tbuckley/cabot-search huggingface dataset:
Abstract 3669: Transcoronary Gene Transfer of Serca2a Enhances Coronary Blood Flow through an Increase of eNOS Activity in Endothelial Cells
Authors: Lahouaria Hadri, Larissa Lipskaia, Yoshiaki Kawase, Nathalie Clement, Tobias Plenge, Djamel Lebeche, Anne-Marie Lompré, Roger J Hajjar
Journal: Circulation (2008)

Congestive heart failure (CHF) is associated with impaired endothelium-dependent nitric oxide (NO)-mediated vasodilatation. Clinical trials using AAV1-SERCA2a myocardial gene delivery in CHF patients are currently underway. We hypothesized that transcoronary SERCA2a gene transfer can increase NO production by endothelial cells (EC). To assess the effects of SERCA2a gene transfer on coronary flow and endothelial function in vivo, we used a preclinical porcine volume-overload heart failure model (severe mitral valve regurgitation (MR)). Two months after MR creation, animals underwent intracoronary injection of AAV1-SERCA2a or saline. Four months post MR creation, the average coronary flow peak velocity (APV) was measured in the mid portion of the left anterior descending artery (LAD), and adjusted to the diameter of coronary artery and the weight of the left ventricle. Compared to saline treated animals, SERCA2a has significantly increased the adjusted coronary flow (ml/min/g) (0.467 ± 0.09, n=6 vs. 0.886 ± 0.18, n=7; P&lt;0.01) but no difference was observed compared to sham operated animals (1.003 ± 0.2137, n=4; P=NS). Confocal immunofluorescence of swine coronary artery sections demonstrated that SERCA2a is expressed in endothelial and vascular smooth muscle cells; however, eNOS was expressed only in EC in all animal groups. Western blot analyses showed down-regulation of SERCA2a and eNOS expression in LAD, LCA and RCA from failing saline-injected animals. In coronary arteries from SERCA2a-transduced animals, expression levels of SERCA2a and eNOS were similar to those in sham-operated animals. To further investigate the effect of SERCA2a gene transfer on endothelial function we used cultured human coronary artery EC. RT-PCR analysis, western blot and e-NOS promoter/ luciferase reporter assay have shown that SERCA2a gene transfer increased expression and Ser-1177 phosphorylation of e-NOS. Furthermore, cGMP production was increased in SERCA2a-infected EC, confirming its possible functional effect on eNOS activity. In conclusion, our results demonstrate that transcoronary SERCA2a gene transfer improves endothelial function in failing hearts through regulation of eNOS expression and activity.
10-Year Follow-Up of a Prospective Randomized Trial Comparing Bare-Metal Stenting With Internal Mammary Artery Grafting for Proximal, Isolated De Novo Left Anterior Coronary Artery Stenosis
Authors: Jean-Jacques Goy, Urs Kaufmann, Michel Hurni, Stéphane Cook, Francesco Versaci, Patrick Ruchat, Osmund Bertel, Michael Pieper, Bernhard Meier, Luigi Chiarello, Eric Eeckhout
Journal: Journal of the American College of Cardiology (2008)
Abstract 223: PBEF/Nampt Protects Against Mouse Sudden Cardiac Arrest Injury
Authors: Jing Li, Huashan Wang, Yuanyu Qian, Chun-pei Lee, Xiangdong Zhu, Ryan Bunney, Jiwang Chen, Roberto Machado, Joe G N Garcia, Terry Vanden Hoek
Journal: Circulation (2014)

