tbuckley/cabot-search huggingface dataset:
Abstract 5255: Differential Effect Of A Novel Adenosine-Agonist On Stimulation-Induced Norepinephrine Release From Rat Hearts
Authors: Lorenz Bott-Flugel, Alexandra Bernshausen, Karl-Ludwig Laugwitz, Heimo Ehmke, Melchior Seyfarth
Journal: Circulation (2008)

Presynaptic modulation of norepinephrine (NE) release plays a major role in the regulation of cardiac sympathetic activity. We tested the effect of the novel, highly selective adenosine A1 subtype agonist BAY 68–4986 on stimulation-induced NE release. Isolated rat hearts (Wistar or SHR) were perfused with a modified Krebs-Henseleit solution (Langendorff technique). Exocytotic NE release was induced by electrical field stimulation with 5 V, 6 Hz for 1 minute. NE was detected by HPLC. Two stimulations (S1, S2) were performed to compare intraindividually NE release under control conditions (S1) and with BAY 68–4986 30ug/ml, 300 ug/ml or CCPA 10–6M (S2). Neuronal uptake was inhibited by desipramine (100 nM) in order to prevent amine elimination and nonexocytotic release of NE. Stimulation of adenosine A1 receptors with BAY 68–4986 led to a concentration dependent decrease of the stimulation-induced NE release only in SHR rats, whereas no effect could be seen in Wistar rats (SHR: S2/S1 = 0.90 +/− 0.08 with 30 ug/l, S2/S1 = 0.54 +/− 0.02 with 300 ug/l, Wistar: S2/S1 = 1.05 +/− 0.12 with 30 ug/l, S2/S1 = 1.03 +/− 0.09 with 300 ug/l, p=0.003). The effect of BAY 68–4986 on stimulation-induced NE release in SHR was similar to the effect of 10–6 M CCPA (S2/S1 = 0.59 ± 0.05). This differential effect in genetically different rats was also observed in vivo, with a blunted increase of the heart rate during stress reaction only in SHR rats, when treated with BAY 68–4986. We could demonstrate that the novel, highly selective A1-adenosine agonist BAY 68–4986 has a differential effect on stimulation-induced NE release and stress responde in SHR rats compared to Wistar rats.
Abstract 18817: Granzyme B-Mediated Proteoglycan Cleavage Results in the Release of Matrix-Sequestered TGF-{beta}: Relevance to Aortic Aneurysm Pathogenesis
Authors: Wendy A Boivin, Lisa S Ang, Sarah J Williams, Marlo Shackleford, Hongyan Zhao, Bruce M McManus, David J Granville
Journal: Circulation (2010)

Background: Granzyme B (GZMB) is a pro-apoptotic serine protease that has been traditionally viewed to function solely in immune-mediated apoptosis wherein perforin facilitates its entry into cells...
We need strong public health leadership
Authors: S. Griffiths, K. McPherson
Journal: BMJ (1997)

Over 13 000 people attended the annual conference of the American Public Health Association last November in New York. Packing into the opening ceremony in the Coliseum, the bleak municipal surroundings buzzed with the theme of “Empowering the Disadvantaged.” We learn of the challenges of social injustice and that young men in Harlem have a life expectancy lower than their counterparts in Bangladesh. Many of the themes resonate with those in British public health. The Guardian had run an article the week before which described public health in Britain as being in crisis–“divided by tribal rivalry, the doctors beleaguered and demoralised, there is no clear voice speaking up for the nation's health,” it had said. Was it any better in the United States?

From an outsider's perspective it was not just the number of people who had …
Interleukin-6 Inhibits Fas-Induced Apoptosis and Stress-Activated Protein Kinase Activation in Multiple Myeloma Cells
Authors: Dharminder Chauhan, Surender Kharbanda, Atsushi Ogata, Mitsuyoshi Urashima, Gerrard Teoh, Michael Robertson, Donald W. Kufe, Kenneth C. Anderson
Journal: Blood (1997)
Abstract 15561: A Novel Functional Model of Cardiac Hypertrophy Using Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes
Authors: Andrea Matter, Alex Stoddard, Donna K Arnett, C. Charles Gu, Steven C Hunt, Emile Nuwaysir, Thomas Burke, Blake Anson, Ulrich Broeckel
Journal: Circulation (2011)

