gail A Laughlin, Paul Clopton, Alan S Maisel, Elizabeth Barrett-Connor
Journal: Circulation (2007)

Background: Minimally elevated levels of cardiac troponin T (TnT), a marker of cardiac myocyte injury, have been found in small subsets of the general population. The significance of these rare elevations is controversial. The purpose of this study was to determine the prognostic value of detectable TnT levels in a population of community-dwelling older adults. Methods: Prospective community-based study of 375 men and 584 women ages 60 to 97 (mean 77) who had plasma TnT measurements (Elecsys® Troponin T, Roche Diagnostics) at baseline (1997–99) and were followed for mortality through July 2006. Participants were divided into 2 groups based on TnT levels: Undetectable (n = 917) and Detectable (≥ 0.01 ng/ml, n = 39). Results: The 39 (4.1%) participants with detectable TnT levels were older and were more likely to be men (both p &lt; 0.01) than those with undetectable TnT. Most of those with detectable TnT levels did not have known heart disease at baseline (79%, 95% C.I. 64 – 89%). During an average 6.3 year follow-up, 220 deaths occurred; 42% were cardiovascular (CV). In Cox proportional hazards regressions, participants with detectable TnT had increased risk of all-cause death (HR = 4.6, 95% CI 3.0 –7.1, Figure ) and of CV death (HR = 5.6, 95% C.I. 3.0 –10.6). Adjusting for age, sex, lifestyle characteristics, and multiple CV risk factors, as well as exclusion of the 152 participants with known heart disease at baseline, did not materially change the TnT-mortality associations. Conclusions: Apparently healthy adults with detectable TnT, even at levels not currently considered abnormal, are at increased risk of death. The prognostic value of TnT persists for years.
Abstract 1954: Activation of Endothelial Cells in Conduit Veins of Dogs With Heart Failure and Veins of Normal Dogs Following Vascular Stretch by Acute Volume Loading
Authors: Paolo Colombo, Sharad Rastogi, Duygu Onat, Valerio Zaca, Hani N Sabbah
Journal: Circulation (2007)

Background: Endothelial dysfunction is an independent predictor of poor prognosis in patients with heart failure (HF). Using a novel approach of endovascular endothelial cell (EC) sampling, we previously showed that ECs collected from conduit veins using J-wires are activated in patients with HF as evidenced by increased expression of pro-inflammatory genes including inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). The underlying cause(s) of this endothelial activation and dysfunction is not known. In this study, we tested the hypothesis that the HF state itself and the vascular strain associated with congestion can both account for these findings. Methods: We studied 6 normal (NL) dogs (LV ejection fraction &gt;50%, central venous pressure (CVP) ~ 8 mmHg) and 6 dogs with HF (ejection fraction ~ 30%, CVP ~9 mmHg) produced by intracoronary microembolizations. This model of HF manifests the disease syndrome in the absence of other co-morbid conditions often present in patients with CHF. NL dogs were studied at baseline and 1 hr after rapid fluid load (500 ml Dextran-40) resulting in CVP&gt;20 mmHg. ECs were scraped from jugular veins. mRNA was analyzed by RT-PCR and quantified in densitometric units (du). Results: Data are shown in the table . Endothelial iNOS and COX-2 were increased in HF dogs compared to NL. Tissue necrosis factor (TNF)-α, early growth response gene (EGR-1), receptor for advanced glycation end products (RAGE) and glutathione peroxidase (GPx) were also up-regulated in HF. In NL dogs, fluid load increased iNOS, COX-2, TNF-α, Egr-1, RAGE and GPx to levels that approached those of HF. Conclusions: The HF state itself, in the absence of other co-morbid conditions, and vascular stretch are both sufficient to activate venous ECs in dogs in a manner consistent with that seen in patients with HF. As such, molecular measures of EC dysfunction may potentially serve as “biomarkers” of severity of HF and possibly of impending decompensation.
Abstract 11493: A New Measurement System of Visceral Fat Area by Bioelectrical Impedance Analysis in a Population of community-Dwelling
Authors: Mika Enomoto, Hisashi Adachi, Yuji Hirai, Ako Fukami, Kuniko Yoshikawa, Eishi Esaki, Kinuka Ogata, Akiko Kasahara, Eri Tsukagawa, Kanako Yokoi, Sachiko Nakamura, Aya Obuchi, Ayako Yoshimura, Tsutomu Imaizumi
Journal: Circulation (2012)

