tbuckley/cabot-search huggingface dataset:
Influence of Posture on Cardiac Output and Minute Ventilation During Exercise
Authors: Mauricemcgregor, Williamadam, Paulsekelj
Journal: Circulation Research (1961)

In four normal subjects, cardiac output, oxygen uptake, and ventilatory volume were compared on 8 occasions at rest and on 20 occasions during exercise in the recumbent and sitting postures. The oxygen uptake was not significantly different in the two postures either at rest or at equal external work loads. In the sitting posture during exercise, the cardiac index was approximately 12 per cent and stroke index 19 per cent lower than in the supine posture. Ventilation was signifi cantly higher because of an increase in respir atory frequency.
Tissue Engineering of Heart Valves
Authors: ErwinRieder, GernotSeebacher, Marie-TheresKasimir, EvaEichmair, BirgittaWinter, BarbaraDekan, ErnstWolner, PaulSimon, GuenterWeigel
Journal: Circulation (2005)

Background— Tissue-engineered or decellularized heart valves have already been implanted in humans or are currently approaching the clinical setting. The aim of this study was to examine the migratory response of human monocytic cells toward decellularized porcine and human heart valves, a pivotal step in the early immunologic reaction. Methods and Results— Porcine and human pulmonary valve conduits were decellularized, and migration of U-937 monocytic cells toward extracted heart valve proteins was examined in a transmigration chamber in vitro. Homogenized tissue specimens were size fractionated by SDS-PAGE. The decellularization procedure effectively reduced the migration of human monocytes toward all heart valve tissue. However, only the antigen reduction of human pulmonary valves abolished the monocytic response (wall, 0.88±0.19% versus 30.20±3.93% migrated cells [mean±SEM]; cusps, 0.10±0.06% versus 10.24±1.83%) and was significantly lower (P<0.05) than that of the decellularized porcine equivalent (w...
Ischemic Preconditioning Prevents the Impairment of Hypoxic Coronary Vasodilatation Caused by Ischemia/Reperfusion
Authors: ElianaGiannella, Hans-ChristianMochmann, RobertoLevi
Journal: Circulation Research (1997)

Abstract We previously reported that hypoxic coronary vasodilatation (HCVD) is initiated by endothelial NO and sustained by adenosine. Prolonged ischemia/reperfusion impairs endothelium-dependent coronary vasodilatation, whereas transient ischemia (ie, preconditioning) protects the myocardium from subsequent ischemic events. Accordingly, we assessed whether prolonged ischemia/reperfusion impairs HCVD and whether preconditioning prevents this dysfunction. HCVD, elicited in isolated guinea pig hearts by a 1-minute exposure to 100% N2, consisted of an ≈70% increase in coronary flow associated with enhanced nitrite/nitrate and adenosine overflow (+40% and 5-fold, respectively). After 30-minute global ischemia and 20-minute reperfusion, HCVD was decreased by ≈60%, and the increases in nitrite/nitrate and adenosine overflow were abolished. Preconditioning (ie, three cycles of 5-minute global ischemia+5-minute reperfusion) prevented the impairment of HCVD and fully restored the increase in nitrite/nitrate overfl...
Identification of non-mutated neoantigens presented by TAP-deficient tumors
Authors: Koen A. Marijt, Laura Blijleven, Els M.E. Verdegaal, Michel G. Kester, Daniel J. Kowalewski, Hans-Georg Rammensee, Stefan Stevanović, Mirjam H.M. Heemskerk, Sjoerd H. van der Burg, Thorbald van Hall
Journal: The Journal of Experimental Medicine (2018)

Most T cell–based immunotherapies of cancer depend on intact antigen presentation by HLA class I molecules (HLA-I). However, defects in the antigen-processing machinery can cause downregulation of HLA-I, rendering tumor cells resistant to CD8+ T cells. Previously, we demonstrated that a unique category of cancer antigens is selectively presented by tumor cells deficient for the peptide transporter TAP, enabling a specific attack of such tumors without causing immunopathology in mouse models. With a novel combinatorial screening approach, we now identify 16 antigens of this category in humans. These HLA-A*02:01 presented peptides do not derive from the mutanome of cancers, but are of “self” origin and therefore constitute universal neoantigens. Indeed, CD8+ T cells specific for the leader peptide of the ubiquitously expressed LRPAP1 protein recognized TAP-deficient, HLA-Ilow lymphomas, melanomas, and renal and colon carcinomas, but not healthy counterparts. In contrast to personalized mutanome-targeted therapies, these conserved neoantigens and their cognate receptors can be exploited for immune-escaped cancers across diverse histological origins.
Abstract 20627: Cardiomyocyte Biology Revealed by Fluorescence Ubiquitination Based Cell-Cycle Indicators (FUCCI)
Authors: Roberto Alvarez, Pearl J Quijada, Bingyan J Wang, Lilian Amheh, Natalie Navarrete, Maya Shaitrit, Thi Ho, Natalie Gude, Mark A Sussman
Journal: Circulation (2017)

