tbuckley/cabot-search huggingface dataset:
Abstract 5717: Mass spectrometry as a tool for MHC class I and II neoantigen discovery
Authors: Michael J. Ford, Richard Jones, David Allen, Ravi Amunugama, Michael Pisano, James Mobley, Paul Domanski, Bill Ho, Daniel Bochar, Melissa Holt
Journal: Cancer Research (2018)

Abstract A neoantigen is a patient-specific tumor antigen resulting from mutations during oncogenesis (1). Advances in genome sequencing of cancer tumor tissues combined with bioinformatics have enabled the identification of tumor specific mutations and the prediction of the peptides that will be presented by the MHC complex. The presented peptides are recognized as foreign by the immune system and can be used to discriminate cancerous from normal cells. Neoantigen prediction by gene sequencing and in silico approaches can be strengthened and further supported by mass spectrometry. The molecular level characterization of peptides associated with molecules of the major histocompatibility complex requires a targeted protein complex enrichment, an unbiased peptide elution, and finally a peptide analysis method. We use immunoaffinity to isolate the target complex, elute the peptides under conditions minimizing protein contamination and finally analyze the peptides by mass spectrometry. Here we present a case studies of our recent work applying workflows for the analysis of peptides associated with both Class I and Class II MHC molecules. Combining state-of-the-art mass spectrometry and bioinformatics, we demonstrate the utility of this approach for neoantigen identification and quantitation. Reference: 1. Sun et al. Cancer Lett 2017;392:17-25. Citation Format: Michael J. Ford, Richard Jones, David Allen, Ravi Amunugama, Michael Pisano, James Mobley, Paul Domanski, Bill Ho, Daniel Bochar, Melissa Holt. Mass spectrometry as a tool for MHC class I and II neoantigen discovery [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 5717.
Ischemic Preconditioning in Pigs: A Graded Phenomenon
Authors: RainerSchulz, HeinerPost, ChristianVahlhaus, GerdHeusch
Journal: Circulation (1998)

Background—A threshold concept for ischemic preconditioning (IPc) has been proposed. It is unclear, however, whether IPc, above a certain threshold, is an all-or-nothing or a graded phenomenon. Methods and Results—In 71 enflurane-anesthetized swine, severe left anterior descending coronary artery hypoperfusion for 90 minutes followed by 2 hours of reperfusion resulted in an infarct size (IS, by triphenyltetrazolium chloride) of 16.7±3.4% (SEM) of the area at risk. IPc by 2 minutes of low-flow ischemia and 15 minutes of reperfusion before the 90-minute target ischemia did not reduce IS (21.9±7.0%). IS was decreased to 9.0±2.6% (P<0.05) by 3 minutes of IPc and reduced further to 1.9±0.9% (P<0.05) by 10 minutes of IPc. The interstitial adenosine concentration (microdialysis, high-performance liquid chromatography) was unchanged with 2 and 3 minutes of IPc but increased with 10 minutes of IPc (by 573±144%). The interstitial bradykinin concentration (microdialysis, radioimmunoassay) remained unchanged with 2 m...
Abstract 1516: BAT-1 up-regulation decreases cell invasion and migration in vitro
Authors: Aileen M. Garcia-Vargas, Maria Sanchez, Magaly Martinez-Ferrer
Journal: Cancer Research (2018)

