tbuckley/cabot-search huggingface dataset:
Abstract 2973: Effects Of Cardiac Resynchronization Therapy On The Mitochondrial Proteome In A Canine Model Of Heart Failure
Authors: Giulio Agnetti, Steven T Elliott, Lesley A Kane, Christina Yung, Khalid Chakir, Daya Samantapudi, Carlo Guarnieri, Claudio M Caldarera, David A Kass, Jennifer E Van Eyk
Journal: Circulation (2007)

Cardiac resynchronization therapy (CRT) is a procedure used in the clinics to ameliorate the symptoms associated with heart failure-induced conduction disturbances and ventricular dyssynchrony. The molecular modifications underlying the beneficial effects of CRT have not been completely clarified. Recent investigations suggest that CRT may reduce apoptosis of cardiac myocytes. Mitochondria are likely to be major players in this benign transition due to their role in both energy production and apoptosis regulation. Therefore the proteome of cardiac mitochondria was investigated in a canine model for heart failure alternatively submitted to CRT. Methods and results: Mitochondria-enriched fractions obtained from sections of the left ventricular free wall of dyssynchrony-induced heart failure (DHF) dogs alternatively submitted to CRT were analyzed through two-dimensional gel electrophoreisis (2DE). Roughly 1200 protein spots were visualized on the 2D gels after silver staining. Software-assisted differential display analysis indicated that the density of almost 50 protein spots was significantly changed upon CRT. These spots were selected and identified through mass spectrometry. Among other changes six forms of ATP synthase beta subunit were decreased 2- to 3-fold (0.0001≤p≤0.047), as well as four forms of cytochrome C (2-fold decrease, 0.002≤p≤0.047). The existence of multiple forms of a protein suggests for the presence of post-translational modifications (PTM). Therefore the phosphorylation (a common PTM) status of mitochondrial proteome was also monitored by combining the differential-in-gel electrophoresis (DIGE) technology with alkaline phosphatase teatment. ATP synthase beta subunit was differently phosphorylated in CRT samples comparing to DHF as indicated by the change in its isoelectric point upon treatment with alkaline phosphatase. Conclusions: The proteomic investigation of mitochondria revealed a previously unseen presence of PTM mechanisms at the mitochondria level in heart failure and CRT. Phosphorylation mechanisms in the mitochondria may play a prominent role in modulating cardiac function, as observed for the beneficial effects of CRT.
Abstract 5547: Can IL-6 Exert Atheroprotective Action on Human Macrophages via Activation of ABCA1 Through the Jak-2/Stat3 Pathway?
Authors: Eric Frisdal, Maryline Olivier, Sandra Larrède, M. J Chapman, Maryse Guérin, Wilfried Le Goff
Journal: Circulation (2009)

Cholesterol-laden macrophage foam cells constitute a hallmark of the inflammatory dimension of atherosclerosis. The ATP-binding cassette A1 transporter (ABCA1) promotes macrophage cholesterol efflux to apolipoprotein AI (apoAI), thereby attenuating atherosclerotic plaque progression. Interleukin-6 (IL-6) is a macrophage secretory product which may modulate intraplaque inflammation, but whose precise role in atherogenesis is unclear. We therefore evaluated the impact of IL-6 on cholesterol homeostasis in human monocyte-macrophages and THP-1 cells. ABCA1-mediated cholesterol efflux to apoAI was significantly increased (2.5-fold) by IL-6 (50 ng/mL) subsequent to the induction of ABCA1 mRNA and protein levels. Stimulation of ABCA1-mediated cholesterol efflux was however abolished by a specific inhibitor of Jak-2 or the Jak-2/Stat3 signalling pathway. The implication of Stat3 in the stimulatory effect of IL-6 was confirmed by the use of a Stat3 inhibitory peptide. In addition, ABCA1-mediated efflux of cholesterol, driven by the ingestion of apoptotic, free-cholesterol-loaded THP-1 cells, was equally induced by IL-6 in THP-1 phagocytes. Finally, IL-6 enhanced phagocytosis of apoptotic Jurkat cells in THP-1 macrophages, an effect abolished by either a Jak-2 inhibitor or glyburide, an inhibitor of ABCA1 activity. Thus, induction of ABCA1 expression by IL-6 in human monocyte-macrophages through the Jak-2/Stat3 pathway may favour reduction in both foam cell formation and growth of the necrotic plaque core, potentially contributing to enhanced plaque stability.
Abstract 14039: High Intensity Signals on TOF-MRA of Atherosclerotic Carotid Plaque Indicate a High Risk for Cerebral Embolism After Carotid Artery Stenting
Authors: Kiyofumi Yamada, Shinichi Yoshimura, Masanori Kawasaki, Toru Iwama, Akira Hara, Takahiko Asano, Marina Ferguson, Jie Sun, Thomas Hatsukami, Baocheng Chu, Chun Yuan
Journal: Circulation (2011)

