tbuckley/cabot-search huggingface dataset:
Abstract 5279: MCPIP1 is an Inducible Corepressor of NF-KappaB
Authors: Jian Liang, Pappachan E Kolattukudy, Mingui Fu
Journal: Circulation (2008)

The transcription factor NF-κB is a central regulator of host immune and inflammatory response. However, excessive and prolonged activation of NF-κB can cause massive damage to host tissues and can result in human inflammatory diseases, such as atherosclerosis and arthritis. Thus, NF-κB activation must be terminated at the appropriate time points. MCPIP1 is a recent identified CCCH-type zinc finger containing protein, which is significantly induced by MCP-1 treatment of human monocytes and thus designated as MCP-induced protein1 (MCPIP1). Here we report that MCPIP1 function as an inducible corepressor of NF-κB to feedback control NF-κB activation. In the transfection experiments, MCPIP1 dose-dependently inhibits inflammatory stimuli-induced NF-κB reporter activity. Overexpression of MCPIP1 does not affect TNFα-initiated IKK activation, NF-κB translocation and DNA binding. Further study reveals that MCPIP1 can directly bind to p65 of NF-κB and recruit NCoR and HDAC1 to form repressing complex, which blocks NF-κB target gene expression. Interestingly, the same stimuli that induce NF-κB activation also can induce MCPIP1 expression and translocation into nucleus. Taken together, our results suggest that MCPIP1 is a novel inducible corepressor of NF-κB and may be a critical player in host immune and inflammatory response. This research has received full or partial funding support from the American Heart Association, AHA Greater Southeast Affiliate (Alabama, Florida, Georgia, Louisiana, Mississippi, Puerto Rico &amp; Tennessee).
Regulation Of CLL Growth and Trafficking By The Enzymatic Functions Of CD38: Implications For Therapeutic Targeting
Authors: Tiziana Vaisitti, Valentina Audrito, Sara Serra, Giovanna Sociali, Antonella Zucchetto, Erika Tissino, Andrea Pagnani, Candida Vitale, Marta Coscia, Valter Gattei, Santina Bruzzone, Silvia Deaglio
Journal: Blood (2013)
Abstract 12847: Cardiogenesis Using Bone Marrow Derived iPS Cells and Their Derivative Cardiac Progenitor Cells
Authors: Stephanie Buccini, Husnain K Haider, Rafeeq P Ahmed, Shujia Jiang, Muhammad Ashraf
Journal: Circulation (2011)

Background —The strategy to reprogram somatic stem cells to pluripotency status has provided an alternative source of stem cells with ES cell like differentiation characteristics. We hypothesized t...
New Appliances
Authors: H B PORTEOUS
Journal: BMJ (1959)

The year also saw the retirement of Dr. ROBERT FORBES, who was Secretary of the Union for 25 years, from 1935 to 1959.A special appreciation of his work appears in the report.Prominence is given in this year's report to cases arising from complaints by patients or their relatives to executive councils, of which 140 were dealt with during the year.The procedure is explained, with illustrative cases of both appearances before Service Committees and appeals against their findings.The Opticians Act is discussed, practitioners are reminded of their legal liabilities for third-party accidents on their premises, and advice is given on the handling of a Jehovah's Witness who refused a necessary blood transfusion.There are sections on disputed accounts, fees for the emergency treatment of road accidents, breach of copyright by a drug firm, inquests, the risks of ship surgeons, and the "duty to warn " about possible hazards of treatment.
Abstract 9724: Impaired Renal Function is Associated with an Increased Risk for Incident Atrial Fibrillation
Authors: Roopinder K Sandhu, Tobias Kurth, David Conen, Nancy R Cook, Paul M Ridker, Christine M Albert
Journal: Circulation (2011)