Introduction: Pre-B-cell colony-enhancing factor or nicotinamide phosphoribosyltransferase (PBEF/Nampt) is critical for NAD + biosynthesis and metabolism. Given the important role of early metabolic recovery to sudden cardiac arrest (SCA) survival, we hypothesized that PBEF/Nampt deficient mice would demonstrate worse SCA outcomes after cardiopulmonary resuscitation (CPR). Methods: C57BL6 wild type and PBEF/Nampt +/- mice underwent 8 min of KCl-induced SCA and were monitored for 4 h survival after CPR. Heart, brain and blood PBEF/Nampt concentrations were measured by Western blot and ELISA. Tissue NAD + concentrations and blood markers of metabolic recovery including plasma lactate, glucose and insulin were measured. Results: At baseline, heart and brain tissue levels of PBEF/Nampt were significantly decreased by 50% in PBEF/Nampt +/- mice with no change of NAD + concentrations. By 4 h after CPR PBEF/Nampt +/- mice had worse survival, with 83% dead of cardiovascular collapse (n=18) compared to 45% of WT mice (n=11) ( p &lt; 0.05). At 4 h after CPR, heart NAD + concentration were significantly decreased by more than 50% in PBEF/Nampt +/- mice versus WT mice (p &lt; 0.05). Blood PBEF/Nampt was significantly increased in both WT and PBEF/Nampt +/- mice compared to sham controls, with PBEF/Nampt +/- mice demonstrating lower blood PBEF/Nampt concentrations and higher plasma glucose, insulin and lactate concentrations. Conclusion: PBEF/Nampt tissue deficiency decreases successful cardiovascular resuscitation within 4 h after SCA and CPR. Early survival after SCA is related to tissue NAD + concentrations in the heart and blood PBEF/Nampt concentrations by 4 h after CPR. The role of tissue PBEF/Nampt as a possible therapeutic target after SCA warrants further study.
The Genesis of Neuroscience
Authors: Boleslav L Lichterman
Journal: BMJ (2000)

A Earl Walker (eds Edward R Laws, George B Udvarhelyi) 

American Association of Neurological Surgeons, £50, pp 371

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ISBN 1 879284 62 6

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T he Genesis of Neuroscience reflects the growing interest of neurosurgeons in the roots of their specialty. For 25 years, its author, Arthur Earl Walker, was a professor of neurosurgery at the Johns Hopkins University School of Medicine. In 1951 he edited A History of Neurological Surgery , which was, for decades, the only comprehensive book on the subject. After retiring from his professorial post, he continued his historical research. During the last decade of his life he was invited to give a series of lectures on the history …

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Post-treatment with the heat shock protein 90 (hsp90) inhibitor, AUY-922, reduces lung hsp90 tyrosine (Y) phosphorylation and pulmonary inflammation in LPS-induced acute lung injury (ALI) in mice
Authors: Christiana Dimitropoulou, Nektarios Barabutis, Haralmbos Birmpas, John Catravas
Journal: European Respiratory Journal (2013)

Pre-treatment with hsp90 inhibitors reduces the magnitude of LPS-induced ALI in mice. Because the most frequent use of any intervention would be after the onset of ALI/ARDS, we now tested the hypotheses that post-treatment with hsp90 inhibitors would also reduce the magnitude of LPS-induced ALI and would decrease hsp90 activation as reflected in hsp90 Y phosphorylation. 24h after the intratracheal instillation of vehicle or LPS (1.5mg/kg), mice were given either vehicle or the hsp90 inhibitor, AUY-922 ; i.p. 10mg/kg. 48h later, lung tissue was collected. LPS, but neither vehicle nor AUY-922, alone, increased 9-fold hsp90 Y phosphorylation, as detected in immunoprecipitation/immunoblotting experiments; when post-treated with AUY-922, hsp90 phosphorylation was significantly and dramatically reduced to near control levels. Furthermore, LPS produced a profound inflammatory response, characterized by an increase in alveolar septal thickness, hemorrhage and cellular infiltration, reflected in lung sections stained with HE inflammation was remarkably reduced in mice post-treated with auyAUY-922. Collectively these data reveal important reparative actions of hsp90 inhibitors when administered after the LPS insult and suggest that prevention of post-translational modifications of hsp90 may be an important therapeutic mechanism. Supported by NHLBI grants HL101902 and HL093460.
Abstract P2-06-02: Breast cancer stem-like cell activity correlates with tumour progression to metastasis but not with clinical or tumour characteristics
Authors: Sacha J Howell, Denis Alferez, Katherine Spence, Rachel Eyre, Fran Shaw, Bruno Simoes, Angelica Santiago-Gomez, Maria Bramley, Mohamed Absar, Zahida Saad, Sumohan Chatterjee, Cliona Kirwan, Ashu Gandhi, Anne C Armstrong, Andrew M Wardley, Gillian Farnie, Robert B Clarke
Journal: Cancer Research (2015)