Background: A major disadvantage of carotid artery stenting (CAS) compared to carotid endarterectomy (CEA) is the increased risk of cerebral embolism. A simple screening method to detect plaques th...
Abstract 1571: Hibernating Myocardium has Reduced High Energy Phosphate Levels and a Preconditioning-Like Effect with Slower ATP Depletion in Response to Acute Ischemia
Authors: Qingsong Hu, Gen Suzuk, John M Canty, James A Fallavollita
Journal: Circulation (2007)

Background. Pigs with a chronic LAD stenosis develop hibernating myocardium with contractile dysfunction and reduced resting flow. We hypothesized that this reduced energy utilization preserves ATP and protects the heart from irreversible injury during acute ischemia. Methods. Pigs with hibernating myocardium were studied 3-months after instrumentation with a 1.5 mm proximal LAD stenosis (n=7). Hibernating myocardium was confirmed by reduced LAD wall thickening (2.4±0.2 vs.6.1±0.6 mm in remote, p&lt;0.05) and reduced resting flow (0.95±0.15 vs. 1.66±0.29 ml/min/g in remote, p&lt;0.05) without infarction. Subendocardial samples were rapidly excised from propofol anesthetized pigs and serial depletion of high energy phosphates quantified by HPLC (in μmol/g dry weight) during simulated total ischemia in vitro (37°C). Results. At Baseline, ATP and ADP were significantly reduced in the hibernating LAD region in comparison to controls (n=8, Table ), with preserved CP/ATP and ATP/ADP ratios. During simulated ischemia, hibernating myocardium displayed a markedly reduced rate of ATP depletion (ΔATP), with ATP levels at 20 min significantly higher than control (Table ). Higher ATP levels were maintained throughout 80 min of ischemia. Interestingly, identical preservation of high energy phosphates occurred in the remote normally perfused region of hearts with hibernating myocardium (Table ). Conclusion. These data indicate that there is a balanced reduction in high energy phosphate levels in hibernating myocardium with chronic protection from ischemia manifested by a slower rate of ATP depletion during acute ischemia. This preconditioning-like effect is global suggesting that it arises from stimuli that are not directly related to ischemia. This raises the possibility that stretch from cyclical elevations in LV filling pressure or a circulating factor released from the heart in response to ischemia can protect the heart in chronic coronary artery disease.
Abstract 8397: Action Registry Guideline Adherences Differ Between ST-Elevation and Non-ST Elevation Myocardial Infarction Patients
Authors: Jeffrey Weiss, Jennifer Fleming, Nancy Levy, Patricia Gortych, Donald Casey, Barry Cohen
Journal: Circulation (2011)