Introduction: The prevalence of atrial fibrillation (AF) and chronic kidney disease (CKD) are rapidly rising. Few prospective studies have explored the association between renal function and risk of incident atrial fibrillation (AF) among an apparently healthy population. Methods: A total of 24,746 women participating in the Women's Health Study who were free of cardiovascular disease (CVD), AF and provided a blood sample at baseline were prospectively followed-up for incident AF from 1993-2010. AF was confirmed by medical chart review. Renal function was measured as estimated glomerular filtration rate (eGFR) calculated from baseline creatinine using the Chronic Kidney Disease - Epidemiology (CKD-EPI) equation. Cox models were used to estimate hazard ratios (HR) and 95%CI for incident AF across eGFR categories (&lt;60, 60-74.9, 75-89, and &gt; 90 ml/min/1.73 m 2 ) controlling for AF risk factors. In a secondary analysis, eGFR was dichotomized at 60 ml/min/1.73 m 2 based on a GFR definition of chronic kidney disease. Multivariable models controlled for age, systolic blood pressure, body mass index, total cholesterol, C reactive protein concentration, antihypertensive treatment, alcohol, exercise, smoking, diabetes, and postmenopausal hormone use. Results: Of the total 24 746 women, 15 374 (62.1%) had an eGFR ≥ 90 ml/min/1.73 m 2 , 5901 (23.8%) had an eGFR 75-89 ml/min/1.73 m 2 , 2463 (10.0%) had an eGFR 60-74 ml/min/1.73 m 2 and 1008 (4.1%) had an eGFR &lt;60 ml/min/1.73 m 2 . During a median 15.4 years of follow-up, 786 incident AF events occurred. The age adjusted incidence rate per 1000 person years across eGFR categories (&lt;60, 60-74.9, 75-89, and &gt; 90 ml/min/1.73 m 2 ) was 2.61, 2.01, 2.21, and 2.15. The multivariable-adjusted HR for eGFR categories were 1.36 (95% CI, 1.00-1.84), 0.90 (95% CI, 0.71-1.14), 0.99 (95% CI, 0.84-1.18) and 1.00 (P for trend, 0.48). Among women with eGFR &lt; 60 compared to those with ≥ 60 ml/min/1.73 m 2 , the multivariable adjusted HR was 1.39 (95% CI, 1.04-1.86, p value 0.03). Conclusions: In this large prospective cohort of apparently healthy women, we observed no increase in risk of incident AF among women with less severe impairment of renal function. However, there was a significant increase in AF risk observed at a threshold GFR of &lt;60 ml/min/1.73 m 2 .
Abstract 14705: The Association of Optimism and Pessimism With Cardiovascular Health: Results From the Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Rosalba Hernandez, Kiarri N Kershaw, Juned Siddique, Julia Boehm, Laura Kubzansky, Ana V Diez-Roux, Hongyan Ning, Donald M Lloyd-Jones
Journal: Circulation (2013)

Background: Research suggests that an individual’s life-orientation, appraised by examining levels of optimism and pessimism, can affect cardiac-related health. This study aimed to examine cross-se...
THE FATE OF BACTERIA WITHIN PHAGOCYTIC CELLS
Authors: Zanvil A. Cohn
Journal: The Journal of Experimental Medicine (1964)

The fate of a heat-stable Escherichia coli agglutinogen within three types of rabbit phagocytic cells was examined. A system is described whereby quantitative ingestion of viable E. coli by suspensions of PMN leucocytes, BCG-induced alveolar macrophages, and oil-induced peritoneal macrophages took place in vitro. After various periods of intracellular residence aliquots were injected intraperitoneally into NCS mice and the resulting agglutinins assayed. The loss of immunogenicity within phagocytes was estimated by comparison with a dose-response titration prepared with bacteria alone. Under these conditions no increase in immunogenic mass occurred in vivo or in vitro when viable organisms were employed. PMN leucocytes and alveolar macrophages destroyed the majority of the immunogen within 2 hours of intracellular residence. In contrast, the immunogenicity of E. coli was maintained within peritoneal macrophages for periods up to 5 hours. The use of heat-killed bacilli or specific immune serum did not significantly influence the intracellular fate of the immunogen. Residual immunogenicity was associated with a particle having the same centrifugal properties as the intact organism and essentially none was released in a soluble form. Intracellular residence within phagocytic cells did not influence the resulting temporal sequence of antibody formation nor the proportions of mercaptoethanol-sensitive and resistant immune globulins.
Myocardial Edema After Ischemia/Reperfusion Is Not Stable and Follows a Bimodal Pattern
Authors: Rodrigo Fernández-Jiménez, Javier Sánchez-González, Jaume Agüero, Jaime García-Prieto, Gonzalo J. López-Martín, José M. García-Ruiz, Antonio Molina-Iracheta, Xavier Rosselló, Leticia Fernández-Friera, Gonzalo Pizarro, Ana García-Álvarez, Erica Dall'Armellina, Carlos Macaya, Robin P. Choudhury, Valentin Fuster, Borja Ibáñez
Journal: Journal of the American College of Cardiology (2014)