Human induced pluripotent stem (iPS) cells are ideal for functional study of disease pathogenesis. Unlike models using animals and primary cell lines, iPS cells provide a unique opportunity to dire...
Abstract 3552: Pharmacological Inhibition or Genetic Disruption of Protein Tyrosine Phosphatase 1B Attenuates both Myocardial and Endothelial Dysfunction in Mice with Heart Failure
Authors: Magali Vercauteren, Baptiste Kurtz, Elodie Gomez, Jean-Paul Henry, Fabrice Bauer, Rob Hooft, Michel L Tremblay, Christian Thuillez, Vincent Richard
Journal: Circulation (2008)

We have shown previously that acute, in vitro inhibition of protein tyrosine phosphatase 1B (PTP1B) improved endothelial function of peripheral resistance arteries in mice with chronic heart failure (CHF), as demonstrated by the restored flow-mediated, NO-dependent vasodila-tation (FMD). This is most likely due to increased tyrosine phosphorylation pathways involved in shear stress-induced activation of eNOS. The present study evaluates the impact of chronic pharmacological inhibition or genetic disruption of PTP1B, on cardiac and endothelial dysfunction in CHF mice. CHF was induced by coronary ligation, either in C57BL/6 mice, or in wild type (WT) or PTP1B-deficient (PTP1B−/−) BALB/c mice. CHF mice (either C57BL/6 or BALB/c WT) were untreated or treated with the PTP1B inhibitor AS279 (60 mg/kg/day) for 2 months. Mice were then anesthetized with isoflurane for echocardiographic evaluation of left ventricular (LV) function and remodeling. After euthanasia, small mesenteric artery segments were isolated and mounted in an arteriograph for the evaluation of FMD. Echocardiographic results are shown in the Table . In parallel, in vitro vascular studies showed that chronic AS279 restored FMD both in C57BL/6 (max FMD: control: 17±2, n=9; CHF untreated: -1±1, n=9; CHF + AS279: 14±2%, n=19; p&lt;0.01 vs. CHF untreated) and BALB/c CHF mice (Control: 29±4, n=16; CHF untreated: 7±1, n=5; CHF + AS279: 24±6%, n=7; p&lt;0.01 vs. CHF untreated). Compared to CHF WT, FMD was also increased in PTP1B−/− CHF mice (WT: 7±1, n=5, PTP1B−/−: 16±6%, n=6, p&lt;0.05). Additionally, in vitro downregulation of PTP1B (by a 3 day incubation with shRNA) also increased FMD in arteries isolated from CHF mice (max FMD: untreated: 6±2; scrambled shRNA: 7±2; shRNA PTP1B: 27±2%, p&lt;0.01). Thus, chronic pharmacological inhibition or genetic disruption of PTP1B both restores endothelial function and improves cardiac dysfunction and remodeling, suggesting that this enzyme may be a new target for the treatment of CHF. Echocardiographic results in mice with 2 months CHF
Depressive mania associated with nonresponse to antimanic agents
Authors: S C Dilsaver, A C Swann, A M Shoaib, T C Bowers, M T Halle
Journal: American Journal of Psychiatry (1993)

Of 39 patients consecutively admitted for the treatment of primary mania, 21 (53.8%) simultaneously met the Research Diagnostic Criteria for major depressive disorder ("mixed" or "depressive" mania). Only nine (42.9%) of the 21 patients with depressive mania responded to antimanic agents. In contrast, 16 (88.9%) of the 18 patients with pure mania responded to these drugs. This finding is consistent with previous reports suggesting that the mixed state is a virulent form of mania.
Abstract 10854: Aleglitazar, a Balanced Dual PPAR alpha/ gamma Agonist, Decreases Lipolysis and Cytokine Production in a Cellular Model of Inflamed Human Adipose Tissue.
Authors: Anna Dzyakanchuk, Matthew B Wright, Elena Sebokova, Martin Wabitsch, Pamela Fischer-Posovszky, Michaela Keuper, Kurt Amrein
Journal: Circulation (2010)

