tbuckley/cabot-search huggingface dataset:
Abstract 3123: Doppler Echocardiography Reliably Predicts Severe Pulmonary Regurgitation (PR) As Quantified by Cardiac Magnetic Resonance (CMR)
Authors: Pierangelo Renella, Jamil Aboulhosn, Derek G Lohan, Praveen Jonnala, J. P Finn, John S Child
Journal: Circulation (2007)

Background: Significant PR is a common sequel to repair of some forms of congenital heart disease (CHD). Grading the severity of PR by Doppler echocardiography (echo-Doppler) is not standardized and may be problematic. CMR is considered the gold standard method for quantifying PR, but is not universally available. We sought to determine the best echo-Doppler predictors of severe PR. Methods &amp; Results: We retrospectively reviewed 36 CHD pts (median age 31 yrs, range 10 – 67 yrs; 33 with Tetralogy of Fallot, 3 with primary pulmonary stenosis) with prior pulmonary valvuloplasty and/or transannular patch placement who underwent both Doppler echo and velocity encoded CMR. Severe CMR PR was defined as ≥40% regurgitant fraction. Echo-Doppler measurements used to predict severe PR were: diastolic flow reversal (DFR) of color flow or spectral pulsed wave Doppler in the main pulmonary artery (MPA) or the branch pulmonary arteries (BPA), a PR jet that fills ≥50% of the pulmonary annular diameter (PAD), PR pressure half-time (PHT) &lt;100 msec, &amp; pulmonary regurgitation index (PRi) &lt;0.77. MPA DFR had 100% sensitivity but low specificity (39%) for detecting severe PR (Table 1 ). BPA DFR remained quite sensitive (87%), but much more specific (87%). Univariate analysis showed each variable (except PRi) was a good individual predictor of severe PR (Table 2 ). Classification &amp; regression tree analysis showed the 2 most useful variables were (first) DFR in the BPA &amp; (second) the PRi &lt;0.77. Conclusions: Readily obtained targeted echo-Doppler measurements reliably identify severe PR as quantified by CMR. BPA DFR is the most specific and MPA DFR is the most sensitive echo-Doppler finding for detecting severe PR. Table 1. Statistical Analysis of 5 Echo-Doppler Measures Table 2. Univariate Analysis of 5 Echo-Doppler Measures
Altered BCR and TLR signals promote enhanced positive selection of autoreactive transitional B cells in Wiskott-Aldrich syndrome
Authors: Nikita S. Kolhatkar, Archana Brahmandam, Christopher D. Thouvenel, Shirly Becker-Herman, Holly M. Jacobs, Marc A. Schwartz, Eric J. Allenspach, Socheath Khim, Anil K. Panigrahi, Eline T. Luning Prak, Adrian J. Thrasher, Luigi D. Notarangelo, Fabio Candotti, Troy R. Torgerson, Ignacio Sanz, David J. Rawlings
Journal: The Journal of Experimental Medicine (2015)

Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency disorder frequently associated with systemic autoimmunity, including autoantibody-mediated cytopenias. WAS protein (WASp)-deficient B cells have increased B cell receptor (BCR) and Toll-like receptor (TLR) signaling, suggesting that these pathways might impact establishment of the mature, naive BCR repertoire. To directly investigate this possibility, we evaluated naive B cell specificity and composition in WASp-deficient mice and WAS subjects (n = 12). High-throughput sequencing and single-cell cloning analysis of the BCR repertoire revealed altered heavy chain usage and enrichment for low-affinity self-reactive specificities in murine marginal zone and human naive B cells. Although negative selection mechanisms including deletion, anergy, and receptor editing were relatively unperturbed, WASp-deficient transitional B cells showed enhanced proliferation in vivo mediated by antigen- and Myd88-dependent signals. Finally, using both BCR sequencing and cell surface analysis with a monoclonal antibody recognizing an intrinsically autoreactive heavy chain, we show enrichment in self-reactive cells specifically at the transitional to naive mature B cell stage in WAS subjects. Our combined data support a model wherein modest alterations in B cell-intrinsic, BCR, and TLR signals in WAS, and likely other autoimmune disorders, are sufficient to alter B cell tolerance via positive selection of self-reactive transitional B cells.
Abstract 562: Pattern Of Microparticle Release And Endothelial Progenitor Cell Recruitment Is Different Across The Spectrum Of Coronary Syndromes
Authors: Luigi M Biasucci, Italo Porto, Luca Di Vito, Giovanni Luigi De Maria, Giuliana Di Rocco, Alessandra Tritarelli, Alessandra Paglia, Gianpaolo Niccoli, Antonio M Leone, Maurizio C Capogrossi, Filippo Crea
Journal: Circulation (2008)

