tbuckley/cabot-search huggingface dataset:
Abstract 11235: Improvement of Defective Channel Function on RyR2 Mediated by CaMKII Activation Suppresses Arrhythmogenesis in TnT-related Hypertrophic Cardiomyopathy
Authors: ShinichiOkuda, YokoSufu-Shimizu, TakayoshiKato, YokoOkamoto, ShigehikoNishimura, TetsuroOda, ShigekiKobayashi, TakeshiYamamoto, MasafumiYano
Journal: Circulation (2016)

Backgrounds: In Familial Hypertrophic Cardiomyopathy (FHC) caused by cardiac troponin T (cTnT) mutations, Ca2+ sensitivity in myofilaments is increased, results in leading to sudden cardiac death. The activation of calcium/calmodulin-dependent protein kinase II (CaMKII) is known to be one of the key elements for the alteration of calcium handling in heart failure, presumably mediated through defective channel function of cardiac ryanodine receptor (RyR2). However, how cTnT mutations lead to lethal arrhythmias and abnormal calcium handling through defective RyR2 remains elusive. Here, we investigated the pathogenic role of CaMKII on aberrant Ca2+ release through RyR2 for arrhythmogenesis in FHC hearts and therapeutic effects of dantrolene, which was found to correct inter-domain interactions between N-terminal and central domain of RyR2 in FHC-related cTnT-mutated transgenic mouse (TG; cTnT-delta160E). TG have been reported myocardial disarray in histology and increased Ca2+ sensitivity in myofilaments. Me...
Abstract 13031: Real-Time Three-Dimensional Transesophageal Echocardiography for Diagnosis of Pannus Formation in Mechanical Aortic Valves: Comparison with Multi-detector Computed Tomography and Surgical Findings
Authors: SahminLee, Seung-PyoLee, Eun-AhPark, Mi-KyungHong, Ji-HyunKim, Han MoYang, Hyung-KwanKim, WhalLee, Yong-JinKim, Dae-WonSohn
Journal: Circulation (2014)

Introduction: Pannus formation is a rare but important complication that can be missed in patients with prosthetic valves. However, currently available methodologies are not sufficient to diagnose subvalvular pannus formation especially in mechanical aortic valves. Hypothesis: In this study, we explored a series of experiences with three-dimensional transesophageal echocardiography (3D-TEE) for the visualization and accurate assessment of subvalvular pannus in patients with mechanical aortic valve. Methods: We enrolled 11 patients (mean age 64±8.6 years, 10 patients with either double or triple valve replacement) who had previously implanted mechanical aortic valve, with transaortic mean pressure gradient >40mmHg or transaortic maximal velocity >4m/sec despite normal occluder motion. All patients underwent 3D-TEE examination to rule out pannus formation and these findings were compared with multi-detector computed tomography (MDCT) images and/or surgical findings. Results: In 10 patients, 3D-TEE allowed g...
Transcriptional profiling of HERV-K(HML-2) in amyotrophic lateral sclerosis and potential implications for expression of HML-2 proteins
Authors: Jens Mayer, Christian Harz, Laura Sanchez, Gavin C. Pereira, Esther Maldener, Sara R. Heras, Lyle W. Ostrow, John Ravits, Ranjan Batra, Eckart Meese, Jose Luis García-Pérez, John L. Goodier
Journal: Molecular Neurodegeneration (2018)