Existing myocyte contribution to new myocyte formation remains an active area of investigation. Novel experimental methodology is needed to faithfully label cardiomyocyte cell-cycle activity after ...
Increased Proinflammatory Cytokines in Patients With Chronic Stable Angina and Their Reduction By Aspirin
Authors: IgnatiosIkonomidis, FelicitaAndreotti, EmanouelEconomou, ChristodoulosStefanadis, PavlosToutouzas, PetrosNihoyannopoulos
Journal: Circulation (1999)

Background—Proinflammatory cytokines released by injured endothelium facilitate interaction of endothelial cells with circulating leukocytes and thus may contribute to development and progression of atherosclerosis. We investigated whether cytokines and C-reactive protein (CRP) are indicative of myocardial ischemia or of diseased vessels and whether they are influenced by aspirin treatment in patients with chronic stable angina. Methods and Results—Plasma macrophage colony stimulating factor (MCSF), IL-1b, IL-6, and CRP were measured in 60 stable patients after 48-hour Holter monitoring and in 24 matched controls. All patients had angiographic documentation of disease and positive exercise ECGs. Patients with ischemia on Holter monitoring (n=40) received aspirin or placebo in a 6-week, randomized, double blind, crossover trial. Blood sampling was repeated at the end of each treatment phase (3 weeks). Compared to controls, patients had more than twice median MCSF (800 versus 372 pg/mL), IL-6 (3.9 versus 1....
Prognostic Significance of Serial Changes in Left Ventricular Mass in Essential Hypertension
Authors: PaoloVerdecchia, GiuseppeSchillaci, ClaudiaBorgioni, AntonellaCiucci, RobertoGattobigio, IvanoZampi, GianpaoloReboldi, CarloPorcellati
Journal: Circulation (1998)

Background—Increased left ventricular (LV) mass predicts an adverse outcome in patients with essential hypertension. The purpose of this study was to determine the relation between changes in LV mass during antihypertensive treatment and subsequent prognosis. Methods and Results—Procedures including echocardiography and 24-hour ambulatory blood pressure (BP) monitoring were performed in 430 patients with essential hypertension before therapy and after 1217 patient-years. Months or years after the follow-up visit, 31 patients suffered a first cardiovascular morbid event. The patients with a decrease in LV mass from the baseline to follow-up visit were compared with those with an increase in LV mass. There were 15 events (1.78 per 100 person-years) in the group with a decrease in LV mass and 16 events (3.03 per 100 person-years) in the group with an increase in LV mass (P=.029). In a Cox model, the lesser cardiovascular risk in the group with a decrease in LV mass (hazard ratio [HR], 0.46; 95% CI, 0.22 to 0...
Abstract 5461: B7-H3 regulates NF-kB signaling in cancer cells by modulating the degradation and re-synthesis of IkBα
Authors: Sarah Glazer, Seth Gammon, David Piwnica-Worms
Journal: Cancer Research (2018)