Microparticles (MP) are fragments released from different cells on activation or apoptosis. Endothelial MP (EMP), in particular, are thought to be markers of endothelial injury, while platelet MP (...
Abstract 15148: HIV-infected Patients on Stable Antiretroviral Therapy Do Not Show Impaired Myocardial Flow Reserve Assessed With 82Rubidium PET/CT
Authors: Andreas Knudsen, Thomas Emil Christensen, Anne-Mette Lebech, Andreas Kjær
Journal: Circulation (2014)

Introduction:  Epidemiological studies have shown that HIV-infected patients are at increased risk of coronary artery disease (CAD), and endothelial dysfunction has been suggested to play a pathogenetic role. Clinical studies of peripheral endothelial dysfunction find a higher prevalens among HIV-infected patients and some studies link these findings with the antiretroviral treatment (ART), especially abacavir. For the first time among HIV-infected patients, we assess the myocardial flow reserve (MFR) by 82Rb PET/CT, which can quantify endothelial function and thereby also detect small vessel disease. MFR has proved highly predictive of future CAD.   Hypothesis:  We assessed the hypothesis that 82Rb PET/CT cardiac perfusion would reveal a decreased MFR among HIV-infected patients compared to healthy controls.   Methods:  We conducted a cross-sectional study of 54 HIV-infected patients and 25 healthy controls using 82Rb PET/CT at rest and stress, thereby obtaining the MFR (stress flow/rest flow), which was stratified into low ≤ 2, borderline 2.1-2.5, and normal ≥ 2.5. Additionally, the coronary calcium score (CACS) was calculated.   Results:  The HIV-infected patients had a median age of 53 years (IQR 46 - 59) and were all on stable ART with full viral suppression. The healthy controls had a median age of 53 (IQR 46 - 60). In the HIV-infected group 75% had a normal MFR, 14% had borderline and 11% low values of MFR. In the healthy control group these values were 76%, 12% and 12%, respectively (p = 0.95).  HIV-infected patients receiving abacavir did not show lower levels of MFR (p = 0.89). There was no difference in CACS between the two groups (median 0 (IQR 0 - 88) among HIV-infected and median 0 (0 - 14) among healthy controls, p = 0.20).   Conclusion:  We found no evidence of decreased MFR among HIV-infected patients on stable ART with full viral suppression as assessed by 82Rb PET/CT, which may question the extent of endothelial dysfunction among optimally treated HIV-infected patients.
Abstract 404: Function of Brg1 chromatin remodeling factor in sonic hedgehog-dependent medulloblastoma development
Authors: Xuanming Shi, Zilai Zhang, Qiu Wang, Jiang Wu
Journal: Cancer Research (2014)