Background: Based on the ACC/AHA 2008 Performance Measures for Adults with Acute Myocardial Infarction, the ACTION Registry-GWTG (Get with the Guidelines) Outcomes Report examines a given site's performance on acute and discharge guideline metrics used in treating heart attacks. We reviewed our data from the Outcomes Report to compare guideline adherences between ST Elevation myocardial infarction (STEMI) and non-ST Elevation myocardial infarction (NSTEMI) patients. Methods: There were 76,493 STEMI and 117,440 NSTEMI ACTION Registry participants between the 4 th quarter of 2007 through the 3 rd quarter of 2010 (i.e., 2008-2010). Acute guideline metrics included aspirin (ASA) on arrival and evaluation of left ventricular systolic function (LVSF). Discharge guideline metrics included aspirin (ASA), beta-blocker (BB), angiotensin-converting enzyme inhibitor (ACE) or angiotensin-receptor blocker (ARB) if ejection fraction &lt;40%, statin, adult smoking cessation advice (ASCA), and cardiac rehabilitation referral (CRR). We analyzed adherences to guidelines in STEMI and NSTEMI patients over three years - nationally (NAT), at our center (MMH), and at the nation's top 10% centers (TOP). Chi square and Fischer's exact test were used to compare the two groups. Results: Conclusions: We found statistically significant discrepancies in metric guideline adherences between STEMI and NSTEMI patients over three years. Adherences were higher in the STEMI compared with NSTEMI groups in nearly all metrics measured. This may reflect the presence of timely and comprehensive “Code STEMI” guidelines in place. Perhaps “Code NSTEMI” guidelines or diagnosis-based (eg, NSTEMI-based) medication reconciliation forms could further improve NSTEMI guideline adherences.
Prior CT May Improve Diagnostic Confidence in Myocardial Perfusion Imaging
Authors: Pareen Mehta, Heidi Wassef, Patrick M. Colletti
Journal: Clinical Nuclear Medicine (2015)

Many patients with matching myocardial perfusion imaging defects may have prior CT examinations that include the myocardial region of interest, such as a CT chest or CT abdomen. We correlate these perfusion defects with available prior CT examinations to determine if this will improve diagnostic confidence.Myocardial perfusion scans were reviewed to identify cases with myocardial perfusion defects and prior CT imaging that included the myocardium. The CT was reviewed for evidence of myocardial injury that correlated with the perfusion defect.A retrospective review of 732 myocardial perfusion scans was performed, of which 69 cases with perfusion defects were identified that also had prior CT imaging available for review. Of this subset of patients, 19 patients had findings on the CT scan compatible with ischemia or infarction in the expected region of the perfusion defect, which allowed for a more confident diagnosis.Reviewing a prior CT scan, if available, during the interpretation of a myocardial perfusion scan, can help improve diagnostic confidence in over 25% of cases. This can lead to decreased indeterminate results and can be used to potentially avoid unhelpful further testing.
Delivery of theophylline as dry powder for inhalation
Authors: Bing Zhu, Mehra Haghi, Anphy Nguyen, Mary Goud, Stewart Yeung, Paul M. Young, Daniela Traini
Journal: Asian Journal of Pharmaceutical Sciences (2015)

Theophylline (TP) is a very well established orally or intravenously delivered antiasthma drug with many beneficial effects. This study aims to improve asthma treatment by creating a dry powder inhalable (DPI) formulation of TP to be delivered directly to the lung, avoiding the side effects associated with conventional oral delivery. The DPI TP formulation was investigated for its physico-chemical characteristics using scanning electron microscopy, laser diffraction, thermal analysis and dynamic vapour sorption. Furthermore, aerosol performance was assessed using the Multi Stage Liquid Impinger (MSLI). In addition, a Calu-3 cell transport assay was conducted in vitro using a modified ACI to study the impact of the DPI formulation on lung epithelial cells. Results showed DPI TP to be physico-chemically stable and of an aerodynamic size suitable for lung delivery. The aerosolisation performance analysis showed the TP DPI formulation to have a fine particle fraction of 29.70 ± 2.59% (P < 0.05) for the TP formulation containing 1.0% (w/w) sodium stearate, the most efficient for aerosolisation. Regarding the deposition of TP DPI on Calu-3 cells using the modified ACI, results demonstrated that 56.14 ± 7.62% of the total TP deposited (13.07 ± 1.69 µg) was transported across the Calu-3 monolayer over 180 min following deposition, while 37.05 ± 12.62% of the deposited TP was retained in the cells. This could be due to the presence of sodium stearate in the current formulation that increased its lipophilicity. A DPI formulation of TP was developed that was shown to be suitable for inhalation.
Abstract 19084: Novel Method Using Intracardiac Myocardial Elastography Provides Real-time Assessment of Right and Left Atrial Radiofrequency Ablation Lesions in Humans
Authors: Elaine Wan, Julien Grondin, Angelo Biviano, William Whang, Alok Gambhir, Elisa Konofagou, Hasan Garan
Journal: Circulation (2014)