It is widely accepted that edema occurs early in the ischemic zone and persists in stable form for at least 1 week after myocardial ischemia/reperfusion. However, there are no longitudinal studies covering from very early (minutes) to late (1 week) reperfusion stages confirming this phenomenon.This study sought to perform a comprehensive longitudinal imaging and histological characterization of the edematous reaction after experimental myocardial ischemia/reperfusion.The study population consisted of 25 instrumented Large-White pigs (30 kg to 40 kg). Closed-chest 40-min ischemia/reperfusion was performed in 20 pigs, which were sacrificed at 120 min (n = 5), 24 h (n = 5), 4 days (n = 5), and 7 days (n = 5) after reperfusion and processed for histological quantification of myocardial water content. Cardiac magnetic resonance (CMR) scans with T2-weighted short-tau inversion recovery and T2-mapping sequences were performed at every follow-up stage until sacrifice. Five additional pigs sacrificed after baseline CMR served as controls.In all pigs, reperfusion was associated with a significant increase in T2 relaxation times in the ischemic region. On 24-h CMR, ischemic myocardium T2 times returned to normal values (similar to those seen pre-infarction). Thereafter, ischemic myocardium-T2 times in CMR performed on days 4 and 7 after reperfusion progressively and systematically increased. On day 7 CMR, T2 relaxation times were as high as those observed at reperfusion. Myocardial water content analysis in the ischemic region showed a parallel bimodal pattern: 2 high water content peaks at reperfusion and at day 7, and a significant decrease at 24 h.Contrary to the accepted view, myocardial edema during the first week after ischemia/reperfusion follows a bimodal pattern. The initial wave appears abruptly upon reperfusion and dissipates at 24 h. Conversely, the deferred wave of edema appears progressively days after ischemia/reperfusion and is maximal around day 7 after reperfusion.
Abstract 221: Value of Initial Middle Latency Auditory Evoked Potential Index for Cardiopulmonary Arrest Resuscitation
Authors: Junya Tsurukiri, Naoyuki Kaneko, Shiro Mishima, Yukiio Ikeda, Shoichi Ohta
Journal: Circulation (2011)