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder. About 90% of ALS cases are without a known genetic cause. The human endogenous retrovirus multi-copy HERV-K(HML-2) group was recently reported to potentially contribute to neurodegeneration and disease pathogenesis in ALS because of transcriptional upregulation and toxic effects of HML-2 Envelope (Env) protein. Env and other proteins are encoded by some transcriptionally active HML-2 loci. However, more detailed information is required regarding which HML-2 loci are transcribed in ALS, which of their proteins are expressed, and differences between the disease and non-disease states. For brain and spinal cord tissue samples from ALS patients and controls, we identified transcribed HML-2 loci by generating and mapping HML-2-specific cDNA sequences. We predicted expression of HML-2 env gene-derived proteins based on the observed cDNA sequences. Furthermore, we determined overall HML-2 transcript levels by RT-qPCR and investigated presence of HML-2 Env protein in ALS and control tissue samples by Western blotting. We identified 24 different transcribed HML-2 loci. Some of those loci are transcribed at relatively high levels. However, significant differences in HML-2 loci transcriptional activities were not seen when comparing ALS and controls. Likewise, overall HML-2 transcript levels, as determined by RT-qPCR, were not significantly different between ALS and controls. Indeed, we were unable to detect full-length HML-2 Env protein in ALS and control tissue samples despite reasonable sensitivity. Rather our analyses suggest that a number of HML-2 protein variants other than full-length Env may potentially be expressed in ALS patients. Our results expand and refine recent publications on HERV-K(HML-2) and ALS. Some of our results are in conflict with recent findings and call for further specific analyses. Our profiling of HML-2 transcription in ALS opens up the possibility that HML-2 proteins other than canonical full-length Env may have to be considered when studying the role of HML-2 in ALS disease.
Randomized Trial Needed to Confirm Whether Dalcetrapib Improves Outcomes for Specific <i>ADCY9</i> Genotype—Reply
Authors: Steven E. Nissen, Sreekumar G. Pillai
Journal: JAMA Cardiology (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
Communication quality between the medical team and the head coach/manager is associated with injury burden and player availability in elite football clubs
Authors: Jan Ekstrand, Daniel Lundqvist, Michael Davison, Michel D’Hooghe, Anne Marte Pensgaard
Journal: British Journal of Sports Medicine (2018)

Objectives We investigated medical staff interpretations and descriptions of internal communication quality in elite football teams to determine whether internal communication was correlated with injuries and/or player availability at training and matches. Methods Medical staff from 36 elite football clubs across 17 European countries produced 77 reports at four postseason meetings to provide their perceptions of internal communications in their teams. They also recorded data on individual players’ exposure to football and time-loss injuries. Results The injury burden and incidence of severe injuries were significantly higher in teams with low quality of communication between the head coach/manager and the medical team (scores of 1–2 on a 5-point Likert scale) compared with teams with moderate or high-quality scores (scores of 3–5; p=0.008 for both). Teams with low scores had 4%–5% lower training attendance (76% vs 83%, p=0.001) and less availability at matches (82% vs 88%, p=0.004) compared with teams with moderate or high communication quality scores. Conclusions The quality of internal communication within a team was correlated with injury rates, training attendance and match availability.
Angioscopic Prediction of Successful Dilatation and of Restenosis in Percutaneous Transluminal Coronary Angioplasty
Authors: AkiraItoh, ShunichiMiyazaki, HiroshiNonogi, SatoshiDaikoku, KazuoHaze
Journal: Circulation (1995)

Background Coronary angiography has been used to assess the anatomy of coronary artery and intraluminal pathological changes. However, it has several limitations in its diagnostic quality and sensitivity in the detection of intraluminal details. Angioscopy has enabled coronary artery lumens to be visualized directly and fine intraluminal morphological changes to be detected. The information obtained by angioscopy is expected to provide new insights into the mechanisms and pathophysiology of transluminal coronary angioplasty. Methods and Results Forty-seven patients (39 men and 8 women) with stable angina were enrolled in the present study. Angioscopy was performed before and after angioplasty with a 0.68-mm angioscope with a double–guiding catheter system. The patients who were successfully evaluated by angioscopy were divided into two groups according to the color of the lesion: group 1, mainly yellow; and group 2, white. Angiographic, angioscopic, and clinical parameters in the two groups were compared....
Rebound Phenomena after Anticoagulant Therapy in Cerebrovascular Disease
Authors: Johnmarshall
Journal: Circulation (1963)

Anticoagulant therapy did not reduce the incidence of further nonfatal cerebrovascular accidents in 90 patients who had already experienced one or more such accidents as compared with a control group. Following gradual withdrawal of therapy, however, there was a significantly increased incidence of nonfatal cerebrovascular accidents during the first three months after therapy. This suggests that following cessation of anticoagulant therapy there is a period of true rebound during which thrombo-embolic incidents are more likely to recur.
Human Monocyte–Endothelial Cell Interaction Induces Synthesis of Granulocyte-Macrophage Colony-Stimulating Factor
Authors: MasafumiTakahashi, SeiichiKitagawa, Jun-IchiMasuyama, UichiIkeda, TadashiKasahara, Yu-IchiTakahashi, YusukeFurukawa, ShogoKano, KazuyukiShimada
Journal: Circulation (1996)