Introduction: Radiofrequency (RF) ablation is an effective method for treatment of cardiac arrhythmias; however, current assessment of RF lesion formation by measuring impedance changes, electrogram dimunition, power and catheter temperature are indirect and may be inaccurate. We present a novel, imaging modality, myocardial elastography (ME), which when used in adjunct with intracardiac echocardiography (ICE) may provide real-time assessment of RF lesion formation, and changes in tissue mechanics after lesion delivery. Methods: 7 patients (mean age 64.3 +/- 14 years) underwent imaging of their left atrium with a 5.8-MHz ICE probe before and after RF ablation with an irrigated catheter at high frame rates (1200 Hz). The channel data was acquired on a clinical ultrasound system, image reconstruction and motion tracking were performed, and cumulative axial strains were obtained from displacement estimations. The location of the ablation lesion was confirmed using ICE imaging, electroanatomic mapping and flu...
Abstract 3207: Ratio of Microparticles To Endothelial Progenitor Cells Is Increased In A Diabetic Population
Authors: Anne M Curtis, Lifeng Zhang, Elizabeth Medenilla, Ming Gui, Patrick F Wilkinson, Erding Hu, Jay Giri, Vijay Doraiswamy, Sampath Gunda, Mark Burgert, Jay M Edelberg, Emile R Mohler
Journal: Circulation (2008)

Diabetes Mellitus (DM) is strongly associated with a high incidence of cardiovascular disease (CVD) although often individuals show no symptoms or signs of disease. Therefore, quantitative measures are needed to distinguish those diabetic patients at higher risk for CV events. Cell derived microparticles (MPs), submicron membrane vesicles released from activated cells, and endothelial progenitor cells (EPCs) are mediators of cellular damage and endothelial reparative capacity respectively. Both are emerging biomarkers of vascular health and have been assessed individually in diabetic populations. To extend on this, we examined whether the relationship of MPs to EPCs could be used as a potential index of vascular pathology. Plasma samples were collected from patients with early-stage (ES, Diagnosis&lt;1yr, n=11, 51±4yrs, 7.2±0.5% HbA1c) and long-term (LT, Diagnosis&gt;5yrs, n=21, 64±3yrs, 7.1±0.3% HbA1c) with type 2 DM and compared to age related healthy volunteers (H, n=18, 57±3yrs, 5.3±0.7% HbA1c). EPCs positive for CD133 + /CD34 + and MP subtypes, AnnexinV + (AnnV + ), platelets (CD41 + ), monocytes (CD14 + ) and endothelial (CD144 + ) were measured by flow cytometry. Pro-coagulant microparticles and quantification of soluble proteins was measured using ELISA based methods. A significant relationship was found between MPs and EPCs which correlated with disease duration (H vs. ES vs. LT). Significant changes of pro-coagulant MPs ( P =0.02) and AnnV + MPs ( P =0.02) were noted. Of particular interest, the ratio of CD144 + MPs/EPC increased dramatically ( P =0.009) followed by ratios of AnnV + ( P =0.01), CD41 + ( P =0.01) and CD14 + ( P =0.03) MPs/EPCs. These indices of compromised vascular function were highest in the LT group despite intensive statin therapy (LDL mg/dL, 109±8 in H, vs. 80±7 in LT, P =0.01). Of note, the ratio of endothelial MPs/endothelial progenitor cells (CD144 + MPs/EPCs) was more informative than CRP and a range of inflammatory mediators. This is the first report of a relationship of MPs and EPCs in DM. This ratio provides a quantitative measurement of both pro-coagulant and endothelial injury and can identify DM patients with potentially increased risk of CV disease.
Abstract 37: Role and regulation of CYP24A1 in endometrial cancer
Authors: Amber A. Bokhari, Laura R. Lee, Raboteau Dewayne, Chad A. Hamilton, George L. Maxwell, Gustavo C. Rodriguez, Viqar Syed
Journal: Cancer Research (2015)