Abstract Introduction: Breast cancers exhibit cellular heterogeneity, containing both stem-like and more differentiated cells. The activity of cancer stem cells (CSC) is likely to be dependent on the microenvironment or niche. Using 158 patient tumour samples, correlations between niche-independent breast CSC activity and clinical and tumour characteristics were tested. Methods: 104 early breast cancer surgical samples and 54 unrelated metastatic samples from pleural or ascitic fluid were harvested. To test CSC activity, isolated cells were grown in both primary (formation) and secondary (self-renewal) mammosphere (MS) culture. Tumour initiating activity was also tested by transplanting breast cancer fragments or cells into the sub-cutaneous flanks of NSG mice (n=84 early and n=10 metastatic). Results: No correlation was found between MS growth, MS formation (%), MS self-renewal (%) or in vivo tumour initiation and breast cancer sub-type, grade, node status or Nottingham prognostic index. 33% of the samples that formed MS in vitro initiated tumours in vivo while only 9% that failed to form MS initiated tumour growth. Metastatic compared to early BC samples grew MS more frequently (53/54 compared to 81/104), and had a higher primary MS formation efficiency (1% vs 0.6%; P&amp;lt;0.001) although rates of MS self-renewal were similar. Tumour initiation in vivo was also more frequent in metastatic than early breast cancer samples (7/10 versus 25/84; P&amp;lt;0.02). Conclusions: In summary, niche-independent breast CSC activity measured in vitro by MS assay and in vivo by xenograft growth is not directly correlated with standard clinical parameters. However, both in vitro and in vivo CSC activity are increased in metastatic samples. These results suggest that breast CSC activity is independent of other prognostic indicators but may predict for poor outcome tumours. Relapse free survival data are maturing and will be presented with analysis of primary tumour ALDH1 expression. Citation Format: Sacha J Howell, Denis Alferez, Katherine Spence, Rachel Eyre, Fran Shaw, Bruno Simoes, Angelica Santiago-Gomez, Maria Bramley, Mohamed Absar, Zahida Saad, Sumohan Chatterjee, Cliona Kirwan, Ashu Gandhi, Anne C Armstrong, Andrew M Wardley, Gillian Farnie, Robert B Clarke. Breast cancer stem-like cell activity correlates with tumour progression to metastasis but not with clinical or tumour characteristics [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-06-02.
Randomized Trial of Aspirin, Sibrafiban, or Both for Secondary Prevention After Acute Coronary Syndromes
Journal: Circulation (2001)

The first Sibrafiban Versus Aspirin to Yield Maximum Protection From Ischemic Heart Events Post-Acute Coronary Syndromes (SYMPHONY) trial showed no benefit of 2 doses of sibrafiban over aspirin for secondary prevention after acute coronary syndromes. In 2nd SYMPHONY, we compared low-dose sibrafiban plus aspirin (LDS+A), high-dose sibrafiban (HDS), and aspirin alone.When the first SYMPHONY results became known, enrollment in 2nd SYMPHONY was stopped prematurely at 6671 patients who had been treated for a median of 90 days. The primary end point of death, myocardial (re)infarction (MI), or severe recurrent ischemia did not differ significantly between aspirin (9.3%) and LDS+A (9.2%; OR, 0.98; 95% CI, 0.80 to 1.20) or HDS (10.5%; OR, 1.14; 95% CI, 0.9 to 1.39) patients. Secondary end points did not differ significantly between aspirin and LDS+A patients. Death or MI occurred significantly more often with HDS (OR, 1.43; 95% CI, 1.14 to 1.80), as did mortality alone (OR, 1.83; 95% CI, 1.17 to 2.88) and MI (OR, 1.32; 95% CI, 1.03 to 1.69). Major bleeding was significantly more frequent in LDS+A patients (5.7%) versus aspirin alone (4.0%) but not in HDS patients (4.6%).Combining aspirin with LDS did not improve outcomes after acute coronary syndromes and caused more bleeding compared with aspirin alone. There was a trend toward increased mortality in this group and a significant increase in the high-dose arm.
Abstract 18106: Reprogramming of Skeletal Myoblasts for Induction of Pluripotent Status: MicroRNA Profiling and Cardiomyogenesis
Authors: Rafeeq P Ahmed, Husnain K Haider, Stephanie Buccini, Longhu Li, Muhammad Ashraf
Journal: Circulation (2010)