Abstract B7-H3, a B7 homologue, is highly expressed on tumors and tumor vasculature. Although its role as a T cell inhibitor or co-stimulator is still under investigation, high expression of membranous B7-H3 in the tumor compartment is correlated with poor overall survival. NF-kB activation, standing at the intersection between inflammation and cancer, can lead to both the production of cytokines that engage the innate immune system, as well as pro-proliferative signals in cancer. B7-H3 has been shown to enhance and suppress inflammatory signaling by modulating NF-kB. However, the mechanism by which this occurs in cancer cells remains unknown. In this study, we aim to understand how B7-H3 modulates the NF-kB pathway in order to regulate incoming inflammatory signals in cancer cells. The human colon cancer cell line, HCT116, was stably transfected with a transcriptionally-coupled post-translational NF-kB luciferase reporter comprising of the inhibitor of NF-kB, IkBα, fused to firefly luciferase and placed downstream of an NF-kB responsive promoter, kB5. This construct allows for the real-time readout of the degradation of IkBα and NF-kB driven transcriptional re-synthesis of IkBα in response to a stimulus. The reporter cell line was treated with two stimulants, TNFα and flagellin, that activate NF-kB through different pathways and to different degrees with or without treatment with human B7-H3. Treatment of the reporter cell line with B7-H3 alone did not induce IkBα degradation or re-synthesis. However, stimulation of the reporter cell line with TNFα or flagellin in combination with B7-H3 attenuated the degradation of IkBα and its re-synthesis compared to stimulation with TNFα or flagellin alone. Maximal re-synthesis of IkBα when stimulated with TNFα was 8.25 ± 1.51 fold (S.D.) and significantly increased compared to cells additionally treated with B7-H3 (5.83 ± 1.23 fold, p = .01). In addition, peak degradation time of IkBα when cells were stimulated by TNFα was 45 ± 5 min (S.D.), and significantly shorter than when cells were also treated with B7-H3 (61.67 ± 2.89 min, p = .01). Similar trends were observed when cells were treated with both flagellin and B7-H3 compared to stimulation with flagellin alone. These studies show that B7-H3 suppresses the response of colon cancer cells to incoming inflammatory stimuli and attenuates NF-kB signaling by tempering the kinetics and dynamics of IkBα. Citation Format: Sarah Glazer, Seth Gammon, David Piwnica-Worms. B7-H3 regulates NF-kB signaling in cancer cells by modulating the degradation and re-synthesis of IkBα [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5461.
Abstract 1232: Familial mesothelioma: BeyondBAP1
Authors: Mitchell Cheung, Jill A. Ohar, Suzanne E. Howard, Timothy D. Howard, Mary Hesdorffer, Joseph R. Testa
Journal: Cancer Research (2018)

Abstract BAP1 germline mutations are associated with some, but not all, familial malignant mesotheliomas. We sought to identify new genetic risk factors from a large cohort of malignant mesotheliomas cases with a family history of cancers but no germline BAP1 mutation. Whole genome sequencing was performed on 15 samples (14 peripheral blood and 1 MM sample). Promising mutated candidate genes were identified in 12 of 14 BAP1 mutation-negative cases, with 3 different candidate genes mutated in 3 cases, 2 different candidates mutated in 5 cases, and 1 candidate mutated in 4 cases. Candidate genes encoded proteins involved in DNA damage repair, DNA polymerase, DNA and histone methytransferase, as well as mitotic control, helicase, and kinase factors. All mutations were confirmed by Sanger sequencing. Mutations included in/dels predicting frameshifts (4), splice site mutations (6), and missense mutations (14). Notably, in addition to being BAP1 mutation-negative, germline mutations were not identified in any of the genes known to be commonly mutated somatically in malignant mesothelioma, i.e., CDKN2A, NF2, TP53, SETD2, or PBRM1. Sequencing of blood and/or tumor DNA from several available affected members of these families validated co-segregation of mutations in candidate genes with the development of various cancers. Malignant mesothelioma specimens from two members of one family showed somatic loss of heterozygosity of the wild-type allele, indicating biallelic inactivation of the candidate gene—a suspected tumor suppressor locus—in these tumors. Citation Format: Mitchell Cheung, Jill A. Ohar, Suzanne E. Howard, Timothy D. Howard, Mary Hesdorffer, Joseph R. Testa. Familial mesothelioma: Beyond BAP1 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1232.
Structurally graduated collagen scaffolds applied to the ex vivo generation of platelets from human pluripotent stem cell-derived megakaryocytes: Enhancing production and purity
Authors: Jennifer H. Shepherd, Daniel Howard, Amie K. Waller, Holly Rebecca Foster, Annett Mueller, Thomas Moreau, Amanda L. Evans, Meera Arumugam, Guénaëlle Bouët Chalon, Eleonora Vriend, Natalia Davidenko, Cedric Ghevaert, Serena M. Best, Ruth E. Cameron
Journal: Biomaterials (2018)
Abstract 17383: Transplantation of Anti-microRNA-377-modified Bone Marrow-derived Progenitor Cells Attenuates Myocardial Infarction-induced Lv Dysfunction in Mouse
Authors: Darukeshwara Joladarashi, Venkata Naga Srikanth Garikipati, Rajarajan A. Thandavarayan, Suresh K. verma, Alexander R. Mackie, Mohsin Khan, Shashirekha Krishnamurthy, Sahana Suresh Babu, Prince Jeyabal, Raj Kishore, Prasanna Krishnamurthy
Journal: Circulation (2015)