Abstract Medulloblastoma is the most common malignant pediatric brain tumor. Overactive Shh signaling in cerebellum granule neuron precursors (CGNPs) is the leading cause of the childhood medulloblastoma (Shh-subtype). Previously we have shown that chromatin remodeler Brg1 is required for Shh target gene expression, and Brg1 deletion reduced CGNP proliferation in developing cerebellum. Current study focuses on the function of Brg1 in mouse model of Shh-subtype medulloblastoma. In CGNP cultured from SmoM2 transgenic mice where Shh pathway is constitutively active, we found Brg1 is required for CGNP mitogenic target gene expression and proliferation. In SmoM2 medulloblastoma cultures, we observed that tumor cell growth was inhibited by conditional knockout of Brg1. In subcutaneous transplantation, we found that tumors were significantly shrunk upon induction of Brg1 deletion. Detailed analysis indicated that Shh-dependent mitogenic target genes decreased by loss of Brg1. Further evidences showed that medulloblastoma cell proliferation was significant inhibited by conditional knockout of Brg1. Effect of Brg1 on the chromatin environment of target genes during medulloblastoma development will be discussed. Our study will provide insights to the epigenetic mechanism of Shh-dependent tumor development and new therapeutic targets. Citation Format: Xuanming Shi, Zilai Zhang, Qiu Wang, Jiang Wu. Function of Brg1 chromatin remodeling factor in sonic hedgehog-dependent medulloblastoma development. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 404. doi:10.1158/1538-7445.AM2014-404
Abstract 19697: Left Ventricular Unloading by Impella® Microaxial Flow Pump for Treatment of Left Ventricular Overload in Venoarterial Ecmo Supported Cardiogenic Shock Patients
Authors: Philipp Roentgen, Christan Kuehn, Gregor Warnecke, Joern Tongers, Andreas Schäfer, Axel Haverich, Johann Bauersachs, Bernhard Schieffer
Journal: Circulation (2012)

Background Venoarterial (VA)-ECMO is an established support for refractory cardiogenic shock (CS), but may be complicated by an increase of cardiac afterload leading to left ventricular (LV) distension with consecutive pulmonary edema and deterioration of left ventricular function. Methods VA-ECMO was instituted in patients with refractory CS of different etiology. Progressive LV overload was detected by clinical signs of pulmonary edema and critical elevated LV end diastolic pressure (LVEDP). LV unloading by Impella ® 2.5 via femoral access was established. Patients were followed up for heart rate, catecholamine demand, white blood cell count (WBC) and serum lactate levels before and after 24 hours (h). Fatal bleeding complications, signs of limb ischemia and 28-day mortality were assessed. Data are presented as mean±SD. Results Six patients, SAPS II-Score on admission 56±15, age 61±18 yrs are presented. Three MI patients complicated with refractory CS. One patient with myocarditis, one due to acute heart failure complicated by septic shock and one due to acute heart transplant rejection. Five/6 patients were on mechanical ventilation and all showed clinical and radiologic signs of pulmonary edema (LVEDP before LV unloading 35±15 mmHg). Under Impella ® support (5±2 days) heart rate decreased after 24 h from 120±15 to 104±20/min. After 24h catecholamine demand decreased (dobutamine and epinephrine p=n.s.; norepinephrine 0.44±0.38 to 0.20±0.19 µg/kg/min, p=0.04). Serum lactate levels declined from 5.5±4.8 to 2.5±1 mmol/l at 24 h and 1.3±0.3 mmol/l at 72 h. WBC declined from 22±6 to 18±6 thd/µl (p=0.004) after 24 h. No fatal bleeding complications or limb ischemia occurred. 28-day mortality was 17 %. One patient with myocarditis died in multiorgan failure. Conclusion VA-ECMO treatment of CS complicated by LV overload can safely and efficiently be treated by LV unloading using microaxial flow pump Impella ® 2.5. This biventricular decompression rapidly reduces catecholamine demand and lactate levels indicating an improved organ function followed by a resolution of SIRS due to cardiac shock (reduced WBC).
Abstract P2-07-06: Niclosamid overcomes epithelial-mesenchymal transition of lapatinib resistance through inhibiting Src activation in HER2 positive breast cancer
Authors: Junjun Liu, Xiaosong Chen, Yan Mao, Kunwei Shen
Journal: Cancer Research (2015)