Abstract Prostate cancer is the most common cancer in men in the United States and is the third cause of cancer related deaths in men. In Puerto Rico, prostate cancer is the most common type of cancer and the leading cause of cancer death in men. Approximately one out of seven men will be diagnosed with prostate cancer in his lifetime. The current available biomarkers are unable to predict malignant outcomes such as recurrence. Thus, there is a critical demand for the development of innovative diagnostic and prognostic tools for the management of prostate cancer. In the current study, we evaluated the biological role of BAT-1 in prostate cancer. Preliminary data from patients who had prostate cancer recurrence identified that HLA-B associated transcript 1 (BAT-1) was down-regulated in patients with prostate cancer recurrence when compared with non-recurrent patients. We up-regulated BAT-1 in androgen independent PC3 and androgen dependent 22RV1 prostate cancer cell lines using a BAT-1 recombinant protein. In vitro assays were performed to measure proliferation, migration and invasion. Proliferation assays using MTS showed no significant change in BAT-1 recombinant protein concentrations ranging from 0.25-2.0μg/mL at 12, 24 and 48hrs for PC3 and 22RV1 cells. Wound healing assay showed that cells treated with BAT-1 recombinant protein at 0.25μg/mL and 2.0μg/mL significantly decreased migration at 6, 12hrs and 24hrs in PC3 cells when compared to control. Boyden assay showed that cells treated with BAT-1 recombinant protein at 0.25μg/mL and 2.0μg/mL significantly decreased invasion in PC3 and 22RV1 cells at 24hrs when compared to control. Our results showed that BAT-1 up-regulation decreased migration and cell motility. Cells did not show a significant change in proliferation. These results were expected due to previous data showing that BAT-1 down-regulation increased cell migration and invasion, suggesting that BAT-1 expression promotes aggressiveness in prostate cancer recurrence. A possible mechanism of action for BAT1 is the modulation of cell migration and invasion. Citation Format: Aileen M. Garcia-Vargas, Maria Sanchez, Magaly Martinez-Ferrer. BAT-1 up-regulation decreases cell invasion and migration in vitro [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 1516.
Which Hemostatic Markers Add to the Predictive Value of Conventional Risk Factors for Coronary Heart Disease and Ischemic Stroke
Authors: AnnSmith, ChrisPatterson, JohnYarnell, AnnRumley, YoavBen-Shlomo, GordonLowe
Journal: Circulation (2005)

Background— Few studies have examined whether hemostatic markers contribute to risk of coronary disease and ischemic stroke independently of conventional risk factors. This study examines 11 hemostatic markers that reflect different aspects of the coagulation process to determine which have prognostic value after accounting for conventional risk factors. Methods and Results— A total of 2398 men aged 49 to 65 years were examined in 1984 to 1988, and the majority gave a fasting blood sample for assay of lipids and hemostatic markers. Men were followed up for a median of 13 years, and cardiovascular disease (CVD) events were recorded. There were 486 CVD events in total, 353 with prospective coronary disease and 133 with prospective ischemic stroke. On univariable analysis, fibrinogen, low activated protein C ratio, D-dimer, tissue plasminogen activator (tPA), and plasminogen activator inhibitor-1 (PAI-1) were associated significantly with risk of CVD. On multivariable analyses with conventional risk factors ...
Abstract 20678: A Systematic Review of World-Wide Characteristics and Management of Patients With ST-Segment Elevation Myocardial Infarction
Authors: YangZhan, ThaoHuynh
Journal: Circulation (2014)

Background: Management of ST elevation myocardial infarction (STEMI) has made tremendous progresses during the last decades. However, it remains uncertain whether all STEMI patients are receiving optimal care and whether variation in care has any impact on their outcomes. We aim to characterize the contemporary global characteristics, managements, and outcomes of STEMI patients. Methods and Results: We searched EMBASE/MedLINE Ovid for observational data of patients with STEMI. We identified 17 studies enrolling 112 772 patients in 20 countries during the last 5 years (2008-2013). The median age ranged from 54 to 66 years with 13%-33% females. Twelve percent to 39% of patients presented in Killip heart failure class 2-4. In-hospital use of aspirin (ASA), P2Y12 inhibitor/thienopyridines, and systemic anticoagulation was 90-99%, 77-97%, and 61-100% respectively. Reperfusion was provided for 63%-97% of patients. Fibrinolysis was used in 0.7%-66% with a door-to-needle (D2N) time of 28-65 minutes; 12%-74% with ...
Antibiotic Discretion in the Treatment of Acute Uncomplicated Diverticulitis
Authors: Bharat Maraj, Charlie M. Wray
Journal: JAMA Internal Medicine (2018)