Abstract The cytochrome P450 enzyme, 24-hydroxylase, encoded by CYP24A1 is critical for the catabolism of 1,25(OH)2D3 (calcitriol). The unbalanced high levels of CYP24A1 seem to be a determinant of calcitriol resistance in tumors. We have previously shown that progesterone enhances calcitriol antitumor activity by upregulating vitamin D receptor expression and promoting apoptosis in endometrial cancer cells. In the present study, we evaluated CYP24A1 protein expression in normal and endometrial tumor tissues, assessed the effect of progesterone and calcitriol on CYP24A1 and its spliced variant expression in endometrial cancer cell lines and correlated this with tumor cell growth. Expression of CYP24A1 was assessed in tissue microarrays by immunohistochemistry. A grade-dependent increase of CYP24A1 expression was found in endometrial carcinomas. Endometrial cancer cells expressed high levels of CYP24A1 compared to immortalized endometrial epithelial cells. Furthermore, CYP24A1 is induced in cells in response to calcitriol. Regulation of CYP24A1 by progesterone, progestin derivatives, calcitriol and their combination was examined by RT-PCR and Western blotting following 8, 24, 72 and 120 h exposure of cells to hormones. In all cancer cell lines, progesterone, medroxyprogesterone acetate and norgestrol attenuated calcitriol-induced CYP24A1, spliced variant CYP24SV transcripts and protein expression at 72 and 120 h of treatment. Furthermore, knockdown of CYP24A1 gene expression by siRNA sensitized endometrial cancer cells to the growth suppressive effect of calcitriol. The data suggest that CYP24A1 overexpression limits calcitriol anti-proliferative signaling in cancer cells, and provide evidence that progestins may be beneficial in preserving calcitriol action in endometrial cancer. Citation Format: Amber A. Bokhari, Laura R. Lee, Raboteau Dewayne, Chad A. Hamilton, George L. Maxwell, Gustavo C. Rodriguez, Viqar Syed. Role and regulation of CYP24A1 in endometrial cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 37. doi:10.1158/1538-7445.AM2015-37
Sarcoptes scabiei mites in humans are distributed into three genetically distinct clades
Authors: V. Andriantsoanirina, F. Ariey, A. Izri, C. Bernigaud, F. Fang, R. Charrel, F. Foulet, F. Botterel, J. Guillot, O. Chosidow, R. Durand
Journal: Clinical Microbiology and Infection (2015)
The Danish vaccination register
Authors: T Grove Krause, S Jakobsen, M Haarh, K Mølbak
Journal: Eurosurveillance (2012)