Introduction: Non-invasive monitoring that can indicate cerebral resuscitation in cardiac arrest patients remains unknown. In an operative setting, middle latency auditory evoked potentials (MLAEP) provide a good discrimination of consciousness and cerebral function during anesthesia. Hypothesis: We seessed the hypothesis that initial MLAEP index (MLAEPi) can predict the return of spontaneous cardiac activity (ROSC) or survival on arrival at the emergency department (ED). Methods: This was a prospective study and included 50 patients with cardiac arrest who received BLS by prehospital paramedics. The patients were then administered ACLS by an emergency medical team member on arrival at ED. Initial MLAEPi was immediately measured using an aepEX monitor (1st version; Audiomex, Glasgow, UK) during the first cycle of ACLS in ED (Figure). Results: Seventeen (34%) patients who showed ROSC were admitted to our hospital (ROSC group); however, 33 patients did not show ROSC on resuscitation at the scene (non-ROSC group). Initial MLAEPi in the ROSC group was significantly higher than that in the non-ROSC groups (39±18 vs. 27±6, p&lt;0.01). In the ROSC group, clinically significant correlations were identified between initial MLAEPi and the time to the beginning of ACLS (r=-0.57, p=0.02); time to ROSC from the beginning of BLS (r=-0.53, p=0.03); and lactate concentrations (r=-0.50, p=0.04). Eight patients were discharged from our hospital (survivors) and 4 of them had no disability as per Cerebral Performance Category 1. Initial MLAEPi of survivors was significantly higher than that of non-survivors (49±23 vs. 28±6, p&lt;0.01). The ROC curve for initial MLAEPi demonstrated that area under the curve of 0.89 (95% CI=0.77-1.01, p&lt;0.01), and MLAEPi cutoff point ≤ 33 predicted no survival with a likelihood ratio of 6.10 (sensitivity=76.2; specificity=87.5). Conclusions: In conclusion, although our sample size is small, it showed that initial MLAEPi is represented by simple numerical values for the initial evaluation of ROSC and survival in cardiac arrest patients. Alternatively, MLAEPi may help emergency medical teams as a clinical predictor for termination of resuscitative efforts in a clinical setting.
Abstract 20587: A Prediction Rule Derived from Clinical Variables and Stress Cardiac Magnetic Resonance Imaging Provided Strong Cardiac Prognostication in Patient with Suspected Myocardial Ischemia
Authors: Otavio R Coelho-Filho, Francois-Pierre Mongeon, Luciana F Seabra, Shuaib M Abdullah, Eri Watanabe, Sanjeev A Francis, Ron Blankstein, Micahel Jerosch-Herold, Raymond Y Kwong
Journal: Circulation (2010)

Objectives:  We derived and validated a parsimonious predictive rule incorporating clinical and stress CMR data in characterizing cardiac events in patients with suspected ischemia.   Methods/Results:  Out of 625 patients referred for CMR assessment of suspected ischemia, 19 were excluded for insufficient imaging quality. The remaining 606 patients were followed for cardiac events (100% follow-up; median of 2.9 years, IQR 2.4–6.9) including cardiac death, acute MI, cardiac hospitalization, and late coronary revascularization (>90 days). We randomized patients 1:1 into a training group (TRAIN, n=303) and a testing group (TEST, n=303). A prediction rule was built by stepwise Cox regression in the TRAIN group, considering clinical, ECG, and CMR data using P   Conclusion:  We derived and validated a prediction rule for cardiac events using clinical and CMR data for patients with suspected myocardial ischemia. PerfSCORE by CMR demonstrated strong prognostication to cardiac events in the prediction rule.
Abstract 17951: Low Total Testosterone is Associated with Inflammation and Dyslipidemia in a Large Population of Asymptomatic Middle Aged Men
Authors: Rupa L Iyengar, Simonette T Sawit, Hany A Messeh, Narayan Escolin, Cynara Maceda, Jacqueline Moline, Mary Ann McLaughlin
Journal: Circulation (2011)

Background: Low testosterone levels are associated with an increased risk of dyslipidemia and the development of atherosclerosis in older men. This study aims to investigate whether a similar relationship exists between total testosterone (TT), triglyceride (TG), high density lipoprotein (HDL) cholesterol levels, and C-reactive protein (CRP) in a large population of asymptomatic middle aged men, between 40 to 60 years of age. In addition, we explore the effect of statin use on dyslipidemia in men with low TT. Methods: We evaluated 2,116 male participants in the Law Enforcement Cardiac Screening Program (LECS), a subset of the World Trade Center Medical Monitoring and Treatment Program. Low Total Testosterone (TT) is defined as TT of &lt; 300 ng/dL. We measured fasting lipids, Apolipoprotein B/A1, glucose and CRP. In a subcohort of 354 (27%) men on statin therapy (HMG CoA reductase inhibitor), we performed independent t-test to see the effect of low TT on TG and HDL. Results: Men with low TT had significantly higher TG, CRP and glucose levels, and lower HDL levels (p &lt; 0.0001) compared to men with normal TT. In the subcohort of men on statin therapy, subjects with low TT had significantly higher TG (p &lt; 0.0001) and CRP (p &lt; 0.001), and lower HDL levels ( p = 0.025) compared to those with normal TT. See Table 1. Conclusions: We detected higher TG and CRP, and lower HDL levels in asymptomatic middle aged men with low TT. Further evaluation of men on statin therapy with low TT, revealed persistent dyslipidemia (elevated TG and reduced HDL) and inflammation (elevated CRP). Clinicians should be encouraged to measure TT in middle-aged men during assessment of cardiovascular disease risk. Source of funding: NY Fraternal Order of Police, through the Office of the NY Attorney General Charity Fund.
Abstract 2194: Predictors of <i>RyR2</i> Genotype Among Patients Referred for Long QT Syndrome Genetic Testing
Authors: David J Tester, Melissa L Will, Michael J Ackerman
Journal: Circulation (2007)