Background Adhesion of monocytes to the endothelium is an initial step in the early stages of atherosclerosis and inflammation. Granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates a range of functional activities of monocytes, including regulation of monocyte adhesion and induction of cytokine production. We investigated in this study whether GM-CSF synthesis was induced by the direct cell-to-cell interaction between human monocytes and human umbilical vein endothelial cells (ECs). Methods and Results The expressions of GM-CSF mRNA and protein were analyzed by Northern blotting and ELISA, respectively. Coculture of monocytes and ECs induced the high levels of GM-CSF mRNA expression, whereas culture of ECs or monocytes alone or coculture of neutrophils with ECs induced no GM-CSF mRNA expression. A large amount of GM-CSF was secreted into the supernatant upon coculture of monocytes with ECs. The supernatant from the coculture markedly stimulated O2− release in neutrophils, and this effect w...
Silent Myocardial Ischemia in Kawasaki Disease
Authors: ShunichiOgawa, RyujiFukazawa, TakashiOhkubo, JiakunZhang, NobuyukiTakechi, YukioKuramochi, YoshiakiHino, OsamuJimbo, YasuhiroKatsube, MitsuhiroKamisago, YukikoGenma, MasaoYamamoto
Journal: Circulation (1997)

Background Myocardial ischemia and myocardial infarction are the most serious complications of coronary artery lesions in children with Kawasaki disease (KD). Therefore, early detection and treatment of myocardial ischemia in patients with KD is essential. We studied the effectiveness of percutaneous transluminal coronary angioplasty (PTCA) in patients with silent myocardial ischemia detected by dobutamine stress 99mTc myocardial scintigraphy (TMS), body surface mapping (BMS), and signal-averaged ECG late potentials (ELP). Methods and Results Eight of 76 asymptomatic patients with a coronary stenosis>25% and a positive dobutamine stress test were considered to have silent myocardial ischemia. All eight patients had>95% stenoses demonstrated by coronary angiography (CAG) just before PTCA. After PTCA, CAG showed that all of the coronary artery stenoses had been reduced to<50%. Additionally, intravascular ultrasonography (IVUS) performed in five patients before and after PTCA demonstrated adequate dilation o...
Abstract 1868: Upregulation of p62/Nrf2 and downregulation of p-eIF2a provide more susceptible to docosahexaenoic acid-induced cell death in LMP-1 expressing nasopnaryngeal carcinoma cells
Authors: Kaipeng Jing, Soyeon Shin, Seung-Hyeon Han, Tong Wu, Kyu Lim
Journal: Cancer Research (2018)

Abstract Docosahexaenoic acid (DHA) induces apoptotic cell death through several mechanisms in cancer cells. We have previously demonstrated that DHA triggers apoptosis by increasing reactive oxygen species (ROS) accumulation and the ROS-mediated apoptosis caused by DHA is associated with Nrf2 signaling activation. Here we report that DHA-induced cell death is more susceptible through upregulation of p62-Nrf2 and downregulation of p-eIF2α in LMP-1-expressing nasopharygeal carcinoma (NPC) cells. Treatment of four human NPC cells (CNE, CNE-LMP1, HONE, HONE-EBV) with DHA for 24 hr resulted in a dose-dependent inhibition of cell growth. The DHA effect was due to the induction of apoptosis, given that DHA increased the cleaved form of PARP as well as the number of TUNEL-positive cells. The inhibition of CNE-LMP1 and HONE-EBV cells after DHA treatment is more susceptible compared with CNE and HONE cells without LMP1 by MTT assay. The level of p62 and Nrf2 of LMP1-NPC cells were increased after DHA pretreatment compared to control NPC cells. On the other hand, the level of p-eIF2α produced reverse result. The activation of Nrf2 signal seems to result from decreased Nrf2 inhibitor, Keap1, because DHA remarkably attenuated Keap1 expression levels. Moreover, silencing Nrf2 by small interfering RNAs inhibited the cytotoxic effect of DHA, indicating that Nrf2 activation plays a positive role in the process of DHA-induced apoptosis. Increased staining for LMP1 and p62 was observed in NPC tissues when compared with the nonneplastic (chronic inflammation) tissues. These results suggest that differential regulation of p62/p-eIF2α/NRF2 contributes to susceptible cell death by DHA in LMP-1-expressing NPC cells. Thus, utilization of DHA may represent a promising therapeutic approach for chemoprevention and treatment of human NPC. [This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (NRF-2015R1D1A1A01056887) and by the framework of international cooperation program managed by National Research Foundation of Korea (2015K2A2A6002008)]. Citation Format: Kaipeng Jing, Soyeon Shin, Seung-Hyeon Han, Tong Wu, Kyu Lim. Upregulation of p62/Nrf2 and downregulation of p-eIF2a provide more susceptible to docosahexaenoic acid-induced cell death in LMP-1 expressing nasopnaryngeal carcinoma cells [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 1868.
Abstract 5374: Uterine sarcomas: A preliminary study for characterization of a specific molecular signature for Brazilian patients
Authors: Leonardo T. Costa, Giovana T. Torrezan, Claudia A. Paula, Glauco B. Neto, Edmund C. Baracat, Dirce M. Carraro, Kátia C. Carvalho
Journal: Cancer Research (2018)