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Abstract 11125: Increasing Stimulus Strength of Coronary Sinus Pacing Improved Left Ventricular Mechanical Dyssynchrony and Contractile Function in Patients With Reduced Ejection Fraction
Authors: KazuhiroTatsumi, HidekazuTanaka, KensukeMatsumoto, DokuniKumiko, YutakaHatani, KeikoHatazawa, HiroakiMatsuzoe, JunichiOoka, HiroyukiSano, HiroyukiShimoura, TakumaSawa, YoshikiMotoji, YasuhideMochizuki, KeikoRyo, KojiFukuzawa, Ken-ichiHirata
Journal: Circulation (2015)

Introduction: Increasing stimulus strength of left ventricular (LV) coronary sinus pacing decreases QRS duration and inter-ventricular conduction time. Hypothesis: Increasing stimulus strength of LV coronary sinus pacing improves LV mechanical dyssynchrony and myocardial function. Methods: We studied 36 patients with 6±4 months after cardiac resynchronization therapy (LV ejection fraction: 39±11%). The LV pacing lead was positioned in lateral or posterolateral coronary sinus vein. We measured standard deviation (SD) of time to negative peak circumferential strain (time-CircS) in 6 segments and peak global circumferential strain value (CircS) using two-dimensional speckle-tracking echocardiography to evaluate LV mechanical dyssynchrony and myocardial contractile function, respectively. Low (1.3±0.6V), clinical (2.6±1.0V), and high (7.3±1.1V) voltage conditions of LV coronary sinus pacing were performed under right ventricular pacing-off. Results: SD of time-CircS and global CircS under high voltage LV coro...
Abstract 15365: Sleep-Disordered Breathing is Associated with Subclinical Myocardial Injury and Disease Severity in Pulmonary Hypertension Patients
Authors: TakashiKohno, YuichiTamura, TakashiKawakami, MasaharuKataoka, YuichiroMaekawa, MotoakiSano, KeiichiFukuda
Journal: Circulation (2014)

Background: Sleep disordered breathing (SDB) is well known to be associated with increased mortality in patients with left-heart failure, however the clinical significance of SDB in patients with pulmonary hypertension (PH) is not established. We sought to investigate the association of SDB with hemodynamic parameters and serum troponin T concentrations in patients with PH. Methods and Results: Overnight polygraphy was performed in 107 clinically stable patients with PH (pulmonary arterial hypertension n=52 [idiopathic n=23, collagen disease n=11, congenital heart disease n=6, others n=12]and chronic thromboembolic PH n=55), and evaluated apnea-hypopnea index (AHI; 7.6±9.3, obstructive apnea 1.8, central apnea 0.4, and hypopnea 5.3 events/h). Based on AHI, these patients were divided into two groups: non SDB (AHI<15/h, n = 90) and SDB groups (AHI≧15/h, n = 17). The presence of SDB was associated with older age (p<0.05), but not associated with gender, BMI, smoking, and the presence of hypertension, dyslip...
Phosphorylation of Glycogen Synthase Kinase-3β During Preconditioning Through a Phosphatidylinositol-3-Kinase–Dependent Pathway Is Cardioprotective
Authors: HaiyanTong, KenichiImahashi, CharlesSteenbergen, ElizabethMurphy
Journal: Circulation Research (2002)

We previously reported that activation of phosphatidylinositol-3-kinase (PI3-kinase) is involved in ischemic preconditioning (PC). Our goal was to determine downstream targets of PI3-kinase. In perfused rat hearts, PC (4 cycles of 5 minutes of ischemia and 5 minutes of reflow) increased phosphorylation of glycogen synthase kinase-3β (GSK-3β), a downstream target of PI3-kinase and protein kinase B (PKB), an effect that was blocked by wortmannin. Because phosphorylation inactivates GSK-3β, we examined whether PC-induced phosphorylation and inhibition of GSK-3β is important in PC by using two inhibitors of GSK-3β, lithium and SB 216763. Pretreatment of perfused rat hearts with lithium or SB 216763, before ischemia, mimicked the protective effects of PC; hearts treated with either lithium or SB 216763 had improved postischemic function and reduced infarct size. These findings indicate that inhibition of GSK-3β is protective and that this PI3-kinase–dependent signaling pathway may play an important role in isc...
Abstract 928: Regulatory heterogeneity in glioblastoma multiforme informs novel drug target discovery
Authors: Yunpeng Liu, Shan He, Michael T. Hemann, Aviv Regev
Journal: Cancer Research (2018)

