tbuckley/cabot-search huggingface dataset:
Abstract 8146: Gene Delivery of Suppressor of Cytokine Signaling 1 Decreases Myocardial Inflammation in Experimental Autoimmune Myocarditis
Authors: Kazuko Tajiri, Kyoko Imanaka-Yoshida, Michiaki Hiroe, Tetsuji Naka, Kazutaka Aonuma, Yasuhiro Yasutomi
Journal: Circulation (2011)

Introduction: Myocarditis and subsequent dilated cardiomyopathy are major cause of heart failure. Recent reports indicate that a subgroup of myocarditis patients may benefit from immune-targeted therapies. Suppressor of cytokine signaling 1 (SOCS1) plays a key role in the negative regulation of immune responses. We therefore hypothesized that overexpression of SOCS1 may have therapeutic effects in the treatment of myocarditis. Methods and Results: Myocarditis was induced by subcutaneous immunization with cardiac specific peptides derived from α myosin heavy chain (MyHC-α) in BALB/c mice. Plasmid DNA encoding SOCS1 (pSOCS1) or empty plasmid was injected intraperitoneally into mice on days 0, 5 and 10 after induction of myocarditis. The heart-to-body weight ratios in pSOCS1-treated mice were significantly decreased compared with control plasmid-received mice (4.8±0.2 mg/g vs 6.2±0.5 mg/g; n=5, P&lt;0.05). pSOCS1-treated mice had fewer infiltrating CD45+ cells in the heart than control plasmid-injected mice analyzed by flow cytometry (4.0±0.6 % of total cells vs 36.4±10.6 % of total cells; n=5, p&lt;0.05). Echocardiography showed preserved contractile function in pSOCS1-treated mice compared with control plasmid-treated mice (fractional shortening: 36±3 % vs 22±1 %; n=9, p&lt;0.01). Western blot analysis of DCs from pSOCS1-treated mice revealed decreased phosphorylation of STAT1. In the culture supernatant of DCs from pSOCS1-treated mice, the amount of proinflammatory cytokines was decreased (IL-6: 472±11 pg/ml vs 762±20 pg/ml, p&lt;0.01; TNF-α: 1.9±0.0 ng/ml vs 3.9±0.1 ng/ml, p&lt;0.01). MyHC-α-specific CD4+ T cells were isolated from myocarditis mice and co-cultured with MyHC-α-pulsed DCs from pSOCS1- or control plasmid-treated mice. The proliferative responses of CD4+ T cells co-cultured with DCs from pSOCS1-treated mice were much lower than with DCs from control plasmid-received mice assessed by measuring [3H]-thymidine uptake (1,401±393 cpm vs 2,584±213 cpm, p&lt;0.05). Conclusion: SOCS1 gene therapy reduced cardiac inflammation and improved cardiac performance in experimental autoimmune myocarditis. Our data suggested that in vivo gene delivery of SOCS1 suppresses the functional capacity of DCs to prime and expand autoreactive CD4+ T cells.
Abstract 18373: Validating ARMYDA-PRO/BLEEDS: a Therapeutic Window in Platelet Reactivity for Patients Undergoing Elective Percutaneous Coronary Intervention
Authors: Fabio Mangiacapra, Giuseppe Patti, Aaron J Peace, Laura Gatto, Bernard De Bruyne, Emanuele Barbato, William Wijns, Germano Di Sciascio
Journal: Circulation (2011)

Aims. Platelet reactivity has been shown to be an important determinant of both thrombotic and bleeding events in patients undergoing percutaneous coronary intervention (PCI). Recently, the ARMYDA-PRO study has shown that a threshold of P2Y12 reaction units (PRU) &gt;240, measured with the VerifyNow assay, is associated with increased risk for thrombotic events at 30 days, while the ARMYDA-BLEEDS study has shown that a threshold of PRU &lt;189 is associated with a increased risk of bleeding events. We aimed at validating the aforementioned PRU thresholds in an independent population of 640 patients taking clopidogrel and aspirin and undergoing elective PCI. Methods and results. Platelet reactivity was measured immediately before the procedure with the VerifyNow P2Y12 assay. Primary end point was the 30-day incidence of net adverse clinical events (NACE), defined as the occurrence of major adverse cardiac events (MACE) or major bleeding/significant entry site complications, in relation to the PRU distribution. Patients were divided in 3 groups on the basis of PRU values: low-PRU (240). At 30-day follow-up, patients in the low-, medium- and high-PRU groups presented an incidence of MACE of 4.6%, 5.0% and 14.6%, respectively (p for trend &lt;0.001), and an incidence of major bleeding or significant entry site complications of 8.8%, 2.2% and 1.5%, respectively (p for trend &lt;0.001). The incidence of NACE was 13.4% in the low-PRU group, 7.2% in the medium-PRU group (p=0.040 vs. low-PRU group), and 15.1% in the high-PRU group (p=0.016 vs. medium-PRU group). At multivariate analysis, a pre-PCI PRU value in the low- or high-PRU group was an independent predictor of increased occurrence of NACE at 30 days. Conclusions. A therapeutic window in platelet reactivity can be identified using validated thresholds that define a group of patients at lower risk for both thrombotic and bleeding events. Tailoring antiplatelet therapy in order to obtain platelet reactivity levels within this range could result in a net lowering of adverse events after PCI.
Proteasome inhibitor PS-341 induced G2-M phase arrest and apoptosis in human glioblastoma multiforme
Authors: Dong Yin, Hong Zhou, Kumagai Takashi, Gentao Liu, Keith L. Black, Phillip H. Koeffler
Journal: Cancer Research (2004)

