tbuckley/cabot-search huggingface dataset:
Abstract 17883: Neutrophil Extracellular Traps as an Interface Between Inflammation and Thrombosis in DVT
Authors: Konstantin Stark, Marie-Luise von Brühl, Alexander Steinhart, Sue Chandraratne, Maria Köllnberger, Michael Lorenz, Susanne Pfeiler, Davit Manukyan, Wolfgang Bergmeier, Denisa Wagner, Bernd Engelmann, Steffen Massberg
Journal: Circulation (2011)

Objective: Neutrophil extracellular traps (NET) have mainly been implicated in antimicrobial host defense, but recently their contribution to arterial and microcirculatory thrombosis has been identified. These extracellular DNA structures also have been found in deep venous thrombosis (DVT), but how they participate in thrombus formation in vivo is unclear. In this study we wanted to assess the dynamics of NET formation and their impact on DVT development in vivo in a murine flow reduction model of the inferior vena cava (IVC). Methods: Thrombosis was induced in C57Bl6 mice by placing a narrowing ligature around the IVC, resulting in a reduction of blood flow velocity (n=16). NET formation in vivo was visualized by intravital epifluorescence microscopy. The IVC was harvested 48h after flow reduction, weighed and stained by immunofluorescence. Thrombogenesis and NET formation were quantified in DNase, anti-H2A-H2B-DNA antibody, and heparin treated animals as well as in GPIb-/- mice. Results: Extracellular DNA could be detected in vivo as early as 3h after flow reduction (n=3). These DNA structures were positive for neutrophil elastase, myeloperoxidase, and histones, confirming that they are indeed NETs. In the IVC harvested 48 hours after the flow restricting procedure, we found that NETs were binding platelets, tissue factor, and fibrinogen. The functional impact of NETs for DVT formation is indicated by the finding that disruption of NETs by DNase (n=5) or anti-H2A-H2B-DNA antibody (n=5) treatment resulted not only in a reduced number of NETs, but also in a significantly reduced thrombus weight compared to wt control. Surprisingly, injection of heparin resulted in a diminished number of NETs inside the IVC, which could add to its antithrombotic effect (n=3). In addition, in the IVC of GPIb-/- mice only very few NETs could be identified, suggesting that platelets trigger NET formation during DVT (n=3). Conclusion: Here we show, that neutrophils contribute to DVT by NET formation. This provides a platform for platelet adhesion and concentration of procoagulatory factors on their surface, linking inflammation and thrombosis at the cellular level. Thus, disruption of NETs could be an interesting new therapeutic approach for prophylaxis and treatment of DVT.
Abstract 1432: Nitric Oxide Bioavailability is Lower in Endothelium of Healthy Mexican American Donors as Compared to Non-Hispanic White Donors: Effect of Nebivolol
Authors: R. P Mason, Ruslan Kubant, Christopher Malinski, Adam Jacoby, Robert F Jacob, Charles A Day, Tadeusz Malinski
Journal: Circulation (2007)

