tbuckley/cabot-search huggingface dataset:
Abstract 360: PKA is Needed for Acute Adaptation for Cardiac Stress
Authors: Jining Yang, Xiaoying Zhang, Shen Ao, Xuewei Xia, Guo Yu, Xiaoyan Wu, Bing Xu, Miyuraj Withanage, Min Zhou, Jie Liu, Wei E Wang, Erliang Zeng, Ying Tian, Weizhong Zhu, Steven R Houser, Yang K Xiang, Chunyu Zeng, Mantian Mi, Xiongwen Chen
Journal: Circulation Research (2019)

In adult mammalian hearts, the ventricles are composed of mostly binucleated myocytes (BVMs) and some mononucleated myocytes (MVMs), which have different properties. However, if the gene expression profile and pathological responses of these two populations of myocytes are different have not reported. We found that these two populations of myocytes differentially expressed 250 genes. While many RNA synthesis and processing genes, and some antiapoptotic genes were highly expressed in MVMs, BVMs had genes related to self-destruction (autophagy and ubiquitination system genes) enriched. In general, expression of genes involved in carbonhydrate metabolism and cell proliferation was also more but the expression of genes involved in fatty acid metabolism was less in MVMs. The expression of some of these genes was confirmed in single-molecule pulldown (SiMPull) method in separated MVMs and BVMs. MVMs grew more in pressure overloaded hearts. MVMs were more resistant to apoptosis induced by β-adrenergic stimulation both in vitro and in vivo , which was due to cytosolic and mitochondrial Ca 2+ and ROS could be more easily increased in BVMs leading to more damage to mitochondria. Ca 2+ current, myocyte contraction and Ca 2+ transients in MVMs had less responses to β-adrenergic stimulation (isoproterenol, 1uM). Furthermore, MVMs gene expression upon β-adrenergic stimulation showed more adaptive responses while BVMs showed more proapoptotic gene (e.g., p53 and AIF), protein post-translational modification and muscle differentiation gene expression. This study suggests that MVMs and BVMs are distinct subpopulations of VMs with different gene expression profile and pathological responses. It underscores the importance of differential pathological responses of cells having different nuclear numbers .
Abstract 723: Cortical Bone Derived Stem Cells Modulates T Cell Response After Myocardial Injury
Authors: Marcus J Wagner, Lena Ma, Christopher F Bryan, Ritu S Vyas, Justin J Kurian, Mohsin Khan, Sadia Mohsin
Journal: Circulation Research (2019)

Rationale: The ischemic environment following myocardial infarction induces a harsh, pro-inflammatory state that facilitates the removal of necrotic tissue. Manipulation of T cell responses after cardiac injury directly impacts the outcome of the reparative response. Previous studies have demonstrated Cortical Bone Derived Stem Cells (CBSCs) improve cardiac function after myocardial infarction. CBSCs produce a diverse paracrine profile; whether this can lead to the modulation of T cell response by manipulating T cell subsets and allowing for increased cardiac wound healing post-MI remains unknown. Objective: To determine whether CBSCs secrete a paracrine profile that promotes wound healing by modulating T cell response following myocardial injury. Methods and Results: CD3+ T-lymphocytes were isolated from the spleen of C57BL/6J male mice ages 8 to 12 weeks via Fluorescent Activated Cell Sorting (FACs). CBSC secretome was introduced to T cell populations via a transwell culture system in the presence of CD3/28 coated beads with IL2. T-regulatory (Treg) populations were quantified via FACs 24 hours after in vitro CBSC exposure. Treg populations exposed to CBSC secretome in hypoxic (1% O2) conditions expanded to 26.9% of the CD4+ compartment, a 4.5 fold increase compared to control conditions. This result was further confirmed via qRT-PCR analysis. T cell culture secretome was quantified via proteome profiling of 111 soluble cytokine proteins 24 hours post CBSC exposure. CBSCs express a robust chemotaxis signature that promotes immune cell recruitment. T cells cultured in the presence of CBSC (pre-conditioned or co-culture conditions) exhibit increased CCL5, CCL22, CD40, CXCL1, and Lipocalin-2. C-reactive protein, a pro-inflammatory marker, was decreased by ~5.5 fold in the presence of CBSCs, promoting wound healing. Conclusions: CBSCs secrete a diverse paracrine profile that promotes Treg expansion during hypoxic conditions. Expansion of Treg populations post-CBSC exposure in the post-IR heart leads to increased inflammation resolution and improved myocardial wound healing, allowing for increased cardiac function and repressed cardiac remodeling.
Predicting Disease Recurrence in Patients with Previous Unprovoked Venous Thromboembolism: The DASH Prediction Score
Authors: Alberto Tosetto, Alfonso Iorio, Maura Marcucci, Trevor Baglin, Mary Cushman, Sabine Eichinger, Gualtiero Palareti, Daniela Poli, Campbell R Tait, James D. Douketis
Journal: Blood (2011)
Abstract 546: Exploring MCUb Function in the Heart and Its Role in Ischemia Reperfusion Injury
Authors: Jiuzhou Huo, Kelly Grimes, Michelle Sargent, Allen York, Jennifer Kwong, Jeff Molkentin
Journal: Circulation Research (2019)

