tbuckley/cabot-search huggingface dataset:
Decreased Expression and Activity of cAMP Phosphodiesterases in Cardiac Hypertrophy and Its Impact on β-Adrenergic cAMP Signals
Authors: AniellaAbi-Gerges, WitoRichter, FlorenceLefebvre, PhilippeMateo, AudreyVarin, ChristopheHeymes, Jane-LiseSamuel, ClaireLugnier, MarcoConti, RodolpheFischmeister, GrégoireVandecasteele
Journal: Circulation Research (2009)

Rationale: Multiple cyclic nucleotide phosphodiesterases (PDEs) degrade cAMP in cardiomyocytes but the role of PDEs in controlling cAMP signaling during pathological cardiac hypertrophy is poorly defined. Objective: Evaluate the β-adrenergic regulation of cardiac contractility and characterize the changes in cardiomyocyte cAMP signals and cAMP-PDE expression and activity following cardiac hypertrophy. Methods and Results: Cardiac hypertrophy was induced in rats by thoracic aortic banding over a time period of 5 weeks and was confirmed by anatomic measurements and echocardiography. Ex vivo myocardial function was evaluated in Langendorff-perfused hearts. Engineered cyclic nucleotide-gated (CNG) channels were expressed in single cardiomyocytes to monitor subsarcolemmal cAMP using whole-cell patch-clamp recordings of the associated CNG current (ICNG). PDE variant activity and protein level were determined in purified cardiomyocytes. Aortic stenosis rats exhibited a 67% increase in heart weight compared to sh...
Abstract 2207: High-risk human papillomavirus detection in head and neck cancers using saliva
Authors: Kai D Tang, Chris Perry, Chamindie Punyadeera
Journal: Cancer Research (2018)

Abstract Human papillomavirus (HPV), a virus vital to the etiology of cervical cancer, is strongly associated with the development of head and neck cancer. Therefore, it is pivotal to develop a noninvasive and cost-effective approach for detecting oral HPV. Accumulating evidence suggested the usefulness of salivary oral rinse as a diagnostic fluid to detect oral HPV DNA within a clinical setting. However, there is little known about the HPV DNA prevalence and type distribution in unstimulated whole mouth saliva (UWMS). In the current study, we show a positive correlation of HPV-16 E2 (r = 0.95, p &amp;lt; 0.0001) and E6/7 (r = 0.93, p &amp;lt; 0.0001) relative copy number as well as high-risk HPV genotypes (HPV 16, 18 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68) and fold change difference between the relative copy numbers of E2 and E6/7 (r = 0.46, p &amp;lt; 0.0098) in both salivary oral rinse and UWMS samples collected from OPC patients. More importantly, in line with the previous study, among HPV-16 positive head and neck cancer cases, most often a mixed HPV-16 form (episomal and integrated) was found in both saliva sampling methods. In conclusion, regardless of the sampling method, detection of HPV in saliva is an attractive, noninvasive method that could change the need for invasive biopsies in head and neck cancer patients. Citation Format: Kai D Tang, Chris Perry, Chamindie Punyadeera. High-risk human papillomavirus detection in head and neck cancers using saliva [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 2207.
Abstract P126: Calpain Protects the Heart from Hemodynamic Stress
Authors: Manabu Taneike, Shungo Hikoso, Osamu Yamaguchi, Kazuhiko Nishida, Naoki Mochizuki, Issei Komuro, Kinya Otsu
Journal: Circulation Research (2011)