Accumulation of visceral fat leads to metabolic syndrome and increases risks of cerebro-cardiovascular diseases. Accurate measurement of visceral fat area (VFA) is commonly performed by the abdomin...
Abstract 5381: Insulin-Stimulated Glucose Oxidation is Increased in Hearts from High Fat Diet-Induced Obese Mice Lacking Malonyl CoA Decarboxylase
Authors: John Edward R Ussher, Timothy R Koves, Jagdip S Jaswal, Christopher B Newgard, Jason R Dyck, Deborah M Muoio, Gary D Lopaschuk
Journal: Circulation (2008)

OBJECTIVE - Diet-induced obesity (DIO) leads to an accumulation of intra-myocardial fatty acid metabolites that have been proposed to cause myocardial insulin resistance and dysfunction. Our goal was to determine the effect of DIO on myocardial fatty acid metabolite accumulation and how this is altered when mitochondrial fatty acid uptake is inhibited. This was achieved by using mice lacking malonyl CoA decarboxylase (MCD−/−), which have higher levels of malonyl CoA, an endogenous inhibitor of mitochondrial fatty acid uptake. METHODS - Wild type (WT) and MCD−/− mice were fed a low (4% kcal from lard) or high (60% kcal from lard) fat diet for 12 weeks to determine the effect of DIO on the intra-myocardial accumulation of long chain acylcarnitines, long chain acyl CoAs, triglycerides (TGs), and ceramides. A parallel feeding study was performed to assess myocardial function and energy metabolism in isolated working hearts in the absence/presence of insulin. RESULTS - We demonstrate that MCD−/− mice do not accumulate intramyocardial long chain acylcarnitines to the same extent as WT mice following DIO (0.56 ± 0.10 vs. 0.28 ± 0.07 pmol myristoylcarnitine/mg protein, P &lt;0.05), but do accumulate similar amounts of long chain acyl CoAs (3.88 ± 0.34 vs. 4.35 ± 1.19 nmol/g wet weight). Interestingly, DIO only lead to an accumulation of TGs in the hearts of MCD−/− mice (3.29 ± 0.62 vs. 10.92 ± 3.72 μmol/g wet weight, P &lt;0.05). Despite this elevation in TGs, MCD−/− mice showed increased insulin-stimulated glucose oxidation (2.46 ± 0.25 vs. 1.74 ± 0.18 fold increase, P &lt;0.05) during aerobic isolated working heart perfusions and did not elicit any dysfunction. CONCLUSIONS - Our data reveal discordance between myocardial TG accumulation and glucose metabolism, suggesting that TG buffers against toxic lipids, and that inhibition of mitochondrial fatty acid oxidation does not cause myocardial dysfunction following DIO.
Copy number variation at the GL7 locus contributes to grain size diversity in rice
Authors: Yuexing Wang, Guosheng Xiong, Jiang Hu, Liang Jiang, Hong Yu, Jie Xu, Yunxia Fang, Longjun Zeng, Erbo Xu, Jing Xu, Weijun Ye, Xiangbing Meng, Ruifang Liu, Hongqi Chen, Yanhui Jing, Yonghong Wang, Xudong Zhu, Jiayang Li, Qian Qian
Journal: Nature Genetics (2015)
Abstract 3802: Frequency, Speed and Efficacy of Guideline Adjudicated Rescue Percutaneous Coronary Intervention Following Contemporary Fibrinolysis
Authors: Christopher E Buller, Robert C Welsh, Cynthia M Westerhout, Blair O'Neill, John Webb, Iqbal Bata, Richard Gallo, Paul W Armstrong
Journal: Circulation (2006)

Background: Rescue PCI improves outcomes in pts with early STEMI and ECG defined failed reperfusion following fibrinolysis. Recent rescue trials have enrolled non-consecutive pts mainly treated wit...
Abstract 9518: Miscarriage and Risk of Atherosclerosis, A Nationwide Cohort Study of One Million Women
Authors: Mattis F Ranthe, Elisabeth W Andersen, Henning Bundgaard, Jan Wohlfahrt, Mads Melbye, Heather A Boyd
Journal: Circulation (2012)