Background: Epidemiologic studies indicate that Mexican Americans (MA) have a higher prevalence of CV risk factors and disease as compared with non-Hispanic whites (NHW). This increase in CV risk may be due, in part, to differences in endothelial function. In this study, we measured endothelial function in cells from normotensive, age-matched MA and NHW donors, as well as the effects of treatment with nebivolol, a new β 1 -selective blocker with vasodilating properties. Methods: Endothelial nitric oxide (NO) and peroxynitrite (ONOO − ) release in human umbilical vein endothelial cells (HUVECs) from age-matched MA and NHW donors were measured simultaneously using a nanosensor array. The effects of nebivolol on NO and ONOO − release were evaluated following pretreatment (24 h) with a calcium ionophore (CaI) as a receptor-independent stimulus. Endothelial NO synthase (eNOS) levels were measured by Western blot analysis, and drug-membrane interactions were determined by small angle x-ray diffraction approaches. Results: NO bioavailability in endothelial cells of MA donors was 30% lower than that of cells from NHW donors (383 ± 10 nM versus 543 ± 8 nM, n=6) following stimulation with CaI (1.0 μM). Pretreatment with nebivolol (1.0 μM) eliminated these interracial differences and enhanced NO release disproportionately in MA cells (57%) versus NHW cells (20%). Nebivolol also reduced ONOO − levels in MA endothelium by 75% (746 ± 12 nM to 195 ± 10 nM) and by 50% in NHW cells (416 ± 7 nM to 191 ± 13 nM). The ratio of NO to ONOO − , an indicator of eNOS coupling, increased more than 5-fold in MA cells following nebivolol treatment. In addition, eNOS levels were 40% lower in MA endothelium compared to NHW, but increased 2-fold with nebivolol treatment. These effects were not observed with atenolol, a hydrophilic β 1 -selective antagonist. Conclusion: We observed differences between Mexican Americans and non-Hispanic whites in endothelial NO bioavailability and nitroxidative stress–factors that may contribute to increased CV risk. Treatment with nebivolol, but not atenolol, enhanced both the expression and coupling efficiency of eNOS in Mexican American endothelium.
Abstract 16482: Ablation of FN14 Reduces Fibrosis in Pulmonary Arterial Hypertension Rescuing Heart Function
Authors: Tatyana Novoyatleva, Yves Schymura, Wiebke Janssen, Astrid Wietelmann, Ralph Schermuly, Felix B Engel
Journal: Circulation (2011)

Right ventricular failure is the leading cause of death in pulmonary arterial hypertension (PAH), which is preceded with sustained right ventricular hypertrophy (RVH) and fibrosis. The molecular me...
Abstract 3139: Beta Adrenoceptor Polymorphisms are Associated with Differential Hemodynamic Responses During Dobutamine Stress Echocardiography
Authors: Alexander Kopelnik, Sirisha Yarlagadda, Ludmila Pawlikowska, Giai Lao, Elyse Foster, Pui-Yan Kwok, William L Young, Jonathan G Zaroff
Journal: Circulation (2006)
Long-term course of anorexia nervosa
Authors: Kathleen M. Pike
Journal: Clinical Psychology Review (1998)

There is no predictable or normative long-term course associated with anorexia nervosa. Some Individuals achieve complete recovery; others are ravaged by a chronic disorder; and some die from it. Predicting course and outcome of anorexia nervosa is complicated by the intrinsic complexity of the disorder; a lack of shared terminology in studying the disorder; and a paucity of controlled clinical treatment studies. This manuscript provides a review of the current state of knowledge based on the long-term studies and discusses ways in which methodological issues limit our ability to generalize more confidently regarding the course and outcome of anorexia nervosa. In order to advance the field, we need to bridge the gap between treatment outcome studies and naturalistic follow-up studies. Further we need to devine more carefully and consistently the milestones of initial treatment response, relapse, remission, and recovery. Building on previous works, criteria for each of these terms are proposed. Based on existing studies, a discussion of treatment outcome and prognostic factors is provided. Finally, clinical recommendations are provided for the clinician who is responsible for the long-term care of an individual with anorexia nervosa.
Abstract 2987: Relationship Between Peripheral Blood Mononuclear Cell Gene Expression and QTc-Interval During Acute Cellular Allograft Rejection After Heart Transplantation
Authors: Khurram Shahzad, Martin Cadeiras, Farhana Latif, Timothy He, Tod Klingler, Anshu Sinha, Sreevalsa Unniachan, Mario Deng
Journal: Circulation (2009)
The role of superspreading in Middle East respiratory syndrome coronavirus (MERS-CoV) transmission
Authors: A J Kucharski, C L Althaus
Journal: Eurosurveillance (2015)