Although calpains are well-known Ca 2+ -dependent intracellular cysteine proteases, the pathophysiological function of calpains in the heart remains to be elucidated. Previous reports have suggested that calpains play detrimental roles to induce apoptotic or necrotic cell death in pathological Ca 2+ -overloaded conditions such as ischemia-reperfusion injury or myocardial infarction. Recent loss of function studies have suggested that calpains play important physiological roles in development, cell migration, organization of actin cytoskeleton, and plasma membrane repair. In the present study, we generated and analyzed cardiac-specific calpain 4-deficient mice (CKO) to answer unresolved questions as to in vivo function of calpains in the heart. Ubiquitous calpain is consisted of a common regulatory subunit (calpain 4) and a large catalytic subunit (calpain 1 for μ-calpain and calpain 2 for m-calpain). In agreement with previous reports, cardiac-specific deletion of calpain 4 markedly resulted in a simultaneous decrease in protein levels of calpain 1 and 2, indicating that calpain activity was almost absent in CKO hearts. CKO showed no cardiac phenotypes under basal conditions. Then, we subjected CKO and control mice (CTL) to pressure overload by means of transverse aortic constriction (TAC). One week after TAC, CKO showed left ventricle dilatation (LVDd, CKO 3.64 ± 0.2 mm versus CTL 2.66 ± 0.05 mm), and contractile dysfunction (FS, CKO 33.2 ± 3.9% versus CTL 47 ± 0.7%). CKO hearts took up Evans blue, a membrane-impermeant dye, within cardiomyocytes after TAC, whereas CTL hearts or sham-operated CKO hearts did not. This indicates plasma membrane was disrupted in CKO hearts in response to pressure overload. We performed membrane repair assays on isolated cardiomyocytes from CKO hearts using a two-photon laser-scanning microscope. CKO cardiomyocytes continued to take up FM1-43FX dye for at least 480 sec after disruption of a plasma membrane by laser irradiation, although CTL cardiomyocytes resealed within 250 sec. These data indicate that plasma membrane of cardiomyocytes disrupted by pressure overload failed to be resealed in CKO hearts. Thus, we conclude that calpains protect the heart from hemodynamic stresses by promoting membrane repair.
Expression of Cell Adhesion Molecules in Dilated Cardiomyopathy
Authors: MichelNoutsias, BettinaSeeberg, Heinz-PeterSchultheiss, UweKühl
Journal: Circulation (1999)

Background—Dilated cardiomyopathy (DCM) is pathogenically linked to inflammatory cardiomyopathy (InfCM), which is characterized by intramyocardial infiltration. The transendothelial migration of immunocompetent cells is mediated by cell adhesion molecules (CAMs). Methods and Results—We investigated the expression pattern of CAMs (immunoglobulin superfamily, 32 selectins, and β1- and β2-integrins) in endomyocardial biopsies from DCM patients (n=152; left ventricular ejection fraction  3 CAMs (inflammatory endothelial activation), nor did any control tissue prove positive for InfCM (>7.0 CD3+ lymphocytes per 1 mm2). In comparison, 64% (n=97) of the DCM biopsies were evaluated positive for InfCM and 67% (n=101) for inflammatory endothelial activ...
Serotonin Inhibits Voltage-Gated K+ Currents in Pulmonary Artery Smooth Muscle Cells
Authors: AngelCogolludo, LauraMoreno, FedericaLodi, GiovannaFrazziano, LauraCobeño, JuanTamargo, FranciscoPerez-Vizcaino
Journal: Circulation Research (2006)

Multiple lines of evidence indicate that serotonin (5-hydroxytryptamine [5-HT]) and voltage-gated K+ (KV) channels play a central role in the pathogenesis of pulmonary hypertension (PH). We hypothesized that 5-HT might modulate the activity of KV channels, therefore establishing a link between these pathogenetic factors in PH. Here, we studied the effects of 5-HT on KV channels present in rat pulmonary artery smooth muscle cells (PASMC) and on hKV1.5 channels stably expressed in Ltk− cells. 5-HT reduced native KV and hKV1.5 currents, depolarized cell membrane, and caused a contraction of isolated pulmonary arteries. The effects of 5-HT on KV currents and contraction were markedly prevented by the 5-HT2A receptor antagonist ketanserin. Incubation with inhibitors of phospholipase C (U73122), classic protein kinase Cs (Go6976), or tyrosine kinases (genistein and tyrphostin 23), the cholesterol depletion agent β-cyclodextrin or concanavalin A, an inhibitor of endocytotic processes, also prevented the effects...
Abstract 5626: Preclinical characterization of Sym022, a novel anti-LAG3 antibody
Authors: Michael M. Grandal, Maria C. Melander, Vikram K. Bhatia, Torben Gjetting, Trine Lindsted, Camilla Fröhlich, Johan Lantto, Ivan D. Horak, Michael Kragh, Klaus Kofoed, Mikkel W. Pedersen
Journal: Cancer Research (2018)