Introduction : Type 1 catecholaminergic polymorphic ventricular tachycardia (CPVT1) is pursuant to mutations in the RyR2- encoded cardiac ryanodine receptor. Recently, we discovered nearly as many CPVT1-causing mutations as LQT3-causing mutations in a large cohort of unrelated LQTS referral patients. Here, we examine potential predictors of RyR2 genotype (CPVT1) among LQTS referral patients. Methods : Previously, comprehensive mutational analysis of the LQT1–10 susceptibility genes was completed for 541 unrelated patients (358 females, average age at diagnosis = 24 years, average QTc = 482 ms) referred for LQTS genetic testing. Using PCR, DHPLC, and DNA sequencing, we performed targeted analysis of RyR2 involving 44 exons (8–15, 37–49, 83–105) for the 260 unrelated referrals (172 females, average age at diagnosis = 25 years, average QTc = 470 ms) that remained “genotype-negative” following LQTS genetic testing. Results : Overall, 22 distinct RyR2 mutations (19 novel) were seen in 23 (8.8%, 12 females, average age at diagnosis = 22 ±14 years) unrelated “genotype-negative” LQTS individuals. Compared to patients with either genetically proven LQTS or the remaining genotype negative cohort, the RyR2 -positive cohort had significantly lower average QTc (419 ms vs 494 ms, p =2.4 ×10 −6 ; vs 472 ms, p = 0.005) and was more likely to experience either syncope (88% vs 66%, p = 0.06 vs 53%, p = 0.008) or cardiac arrest (56% vs 23%, p = 0.006 vs 17%, p = 0.001). Overall, 123 of the 541 LQTS referrals (23%) exhibited exertion-induced cardiac events (68 LQTS gene positive; 42 gene negative, and 13 RyR2-positive). Every RyR2 -positive case with an exertionally-triggered event had a QTc ≤ 460 ms, compared to only 17% of LQTS gene positive cases (p = 0.1 × 10 −8 ) and 24% of LQT1 cases. None of the exertion-induced LQTS gene positive cases had a QTc ≤ 420 ms. Conclusions: Failure to distinguish CPVT from LQTS can be a fatal mistake, as individuals with CPVT1 have a more severe phenotype and are much less protected by beta blocker therapy than those with LQT1. CPVT1, rather than concealed LQT1, should lead the differential diagnosis in the setting of syncope/cardiac arrest during exercise and a normal resting QTc.
Abstract 944: TNF-{alpha} Enhances the Engraftment of Mesenchymal Stem Cells onto Infarcted Myocardium via BMP-2
Authors: Yong Sook Kim, Youngkeun Ahn, Hye Jeong Park, Young Hee Shin, Soo Yeon Joo, Sang Rok Lee, Kye Hun Kim, Hyung Wook Park, Young Joon Hong, Ju Han Kim, Myung Ho Jeong, Jeong Gwan Cho, Jong Chun Park
Journal: Circulation (2006)
Abstract 4472: Validation of an Angiography based Algorithm to Calculate the Coronary Flow Reserve
Authors: Harald Rittger, Asher Kuper, Anil Sinha, Martin Schmidt, Johannes Rieber, Johannes Brachmann
Journal: Circulation (2008)