As at 15 June 2015, a large transmission cluster of Middle East respiratory syndrome coronavirus (MERS-CoV) was ongoing in South Korea. To examine the potential for such events, we estimated the level of heterogeneity in MERS-CoV transmission by analysing data on cluster size distributions. We found substantial potential for superspreading; even though it is likely that R 0 &lt; 1 overall, our analysis indicates that cluster sizes of over 150 cases are not unexpected for MERS-CoV infection.
Abstract 12236: Redistribution of Gsk-3β to Cardiac Intercalated Discs in Arrhythmogenic Cardiomyopathy
Authors: Angeliki Asimaki, Stephen Chelko, Daniel P Judge, Andre G Kleber, Jeffrey E Saffitz
Journal: Circulation (2014)

Reduced signal at intercalated discs (IDs) and nuclear accumulation of the desmosomal protein plakoglobin (γ-catenin) in arrhythmogenic cardiomyopathy (ACM) have been linked to suppression of canonical Wnt/β-catenin signaling. In a chemical screen in a zebrafish model of ACM, we found that SB216763, annotated as an inhibitor of glycogen synthase kinase-3β (GSK-3β), prevents heart failure and reduces mortality. It also prevents arrhythmias and myocyte injury and apoptosis in cultured neonatal rat ventricular myocytes (NRVM) and intact mouse hearts expressing ACM mutations in 3 different desmosomal genes. Given the role of GSK-3β in the canonical Wnt/β-catenin pathway, we further examined GSK-3β in ACM pathogenesis. To determine if GSK-3β is redistributed in ACM, we immunostained myocardium from 11 patients who met diagnostic criteria, including 8 with desmosomal gene mutations. GSK-3β immunoreactive signal accumulated at ventricular myocyte IDs in the hearts of all patients with ACM but not in control hearts or samples from patients with end-stage ischemic, dilated or hypertrophic cardiomyopathies (n=5 for each) or cardiac sarcoidosis (n=10). The GSK-3β binding partner adenomatous polyposis coli (APC) also localized to cell-cell junctions in ACM hearts only, consistent with the presence of the GSK-3β/axin/APC complex at IDs in ACM. GSK-3β and APC also showed marked junctional localization in NRVM expressing mutant forms of plakoglobin (2057del2) or plakophilin2 (1851del123), and in the hearts of adult mice expressing 2057del2 plakoglobin and a cardiac myocyte-specific Dsg2 knock-in mouse, but not in normal controls cells or tissues. GSK-3β and APC distributions were normalized by SB216763 in these in vitro and in vivo models of ACM. Immunoblotting showed no apparent change in the total cellular content of GSK-3β in the presence of ACM-causing desmosomal gene mutations. However, in addition to restoring the normal cytoplasmic localization of the GSK-3β/APC complex, SB216763 also decreased the total cellular content of the active (non-phospho) form of GSK-3β in all 4 experimental models. These observations suggest a role for GSK-3β distribution in the ACM disease mechanism independent of the specific underlying desmosomal mutation.
Abstract 1838: Neural Crest Stem Cells Supply Intrinsic Cardiac Adrenergic Cells and Contribute to Reinnervation after Myocardial Infarction in Mice
Authors: Yuichi Tamura, Masaki Ieda, Keisuke Matsumura, Hideaki Kanazawa, Kensuke Kimura, Yasuyo Ieda, Jin Endo, Takahide Arai, Haruko Kawaguchi-Manabe, Yuichi Tomita, Shinsuke Yuasa, Motoaki Sano, Kazuto Kobayashi, Satoshi Ogawa, Keiichi Fukuda
Journal: Circulation (2008)