Background:  Encompassing the advantages of SMs, we report SMs derived iPS (SM-iPS) cells and their microRNA (miR) profile during induction of pluripotent status and cardiogenesis in comparison with native SMs ( Nat SMs).   Methods and Results:  The pMXs vector containing mouse cDNAs for Yamanaka9s quartet of pluripotency factors were used for transduction of SMs purified from male Oct4-GFP +  transgenic mouse. Three weeks later, GFP +  colonies of SM-iPS cells, having morphological similarity with mouse embryonic stem (ES) cells, were isolated and propagated i n vitro.  SM-iPS cells were positive for alkaline phosphatase staining, expressed SSEA1 and displayed a panel of pluripotency markers similar to ES cells. SM-iPS derived embryoid bodies yielded beating cardiomyocyte-like cells that were positive for early and late cardiac specific markers such as myosin heavy chain, troponin-I, connexin-43, MEF-2c and NKX2.5. miR profiling showed abrogation of let-7 family in SM-iPS cells (P,0.05  vs  native myoblasts). Of the five miR-200 family members, miR-200a-c were not detected in  Nat SMs and SM-iPS cells but were found in SM-iPS cell derived cardiomyocytes, which indicated that  Nat SMs were not totally differentiated, however, still retaining some undifferentiated characteristics. On the contrary, ES cell specific family of miR-290 to 295 which was regulated by Oct, Nanog and Sox, was upregulated in SM-iPS cells which indicated that SM-iPS cells were similar to ES cells in their miR profile.  In vivo  studies in an experimental animal model of acute myocardial infarction showed extensive survival of SM-iPS cells and SM-iPS cell derived cardiomyocytes in the mouse heart 7 days after transplantation. Our results from 4-week studies in control DMEM without cells (group-1), native SMs (group-2), SM-iPS cells (group-3) and SM-iPS cell derived cardiomyocytes (group-4) showed extensive myogenic integration of the transplanted cells in group-4 with attenuation of infarct size.   Conclusions:  Successful generation of SM-iPS cells and their cardiac differentiation were observed  in vitro . Mir profiling revealed down-regulation of differentiated tissue specific let-7 family and induction of ES cell specific miR-290–295 cluster during reprogramming of SM into iPS cells.
James Colquhoun Petrie Patrick David Wall Sir William Ferguson Anderson Denys Elwyn Howells Ronald Herbert Jones Rubi Alexandra Koyotsu Padi William Patrick Reynish
Authors: J. Petrie, R. MacDonald, C. Richmond, B. Williams, J. Dall, H. V Howells, J. A Jones, D. Harrison, B. Owen, B. Appleton, D. Watkins
Journal: BMJ (2001)
Emergence of four cases of KPC-2 and KPC-3-carrying Klebsiella pneumoniae introduced to Switzerland, 2009–10
Authors: B Babouee, A F Widmer, O Dubuis, D Ciardo, S Droz, B Y Betsch, C Garzoni, U Führer, M Battegay, R Frei, D Goldenberger
Journal: Eurosurveillance (2011)