Background: Atherosclerosis might share aetiology with adverse pregnancy events through metabolic and vascular pathology or inflammatory responses. Knowledge on risk of atherosclerotic diseases in women experiencing spontaneous abortion/miscarriage is limited. In this nationwide cohort study we aimed to examine risk of three different atherosclerotic conditions in women who had experienced miscarriage. Methods: In Danish registers, we identified women experiencing a miscarriage or giving birth to a live singleton from 1977-2008. Women aged ≥12 years and free of cardiovascular disease were followed for incident cases of myocardial infarction, cerebral infarction and renovascular hypertension. Using Poisson-regression we estimated incidence rate ratios with 95% confidence intervals for these conditions by history of miscarriages. Results: In 1,031,279 women followed for more than 15 million person-years, we identified 2,798 incident cases of myocardial infarction, 4,053 incident cerebral infarcts and 1,448 incident cases of renovascular hypertension. Incidence rate ratios with 95% confidence intervals (adjusted for age, calendar-period, and number of children) for one and ≥four miscarriages respectively compared to no miscarrriages, were 1.11 (1.00-1.23) and 2.08 (1.25-3.45) for myocardial infarction, 1.13 (1.03-1.23) and 1.89 (1.20-2.96) for cerebral infarction, and 1.15 (0.99-1.34) and 3.78 (2.08-6.85) for renovascular hypertension. Trends with 95% confidence intervals for step-wise increase in risk for the three conditions given one additional miscarriage was 9% (3-16%), 13% (7-19%) and 19% (9-30%), in those aged ≤32 years all trends rose to around 60%. Adjusting for smoking, diabetes mellitus, polycystic ovarian syndrome and thrombophilia left estimates unchanged. Similar strong and consistent trends were not observed for live birth history. Conclusion: We found a consistent association between previous miscarriages and increased risk of myocardial infarction, cerebral infarction and renovascular hypertension. This is suggestive of shared aetiology in atherosclerosis and miscarriage, or possible pathological processes initiated by a miscarriage and leading to atherosclerosis.
Abstract 992: Novel Role of Copper-dependent Transcription Factor Antioxidant-1 in Cell Proliferation and Wound Healing
Authors: Ha Won Kim, Kiyoshi Ozumi, McKinney D Ronald, Shinichi Itoh, Jay Yang, Osamu Nakagawa, Susan Lessner, Masuko Ushio Fukai, Tohru Fukai
Journal: Circulation (2007)

Copper plays a fundamental role in regulating cell proliferation involved in wound healing and angiogenesis. Recently, we found that antioxidant-1 (Atox1), previously appreciated as a copper chaperone at the transGolgi network (TGN), stimulates cyclin D1 transcription and cell proliferation in a copper dependent manner. However, functional role of Atox1 in wound healing in vivo remains unknown. Here we show that Atox1 was highly expressed at the BrdU positive nuclei in the wounding tissue, which was associated with an increase in copper content (2.1-fold), as assessed by ICP-mass spectrometry, as compared to non-wounded skin. In Atox1 knockout (KO) mice, the rate of wound closure was markedly delayed as compared to wild-type (WT) mice (7.1 day vs. 11.2 day for complete wound closure in WT vs. Atox1 KO mice, p &lt; 0.001), and BrdU-positive proliferating cells and cyclin D1 protein expression were significantly decreased. Capillary density in healing wound tissue was also reduced in Atox1 KO mice (27.8% decrease). To segregate a copper-dependent transcription factor and a copper chaperone function of Atox1, we have generated lentivirus expressing nuclear targeted Atox1 (Atox1-NLS), TGN-targeted Atox1 (Atox1-TGN) or Atox1-WT. and examine their effect on cell proliferation and wound healing in vitro and in vivo. In cultured Atox1 KO mouse fibroblasts, copper-induced cell proliferation and cyclin D1 expression were abolished, which was rescued by re-expression of both Atox1-NLS and Atox1-WT, but not Atox1-TGN. Promoter deletion analysis identified Atox1 responsive element (Atox1-RE) at cyclin D1 promoter and EMSA and ChIP assays demonstrated that Atox1 binds to Atox1-RE at the cyclin D1 promoter in a copper dependent manner. The impairment of wound healing in Atox1 KO mice was rescued by re-expression with lenti-Atox1-NLS and Atox1-WT, but not Atox1-TGN, which was associated with the increase in cyclin D1 expression as well as number of BrdU positive proliferating nuclei. In summary, transcription factor function of Atox1, but not copper-chaperone function of Atox1, plays a critical role in copper-induced cell proliferation, which may contribute to wound repair process in response to injury in vivo.
Abstract 1563: Weight Loss Improves Right Atrial and Ventricular Function and Metabolism in Obese Humans
Authors: Suraj Kurup, C H Lin, Pilar Herrero, Jasdeep Sidhu, Vineet Venugopal, Alan D Waggoner, Richard I Stein, J C Eagon, Samuel Klein, Robert J Gropler, Linda R Peterson
Journal: Circulation (2009)

Obesity is a major risk factor for right- and left-sided heart failure and atrial fibrillation. Weight loss improves obesity-related left ventricular metabolism and function and left atrial size ab...