Immunisation information systems (IIS) are valuable tools for monitoring vaccination coverage and for estimating vaccine effectiveness and safety. Since 2009, an advanced IIS has been developed in Denmark and will be implemented during 2012–14. This IIS is based on a database existing since 2000. The reporting of all administered vaccinations including vaccinations outside the national programme will become mandatory. Citizens will get access to data about their own vaccinations and healthcare personnel will get access to information on the vaccinations of their patients. A national concept of identification, a national solution combining a personal code and a card with codes, ensures easy and secure access to the register. From the outset, the IIS will include data on childhood vaccinations administered from 1996 and onwards. All Danish citizens have a unique identifier, a so called civil registration number, which allows the linking of information on vaccinations coming from different electronic data sources. The main challenge will be to integrate the IIS with the different electronic patient record systems currently existing at general practitioner, vaccination clinic and hospital level thereby avoiding double-entry. A need has been identified for an updated international classification of vaccine products on the market. Such a classification would also be useful for the future exchange of data on immunisations from IIS between countries.
Abstract 10526: Low Literacy is Associated with Increased Risk of Hospitalization and Death Among Individuals with Heart Failure
Authors: George M Holmes, Aurelia Macabasco-O'Connell, Darren A DeWalt, Kimberly A Broucksou, Victoria Hawk, David W Baker, Dean Schillinger, Bernice Ruo, Kirsten Bibbins-Domingo, Brian Erman, Morris Weinberger, Crystal Cene, Christine DeLong Jones, Jia-Rong Wu, Michael Pignone
Journal: Circulation (2011)

Background: Low literacy skills increase the risk for many adverse health outcomes, but the relationship between literacy and adverse outcomes in heart failure (HF) has not been well studied. Metho...
Ing2 sumoylation regulates cell proliferation
Authors: Damien Ythier, Romuald Binet, Damien Nissou, Delphine Larrieu, Christian Brambilla, Elisabeth Brambilla, Remy Pedeux
Journal: Cancer Research (2008)

910   ING genes (Inhibitor of Growth, ING1-5) are candidate tumor suppressor genes which have been recently identified and characterized. ING proteins contain a very highly conserved C-terminus region in which a Nuclear Localization Sequence (NLS) and a Plant HomeoDomain (PHD) are present. PHD fingers are commonly found in chromatin-regulatory proteins. All ING proteins are components of Histone AcetylTransferase (HAT) or Histone DeACetylase (HDAC) complexes. Regarding ING2, it is a stable component of the Sin3A/HDAC1 complex. The PHD of ING2 has a high affinity for the tail of histone 3 tri-methylated on the lysine 4. This interaction allows the recruitment of the Sin3A-HDAC chromatin remodeling complex to the promoter of proliferative genes such as cyclin D1 and c-myc.  Immunoprecipitation of Sin3A resulted in the detection of ING2 but in addition a second band about 10 kDa higher was detected. It suggested that ING2 may be post-translationally modified.  In-vitro  SUMOylation experiments performed on GST-ING2 showed that ING2 can be SUMOylated on at least two residues. We confirmed by co-transfection experiments of ING2 and SUMO in U2OS cells that ING2 can also be SUMOylated  in-vivo . Using truncated constructs of ING2 we have zeroed-in the region of ING2 that is SUMOylated. In parallel, a bioinformatics analysis of the amino acid sequence of ING2 revealed the presence of several known consensus sites for SUMOylation (ΨKXE). These experiments allowed us to identify two potential sites for SUMOylation. Directed mutagenesis on these two candidate SUMOylated residues were performed, allowing the identification of one lysine residue strongly SUMOylated  in-vivo . Subsequently, we showed that ING2 SUMOylation did not affect its nuclear localization but was important for ING2 binding to the Sin3A complex. Taking into account the recently published data involving ING2 in the recruitment of the Sin3A-HDAC complex to the promoter of proliferative genes, we have tested the involvement of ING2 SUMOylation on the repression of proliferative genes. Cell growth experiments (growth curve and colony formation assays) revealed that ING2 SUMOylated mutant was not able to repress cell proliferation as wild-type ING2 did.  Taken together our results show that the candidate tumor suppressor protein ING2 is SUMOylated and that this SUMOylation is necessary for ING2 binding with Sin3A complexes. Moreover, SUMOylation of ING2 appears to be essential for repressing cell proliferation. Thus, our results suggest that SUMOylation could regulate ING2 ability to recruit Sin3A-HDAC complex to the chromatin. Therefore, SUMOylation of ING2 would be critical to regulate the expression of genes involved in cell cycle control.