Mitochondrial calcium alterations can promote oxidative metabolism to match increasing functional demands during stress stimulation. However, mitochondrial calcium overload-induced cell death contributes to the pathogenesis of several cardiac disorders including ischemia reperfusion injury. The mitochondrial calcium uniporter (MCU) complex is the only identified transporter that permits rapid calcium uptake into mitochondria. While the biological function of the MCU pore-forming subunit has been annotated, much less is known about the MCUb protein, a high similarity paralog that is part of the greater MCU complex. The goal of our study was to investigate the biological function of MCUb, its role in mitochondrial calcium uptake, and its contribution to the pathogenesis of ischemia reperfusion injury in the heart. To address these questions, we generated both MCUb overexpressing mice as well as MCUb null mice. We observed that the cardiac-specific overexpression of MCUb inhibited mitochondrial calcium uptake, although basal mitochondrial calcium levels remained unchanged. Genetic ablation of MCUb, conversely, did not influence mitochondrial calcium uptake in the heart. MCUb null mice did not have differences in cardiac function by echocardiography, nor were tissue histological changes observed. This lack of an overt phenotype in MCUb null mice may be attributable to very low or even absent expression in the heart at baseline. However, induction of MCUb protein was observed in the hearts of mice subjected to ischemia reperfusion injury. Thus, mice were challenged with one-hour ischemia followed by 24-hour reperfusion and the ischemic area/area at risk was analyzed. Deletion of MCUb did not change the initial infarct size of the heart. However, MCUb null mice showed decreased fractional shortening 4-weeks after the ischemic injury. Gravimetric analysis as well as histological examination further supported the conclusion that MCUb deletion exacerbated damage in the heart after ischemia reperfusion injury. We are currently investigating the underlying mechanisms of this greater functional deficit.
Abstract 471: Exploring Haploinssuficiency Drivers in a Set of cMyBP-C Missense Mutations Causing Hypertrophic Cardiomyopathy
Authors: Carmen Suay-corredera, Maria R Pricolo, Elías Herrero-Galán, Diana Velázquez-Carreras, David Sánchez-Ortiz, Diego García-Giustiniani, Javier Delgado, Silvia Vilches, Fernando Domínguez, Roberto Barriales-Villa, Giulia Frisso, Luis Serrano, Pablo García-Pavia, Lorenzo Monserrat, Jorge Alegre-Cebollada
Journal: Circulation Research (2019)