Cardiac nerve sprouting and heterogeneous reinnervation after myocardial infarction (MI) lead to arrhythmogenesis and sudden cardiac death. Despite its importance, little is known about the contribution of the intrinsic cardiac nervous system on reinnervation. We previously reported that neural crest stem cells (NCSC) reside in the heart, and can differentiate into neuron, glia, smooth muscle cells, and cardiomyocytes. The present study scrutinized the developmental origin of intrinsic cardiac adrenergic (ICA) cells, and investigated whether NCSC supply ICA and contribute to reinnervation after MI. (1) We analyzed two distinct double transgenic mice, encoding protein 0-Cre/Floxed-EGFP (P0-EGFP) and dopamine β -hydroxylase-Cre/Floxed-EGFP (DBH-EGFP), to map neural crest-derived cell fate and catecholaminergic cell fate, respectively. ICA cells, demarcated with tyrosine hydroxylase (TH, catecholaminergic marker)-immunopositive cells within ventricles, co-expressed EGFP in both P0-EGFP and DBH-EGFP mice. Most ICA cells were nucleated and round-shaped, although 5% of the cells extended nerve fibers. (2) NCSC were marked with EGFP in P0-EGFP mice, expressed nestin, musashi-1 and p75 nerve growth factor (NGF) receptor, and showed sphere formation. They frequently resided in the outflow tract, but also existed in all parts of the heart. (3) ICA cell number and TH mRNA expression within ventricles were increased in transgenic mice overexpressing NGF in the heart. (4) P0-EGFP mice were subjected to MI by coronary artery occlusion. EGFP-positive cells were markedly increased after MI, and more so in the border zone area than in the non-infarcted area. (5) Similarly, DBH-EGFP subjected to MI revealed an increase in EGFP-positive cells at the border zone area, and some of them extended neurites among the sprouting nerves. (6) TH and EGFP mRNA were increased in DBH-EGFP ventricles, concomitant with cardiac NGF upregulation. These findings demonstrated that ICA cells were derived from neural crest cells, and dependent on NGF synthesized in the heart. NCSC were mobilized to the infarcted myocardium, differentiated into TH-positive nerves, and contributed to reinnervation after MI.
Abstract 525: New Candidate Biomarkers for Cardiovascular Risk in Early Menopausal Women
Authors: Muthuvel Jayachandran, Robert D Litwiller, Whyte G Owen, Virginia M Miller
Journal: Circulation (2008)

Little is known about the cellular mechanisms by which estrogen deprivation with menopause contributes to thrombosis and associated cardiovascular events. Experiments were designed to examine the r...
Effects of Dietary Nitrate on Blood Pressure
Authors: André Dejam, Christian J Hunter, Mark T Gladwin
Journal: New England Journal of Medicine (2007)

To the Editor: Larsen and colleagues (Dec. 28 issue)1 report that oral nitrate (NO3) can lower mean arterial blood pressure and is associated with an elevation in blood levels of nitrite (NO2). They point out that nitrate is reduced by oral bacteria to nitrite, which can be converted into nitric oxide or absorbed, and they suggest that the mechanism involved in the blood-pressure–lowering effect needs to be clarified. In studies conducted over the past 5 years, we have shown that nitrite is an intrinsic vasodilator.2,3 Within the vasculature, nitrite is reduced to nitric oxide by reaction with deoxygenating hemoglobin and possibly other heme proteins.4,5 These studies show that nitrite levels are higher in the arteries than in the veins in humans, indicating metabolism across the peripheral circulation, and that when nitrite is infused into the brachial artery, it causes vasodilatation. We recently completed a study evaluating the effect of low-dose nitrite infusion in 15 healthy volunteers and found that levels as low as 350 nM resulted in measurable vasodilatation in the forearm; mean (±SE) values of blood flow ranged from 3.0±0.3 to 3.4±0.3 ml per minute per 100 ml of forearm tissue (P = 0.04). We are therefore not surprised that increases in nitrite levels from 138 nM to 219 nM caused by increased dietary intake of nitrate are associated with decreases in blood pressure.
Abstract 3016: Spirituality and Medication Adherence in Older African American Adults Diagnosed with Hypertension: A Qualitative Study
Authors: Lisa M Lewis
Journal: Circulation (2007)