Aleglitazar is a balanced dual peroxisome proliferator-activated receptor (PPAR) alpha/ gamma agonist, designed to optimize lipid and glycemic benefits. It is currently in Phase III development for reduction of morbidity and mortality in patients who have recently suffered an acute coronary syndrome (ACS) event and have type 2 diabetes. Subclinical inflammation, demonstrated by increases in plasma and adipose tissue concentrations of inflammatory mediators such as interleukin-6 (IL-6), IL-8, monocyte chemotactic factor-1 (MCP-1) or tumor necrosis factor-alpha (TNF-alpha) and increased basal lipolysis, may contribute to the increased insulin resistance and cardiovascular risk of these patients. The Objectives of this study was to investigate the anti-inflammatory effects of aleglitazar in comparison to agonists selective for either PPAR-gamma (pioglitazone, 2.8 microM) or PPAR-alpha (fenofibric acid, 150 microM) in a co-culture system consisting of human adipocytes (SGBS-cells) and human macrophage-like ce...
Prophylaxis with aspirin should be considered
Authors: K T Moriarty
Journal: BMJ (1995)

We are particularly concerned that the box giving clinical implications states that "computed tomography is recommended as part of the diag- nostic investigation for adults with a first generalised seizure."Approximately 4-7% of men and 3-7% of women in the whole population will have at least one epileptic seizure during their life,' and we need cost effective policies.The decision whether scanning should be performed depends, as always, on a careful history (which will include the possible role of alcohol, as discussed by Schoenberger and Heim) and physical examina- tion.We believe that previously suggested practice remains valid: people who have had a first seizure should be scanned if the clinical onset of the seizure was clearly partial or if there are focal neurological signs that are not clearly accounted for by known pre-existing neurological damage such as cerebral palsy or embolus.4
Abstract 6262: Obesity in Childhood is Associated With an Impaired Regenerative Capacity of Circulating Progenitor Cells and Vascular Dysfunction
Authors: Sandra Erbs, Robert Höllriegel, Axel Linke, Agnieszka Burman, Daniela Friebe, Marcus Sandri, Volker Adams, Madlen Töpfer, Claudia Walther, Gerhard Schuler, Antje Körner
Journal: Circulation (2008)

The raising prevalence of obesity in childhood appears to preceed the development of atherosclerosis and the increased incidence of cardiovascular diseases in adulthood. This might be related to the fact that already in children, obesity is associated with classical risk factors for coronary disease, like hypertension, hyperlipidemia, or diabetes. Therefore, aim of the present study was to evaluate, whether obese children (compared to lean controls) are characterized by vascular damages and altered regenerative capacity of circulating endothelial progenitor cells (CPCs) as an early indicator of developing atherosclerosis. Methods: In 30 obese (11±3 years of age, BMI 28.1±1.3) and 30 lean control children (12±3 years of age, BMI 17.5±0.4) insulin sensitivity was evaluated by oral glucose tolerance testing (OGT). Peripheral flow-mediated dilatation (FMD) and intima media thickness (IMT) of the carotid artery were assessed as measures of vascular integrity. The number of CD34/KDR+ CPCs was quantified using FACS analysis and the functional capacity of CPCs was determined by migration assay. Results: Obesity in early childhood is associated with peripheral insulin resistance as an early manifestation of diabetes (serum insulin in OGT after 120 min: 543±102 pmol/L in obese vs. 275±39 pmol/L in lean, p&lt;0.05). FMD was significantly impaired in obese compared to lean children (reactive hyperemia index 1.25±0.05 vs. 1.55±0.08, p&lt;0.05). Already in childhood, obesity was accompanied by a gain in IMT (0.40±0.01 mm vs. 0.30±0.01 mm in lean, p&lt;0.05). Obese children had significantly reduced numbers of circulating CPCs compared to lean children (70±7 vs. 119±13 cells/mL blood, p&lt;0.05). There was an inverse correlation between the number of CPCs and the extent of obesity as determined by BMI-SDS (r=−0.27, p&lt;0.05). Additionally, functional capacity of CPCs was significantly reduced in obese children (migration following a SDF-1 gradient: 170±31 CPCs/1000 plated CPCs in obese vs. 258±37 CPCs/1000 plated CPCs in lean, p&lt;0.05). Conclusion: Already in childhood, obesity is associated with an impaired endogenous regenerative capacity, which might result in generalized vascular damage as an early stage of atherosclerosis.
Abstract 3173: Have Door-to-Balloon Times Improved After Initiation of the D2B Alliance? An Analysis of the Get-with-the-Guidelines Registry
Authors: Brahmajee K Nallamothu, Harlan M Krumholz, Eric D Peterson, Wendy Pan, Frederick A Masoudi, Elizabeth H Bradley, Amy Stern, David Janicke, Adrian Hernandez, Christopher Cannon, Gregg C Fonarow
Journal: Circulation (2008)