Binary file ES_Abstracts_Final_ECDC.txt matches
A longitudinal study of body mass index and lens opacities
Authors: Rita Hiller, Marvin J Podgor, Robert D Sperduto, Leila Nowroozi, Peter W.F Wilson, Ralph B D’Agostino, Theodore Colton
Journal: Ophthalmology (1998)

The purpose of the study was to determine whether body mass index (BMI) is an independent risk factor for the development of nuclear, cortical, or posterior subcapsular lens opacities.A cohort study.Eye examinations were conducted on surviving members of the Framingham Heart Study Cohort from 1973 to 1975 (Framingham Eye Study I) and again from 1986 to 1989 (Framingham Eye Study II). Data from the Framingham Heart Study, including weight measurements collected biennially from 1948, were used to examine associations between BMI (mean BMI across examinations, slope of BMI over time, and fluctuations in BMI) and the development of lens opacities. This analysis included 714 individuals, aged 52-80 years, who were free of lens opacities at the first eye examination.Development of nuclear, cortical, and posterior subcapsular lens opacities.A total of 444 persons developed lens opacities during the approximately 13 years between eye examinations. In logistic regression analyses that controlled for age, sex, education, diabetes, and smoking, the risk of developing cortical opacity increased with higher BMI at the time of the first eye examination (P = 0.002). Risk of cortical opacities also increased, at a borderline level of significance, with higher average BMI (P = 0.09) across examinations and increasing BMI levels over time (P = 0.10). There was a strong association between increasing BMI over time and the development of posterior subcapsular lens opacities (P = 0.002). No associations were found for nuclear lens opacities.Although the mechanism explaining the association is unclear, these findings suggest that BMI, a potentially modifiable characteristic, is associated with the development of cortical and posterior subcapsular lens opacities.
Abstract P033: Sugar Sweetened Beverage Intake, Chromosome 9p21 Variants, and Risk of Myocardial Infarction in Hispanics
Authors: Yan Zheng, Yanping Li, Tao Huang, Han-Ling Cheng, Hannia Campos, Lu Qi
Journal: Circulation (2015)

Introduction: Chromosome 9p21 variants are among the most robust genetic markers for coronary heart disease (CHD). Our previous study showing that intake of sugar-sweetened beverages (SSB) interacts with genetic factors to affect risk of obesity, a major CHD risk factor, suggests that SSB could modify the effect of chromosome 9p21 variants on CHD. SSB are the main source of added sugar in the diet among Hispanics living in the United States and Latin America. Thus, this study is aimed to test whether SSB intake modifies the association between chromosome 9p21 variants and CHD risk in Hispanics. Methods: The study population included 1,603 incident cases of non-fatal myocardial infarction (MI) and 1,778 population-based controls living in Costa Rica. Three independent single-nucleotide polymorphisms (SNPs) at chromosome 9p21 locus were genotyped. SSB intake was defined as the frequency of daily servings of commercially available and home-made sweetened beverages, and fruit juice assessed using a food-frequ...
Sex Differences in Presentation and Outcome Among Patients With Type 2 Diabetes and Coronary Artery Disease Treated With Contemporary Medical Therapy With or Without Prompt Revascularization
Authors: Jacqueline E. Tamis-Holland, Jiang Lu, Mary Korytkowski, Michelle Magee, William J. Rogers, Neuza Lopes, Lisa Mighton, Alice K. Jacobs
Journal: Journal of the American College of Cardiology (2013)
Abstract 11525: Blood Pressure Reduction and Increase of Circulating MicroRNA-126 Indicate Improvement of Vascular Endothelial Damage After Smoking Cessation Intervention in Middle-Aged Habitual Smokers
Authors: Tomonori Sugiura, Yasuaki Dohi, Sumiyo Yamashita, Akimasa Sanagawa, Soichiro Iwaki, Nobuyuki Ohte, Satoshi Fujii
Journal: Circulation (2014)