Background : Medication adherence (ADH) is key to decreasing hypertension (HTN)-related morbidity and mortality in older African-American (AA) adults. However, older AA adults have poorer ADH to prescribed antihypertensive medications when compared to their younger and Caucasian-American counterparts. Patient beliefs and cultural concepts about their medications influence their medication ADH. An important cultural concept in this regards is spirituality, which is a significant resource in the AA community. Thus, the purpose of this qualitative study was to explore the role of spirituality in ADH to antihypertensive medications for older AA adults. Methods: Older AA adults who were members of a Program of All Inclusive Care for the Elderly (PACE) and who were (a) diagnosed with HTN; (b) prescribed at least one antihypertensive medication; (c) self-identified as African-American or Black; and (d) self-identified as spiritual completed one in-depth individual face-to-face in this qualitative descriptive study informed by grounded theory. Demographic data were also collected. Results : Twenty-one PACE members completed the study. All of the participants were female. The mean age of participants was 73 years with most completing high school (67%). The mean HTN diagnosis was16.7 years and mean number of prescriptions for antihypertensives was 3.3. Participants indicated that their spirituality was used in a collaborative process with formal health care to manage their ADH to antihypertensive medications. This process was identified as Partnering with God to Manage My Medications. Partnering with God to Manage My Medications indicated that the PACE members acknowledged personal responsibility for adhering to their antihypertensive medication regimen but used their spirituality as a resource for making decisions to remain adherent; coping with medication side effects; and increasing their self-efficacy to deal with barriers to ADH . Conclusions : Spirituality played a positive role in medication adherence for the PACE members. Incorporating individual beliefs, such as spirituality, into patient treatment for HTN may capitalize on their inner resources for medication ADH and demonstrates culturally appropriate care.
Abstract #LB-142: Immunoglobulin gene transcripts from human epithelial cancer cells have distinct VHDJH or VKJK recombination
Authors: Qiu Xiaoyan, Jie Zheng, Jing Huang, Yuntao Mao, Xiaohui Zhu, C. Cameron Yin
Journal: Cancer Research (2009)

We have recently reported that immunoglobulin (Ig) gene can also be expressed in epithelial cancer cells. To elucidate the structure and function of these non-B-cell-derived Ig, we have cloned and sequenced 89 V H DJ H  transcripts by microdissecting cells from eight different types of epithelial cancers and two cancer cell lines (HT-29 and HeLaS3), as well as 37 V k J k  transcripts by microdissecting cells from five different types of epithelial cancers and a cancer cell line (HT-29). We detected seven dominant V H DJ H  sequences, including V H 5-51/D3-9/J H 4 in carcinomas from the breast, colon, oral cavity and lung, V H 3-30/D6-19/J H 4 in carcinomas from the breast, colon and lung, V H 3-15/D3-10/J H 4 in carcinomas from the breast and colon, V H 6-1/D6-13/J H 4 in carcinomas from the lung and oral cavity, as well as V H 4-30-2/D3-22/J H 4 in carcinomas from the breast and colon. Of the V H DJ H  sequences studied ,  the cancer-derived Ig gene repertoire within an individual cancer showed a specific restricted pattern of V H DJ H  recombination. Suprisingly, all of the V k J k  recombinations from different types of epithelial cancers showed Vk4-1/Jk3 recombination. More interestingly, within a set of dominant V H DJ H  or V k J k  recombinations, the V sequences derived from different cancer types had not only identical variable region (V H  or V k ), D, and J (J H  or J k ) segments usage but also identical junctions and mutation targets in the V H  or V k  region, unlike that of B-cell-derived Ig. The V H\#947; DJ H\#947;  and  V k J k  (but not V H\#956; DJ H\#956; ) had a high mutation rate; however, the mechanism of hypermutation was different from the antigen selection mechanism in B-cell-derived V H\#947; DJ H\#947;  sequences. In contrast with V H\#956; DJ H\#956; , the V H\#947; DJ H\#947;  sequences did not appear to originate from classical class switching. These results suggest that cancer-derived Ig genes have a distinct repertoire and may possess unknown functions in diverse cancer cell types.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr LB-142.
Abstract 18589: Blood Pressure Lowering Persists for 36 Weeks After Lifestyle Interventions: The ENCORE Follow-up Study
Authors: Alan L Hinderliter, Michael Babyak, Andrew Sherwood, James Blumenthal
Journal: Circulation (2010)