Abstract Glioblastoma multiforme (GBM) is one of the most malignant forms of cancer. Its heterogeneity has been assessed at multiple levels, including bulk and single-cell transcriptome profiling. The disease has been stratified into four molecular subtypes - Classical, Neural, Proneural and Mesenchymal according to their gene expression profiles, and each of these subtypes display distinct mutational signatures and histological features reflective of their nomenclature. However, the underlying regulatory circuitry that gave rise to such heterogeneity and its implications for specialized therapeutic options are unclear. To dissect subtype-specific regulatory programs, we have developed a nonlinear regression model to unveil key transcriptional rewiring across the four GBM subtypes. Using a backbone network of potential transcription factor (TF) - target gene pairs, we applied nonlinear regression using expression profiles of each subtype to derive subtype-specific regulatory parameters for each TF-gene pair. Coupled with a novel analysis pipeline, the model revealed a set of transcription regulators whose regulatory capacities for target genes are unique to each subtype. The target genes of these signature TFs are enriched for expression signature genes for the corresponding subtype, implying that subtype-specific rewiring of TFs play a significant role in shaping differential transcription landscapes. The model was also able to capture known physical and functional interactions between TFs, as well as identify potential new co-regulatory relationships. Detailed examination of both expression and co-regulatory profiles of signature TFs showed that altered regulatory behavior could be a result of differential expression of the TF itself, differential functional partnering of the TF with other TFs, or a combination of both mechanisms. Importantly, our model also demonstrates that differential regulatory programs could provide new options for targeted therapy in GBM. We simulated the effects of knockdown/inhibition of these co-regulatory partners by propagating changes in expression to the corresponding target genes and then to the protein signaling layer using a novel random walk-based algorithm. Using the apoptosis pathway as readout, we show that targeting the retinoic acid receptor RXRA may be specifically beneficial for killing tumor populations of the Neural subtype, whereas the HNF4A gene is a potentially beneficial drug target for cells of the Mesenchymal subtype. Citation Format: Yunpeng Liu, Shan He, Michael T. Hemann, Aviv Regev. Regulatory heterogeneity in glioblastoma multiforme informs novel drug target discovery [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 928.
Aging and Endothelial Function in Normotensive Subjects and Patients With Essential Hypertension
Authors: StefanoTaddei, AgostinoVirdis, PaolaMattei, LorenzoGhiadoni, AlessandraGennari, Ciro BasileFasolo, IsabellaSudano, AntonioSalvetti
Journal: Circulation (1995)

Background Experimental data from normotensive and hypertensive animals indicate that aging is associated with impaired endothelium-dependent relaxations to acetylcholine, and this possibility appears to be confirmed in the human coronary artery. In the present study, we evaluated the effect of age on endothelial responsiveness in the forearm vessels of either normotensive control subjects or essential hypertensive patients. Methods and Results Within the normotensive or hypertensive group (n=53 and n=57, respectively), subjects were selected with similar blood pressure, plasma cholesterol, and glucose values, and hypercholesterolemic subjects, diabetics, and smokers were excluded. We evaluated forearm blood flow (by strain-gauge plethysmography) modifications induced by intrabrachial acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 μg/100 mL per minute), an endothelium-dependent vasodilator, and sodium nitroprusside (1, 2, and 4 μg/100 mL per minute), an endothelium-independent vasodilator. Acetylcholine caus...
Predictors of Outcome in Patients With Suspected Myocarditis
Authors: IngridKindermann, MichaelKindermann, ReinhardKandolf, KarinKlingel, BurkhardBültmann, ThomasMüller, AngelikaLindinger, MichaelBöhm
Journal: Circulation (2008)