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease. Mutations in cardiac myosin-binding protein C (cMyBP-C) are a leading cause of HCM. However, as for many other genetic diseases, it remains challenging to define whether specific gene variants found in patients are pathogenic or not. Here, we have examined pathogenicity drivers in a group of clinically annotated exonic variants of MYBPC3, the gene encoding cMyBP-C. First, we did bioinformatics predictions of RNA splicing and of protein thermodynamic stability. To validate results, we studied RNA splicing of the MYBPC3 gene using peripheral blood from variant carriers, and circular dichroism measurements on purified recombinant proteins. Our results show that around half of the pathogenic exonic mutations alter RNA splicing or protein thermodynamic stability, both of which can lead to cMyBP-C haploinsufficiency. These molecular phenotypes are not found in control, non-pathogenic variants. Remarkably, the remaining pathogenic missense mutations appear to result in stable proteins, for which the cause of pathogenicity remains unknown. We propose that examination of protein haploinsufficiency drivers can define pathogenicity of genetic variants associated with HCM, decisive for the clinical management of patients and their families.
Venetoclax in Combination with NAMPT Inhibitors Decreases Mitochondrial Bioenergetics through the Impaired AMPK/SIRT/PGC1α Signaling Pathway in CLL
Authors: Subir Roy Chowdhury, Saleh Ryan, Cheryl Peltier, Mandy Squires, Donna Hewitt, Paul Fernyhough, Spencer Bruce Gibson, Versha Banerji
Journal: Blood (2018)
Primary Cutaneous Follicle Center Lymphomas (PCFCL) Express Heavily Mutated B-Cell Receptors with Acquired N-Glycosylation Motifs and Lack Ongoing Somatic Hypermutation
Authors: Marvyn T. Koning, Edwin Quinten, Willem H. Zoutman, Sander A.J. van der Zeeuw, Szymon M. Kielbasa, Hailang Mei, Cornelis A.M. van Bergen, Patty M. Jansen, Rein Willemze, Christian Schmidt, Maarten Vermeer, Cornelis P. Tensen, Hendrik Veelken
Journal: Blood (2018)
A Practical Treatise of Diseases of the Skin, for the Use of Students and Practitioners
Journal: JAMA (1900)

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Daratumumab, Pomalidomide, and Dexamethasone (DPd) As Salvage Treatment for Relapsed/Refractory Myeloma Eligible for High-Dose Chemotherapy/Autologous Stem Cell Transplantation
Authors: Al-Ola Abdallah, Neil Dunavin, Brian McClune, Leyla Shune, Ajoy L. Dias, Zahra Mahmoudjafari, Erica Hochard, Joseph P. McGuirk, Siddhartha Ganguly
Journal: Blood (2018)
Allogeneic Stem Cell Transplantation for Multiple Myeloma: A 34-Year Experience
Authors: Courtney Venegas, Matthew A. Lunning, Zaid S. Al-Kadhimi, Vijaya R. Bhatt, Elizabeth R. Lyden, Kimberly Schmit-Pokorny, James O. Armitage, Julie M. Vose, Sarah A. Holstein, Muhamed Baljevic
Journal: Blood (2018)
Classifying AML Patients with Inv(16) into High-Risk and Low-Risk Relapsed Patients Based on Peritransplantation Minimal Residual Disease Determined By CBFÎ²/MYH11 Gene Expression
Authors: Xiaosu Zhao, Leqing Cao, Yazhen Qin, Xiaohui Zhang, Lanping Xu, Xiaojun Huang, Ying-Jun Chang
Journal: Blood (2018)
Efficacy and Safety of Once-Weekly Bortezomib Infusion in the Treatment of Relapsed/Refractory Multiple Myeloma
Authors: Hyun-Kyung Kim, Yeung-Chul Mun, Eun-Sun Yoo, Kyoung Eun Lee, Eunmi Nam, Soon Nam Lee, Chu-Myong Seong
Journal: Blood (2011)
Malignant Progression of an MDS-Derived Cell Line Serves As an in Vitro Model for the Leukemic Evolution of MDS
Authors: Jun-ichiro Kida, Takayuki Tsujioka, Shin-ichiro Suemori, Shuichiro Okamoto, Kanae Sakakibara, Takahiro Yamauchi, Akira Kitanaka, Yumi Tohyama, Kaoru Tohyama
Journal: Blood (2018)
Notes from the field: Multistate outbreak of Salmonella infantis, newport, and lille infections linked to live poultry from a single mail-order hatchery in Ohio--March-September, 2012.
Authors: Tony M. Forshey, Scott Nowicki, Marika Mohr, C. Stephen Roney, Thomas M. Gomez, Jennifer R. Mitchell, Thai-An Nguyen, Casey Barton Behravesh
Journal: MMWR Morbidity and Mortality Weekly Report (2013)
Abstract 285: Oxidized Low Density Lipoprotein and Angiotensin II Causes Vascular Senescence Via AT1R Signal-mediate Mitochondrial Fission
Authors: Yoshihiro Uchikado, Yoshiyuki Ikeda, Yuichi Sasaki, Yuichi Akasaki, Mitsuru Ohishi
Journal: Circulation Research (2019)