Cardiac diseases are the predominant cause of human mortality in the United States and around the world. MicroRNAs (miRNA/miR) are small non-coding RNAs that have been shown to modulate a wide range of biological functions under various pathophysiological conditions. MiRNA act as molecular switches of gene expression and are thought to regulate complex cardiac signaling and transcriptional circuits during cardiac development and disease. However, its effects on endothelial progenitor cells (EPC) biology and function, particularly in the context of cell-based therapy for cardiomyopathy are not fully understood. The purpose of this study was to determine the miRNA profile of EPCs in response to chronic inflammatory stimuli and evaluate if miRNA-377 impairs differentiation and function of mouse bone marrow-derived EPCs after transplantation in myocardial ischemic conditions. MiRNA array profile of EPCs in response to inflammatory stimuli (LPS, 20ng/ml) for 12 hrs, EPC migration and invitro vascular tube formation was analyzed. GFP-labeled EPC (transfected with either anti-miR-377 or control-anti-miR) were transplanted intramyocardially after induction of MI in mice. miRNA array data from EPCs in response to inflammatory stimuli has indicated modulation of number of miRNAs related to angiogenesis with a robust decrease in miR-377. Pre-miR-377 transfection in EPCs inhibits their migration P&lt;0.05) and vascular tube formation ability (P&lt;0.05). Furthermore, EPCs treated with miR-377 mimic showed decrease in protein expression of HAND2. Interestingly, in a relevant mouse model of myocardial infarction (MI), intramyocardial transplantation of miR-377-silenced (anti-miR-377 transfected, GFP-labeled) EPCs promote neovascularization (at 28 days, post-MI) leading to improvement in myocardial repair (reduced fibrosis and infarct size). Echocardiography showed LV function was significantly improved in mice receiving miR-377-silenced EPCs compared to control-miR-transfected EPCs. Taken together, these data suggest that inhibiting miR-377 in EPCs might promote their engraftment and angiogenic ability after transplantation into ischemic myocardial tissue, possibly through activation of HAND2 signaling axes.
Low Concentration of Oxidized Low-Density Lipoprotein and Lysophosphatidylcholine Upregulate Constitutive Nitric Oxide Synthase mRNA Expression in Bovine Aortic Endothelial Cells
Authors: Ken-ichiHirata, NobuhikoMiki, YuichiKuroda, TsuyoshiSakoda, SeinosukeKawashima, MitsuhiroYokoyama
Journal: Circulation Research (1995)

Abstract Endothelium-dependent relaxation is markedly reduced in atherosclerotic arteries. Recently, the endothelium-dependent relaxing factor has been identified as nitric oxide (NO). We used RNase protection assay and immunoblotting to elucidate the effect of atherogenic lipoprotein on the expression of constitutive NO synthase (cNOS) mRNA and protein levels in bovine aortic endothelial cells. Twenty-four-hour exposure to a low concentration of oxidized low-density lipoprotein (10 μg protein/mL) upregulated cNOS mRNA levels (2.4±0.4-fold, P<.01). However, native low-density lipoprotein and high-density lipoprotein did not have any effect on cNOS mRNA levels. Furthermore, 5 μg/mL of lysophosphatidylcholine (LPC) also upregulated cNOS mRNA levels (2.6±0.5-fold, P<.01) at 8 hours. This action of LPC was abolished with cycloheximide but not with staurosporine. We concluded that atherogenic lipoproteins upregulate cNOS mRNA and protein levels in bovine aortic endothelial cells. This observation supports the ...
Mechanisms by Which Late Coronary Reperfusion Mitigates Postinfarction Cardiac Remodeling
Authors: MunehiroNakagawa, GenzouTakemura, HiromitsuKanamori, KazukoGoto, RumiMaruyama, AkikoTsujimoto, TakamasaOhno, HideshiOkada, AtsushiOgino, MasayasuEsaki, ShusakuMiyata, LonghuLi, HiroakiUshikoshi, TakumaAoyama, MasanoriKawasaki, KenshiNagashima, TakakoFujiwara, ShinyaMinatoguchi, HisayoshiFujiwara
Journal: Circulation Research (2008)