4006   The proteasome plays a pivotal role in the control of cell proliferation, apoptosis and differentiation in a variety of normal and tumor cells. PS-341, a novel boronic acid dipeptide that inhibits 20S proteasome activity, has been shown to have prominent activity both in vitro and in vivo systems, against various solid tumor types including breast, lung, colon, bladder, ovarian, pancreatic, prostate, and squamous cell cancers. Using 3 human glioblastoma multiforme (GBM) cell lines and 5 primary GBM explants, we examined the effect of PS-341 on their proliferation, cell cycle, apoptosis, as well as expression of proteins involved in cell growth. We also explored whether the effect of PS-341 on GBM cells is dependent on the mutational status of p53. PS-341 markedly inhibited growth of GBM cell lines and explants with a mean IC50 of PS-341 at about 1x10 -7  M. The cells developed a cell cycle block at G2/M with a concomitant decrease in S phase (≈ 2-fold), an increase of p21 WAF1 , p27 KIP1  and a down-regulation of CDK2, CDK4 and E2F4. About 20 –40 % of the cells became apoptosis when exposed to 1x10 -7  M PS-341 for 24 hrs as shown by Tunel analysis. Immunoblot analysis of poly (ADP-ribose) polymerase (PARP) showed that a C-terminal 85 kDa apoptotic fragment was generated and levels of Bcl2 and Bcl-xl were decreased. These changes occurred in the cells irrespective of their p53 mutant status. One major effect of proteasome inhibition in many cell types is the inhibition of NF- k B translocation to the nucleus, due to blocking of the cytosolic degradation of I k -B. We found that PS-341 decreased nuclear NF- k B and transcriptional activity of NF- k B as measured by a reporter gene containing NF- k B binding sites fused to the luciferase gene. We conclude that PS-341 has profound effects on GBM cells including inhibiting their cell growth and inducing their G2/M phase arrest, apoptosis and accumulation of p21 WAF1  and p27 KIP1  in a p53-independent fashion, as well as inhibiting NF- k B nuclear translocation and transcriptional activity. These findings suggested that PS-341 may be highly effective as a therapy for gliomas in patients.
Embolic Protection Devices for Carotid Artery Stenting
Authors: Ralf Zahn, Thomas Ischinger, Bernd Mark, Sabine Gass, Uwe Zeymer, Wolfgang Schmalz, Klaus Haerten, Karl Eugen Hauptmann, Enz-Rüdiger von Leitner, Wolfgang Kasper, Ulrich Tebbe, Jochen Senges
Journal: Journal of the American College of Cardiology (2005)
Involvement of tumor-associated macrophages in colon tumorigenesis
Authors: Aniruddha Ganguly
Journal: Cancer Research (2008)

3588   Tumor progression is associated with simultaneous proliferation of cancer cells and the development of tumor stroma that is composed of different types of cells including tumor-associated monocyte/macrophages (TAM). TAMs are observed in human tumors and are though to play a role in tumor vascular development. It is known that tumor derived products are able to block or activate TAM. Following activation TAM may produce a number of factors to promote tumor growth and contribute to vascular development. We have identified a protein of approximate MW 115 kDa on monocytes that binds to carcinoembryonic antigen (CEA). Engagement of the monocyte protein to CEA leads to activation of monocytes to produce cytokines including TNF-alpha ( Biochem Biophys Res Commun , 331:319-323, 2003), and that changes the tumor microenvironment. This has implications in colon tumorigenesis. Since TNF-alpha is implicated in tumor vascularization, we therefore wanted to examine the specificity of CEA binding to the monocyte protein and evaluate its implication in tumor vascular development, which is a prerequisite for tumor development. Binding studies with the purified monocyte protein using immobilized CEA on the surface of a sensor chip suggest that the association of CEA with the monocyte protein was complete within 60 seconds. The binding was specific since monocyte protein binding was not detected on the control surface containing immobilized irrelevant antibody. To examine the relationship between CEA-producing tumors and nature of tumor vasculature, formalin-fixed paraffin embedded colon tumor tissues were stained by immunoperoxidase assay using anti-CEA antibody and anti-CD34 antibody to identify the CEA positive tumors and blood vessels respectively. Blood vessels were counted under a microscope and the number of blood vessels present in randomly selected tumor areas of CEA-positive and CEA-negative tumors was compared. Results suggest that there is significantly higher number of blood vessels present in CEA-positive tumors compared to CEA-negative tumors and the normal colon. The studies suggest that binding of CEA to the monocyte protein is specific and there is a possible correlation between CEA-producing tumors and the presence of increased number of blood vessels in the tumor area. The study is supported by a grant from the National Cancer Institute.
NHS rethink: charade or cause for new hope?
Authors: K Arden, J Black, K Boomla, A Haines, L Smeeth, DJ Hunter, S Lawrence, J Lindeck, AM Pollock, M Roland, P Watts
Journal: BMJ (2011)