Background— The objective of this study was to identify the prognostic indicators in patients with suspected myocarditis who underwent endomyocardial biopsy. Methods and Results— Between 1994 and 2007, 181 consecutive patients (age, 42±15 years) with clinically suspected viral myocarditis were enrolled and followed up for a mean of 59±42 months. Endomyocardial biopsies were studied for inflammation with histological (Dallas) and immunohistological criteria. Virus genome was detected by polymerase chain reaction. The primary end point was time to cardiac death or heart transplantation. In 38% of the patients (n=69), the Dallas criteria were positive. Immunohistological signs of inflammation were shown in 50% (n=91). Genomes of cardiotropic virus species were detected in 79 patients (44%). During follow-up, 22% of the patients (n=40) reached the primary end point. Three independent predictors were identified for the primary end point, namely New York Heart Association class III or IV at entry (hazard ratio,...
Deletion of Cardiomyocyte Mineralocorticoid Receptor Ameliorates Adverse Remodeling After Myocardial Infarction
Authors: DanielaFraccarollo, StefanBerger, PaoloGaluppo, SusanneKneitz, LutzHein, GüntherSchütz, StefanFrantz, GeorgErtl, JohannBauersachs
Journal: Circulation (2011)

Background—Mineralocorticoid receptor (MR) blockade improves morbidity and mortality among patients with heart failure; however, the underlying mechanisms are still under investigation. We studied left ventricular remodeling after myocardial infarction in mice with cardiomyocyte-specific inactivation of the MR gene (MRMLCCre) that were generated with a conditional MR allele (MRflox) in combination with a transgene expressing Cre recombinase under control of the myosin light-chain (MLC2a) gene promoter. Methods and Results—Control (MRflox/flox, MRflox/wt) and MRMLCCre mice underwent coronary artery ligation. MR ablation had no detectable baseline effect on cardiac morphology and function. The progressive left ventricular chamber enlargement and functional deterioration in infarcted control mice, detected by echocardiography and conductance catheter analysis during the 8-week observation period, were substantially attenuated in MRMLCCre mice. Chronically infarcted MRMLCCre mice displayed attenuated pulmonar...
Friedrich Daniel von Recklinghausen
Authors: Tudor Crihalmeanu, Varun Ayyaswami, Arpan V. Prabhu
Journal: JAMA Dermatology (2018)

Friedrich Daniel von Recklinghausen, MD, was one of the most prominent German pathologists of his time. His contributions resulted in the identification of several eponymous conditions, most notably von Recklinghausen disease, or neurofibromatosis type 1.1,2
Interarterial Coronary Anastomoses
Authors: Bertrampitt
Journal: Circulation (1959)

It is generally recognized that interarterial coronary anastomoses of functionally significant size occur with great frequency in the presence of occlusive coronary artery disease and in other conditions such as anemia and cardiac hypertrophy in which myocardial anoxia may be present. Disagreement has been expressed by some investigators regarding the incidence of these anastomoses in normal and abnormal hearts. The problem has therefore been reinvestigated by means of a technic of infusion of saline solution and injection of wax spheres of known size. The results of these observations in 75 hearts are presented and their significance is discussed.
MicroRNA-223 Antagonizes Angiogenesis by Targeting β1 Integrin and Preventing Growth Factor Signaling in Endothelial Cells
Authors: LeiShi, BeateFisslthaler, NinaZippel, TimoFrömel, JiongHu, AmroElgheznawy, HeinrichHeide, RüdigerPopp, IngridFleming
Journal: Circulation Research (2013)

Rationale:Endothelial cells in situ are largely quiescent, and their isolation and culture are associated with the switch to a proliferative phenotype. Objective:To identify antiangiogenic microRNAs expressed by native endothelial cells that are altered after isolation and culture, as well as the protein targets that regulate responses to growth factors. Methods and Results:Profiling studies revealed that miR-223 was highly expressed in freshly isolated human, murine, and porcine endothelial cells, but those levels decreased in culture. In primary cultures of endothelial cells, vascular endothelial cell growth factor and basic fibroblast growth factor further decreased miR-223 expression. The overexpression of precursor-miR-223 did not affect basal endothelial cell proliferation but abrogated vascular endothelial cell growth factor–induced and basic fibroblast growth factor–induced proliferation, as well as migration and sprouting. Inhibition of miR-223 in vivo using specific antagomirs potentiated postna...