Abstract Immunotherapy has become a major focus of research in oncology and blockade of immune checkpoints such as cytotoxic T-Lymphocyte associated protein 4 (CTLA4) and programmed cell death protein 1 (PD1) has been some of the most successful immunotherapies. Lymphocyte-activation gene 3 (LAG3) belongs to the second-generation immune modulatory targets. LAG3 is expressed by activated T-cells and tumor infiltrating lymphocytes (TILs) and negatively regulates T-cell activity upon ligand engagement. LAG3 binds major histocompatibility complex class II (MHCII) molecules found on the surface of antigen presenting cells and tumor cells. Sym022 is a Fc-inert human monoclonal antibody targeting LAG3. Sym022 binds to human and cynomolgus monkey LAG3 with high affinity and blocks the interaction between LAG3 and MHCII molecules. Functionally, Sym022 increases cytokine production by T-cells in vitro and tumor growth inhibition in vivo. Mechanistically, Sym022 not only blocks ligand binding, but also decreases total LAG3 surface levels through internalization and/or shedding. Citation Format: Michael M. Grandal, Maria C. Melander, Vikram K. Bhatia, Torben Gjetting, Trine Lindsted, Camilla Fröhlich, Johan Lantto, Ivan D. Horak, Michael Kragh, Klaus Kofoed, Mikkel W. Pedersen. Preclinical characterization of Sym022, a novel anti-LAG3 antibody [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 5626.
<i>HLA-B*5801</i> Testing to Prevent Allopurinol Hypersensitivity Syndrome
Authors: Cuong Quach, Benjamin T. Galen
Journal: JAMA Internal Medicine (2018)

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High-Resolution Electrophysiological Assessment of Human Embryonic Stem Cell-Derived Cardiomyocytes
Authors: IzhakKehat, AmiraGepstein, AlonSpira, JosephItskovitz-Eldor, LiorGepstein
Journal: Circulation Research (2002)

The goal of the present report was to establish a new in vitro model for the study of impulse propagation in human cardiac tissue. By using the human embryonic stem cell differentiating system, spontaneously contracting areas were generated in three-dimensional differentiating cell aggregates (embryoid bodies). Morphological analysis revealed an isotropic tissue of early-stage cardiac phenotype. Gap junctions, assessed by immunostaining of connexin43 and connexin45, were distributed along the cell borders. High-resolution activation maps demonstrated the presence of a functional syncytium with stable focal activation and conduction properties. Conduction was significantly slower in narrow bands of contracting tissue compared with broad cardiomyocyte regions. Establishment of this unique in vitro human model may be used for the assessment of long-term structure-function relationships, for pharmacological studies, for tissue engineering, and may permit the study of genetically modified cardiomyocytes.
Abstract 13994: Anti-cellular Proliferation Therapy Reduces Atherosclerotic Plaques and Vascular Inflammation in Experimental Hypercholesterolemia
Authors: Fernando L Gomes, Raul C Maranhao, Elaine R Tavares, Priscila C Oliveira, Thiago V Machado, Alexandre M Soeiro, Maria de Lourdes Higuchi, Roberto Kalil-Filho, Carlos V Serrano
Journal: Circulation (2016)