Abstract Background: Uterine sarcomas are the most common gynecological sarcomas, comprising around 90% of all of the cases. These tumors can arise either from the endometrial stroma or from the muscle itself. They are genetically heterogeneous tumors and have no specific molecular and radiological diagnosis, or treatment. Histologically, uterine sarcomas are classified according to their cell of origin and are divided into: carcinosarcomas (CCS), leiomyosarcomas (LMS), endometrial stromal sarcoma (ESS) and adenosarcomas (ADS). There are many factors that can be attributed to uterine sarcomas etiopathogeny such as ethnic, hormonal and hereditary factors. However, few studies were performed searching for specific molecular signature in these tumors, especially concerning a singular population. Objective: To assess the oncogenic profile of Brazilian patients with different histological types of uterine sarcomas. Methods: Until now, we performed the Next Generation Sequencing for 13 samples of uterine sarcomas (comprising: 5 CCS, 3 LMS, 4 SEE and 1 ADS) using the Ion Proton System (ThermoFisher) with the Comprehensive Cancer Panel (containing 409 genes related to carcinogenesis). Results: The genetic sequencing profile analysis showed 140 specific mutations in our samples. Among them, the most common were TP53 (58%), JAK3 (33%), NF1 (33%), KMT2D (33%), MTOR (25%) and PIK3CA (25%). Some findings corroborate the literature on uterine sarcomas, with an exception of the KMT2D gene, that despite of being known and described in other tumors, including the ones of the genital tract, such as vulva, ovary and endometrium, has never been described in uterine sarcomas Conclusion: We found the most frequent mutations in 6 genes in our samples. Only one mutation had not been described before for uterine sarcomas (KMT2D). These are preliminary results, and further analyzes are ongoing.Key words: Uterine Sarcomas, Carcinosarcomas, Next Generation Sequencing Citation Format: Leonardo T. Costa, Giovana T. Torrezan, Claudia A. Paula, Glauco B. Neto, Edmund C. Baracat, Dirce M. Carraro, Kátia C. Carvalho. Uterine sarcomas: A preliminary study for characterization of a specific molecular signature for Brazilian patients [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 5374.
Abstract 18132: The American Heart Association’s Life Simple 7 and Risk of Peripheral Arterial Disease: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Parveen Garg, Wesley T O'Neal, Yejin Mok, Joseph Coresh, Gerardo Heiss, Kunihiro Matsushita
Journal: Circulation (2017)

Introduction: The American Heart Association’s Life’s Simple 7 (LS7) includes metrics of ideal cardiovascular (CV) health to target for cardiovascular disease (CVD) prevention. While LS7 has been linked to coronary disease and stroke, its association with incident PAD has not been explored. Considering that over 8 million people in the United States have PAD, identifying strategies to reduce PAD incidence are also important. Methods: The Atherosclerosis Risk in Communities study is a biracial prospective study of 15,792 individuals aged 45-64 years at baseline. Eligible participants included those without PAD who had data on all LS7 components (blood pressure, body mass index, cholesterol, diet, glucose, physical activity, and smoking) at baseline. An overall LS7 score was calculated as the sum of the LS7 component scores (2 points for ideal, 1 for intermediate, and 0 for poor). This score was classified as inadequate (0-4), average (5-9), or optimum (10-14) CV health and linked to incident PAD identified...
Identification of Cell Cycle Regulatory and Inflammatory Genes As Predominant Targets of p38 Mitogen-Activated Protein Kinase in the Heart
Authors: OlliTenhunen, JaanaRysä, MikaIlves, YlermiSoini, HeikkiRuskoaho, HannaLeskinen
Journal: Circulation Research (2006)