Introduction: Metabolic stress including oxidized low density lipoprotein (ox-LDL) and angiotensin II (AngII) cause mitochondrial dysfunction and vascular senescence. Mitochondria are highly dynamic organelles that constantly change their morphology to fusion or fission. This study aims to clarify how mitochondrial dynamics are involved in the etiology of vascular senescence. Methods: VSMC and HUVEC were stimulated by either ox-LDL or AngII. We also conducted in vivo experiment using C57BL6 (WT), apolipoprotein E (ApoE) deficient and the double knockout of ApoE and AT1R (DKO) mice. Results: Either ox-LDL or AngII induced excessive mitochondrial fission though phosphorylation of Drp1 at Ser616, mitochondrial dysfunction assessed by JC1, reactive oxygen species production measured with Mito-Sox Red and Amplex assay and cellular senescence analyzed by senescence associated beta galactosidase staining and immunoblot of p53 and p21 in cells. Administration of mdivi-1, a specific inhibitor of Drp1, restored imbalance of mitochondrial dynamics and these detrimental alterations. Treatment with angiotensin II type1 receptor (AT1R) inhibitor also inactivated Drp1 and improved imbalance of mitochondrial dynamics, mitochondrial dysfunction and cellular senescence. These results suggest that ox-LDL- or AngII-induced mitochondrial dysfunction and cellular senescence were derived from Drp1-dependent mitochondrial fission. Administration of AT1R inhibitor to HUVEC or SMC with ox-LDL prevented cells against excessive mitochondrial fission, its dysfunction and cellular senescence. The degree of vascular senescence was higher, the number of fused mitochondria and mitochondrial function were lower and mitochondrial oxidative stress were higher in either C57BL6 with AngII infusion or ApoE KO mice than those of control or WT mice, respectively. Treatment with mdivi-1 to these mice reduced mitochondrial fission, oxidative stress and attenuated vascular senescence. The number of fused mitochondria and its function were higher and the degree of vascular senescence were lower in DKO than those in ApoE KO mice. Conclusion: Either ox-LDL or AngIIcauses cellular and vascular senescence through AT1R signal-mediated mitochondrial fission.
Abstract 529: Circulating Pro Fibrotic Protein Promotes Fibrosis in Liver and Heart
Authors: Yuki Tsukano, Ippei Shimizu, Yohko Yoshida, Ryutaro Ikegami, Yuka Hayashi, Masayoshi Suda, Goro Katsuumi, Takayuki Wakasugi, Masaaki Nakao, Tohru Minamino
Journal: Circulation Research (2019)

Analyzing two sets of DNA micro array data with bioinformatics, we identified a secreted form pro-fibrotic protein (sPFP) expressed in dysfunctional brown adipose tissue (BAT) in mice. Testing our biobank samples, we found this protein increased in plasma of non-alcoholic steatohepatitis (NASH) patients or aged individuals. We generated a murine obese NASH model by imposing a high fat diet in C57BL/6NCr mice for 9-10 months since 4 weeks of age, and found that sPFP is produced predominantly by BAT. In this model, we also found that sPFP increased in plasma. We generated a murine systemic sPFP knockout (KO) model and found that liver fibrosis ameliorated in sPFP-KO model. We also suppressed circulating sPFP with a peptide vaccine targeting this molecule, and found that sPFP vaccination therapy inhibited liver fibrosis. Next, we generated sPFP gain of function (GOF) model by the administration of plasmid encoding sPFP into skeletal muscle. Liver fibrosis augmented in sPFP-GOF model, and these results suggested that sPFP has causal role for the progression of fibrotic response in liver. In the obese NASH model, we found that cardiac fibrosis also developed and it ameliorated in sPFP-KO model, indicating that sPFP may have pathological roles for heart failure with preserved ejection fraction (HFpEF) related with age-related disorders. In addition to an increase in circulating sPFP in aged individuals, we found that sPFP increased in BAT of chronological aged mice model. In vitro studies with differentiated brown adipocytes showed that c-Fos upregulated sPFP in transcript level. Our results suggest that sPFP contributes for the progression of fibrotic responses in obese or aged models. Inhibition of sPFP may become a therapy for NASH or HFpEF.
Quality Of Life After Allogeneic Stem Cell Transplantation In Patients With Myelofibrosis (CMWP of EBMT)
Authors: Nora Machate, Haefaa Alchalby, Susanne Sehner, Tatjana Zabelina, Daniel Wolff, Guido Kobbe, Martin Bornhäuser, Herrad Baurmann, Wolfgang A Bethge, Gerald Wulf, Axel R. Zander, Nicolaus Kröger
Journal: Blood (2013)
Evolution of pathologic T-cell subsets in patients with atopic dermatitis from infancy to adulthood
Authors: Tali Czarnowicki, Helen He, Talia Canter, Joseph Han, Rachel Lefferdink, Taylor Erickson, Stephanie Rangel, Naoya Kameyama, Hyun Je Kim, Ana B. Pavel, Yeriel Estrada, James G. Krueger, Amy S. Paller, Emma Guttman-Yassky
Journal: Journal of Allergy and Clinical Immunology (2019)
Recombinant Activated Coagulation Factor VII (rFVIIa) for Treatment of the Tracheobronchial Bleeding in Mechanically Ventilated (MV) Thrombocytopenic Patients (pts)
Authors: Gennadii M. Galstian, Olesya A. Polevodova, Vladimir Yu. Zorenko, Valeriy G. Savchenko
Journal: Blood (2018)
Abstract 620: Molecular Mechanisms and Therapeutic Approaches to Myofilament Glycation as a Result of Diabetes
Authors: Maria Papadaki, June Theerachat, Jonathan A Kirk
Journal: Circulation Research (2019)