Introduction: The lipid nanoemulsion (LDE) binds intensely to LDL receptors due to similarity in molecular composition. Anti-proliferative agents paclitaxel (PTX) and methotrexate (MTX) may have beneficial effects on atherosclerosis by preventing proliferation of inflammatory cells and vascular smooth muscle cells. Hypothesis: By combining LDE to PTX and MTX, effective regression of hypercholesterolemic atherosclerosis and vascular inflammation occurs. Methods: Rabbits underwent induction of atherosclerosis by consuming a cholesterol diet for 8 weeks. Afterwards, 7 rabbits were sacrificed and had their aortas analyzed (Control group). The other rabbits had diet replaced by regular diet, and were divided into 3 groups (n=7 each), according to the 8-week treatment offered: LDE-PTX, LDE-PTX+MTX and Diet (no agent). The rabbits were then sacrificed and the aortas analyzed. Vascular tumor necrosis factor-α (TNF) gene expression was determined in all aorta samples. Results: See graph. LDE-PTX and LDE-PTX+MTX treatments presented marked gross regressions of plaque areas when compared to Control. Diet treatment alone did not reduce significantly plaque area. Regarding TNF gene expression, Control group presented 1.70±1.01 mRNA levels while LDE-PTX, LDE-PTX+MTX and diet alone groups presented 1.01±0.03, 0.31±0.10 and 0.20±0.09 levels (p&lt;0.01 ANOVA). All 3 treatment groups produced significant decrease in LDL blood levels. Conclusions: Therefore, this study demonstrates that anti-cellular proliferation by PTX+MTX, combined to LDE, produces marked gross atherosclerotic regression and beneficial effect on vascular inflammation.
Bisphosphonate Functionalized Gadolinium Oxide Nanoparticles Allow Long‐Term MRI/CT Multimodal Imaging of Calcium Phosphate Bone Cement
Authors: Simone Mastrogiacomo, Alicja E. Kownacka, Weiqiang Dou, Benjamin P. Burke, Rafael T. M. de Rosales, Arend Heerschap, John A. Jansen, Stephen J. Archibald, X. Frank Walboomers
Journal: Advanced Healthcare Materials (2018)

Abstract Direct in vivo monitoring of bioconstructs using noninvasive imaging modalities such as magnetic resonance imaging (MRI) or computed tomography (CT) is not possible for many materials. Calcium phosphate–based composites (CPCs) that are applicable to bone regeneration are an example where the materials have poor MRI and CT contrast; hence, they are challenging to detect in vivo. In this study, a CPC construct is designed with gadolinium‐oxide nanoparticles incorporated to act as an MRI/CT multimodal contrast agent. The gadolinium(III) oxide nanoparticles are synthesized via the polyol method and surface functionalized with a bisphosphonate (BP) derivative to give a construct (gadolinium‐based contrast agents (GBCAs)‐BP) with strong affinity toward calcium phosphate. The CPC‐GBCAs‐BP functional material is longitudinally monitored after in vivo implantation in a condyle defect rat model. The synthetic method developed produces nanoparticles that are stable in aqueous solution (hydrodynamic diameter 70 nm) with significant T 1 and T 2 relaxivity demonstrated in both clinical 3 T and preclinical 11.7 T MRI systems. The combination of GBCAs‐BP nanoparticles with CPC gives an injectable material with handling properties that are suitable for clinical applications. The BP functionalization prolongs the residence of the contrast agent within the CPC to allow long‐term follow‐up imaging studies. The useful contrast agent properties combined with biological compatibility indicate further investigation of the novel bone substitute hybrid material toward clinical application.
Aberrant hyperediting of the myeloma transcriptome by ADAR1 confers oncogenicity and is a marker of poor prognosis
Authors: Phaik Ju Teoh, Omer An, Tae-Hoon Chung, Jing Yuan Chooi, Sabrina H. M. Toh, Shuangyi Fan, Wilson Wang, Bryan T. H. Koh, Melissa J. Fullwood, Melissa G. Ooi, Sanjay de Mel, Cinnie Y. Soekojo, Leilei Chen, Siok Bian Ng, Henry Yang, Wee Joo Chng
Journal: Blood (2018)
Abstract 285: The Effects of Shengfu Injection on Postresuscitation Myocardial Dysfunction and the Impressions of ?-Opioid Receptor in Myocardium in Cardiac Arrest and Cardiopulmonary Rats
Authors: Yi Shan, Jian Wan, Xingyi Yang, Dechang Chen, Wenfang Li, Zhaofen Lin
Journal: Circulation (2012)