In an effort to improve DTB times, the D2B Alliance enrolled ~900 PCI hospitals across the U.S. in a large quality improvement initiative. We compared changes in DTB times for hospitals in the GWTG Registry that enrolled in the D2B Alliance with those that did not. We used data on DTB times from Jul 06 to Mar 08 to allow for 1 quarter of baseline data prior to the D2B Alliance launch and 1 year of follow-up data. We limited our analysis to STEMI patients undergoing primary PCI and excluded transfer-in cases. DTB times were defined from hospital arrival to first device. We evaluated the % of patients treated within 90 minutes using GEE models to examine trends over time, with interaction terms added to assess the specific effect of the D2B Alliance. 5801 patients at 167 hospitals - 98 in the D2B Alliance and 69 that were not - were included. No significant differences were noted in age, gender, race, prior CAD and rates of compliance with composite AMI performance measures between patients at D2B Alliance and non-D2B Alliance hospitals; however, more D2B Alliance hospitals had on-site cardiac surgery (89% vs. 74%). At baseline 54.6% and 53.1% of patients at D2B Alliance and non-D2B Alliance hospitals were treated within 90 minutes, respectively; these numbers increased to 75.3% and 71.6% (both p&lt;0.001) by the end of the study period (Figure ). However, no significant differences were noted in rate of change between D2B Alliance and non-D2B Alliance hospitals. The proportion of STEMI patients treated within 90 minutes improved since initiation of the D2B Alliance. Among GWTG hospitals, this improvement was not limited to facilities that directly participated.
Abstract 577: Long Pentraxin 3: A New, Independent Marker of Mortality in Acute Chest Pain
Authors: Frederic Kontny, Trygve Brügger-Andersen, Harry Staines, Heidi Grundt, Kyoko Miyamoto, Chihiro Miyazawa, Tadashi Matsuura, Mina Sagara, Dennis W Nilsen
Journal: Circulation (2008)

Long Pentraxin 3 (PTX3) is a newly identified member of the Pentraxin protein family that includes C-reactive protein (CRP). Unlike CRP, PTX3 is produced by the major cell types involved in atherosclerotic lesions in response to inflammatory stimuli. Increased PTX3 levels are found in acute coronary syndromes (ACS). Its role in long-term prediction of clinical outcome is, however, unknown. The aim of the current study was to assess the predictive value of PTX3 concerning all-cause mortality in patients hospitalized for acute chest pain. Plasma PTX3 was measured with a new, high-sensitive ELISA method (PPMX, Tokyo, Japan) in blood samples taken on admission in 784 patients admitted for acute chest pain suggestive of ACS. The patients were followed for 24 months concerning clinical outcome. For statistical analysis, the study cohort was divided into quartiles according to PTX3 levels. A multiple logistic regression model was fitted to include standard risk measures. At 24 months follow-up 121 patients had died. By logistic regression, the odds Odds Ratio for death among patients with highest PTX3 levels was 3.13 as compared to those with lowest levels (p=0.007) (table). Long Pentraxin 3 is a new, independent marker that strongly predicts long-term all-cause mortality in patients with acute chest pain.
Abstract 15676: Chronic Activation of Platelet-derived Growth Factor {beta}Receptor Signaling in Vascular Smooth Muscle Cells Increases Apoptosis in Atherosclerotic Plaques via Downregulation of Bcl-2
Authors: Marius Vantler, Li Zhou, Moritz Schwab, Mario Zierden, Wolfram-Hubertus Zimmermann, Evren Caglayan, Michelle Tallquist, Joachim Herz, Stephan Rosenkranz
Journal: Circulation (2011)