Abstract Background: The Src pathway is known to regulate tumor matastasis and plays a role in epithelial-mesenchymal transition(EMT). Lapatinib, although, has improved clinical outcome for HER2 positive breast cancer patients, acquired resistance to lapatinib remains an important reason influencing its clinical efficacy. Our previous research shows lapatinib acquired resistance HER2 positive breast cancer cell lines, SKBR3-R and BT474-R have EMT phenomenon and multiple pathway activated. Niclosamide is an FDA-approved antihelminthic agent, which is found has cytotoxicity effect on tumor stem cells recently. We wished to determine the effect of niclosamide on EMT and lapatinib resistance cells and investigate niclosamide as a potential therapeutic agent for HER2 positive breast cancer. Methods: SKBR3 and BT474, two HER2 positive breast cancer cell lines, were continuously exposed to increasing doses of lapatinib to establish two stable cell lines resistant to lapatinib, SKBR3-R and BT474-R. Cell proliferation was determined by CCK8 assay. Protein expression was determined by western-blotting. Invasion ability was analyzed by transwell assay. FITC staining flow cytometry (FCM) was conducted to observe the percentage of apoptosis. Results: Both two HER2 positive lapatinib resistant cell lines, SKBR3-R and BT474-R had EMT phenomenon. Niclosamide had a stronger inhibition effect on lapatinib resistant cell lines than parental cell lines, and induced more apoptosis by FCM. Western-blot showed niclosamide could reverse the EMT phenomenon of SKBR3-R and BT474-R with E-cadherin up-regulated and snail,vimentin down-regulated at the concentration of 0.5-1μM. A significant reduction of Src signaling was also confirmed, as well as the downstream Akt and Erk pathway. After adding niclosimide for 48 hours, SKBR3-R and BT474-R’s capability of invasion were inhibited. Conclusion: Our results suggested that niclosamide had a strong cytotoxic effect on HER2 positive lapatinib resistant breast cancer cell lines. The EMT induced by lapatinib resistance could be reversed by niclosamide, associated with the inhibition of Src pathway activation, as well as the downstream pathways. Niclosamide treatment produced reduced levels of invasion, serving as a novel therapeutic way for lapatinib-resistant breast cancer patients. Citation Format: Junjun Liu, Xiaosong Chen, Yan Mao, Kunwei Shen. Niclosamid overcomes epithelial-mesenchymal transition of lapatinib resistance through inhibiting Src activation in HER2 positive breast cancer [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 P2-07-06.
Bacteriological and Crystallographical Analysis of Urinary Calculi: Aid to Patient Management
Authors: Isobel Rosenstein, Ruth S Osborn, J P Hopewell, J M T Hamilton-Miller, W Brumfitt
Journal: Journal of the Royal Society of Medicine (1984)

In an analysis, by both crystallographic and microbiological methods, of 50 urinary calculi recently removed by surgical operation, 33 proved to be of metabolic origin (mostly calcium oxalate and some uric acid or urate) and 17 of ‘infective’ origin (struvite, apatite or a mixture of the two). Metabolic stones were usually bacteriologically sterile or contained only small numbers (&lt; 10 3 /g of stone) of bacteria which did not produce urease, while infective stones always contained urease-producing organisms, usually Proteus mirabilis, in large numbers (&gt; 10 5 /g). The combined approach of stone analysis by crystallography and microbiological culture yields more information than conventional techniques on which to base the treatment of urinary calculi and the prevention of their recurrence.
Physical activity and asthma symptoms in a population-based cohort
Authors: Corina S. Rueegg, Marie-Pierre F. Strippoli, Caroline S. Beardsmore, Michael Silverman, Claudia E. Kuehni
Journal: European Respiratory Journal (2011)