Objective: The effects of a Chinese traditional medicine Shenfu injection on postresuscitation myocardial dysfunction and the impressions of kappa-opioid receptor in myocardium were investigated in CA/CPR rats, for better understanding of resuscitation medication clinical applications. Methods: 60 male SD rats were randomized into Shenfu injection (SF) group (n=30) and Control group (n=30). Asphyxia-induced CA was performed by turning-off the ventilator and clamping the endotracheal tube. CPR with chest compression and mechanical ventilation were started after 7min of asphyxia. Shenfu (20ml/kg·h) or saline (20ml/kg·h) was infused from on set of CPR in each group. The baseline blood gas, dP/dt40, LVDP and -dP/dt max were measured. The rat hearts were harvested at 0.5h, 2h, 4h, 6h and 24h post resuscitation (PR). The mRNA and protein impressions of κ-OR in postresuscitation myocardium were measured. Results: All animals in SF group were successfully resuscitated. 2 were non-resuscitated, 3 occurred VF during CA/CPR in Control group. The 24h survival rate was no statistics difference between SF and control group(50% vs 75%, P =0.264). The postresuscitation myocardial dysfunctions were progressively reversed in Shengfu group. Secifically, HR and MAP were reversed to baseline after PR6h; dP/dt 40 and -dP/dt max were significantly increased at PR24h in Shengfu group, in comparison to Control group (P&lt;0.01). The mRNA and protein impressions of κ-OR in postresuscitation myocardium were with a trend of rise up and fell down in all groups, with the highest κ-OR impressions at PR2h. The κ-OR impressions were significantly decreased in SF group, in comparison to Control group (P&lt;0.05). Conclusions: The postresuscitation myocardial dysfunctions were remarkably decreased in Shenfu group in comparison to control group. The mRNA and protein impressions of κ-OR in postresuscitation myocardium were significantly decreased after shenfu infusion.
Hepatocellular Carcinoma After Fontan Operation
Authors: Alexander C. Egbe, Joseph T. Poterucha, Carole A. Warnes, Heidi M. Connolly, Shankar Baskar, Salil Ginde, Paul Clift, Brian Kogon, Wendy M. Book, Niki Walker, Lodewijk Wagenaar, Tabitha Moe, Erwin Oechslin, W. Aaron Kay, Mark Norris, Timothy Gordon-Walker, Jonathan R. Dillman, Andrew Trout, Nadeem Anwar, Arvind Hoskoppal, Gruschen R. Veldtman
Journal: Circulation (2018)
Abstract 16296: The Contribution of Macrophage Subpopulations During Collateral Growth
Authors: Matthias Willmer, Christian Troidl, Georg Jung, Kerstin Troidl, Hoffmann Jedrzej, Sebastian Szardien, Sandra Voss, Christoph Liebetrau, Helge Möllmann, Holger Nef, Wolfgang Schaper, Christian Hamm, Thomas Schmitz-Rixen
Journal: Circulation (2012)

Arterial occlusion leads to growth of collaterals, in which macrophages (MAC) play a prominent role. However, a detailed analysis which MAC-subpopulations are involved in arteriogenesis has never b...
QT Dispersion Has No Prognostic Information for Patients With Advanced Congestive Heart Failure and Reduced Left Ventricular Systolic Function
Authors: BenteBrendorp, HanneElming, LiJun, LarsKøber, MarekMalik, Gorm BojeJensen, ChristianTorp-Pedersen
Journal: Circulation (2001)