Introduction: Cigarette smoking promotes vascular endothelial damage and accelerates progression of atherosclerosis. The purpose of this study was (1) to examine effects of smoking cessation intervention on vascular function and (2) to investigate whether circulating level of microRNA-126 (miR-126), a vascular endothelium-enriched microRNA, would recover from smoking-related endothelial damage in middle-aged habitual smokers. Methods: Middle-aged male smokers (n=30) were enrolled and instructed to stop smoking. Their clinical profiles of vascular function and laboratory findings including serum levels of cotinine, a principal metabolite of nicotine, and expression of miR-126 were investigated at baseline and 8 weeks after the instruction. Vascular function for peripheral small vessels was assessed using End-PAT 2000 and expressed as reactive hyperemia peripheral arterial tonometry (RH-PAT) index. The expression of miR-126 in plasma was analyzed by quantitative real-time PCR. Results: At baseline, serum co...
Abstract 227: Activity of Soluble Guanylyl Cyclase, the Nitric Oxide Receptor, is Modulated by Cysteines Redox
Authors: Samba Couloubaly, Nazish Sayed, Jamila Hedhli, Padmamalini Baskaran, Annie Beuve
Journal: Circulation (2008)

The enzyme soluble guanylyl cyclase (sGC) increases cellular level of the second messenger cGMP upon stimulation by nitric oxide (NO), whose role is exemplified in the cardiovascular system where it governs smooth muscle cell proliferation, vascular relaxation and platelet aggregation. Various pathologies like diabetes, hypertension and hypercholesterolemia are associated with enhanced oxidative stress with increased formation of reactive oxygen (ROS) and nitrogen species (RNS). We recently showed that cysteines beta1C243 and beta1C122 are S-nitrosylated in sGC leading to its desensitization. We have now identified by Mass Spectrometry, two additional cysteines (beta1C571 and alpha1C516) as potentially modified. Our hypothesis is that loss in vascular reactivity in oxidative pathologies is mediated, in part, by desensitization of sGC via thiols oxidation. We studied the effect of oxidative stress on sGC in primary vascular smooth muscle cells (VSMC) by directly exposing them to hydrogen peroxide (H2O2) in the absence or presence of a catalase inhibitor Amino-Triazole (AT). H2O2 induced inhibition of NO-stimulated sGC activity in VSMC and in COS 7 cells transiently transfected with sGC. Desensitization of sGC was further increased in VSMC treated with both H2O2 and AT. Next, we conducted mutational analysis of the 4 cysteines to assess their involvement in redox sensing. Replacement of C571 and C122 eliminated the oxidative-dependent desensitization observed in the wild-type. In addition, peroxynitrite, a strong oxidant, inhibited the NO-stimulated sGC activity in a purified system without oxidation of the heme. In conclusion, our results suggest that sGC activity is directly modulated by the redox state of the cells. Moreover, the identified 4 cysteines can be modified by both ROS and RNS suggesting a complex modulation. Ultimately, our goal is to determine whether loss of vascular reactivity in oxidative pathophysiologies is in part mediated by desensitization of sGC and what are the involved cysteines. This work was supported by NIH GM067640, HL089771.
Abstract 20257: A Sensitive Cardiac Troponin T Assay In Cardiac Allograft Recipients
Authors: Christian Erbel, Rukiye Taskin, Susanne Wangler, Andreas Doesch, Evangelos Giannitsis, Thomas J Dengler, Hugo A Katus
Journal: Circulation (2010)

Although improvements have been made in the prevention and treatment of acute transplant rejection and infection, first year mortality still limits the success of heart transplantation. In addition...
Abstract 15637: AKT Regulates Cardiomyocyte Homeostasis by Regulating the Expression of the Voltage-Dependent L-Type Ca2+ Channel (Cav1.2)
Authors: Kensuke Tsushima, Angelica Lopez-Izquierdo, Kenneth W Spitzer, Morris J Birnbaum, Jaetaek Kim, E. Dale Abel
Journal: Circulation (2013)

Recent studies have shown that insulin-Akt-mTORC1 signaling contributes not only to embryonic and postnatal physiological heart growth, but also to adverse LV remodeling in pathological hypertrophy...