NHS rethink: charade or cause for new hope?We asked a range of commentators from clinicians to academics for their thoughts on the proposed changes to the NHS Health and Social Care Bill.Do the changes move us to a healthcare model we can be proud of or do they take us back to pre-1948 inequity and a "return to fear"?
Abstract 5392: Chronic Cervical Vagus Nerve Stimulation Attenuates Systemic Inflammation and Heart Failure Progression in a Canine Rapid Ventricular Pacing Model
Authors: Youhua Zhang, Zoran B Popovic, Steve Bibevski, Don W Wallick, David R Van Wagoner, Todor N Mazgalev
Journal: Circulation (2008)
Abstract 3600: An Obesity Paradox Among Apparently Healthy Male Veterans
Authors: Paul McAuley, Jonathan Myers, Joshua Abella, Ricardo Oliveira, Leon Hsu, Victor F Froelicher
Journal: Circulation (2007)

Background: Body mass index (BMI) is inversely related to mortality in patients with cardiovascular disease (CVD), the so-called obesity paradox. We studied a group of male veterans referred to exercise testing for clinical reasons, but determined to be free of CVD, to evaluate whether this occurs in such individuals. Methods: After excluding 40 patients with BMI &lt;20 kg/m 2 , we evaluated a total of 3317 consecutive men (mean age 57 ± 12 years) referred for exercise testing between 1992 and 2004. Patients were classified according to three predetermined BMI groups: 20.0 –24.9, 25.0 –29.9, and ≥30.0 kg/m 2 . The association of BMI and all-cause mortality was assessed by Cox proportional hazards analysis. Results: During a mean follow-up of 5.8 ± 3.3 years, a total of 212 patients (6.4%) died. After adjusting for age, ethnicity, smoking and fitness level, subjects with BMI-defined normal weight were 60% more likely to die (HR [95% CI] 1.63 [1.21–2.19]; Figure ) than overweight or obese men. Further adjustment for hypertension, hypercholesterolemia and diabetes did not appreciably alter these results. Conclusions: Veterans are a select group in that they must meet weight criteria to qualify for military service. In this cohort of apparently healthy male veterans, we observed a strong inverse relation of BMI to mortality. This warrants further investigation into the extent and nature of the obesity paradox.
Update of Clostridium difficile-associated disease due to PCR ribotype 027 in Europe
Authors: E  J Kuijper, B Coignard, J  S Brazier, C Suetens, D Drudy, C Wiuff, H Pituch, P Reichert, F Schneider, A F Widmer, K EP Olsen, F Allerberger, D  W Notermans, F Barbut, M Delmée, M Wilcox, A Pearson, B Patel, D  J Brown, R Frei, T Akerlund, I R Poxton, Peet Tüll
Journal: Eurosurveillance (2007)

Recent outbreaks of Clostridium difficile-associated diarrhoea (CDAD) with increased severity, high relapse rate and significant mortality have been related to the emergence of a new, hypervirulent C. difficile strain in North America, Japan and Europe. Definitions have been proposed by the European Centre of Disease Prevention and Control (ECDC) to identify severe cases of CDAD and to differentiate community-acquired cases from nosocomial CDAD (http://www.ecdc.europa.eu/documents/pdf/Cl_dif_v2.pdf). CDAD is mainly known as a healthcare-associated disease, but it is also increasingly recognised as a community-associated disease. The emerging strain is referred to as North American pulsed-field type 1 (NAP1) and PCR ribotype 027. Since 2005, individual countries have developed surveillance studies to monitor the spread of this strain. C. difficile type 027 has caused outbreaks in England and Wales, Ireland, the Netherlands, Belgium, Luxembourg, and France, and has also been detected in Austria, Scotland, Switzerland, Poland and Denmark. Preliminary data indicated that type 027 was already present in historical isolates collected in Sweden between 1997 and 2001.
Abstract 13327: Modulation of Proprotein Convertase Subtilisin/Kexin Type 9 Function via Interaction with Apolipoprotein B/Lipoprotein Particles
Authors: Susan Shetterly, Mei Di, Margrit Schwarz, Simon Jackson
Journal: Circulation (2012)