Background—QT dispersion is a potential prognostic marker of tachyarrhythmic events and death, but it is unclear whether this applies to patients with congestive heart failure (CHF). Methods and Results—Of the 1518 patients with advanced CHF and left ventricular dysfunction enrolled in the Danish Investigations of Arrhythmia and Mortality on Dofetilide-CHF (Diamond-CHF) study, a baseline ECG was available in 1319 patients. Of these, QT dispersion could be measured in 703 patients. During a median follow-up of 18 months (minimum 1 year), 285 patients (41%) died. The median QT dispersion was 70 ms (34/155 ms [5%/95% percentiles]), with no difference between survivors and nonsurvivors. Survival analysis revealed no prognostic information derived from QT dispersion regarding all-cause mortality (risk ratio 1.00, 95% CI 1.00 to 1.00; P=0.74), cardiac mortality (risk ratio 1.00, 95% CI 1.00 to 1.01; P=0.55), or cardiac arrhythmic mortality (risk ratio 1.00, 95% CI 0.99 to 1.01; P=0.38). Conclusions—QT dispersio...
Hypersensitivity of BKCa to Ca2+ Sparks Underlies Hyporeactivity of Arterial Smooth Muscle in Shock
Authors: GuilingZhao, YanZhao, BingxingPan, JieLiu, XuliangHuang, XiuqinZhang, ChunmeiCao, NingHou, CaihongWu, Ke-sengZhao, HepingCheng
Journal: Circulation Research (2007)

Large conductance Ca2+-activated K+ channels (BKCa) play a critical role in blood pressure regulation by tuning the vascular smooth muscle tone, and hyposensitivity of BKCa to Ca2+ sparks resulting from its altered β1 subunit stoichiometry underlies vasoconstriction in animal models of hypertension. Here we demonstrate hypersensitivity of BKCa to Ca2+ sparks that contributes to hypotension and blunted vasoreactivity in acute hemorrhagic shock. In arterial smooth muscle cells under voltage-clamp conditions (0 mV), the amplitude and duration, but not the frequency, of spontaneous transient outward currents of BKCa origin were markedly enhanced in hemorrhagic shock, resulting in a 265% greater hyperpolarizing current. Concomitantly, subsurface Ca2+ spark frequency was either unaltered (at 0 mV) or decreased in hyperpolarized resting cells. Examining the relationship between spark and spontaneous transient outward current amplitudes revealed a hypersensitive BKCa activity to Ca2+ spark in hemorrhagic shock, w...
Coronary Artery Spasm Does Not Depend on the Intracellular Calcium Store but Is Substantially Mediated by the Protein Kinase C–Mediated Pathway in a Swine Model With Interleukin-1β In Vivo
Authors: ToshiakiKadokami, HiroakiShimokawa, YoshihiroFukumoto, AkiraIto, TsuneoTakayanagi, KensukeEgashira, AkiraTakeshita
Journal: Circulation (1996)

Background The intracellular mechanism for coronary artery spasm is still unknown. Since the protein kinase C (PKC)–mediated pathway and Ca2+ release from sarcoplasmic reticulum (SR) are important intracellular mechanisms of vascular smooth muscle contraction, we examined the possible role of these two mechanisms in the pathogenesis of coronary spasm in our swine model in vivo. Methods and Results In 25 pigs, interleukin-1β (IL-1β) was applied chronically to the coronary arteries from the adventitia to induce an inflammatory/proliferative lesion. Two weeks after the operation, either intracoronary serotonin or histamine repeatedly induced coronary spasm at the IL-1β–treated site. At those spastic sites, phorbol-12,13-dibutyrate, a PKC-activating phorbol ester, also induced coronary spasm, which was blocked by pretreatment with the PKC inhibitors staurosporine and sphingosine. Serotonin- and histamine-induced coronary spasm was also significantly inhibited by pretreatment with staurosporine, sphingosine, o...