Aim:  Longitudinal data on physical activity and asthma in children are scarce. We aimed to assess, whether physical activity differs between children with and without asthma symptoms.   Methods:  In a population-based cohort, we collected information on physical activity and respiratory symptoms (wheeze, cough without colds, night cough) by questionnaire at ages 4-8 (N= 5212) and 6-10 years (N=4236). We compared prevalence of symptoms between inactive (0-1 hour/day of outdoor play) and active (≥2 hours/day) children.   Results:  At age 4-8, 4447 children (85%) were active, at age 6-10, 3686 (87%). In 4-8 years olds, 17% of active and 19% of inactive children had current wheeze (p=0.139), 38% vs. 41% had cough without colds (p=0.142), 27% vs. 33% had cough at night (p=0.003), 12% vs. 12% had moderate wheeze needing inhaler treatment (p=0.565). In 6-10 year olds, 15% of active vs. 16% of inactive children had current wheeze (p=0.636), 36% vs. 40% had cough without colds (p=0.066), 25% vs. 30% had cough at night (p=0.008), and 10% in both groups had wheeze necessitating treatment (p=0.701).   Conclusions:  Physical activity levels were comparable between children with and without asthma related symptoms, with small differences only seen mainly for cough at night. Further analysis will investigate whether this is due to insufficient asthma treatment, and determine potential long-term effects of physical activity on prognosis of symptoms and lung function.
Abstract 3788: The Deleterious Effects of Tumor Necrosis Factor on Cardiac Remodeling Are Mediated by TNF Receptor Associated Factor 2
Authors: Vijay G Divakaran, Jana Burchfield, Huei-Ping Tzeng, Feng Gao, Libby R Garza, Natarajan Sivasubramanian, Douglas L Mann
Journal: Circulation (2008)
Abstract 17082: Carotid Body Denervation Improves Autonomic Balance and Prevents the Worsening of Heart Failure in Rats After Large Myocardial Infarction
Authors: Keita Saku, Takuya Kishi, Akiko Nishizaki, Kana Fujii, Takuya Akashi, Takako Takehara, Yasuhiro Oga, Takamori Kakino, Masataka Ikeda, Tomomi Ide, Kenji Sunagawa
Journal: Circulation (2014)

Introduction: Carotid body denervation (CBD) abolishes the carotid body hypersensitivity induced sympathoexcitatory hypertension. Since the carotid body hypersensitivity is a salient feature and predicts poor outcome of chronic heart failure (CHF), we hypothesized that CBD restores normal autonomic balance, thus improves CHF in rats after large myocardial infarction (MI). Methods: We created MI in 8 weeks Sprague-Dawley rats. Surviving rats at 2 weeks after MI were randomized into CBD (n=11) and sham-operated (Sham; n=13) groups. We removed the tissues around the carotid bifurcation and established CBD. In some rats (Sham; n=5, CBD; n=5), we telemetrically recorded heart rate (HR). One month after CBD, we compared physiological, histological and immunochemical findings between CBD and Sham. Results: CBD significantly reduced HR (337±15 vs. 364±12 bpm, p&lt;0.05). CBD markedly increased the power spectral density of HR in the high frequency range (81.0±9.5 vs. 29.0±8.2 n.u., p&lt;0.05) and decreased that of the low frequency/high frequency ratio (0.6±0.2 vs. 1.8±0.5, p&lt;0.05) indicating the restoration of autonomic balance. CBD significantly reduced biventricular weight (3.1±0.3 vs. 3.7±0.3 g/kg, p&lt;0.05) and left ventricle (LV) end-diastolic pressure (22±5 vs. 33±5 mmHg, p&lt;0.01) and increased maximum LV dp/dt (5118±809 vs. 4217±472 mmHg/sec, p&lt;0.05). CBD reduced lung weight (a marker of pulmonary edema) (6.8±2.0 vs. 12.4±1.5 g/kg, p&lt;001). Furthermore, CBD reduced plasma brain natriuretic peptide (70±43 vs. 166±71 pg/ml, p&lt;0.01) and plasma norepinephrine as an index of sympathetic drive (384±202 vs. 1048±997 pg/ml, p&lt;0.05). CBD significantly reduced the number of inflammatory macrophages (345±45 vs. 474±73 counts/mm2, p&lt;0.05) in the LV and the plasma concentration of interleukin-1β (14.3±4.7 vs. 24.5±11.8 pg/ml, p&lt;0.05) indicating that CBD also suppressed the inflammatory response in CHF. Conclusions: CBD restores normal autonomic balance and prevents the worsening of heart failure in rats after large myocardial infarction. CBD may serve as a novel neuro-modulatory therapy for CHF patients.
Sexual Violence and HIV Infection Associated With Adolescent vs Adult Entry Into the Sex Trade in Mexico
Authors: Jay G. Silverman, Argentina Servin, Shira M. Goldenberg, Carlos Magis-Rodriguez, Julie Ritter, Anita Raj, Kimberly C. Brouwer
Journal: JAMA (2015)