Background: Short-term lifestyle modification programs are effective in lowering blood pressure (BP), but the long-term benefits of these interventions have not been extensively studied. We examined the persistence of changes in dietary habits, exercise behavior, body weight, and blood pressure in participants in the ENCORE study at 1 year after enrollment. Methods: Participants included 144 unmedicated, overweight or obese participants (67% F; 59% Caucasian; mean age = 52 yr) with pre-hypertension or stage 1 hypertension (BP 130-160/80-99 mm Hg). Subjects were randomized to 16 weeks of DASH diet plus behavioral weight management (consisting of supervised exercise and a behavioral modification program) (DASH+WM), DASH diet alone (consisting of nutritional counseling without exercise or caloric restriction) (DASH), or usual care (UC). Results: Data were available in 124 subjects at 52 weeks (36 weeks following completion of the intervention). At 52 weeks, consumption of sodium was lower and dietary intake ...
Abstract 13944: Cardiovascular Outcomes in Drug Eluting Stent Patients on Clopidogrel Based Genetic Variants in CYPC219*2, CYP2C19*17, and ABCB1
Authors: Stacey Knight, Jeffrey L Anderson, Benjamin D Horne, Joseph B Muhlestein, John A Huntinghouse, Tami L Bair, John F Carlquist
Journal: Circulation (2011)

Background: Clopidogrel requires the P-450 enzyme CYP2C19 for activation. Failure of anti-platelet therapy with clopidogrel has been associated with a loss of function variant in the CYP2C19 gene (...
European pilot studies are under way
Authors: S. Y Mills
Journal: BMJ (1995)

EDITOR,--Guy Vautier and R C Spiller call for better monitoring of the safety of herbal remedies.1 They are correct in identifying a serious gap in provisions. It may be helpful to elaborate on the situation and outline some steps that are being taken to improve matters.

Several hundred herbal products are available in Britain with full product licences as medicines under the terms of the Medicines Act and relevant European directives. These have to comply with tight criteria concerning quality, and their manufacturers are obliged …
Abstract 2432: Effect of Left Ventricular Systolic Dysfunction on Wasted Left Ventricular Energy and Tension-Time Index
Authors: Scott J Denardo, Wilmer W Nichols
Journal: Circulation (2008)

Information obtained from the aortic pressure waveform is affected by age, physical condition, systemic hypertension, diabetes mellitus and coronary artery disease. However, alterations in the aortic pressure waveform in patients (pts) with heart failure and left ventricular systolic dysfunction (LVSD) have not been fully described, including a description of the effect on wasted LV pressure energy and tension-time index. Non-invasive high-fidelity radial artery tonometry was used for data acquisition, and a mathematical transfer function used to generate aortic pressure waveforms (see figure ). Pulse wave analysis (PWA) of the aortic pressure waveform was used to obtain information associated with LV/vascular coupling in 23 pts age 55±9.5 yrs with LVSD (mean LV ejection fraction, 22±6%) and compared to data collected from 23 normal subjects matched for age, gender, height, weight and heart rate. Measurements obtained using PWA in heart failure pts with LVSD demonstrate decreased wasted LV energy and tension time index, consistent with poor LV mechanical performance, in addition to decreased unaugmented pressure, pulse pressure, ejection duration and augmentation index. Further standardization of these aortic pressure waveform findings in heart failure pts may allow for the clinical use of arterial PWA to non-invasively estimate LVSD.