Mitogen-activated protein kinases (MAPKs) regulate cardiomyocyte growth and apoptosis in response to extracellular stimulation, but the downstream effectors that mediate their pathophysiological effects remain poorly understood. We determined the targets and role of p38 MAPK in the heart in vivo by using local adenovirus-mediated gene transfer of constitutively active upstream kinase mitogen-activated protein kinase kinase 3b (MKK3bE) and wild-type p38α in rats. DNA microarray analysis of animals with cardiac-specific overexpression of p38 MAPK revealed that 264 genes were upregulated more than 2-fold including multiple genes controlling cell division, cell signaling, inflammation, adhesion, and transcription. A large number of previously unknown p38 target genes were found. Using gel mobility-shift assays we identified several cardiac transcription factors that were directly activated by p38 MAPK. Finally, we determined the functional significance of the altered cardiac gene-expression profile by histolo...
Direct Current Make and Break Thresholds for Pacemaker Electrodes on the Canine Ventricle
Authors: Egbartdekker
Journal: Circulation Research (1970)

Thresholds to anodal make, anodal break, cathodal make and cathodal break have been studied throughout the cardiac cycle in 13 dogs under pentobarbital anesthesia. Unipolar direct current pulses were applied through epicardial pacemaker electrodes to the left ventricle. Make and break responses were separated by letting the break and make occur in the refractory periods of the following and preceding cycle, respectively. Four distinct threshold interval curves were obtained from each of 17 electrodes. The anodal break and cathodal break curves showed an early diastolic dip. Dips were deepest in the anodal break curves. These also had the shortest effective refractory period. Thresholds for cathodal make and anodal make first dipped steeply, then gradually sloped down towards end-diastolic levels. The magnitude of end-diastolic mean threshold values increased in the following order: cathodal make, anodal make, cathodal break, anodal break. Comparison of threshold interval curves for make and break response...
MYBL2 Supports DNA Double Strand Break Repair in Hematopoietic Stem Cells
Authors: Rachel Bayley, Daniel Blakemore, Laila Cancian, Stephanie Dumon, Giacomo Volpe, Carl Ward, Ruba Almaghrabi, Jidnyasa Gujar, Natasha Reeve, Manoj Raghavan, Martin R. Higgs, Grant S. Stewart, Eva Petermann, Paloma García
Journal: Cancer Research (2018)

Myelodysplastic syndromes (MDS) are a heterogeneous group of diseases characterized by blood cytopenias that occur as a result of somatic mutations in hematopoietic stem cells (HSC). MDS leads to ineffective hematopoiesis, and as many as 30% of patients progress to acute myeloid leukemia (AML). The mechanisms by which mutations accumulate in HSC during aging remain poorly understood. Here we identify a novel role for MYBL2 in DNA double-strand break (DSB) repair in HSC. In patients with MDS, low MYBL2 levels associated with and preceded transcriptional deregulation of DNA repair genes. Stem/progenitor cells from these patients display dysfunctional DSB repair kinetics after exposure to ionizing radiation (IR). Haploinsufficiency of Mybl2 in mice also led to a defect in the repair of DSBs induced by IR in HSC and was characterized by unsustained phosphorylation of the ATM substrate KAP1 and telomere fragility. Our study identifies MYBL2 as a crucial regulator of DSB repair and identifies MYBL2 expression levels as a potential biomarker to predict cellular response to genotoxic treatments in MDS and to identify patients with defects in DNA repair. Such patients with worse prognosis may require a different therapeutic regimen to prevent progression to AML.Significance: These findings suggest MYBL2 levels may be used as a biological biomarker to determine the DNA repair capacity of hematopoietic stem cells from patients with MDS and as a clinical biomarker to inform decisions regarding patient selection for treatments that target DNA repair.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/20/5767/F1.large.jpg Cancer Res; 78(20); 5767-79. ©2018 AACR.