Apoptosis of vascular smooth muscle cells (VSMC) promotes instability of atherosclerotic plaques thereby contributing to plaque rupture and myocardial infarction. Receptor tyrosine kinases like the...
Scheme in Peterborough is expanding
Authors: J W Myles, G A Pryor, M Parker, J K Anand
Journal: BMJ (1996)

EDITOR,—Sasha Shepperd and Steve Iliffe raise some important questions about hospital at home services and suggest that their future is uncertain.1 We confess a personal interest. One of us (JKA) was involved in the early phase of the scheme in Peterborough, another (JWM) was responsible for its extension to early postoperative care of patients with fractured hips,2 and GAP and …
Resynchronization Therapy in Pediatric and Congenital Heart Disease Patients
Authors: Anne M. Dubin, Jan Janousek, Edward Rhee, Margaret J. Strieper, Frank Cecchin, Ian H. Law, Kevin M. Shannon, Joel Temple, Eric Rosenthal, Frank J. Zimmerman, Andrew Davis, Peter P. Karpawich, Amin Al Ahmad, Victoria L. Vetter, Naomi J. Kertesz, Maully Shah, Christopher Snyder, Elizabeth Stephenson, Mathias Emmel, Shubhayan Sanatani, Ronald Kanter, Anjan Batra, Kathryn K. Collins
Journal: Journal of the American College of Cardiology (2005)
Pyridoxine Refractory X-Linked Sideroblastic Anemia Caused by a Point Mutation in the Erythroid 5-Aminolevulinate Synthase Gene
Authors: Kazumichi Furuyama, Hiroyoshi Fujita, Tadashi Nagai, Kentaro Yomogida, Hiroshi Munakata, Masao Kondo, Akiro Kimura, Atsushi Kuramoto, Norio Hayashi, Masayuki Yamamoto
Journal: Blood (1997)
Abstract 974: Endothelial NOS (eNOS) Regulates Mitochondrial Oxidative Stress in Fetal Pulmonary Artery Endothelial Cells (PAEC)
Authors: Girija Konduri, Annie Eis, Ivane Bakhutashvili
Journal: Circulation (2007)

Background : Endothelial NOS regulates pulmonary vasodilation at birth by synthesis and release of NO. Exposure of fetal lung to O 2 results in increased oxidative phoshporylation and ATP release at birth. ATP stimulates NO release from eNOS. Superoxide (O 2 − ) is generated by mitochondria as a byproduct of oxidative phosphorylation. The regulation of mitochondrial O 2 during this transition and its role in impaired vasodilation that occurs in persistent pulmonary hypertension of newborn (PPHN) remain unknown. Objective : We investigated the hypothesis that targeting of eNOS to mitochondrial outer membrane regulates O 2 − in fetal PAEC in response to ATP and O 2 . Methods : Studies were done in isolated PAEC and pulmonary arteries (PA) from fetal lambs. PPHN was induced by prenatal ductal constriction for 8 days. Association of eNOS with outer membrane protein, porin and chaperone, hsp90 was determined by immunoprecipitation and double label immuno-fluorescence. Mitochondrial NO and O 2 − levels were determined by DAF-2 and mito-HE reagents. Relaxation responses of PA rings to ATP and NO were determined in the presence/absence of decoy peptides that inhibit eNOS association with hsp90 and porin and mitochondrial targeted ubiquinones. Results : Mitochondria from PAEC showed presence of eNOS on outer membrane but no nNOS. Exposure of PAEC to ATP or O 2 increased the association of eNOS with porin and hsp90 in the mitochondria. ATP increased mitochondrial NO release. Inhibition of eNOS-hsp90 association or eNOS-porin association with decoy peptides that mimic specific eNOS domains required for these interactions resulted in increased mitochondrial O 2 − and attenuated the relaxation response of PA rings to ATP and NO. PAEC from PPHN lambs showed increased basal O 2 consumption, decreased NO-regulation of O 2 consumption and increased mitochondrial O 2 − . PA rings from PPHN lambs showed impaired relaxation responses to ATP and NO and improved relaxation when treated with mitochondrial targeted ubiquinone. Conclusion : Interaction of eNOS with mitochondria plays an important role in the regulation of O 2 − in PAEC during postnatal transition to the O 2 rich environment. Pulmonary hypertension is associated with impaired targeting of eNOS and increase in mitchondrial O 2 − .
Abstract 1621: Decreased Blood Levels of Active Glucagon-like Peptide 1 and Dipeptidyl Peptidase 4 Concentrations in Patients With Coronary Artery Disease
Authors: Masaaki Konishi, Seigo Sugiyama, Eichi Akiyama, Jun-ichi Matsubara, Toshimitsu Nozaki, Kenji Sakamoto, Hitoshi Sumida, Hisao Ogawa
Journal: Circulation (2009)
Abstract 15399: Endothelin-1 Knockdown From Endothelial Cells Reduce Kidney Fibrosis, Peritubular Capillary Loss and Tubular Damage in Unilateral Ureteral Obstruction Model in Mice
Authors: Nur Arfian, Noriaki Emoto, Keiko Yagi, Kazuhiko Nakayama, Dyah S Mayasari, Hirowati Ali, Eko Purnomo, Dwi A Nugrahaningsih, Anggoro B Hartopo, Masashi Yanagisawa, Ken-ichi Hirata
Journal: Circulation (2011)