Coronary Flow Reserve (CFR) is defined as the ratio between flow in a coronary vessel at maximum hyperemia and at rest. It is considered as a marker for the integrity of the coronary mircrocirculation. The measurement is typically performed using dedicated Doppler guidewires and pharmacologic stimulation (CFRdoppler). This measurement is costly, time-consuming and potentially harmful since the Doppler wire has to be advanced into the coronary artery. Today a new angiography based algorithm is available using the first pass kinetic of the injected contrast dye to calculate the CFR. The aim of the present study was, to compare this new algorithm with the conventionally Doppler wire technique. CFR measurements were performed during 27 coronary interventions (10 female, mean age 64 ± 11 years). CFR doppler (Flowire, Volcano corp.) was calculated as the ratio of average peak velocity (APV) during hyperemia (140μg/kg·min −1 ) and at rest. For calculation of angiographic CFR angio , two angiograms were analised, one at base line flow and one at hyperemia state. CFR was calculated by the ratio between the hyperemia representing numbers of the logarithmic Time Density Curve (TDC) linear slope, multiplied with the coronary cross-sections, and the respective baseline representing numbers. An excellent correlation was found between the CFR doppler and the CFR angio values: CFR angio = 1× CFR doppler (r=0.87; p&lt;0.0001). The average absolute difference between both indexes was 0.36±0.31. Angiographic measurement of CFR is a feasible and valid method in daily routine with an excellent correlation to doppler-wire derived measurements and moreover less potential of adverse interventional health effects.
Biodegradable Polymer Biolimus-Eluting Stent Versus Durable Polymer Everolimus-Eluting Stent
Authors: Masahiro Natsuaki, Ken Kozuma, Takeshi Morimoto, Kazushige Kadota, Toshiya Muramatsu, Yoshihisa Nakagawa, Takashi Akasaka, Keiichi Igarashi, Kengo Tanabe, Yoshihiro Morino, Tetsuya Ishikawa, Hideo Nishikawa, Masaki Awata, Mitsuru Abe, Hisayuki Okada, Yoshiki Takatsu, Nobuhiko Ogata, Kazuo Kimura, Kazushi Urasawa, Yasuhiro Tarutani, Nobuo Shiode, Takeshi Kimura
Journal: Journal of the American College of Cardiology (2013)

NEXT (NOBORI Biolimus-Eluting Versus XIENCE/PROMUS Everolimus-Eluting Stent Trial) was designed for evaluating the noninferiority of a biolimus-eluting stent (BES) relative to an everolimus-eluting stent (EES) in terms of target lesion revascularization (TLR) at 1 year.Efficacy and safety data comparing biodegradable polymer BES with durable polymer cobalt-chromium EES are currently limited.The NEXT trial is a prospective, multicenter, randomized, open-label, noninferiority trial comparing BES with EES. Between May and October 2011, 3,235 patients were randomly assigned to receive either BES (n = 1,617) or EES (n = 1,618).At 1 year, the primary efficacy endpoint of TLR occurred in 67 patients (4.2%) in the BES group, and in 66 patients (4.2%) in the EES group, demonstrating noninferiority of BES relative to EES (p for noninferiority <0.0001, and p for superiority = 0.93). Cumulative incidence of definite stent thrombosis was low and similar between the 2 groups (0.25% vs. 0.06%, p = 0.18). An angiographic substudy enrolling 528 patients (BES: n = 263, and EES: n = 265) demonstrated noninferiority of BES relative to EES regarding the primary angiographic endpoint of in-segment late loss (0.03 ± 0.39 mm vs. 0.06 ± 0.45 mm, p for noninferiority <0.0001, and p for superiority = 0.52) at 266 ± 43 days after stent implantation.One-year clinical and angiographic outcome after BES implantation was noninferior to and not different from that after EES implantation in a mostly stable coronary artery disease population. One-year clinical outcome after both BES and EES use was excellent, with a low rate of TLR and extremely low rate of stent thrombosis.