This sampling of sex workers in Mexico investigated entry in the sex trade as an adolescent vs as an adult and risk for human immunodeficiency virus infection and sexual violence. Adolescents migrating from Central America and Mexico to the United States are at risk for being trafficked into the sex industry in Mexico’s northern border cities. Research from other regions indicates that those entering the sex trade as adolescents (vs as adults) are more likely to experience sexual violence and human immunodeficiency virus (HIV) risk during initiation to the sex trade and to become infected with HIV. Language: en
Epidemiological and transmissibility analysis of influenza A(H1N1)v in a southern hemisphere setting: Peru
Authors: C V Munayco, J Gómez, V A Laguna-Torres, J Arrasco, T J Kochel, V Fiestas, J Garcia, J Perez, I Torres, F Condori, H Nishiura, G Chowell
Journal: Eurosurveillance (2009)

We present a preliminary analysis of 1,771 confirmed cases of influenza A(H1N1)v reported in Peru by 17 July including the frequency of the clinical characteristics, the spatial and age distribution of the cases and the estimate of the transmission potential. Age-specific frequency of cases was highest among school age children and young adults, with the lowest frequency of cases among seniors, a pattern that is consistent with reports from other countries. Estimates of the reproduction number lie in the range of 1.2 to 1.7, which is broadly consistent with previous estimates for this pandemic in other regions. Validation of these estimates will be possible as additional data become available.
A new splice of life for the μ-opioid receptor
Authors: Michael J. Iadarola, Matthew R. Sapio, Andrew J. Mannes
Journal: Journal of Clinical Investigation (2015)

μ-Opioid agonists mediate their analgesic effect through GPCRs that are generated via alternate splicing of the Oprm1 transcript. While the majority of μ-opioids interact with receptors comprising the canonical 7 transmembrane (7TM) domain, a recently identified class of μ-opioids appears to require a 6TM domain variant. In this issue of the JCI, Lu and colleagues provide an in vivo proof-of-concept demonstration that a 6TM isoform of the μ-opioid receptor can support functional analgesia in Oprm1-deficent animals. The 6TM isoform was pharmacologically distinct from the canonical 7TM μ-opioid receptor, and 6TM agonists had a reduced side effect profile, which confers a strong therapeutic advantage over standard opioid analgesics. The observations of Lu et al. extend the reach of opioid-receptor neurobiology and pharmacology into a new era of analgesic discovery. This advance emerges from a series of fundamental research analyses in which elements of the endogenous opioid system were frequently in the vanguard.
Abstract 1332: Fluid Shear Stress-Dependent Activation of the AMP-Activated Protein Kinase Attenuates Ras-Dependent Signaling by Inhibiting the Activity and Expression of the Hydroxy-Methylglutaryl Coenzyme A Reductase in Endothelial Cells
Authors: Beate Fisslthaler, Ingrid Fleming, Rudi Busse
Journal: Circulation (2006)

The hydroxy-methylglutaryl coenzyme A reductase (HCR) is the rate-limiting enzyme for cholesterol synthesis and is phosphorylated and inactivated by the AMP-activated kinase (AMPK). As shear stress...