Although recanalization of the infarct-related artery late after myocardial infarction (MI) is known to reduce both cardiac remodeling and mortality, the mechanisms responsible are not yet fully understood. We compared infarcted rat hearts in which the infarct-related coronary artery was opened 24 hours after infarction (late reperfusion [LR] group) with those having a permanently occluded artery. Left ventricular dilatation and dysfunction were significantly mitigated in the LR group 1, 2, and 4 weeks post-MI. Attributable, in large part, to the greater number of cells present, the infarcted wall was significantly thicker in the LR group, which likely reduced wall stress and mitigated cardiac dysfunction. Granulation tissue cell proliferation was increased to a greater degree in the LR group 4 days post-MI, whereas the incidence of apoptosis was significantly lower throughout the subacute stage (4 days, 1 week, and 2 weeks post-MI), further suggesting preservation of granulation tissue cells contributes ...
Subunit Expression of the Cardiac L-Type Calcium Channel Is Differentially Regulated in Diastolic Heart Failure of the Cardiac Allograft
Authors: RogerHullin, FriedrichAsmus, AndreasLudwig, JoachimHersel, PeterBoekstegers
Journal: Circulation (1999)

Background—Left ventricular diastolic dysfunction is a major cause of cardiac allograft failure. Multimeric L-type calcium channels (α1-, α2/δ-, and β-subunits) are essential for excitation/contraction coupling in the heart. Their gene expression was studied in allografts that developed diastolic heart failure. Methods and Results—mRNA levels of calcium channel subunits were measured by competitive reverse transcriptase–polymerase chain reaction in microbiopsy samples from the interventricular septum. Size and tissue variabilities between biopsy samples were assessed by determination of cardiac calsequestrin mRNA levels. In the cardiac allografts studied, mRNA levels in microbiopsy samples were considered to represent left ventricular gene expression, because septal and left ventricular gene expression in Northern blots was equivalent, and left ventricles contracted homogeneously. Biopsy samples (n=72) were taken from allografts with normal left ventricular end-diastolic pressure (LVEDP; 8 to 13 mm Hg; n=...
Abstract 16069: Low-Density Lipoprotein of Systemic Lupus Erythematosus Patients Contains Lysophosphatidylcholine-Rich Lipid That Induces Overexpression of CX3CL1 in Endothelial Cells
Authors: Hua-ChenChan, Liang-YinKe, Hsiu-ChuanChan, HungSu, An-ShengLee, JonathanLu, Wen-ChanTsai, Tsan-TengOu, Cheng-ChinWu, Chih-ShengChu, JentaieShiea, Jeng-HsienYen, Chu-HuangChen
Journal: Circulation (2014)

Background: Patients with systemic lupus erythematosus (SLE) are twice more likely to develop cardiovascular disease than the general population, even though their plasma LDL cholesterol (LDL-C) levels are usually not elevated. To delineate the mechanisms, we examined the chemical properties of their LDL. Methods and Results: LDL isolated from SLE patients (LDL-C, 105±33 mg/dL; n=24) exhibited greater mobility in agarose gel electrophoresis than LDL of healthy control subjects (LDL-C, 121±25 mg/dL; n=24), secondary to an increased distribution of L5 (2.30±1.3% vs. 0.7±0.3%; P<0.0001), the most electronegative subfraction of LDL identified by anion-exchange chromatography, in total LDL. CX3CL1 is a membrane-bound chemokine expressed in injured endothelial cells (ECs). CD16+ monocytes are CX3CR1-expressing cells that recognize CX3CL1. Compared with control, SLE patients had a twofold (P<0.001) increase in CX3CL1 and a threefold (P<0.0001) increase in CD16+ monocytes in the plasma. Moreover, there was a posi...
Blockage of VEGF-Induced Angiogenesis by Preventing VEGF Secretion
Authors: MeitBjörndahl, RenhaiCao, AnnaEriksson, YihaiCao
Journal: Circulation Research (2004)

Vascular endothelial growth factor (VEGF)/vascular permeability factor is one of the most frequently expressed angiogenic factors in several pathological tissues. Development of VEGF antagonists has become an important approach in the treatment of angiogenesis-dependent diseases. Here we describe a novel anti-VEGF strategy by preventing the secretion of VEGF. We utilize the fact that placenta growth factor (PlGF)-1, a member of the VEGF family lacking detectable angiogenic activity, preferentially forms intracellular heterodimers with VEGF in cells coexpressing both factors. We constructed a retroviral vector containing human PlGF-1 or VEGF with a C-terminal KDEL sequence, which is a mammalian retention signal for the endoplasmic reticulum. Transduction of murine Lewis lung carcinoma cells with the retro-hPlGF-1-KDEL construct almost completely abrogated tumor growth. Consistent with the dramatic antitumor effect, most mouse VEGF molecules remained as intracellular mVEGF/hPlGF-1 heterodimers, and only a n...