Cardiovascular disease (CVD) is one of the complication and mortality cause of chronic kidney diseases (CKD). CKD prevention and treatment lead to both renal and cardiovascular improvements. One of...
Abstract 11800: ABSORB Cohort B Trial: Two Year IVUS and IVUS-VH Results of the ABSORB Bioresorbable Everolimus Eluting Vascular Scaffold
Authors: Dougal McClean, John Ormiston, Patrick W Serruys
Journal: Circulation (2011)

Background: The ABSORB Cohort B trial is a continuation of the ABSORB Cohort A trial in the assessment of the safety and performance of a modified ABSORB Everolimus Eluting Vascular Scaffold (Abbot...
Abstract 2594: Coronary Multidetector Computed Tomography in the Prognostic Assessment of Patients with Equivocal or Mildly Abnormal Non-Invasive Cardiac Stress Tests
Authors: Clerio Azevedo, Mariane Spotti, Sabrina Bezerra, Marcelo Hadlich, Humberto Villacorta, Carlos Pereira, Alvaro Pontes, Plinio Junior, Olga Souza, Denilson Albuquerque, Jorge Moll
Journal: Circulation (2007)

Background: Patients with low or moderate pre-test probability of significant coronary artery disease (CAD) and equivocal or mildly abnormal non-invasive cardiac stress tests represent a frequent management challenge. Coronary multidetector computed tomography (MDCT) has been shown to have excellent diagnostic accuracy to exclude the presence of significant CAD. Methods: The study included 218 patients (mean age 59±12 years, 60% male) with equivocal or mildly abnormal exercise electrocardiography (n=93), stress SPECT perfusion scans (n=121), stress echocardiography (n=3) and stress cardiac MRI (n=1). Patients were either asymptomatic (n=113) or had atypical chest pain (n=105). All patients underwent contrast-enhanced 64-slice MDCT coronary angiography and datasets were evaluated for the presence of coronary atherosclerotic plaques and significant coronary artery stenosis. Patients were followed for 8±3 months and the endpoints evaluated were: cardiac death, myocardial infarction, revascularization procedure performed &gt;3 months after MDCT coronary angiography and unstable angina requiring hospitalization. Results: MDCT coronary angiography was either normal (n=90; 41%), demonstrated non-obstructive coronary atherosclerotic plaques (n=66; 30%) or exhibited significant coronary stenosis (n=62; 29%). Event-free survival was 100% for patients with normal coronary angiography, 98% for patients with non-obstructive plaques and 92% for patients with coronary stenosis (log-rank test P=0.01). One patient with a non-obstructive plaque involving the left main coronary artery died following an AMI (hazard ratio, 0.38; 95% confidence interval, 0.04 to 3.24). Among patients with coronary stenosis, 3 underwent revascularization procedures and 2 died (hazard ratio, 12.59; 95% confidence interval, 1.47 to 107.86). Conclusion: Among patients with equivocal or mildly abnormal non-invasive cardiac stress tests, a normal MDCT coronary angiography is associated with a very low risk for subsequent cardiac events. Further studies are necessary to determine the clinical significance of non-obstructive atherosclerotic plaques detected by MDCT coronary angiography in this patient population.