Methylglyoxal (MG), a glycolysis byproduct, is significantly elevated in the blood of patients with diabetes and modifies proteins by reacting with arginine and lysine residues to form irreversible adducts. We previously found that patients with diabetes and heart failure (dbHF) exhibited an increase in MG-modifications on cardiac myofilament proteins compared to non-failing hearts. We discovered these modifications reduced myofilament calcium sensitivity and maximal calcium-activated force, and despite being primarily on actin and myosin, did not affect their direct binding. The aim of this study was to elucidate MG’s molecular effects on muscle mechanics as well as to identify effective therapeutic options for dbHF patients. We first utilized a custom loaded fiber system to simultaneously measure isometric force and ATPase activity. When mouse fibers were treated with 100 μM Mg for 20 mins, similar to previous studies, there was a decrease in force production, but there was a concomitant decrease in ATPase activity as well. Thus, the tension cost was not altered by MG, supporting our hypothesis that MG modifications on myosin do not alter myosin function, instead altering its interactions with thin filament proteins. MG modifications are irreversible so therapeutic approaches should compensate for the functional defects induced. We pre-treated mouse skinned myocytes with MG, and then measured force-calcium relationships before and after treatment with different drugs. We first used 1 mM aminoguanidine (AG), an MG scavenger that has been efficacious in basic science studies but failed in clinical trials. Agreeing with the clinical trial, we show AG cannot reverse MG’s effects. We then treated the myocytes with omecamtiv mecarbil (OM), a myosin activator currently in clinical trials. In myocytes not pretreated with MG, OM increased calcium sensitivity and decreased maximum force, as reported previously. Interestingly, OM had no effect of calcium sensitivity but still decreased Fmax, suggesting OM may have less effect in patients with diabetes. Overall, in this study we further elucidate the mechanism of MG effect’s on the myofilament, and also show these modifications may reduce the efficacy of OM, a small molecule currently in clinical trials.
Abstract 15874: The Effect of Socioeconomic Status on Patients Supported With Contemporary Left Ventricular Assist Devices
Authors: Autumn M Clemons, Raul Flores, Raia Blum, Danielle L Brunjes, Raymond C Givens, Arthur R Garan, Lauren K Truby, Hiro Takayama, Koji Takeda, Yoshifumi Naka, Maryjane A Farr, Melana Yuzefpolskaya, Paolo C Colombo, Veli K Topkara
Journal: Circulation (2017)

Introduction: Continuous-flow left ventricular assist devices (CF-LVADs) are increasingly used in patients with advanced heart failure. Recent studies suggest that low socioeconomic status (SES) pr...
Different Time-Dependent Risk for Disease Evolution in Chronic Lymphocytic Leukemia with Distinct IGHV Gene Somatic Hypermutation Status
Authors: Theodoros Moysiadis, Panagiotis Baliakas, Davide Rossi, Mark Catherwood, Jonathan C Strefford, Julio Delgado, Achilles Anagnostopoulos, Chrysoula Belessi, Niki Stavroyianni, Sarka Pospisilova, David Oscier, Gianluca Gaidano, Elias Campo, Richard Rosenquist, Paolo Ghia, Kostas Stamatopoulos
Journal: Blood (2017)