Proprotein convertase subtilisin/kexin type 9 (PCSK9), is secreted from the liver and circulates in plasma where it modulates low density lipoprotein cholesterol (LDL-C) by mediating the degradatio...
Femur fractures after limb-sparing treatment of soft-tissue sarcomas: One institution's experience.
Authors: A. H. Blaes, B. Lindgren, D. A. Mulrooney, L. Willson, L. C. Cho
Journal: Journal of Clinical Oncology (2010)

e19601 Background: Local control for soft tissue sarcomas of the long bones often includes limb sparing surgery with the addition of radiation therapy. While effective, there are potential complications including poor wound healing and late-onset fractures. Methods: This analysis includes patients treated for a soft tissue sarcoma of the thigh with limb-sparing surgery and radiation therapy between 1986 and 2000 at the University of Minnesota Masonic Cancer Center (n=89). Demographic, tumor, and treatment characteristics including age, sex, histology, location (anterior, posterior, medial, buttock, popliteal fossa), use of adjuvant chemotherapy (yes/no), use of periosteal stripping (yes/no), timing of radiation (pre-/post-operative, both), radiation dose [high (>60 Gy), low (</+60 Gy), radiation field length [> 30 centimeters (cm), </= 30 cm], circumference of radiation field (100%/< 100% of femur) were abstracted from the medical record. Univariate analysis was conducted to identify significant risk factors for fracture. Given the small numbers of patients with a femoral fracture, multivariate analysis was unable to be performed. Results: Survivors (58 % male) with a median age of 50 (7-88) years reported_8 (9%) fractures at a median of 7.3 (0.8 – 21.9) years from diagnosis after a median of 6300 (2000-7020) cGy of radiation. All fractures occurred within the previous radiation field, after minimal or no trauma. Three of the 8 (37.5%) had delayed union, 2 (25%) nonunion healing. Significant risk factors included periosteal stripping (p=0.006), anterior location (p=0.022), and having 100% of the femoral circumference irradiated (p=0.018). Taking into account time to fracture using Kaplan Meier and log rank tests, these same predictors were identified. Older age, female sex, use of chemotherapy, and timing of radiation were not predictive of femoral fracture. Conclusions: Anterior tumor location, the presence of periosteal stripping, and radiation to 100% of the femur circumference are significantly associated with femoral fracture. These patients require long-term monitoring and may warrant prophylactic intramedullary pinning or other protective measures. No significant financial relationships to disclose.
Abstract 3608: Lipoprotein (a) Cholesterol, But Not Lp(a) Mass, Is An Independent Predictor Of Angiographic Coronary Artery Disease And Subsequent Cardiovascular Events In Patients Referred For Coronary Angiography.
Authors: Joseph P McConnell, Linnea M Baudhuin, Peter B Berger, Iftikhar J Kullo, John F O'Brien, Sandra C Bryant, Stacy J Hartman, Jennie N Ward, Ryan J Lennon, Virend K Somers, George G Klee, Allan S Jaffe
Journal: Circulation (2007)
Drug points: Myoclonus associated with propafenone
Authors: T P Chua, T Farrell, D P Lipkin
Journal: BMJ (1994)

We report a case of myoclonus in a patient who took propafenone for paroxysmal atrial fibrillation.

An 82 year old woman with a history of paroxysmal atrial fibrillation had been taking amiodarone for three years. Treatment was stopped because of pulmonary fibrosis. She was also taking a thiazide diuretic for …
Abstract 5661: Three-Dimensional Reconstructions of Left Atrium and Pulmonary Veins based on Intraprocedural C-Arm Rotational Angiography in Comparison to Electroanatomical Mapping: Integration of a Novel Modality into Atrial Fibrillation Ablation
Authors: Georg Noelker, Stefan Asbach, Klaus Juergen Gutleben, Anil Sinha, Guido Ritscher, Harald Marschang, Harald Rittger, Nassir Marrouche, Johannes Brachmann
Journal: Circulation (2008)

Preprocedural imaging and its integration into electroanatomical mapping (EAM) is commonly used in atrial fibrillation (AF) ablation. However, intraprocedural imaging based on rotational angiography (DynaCT Cardiac) may be superior in terms of actuality and may lead to an improved work-flow. Feasibility of integrating Dyna CT Cardiac into EAM has not yet been shown. In 23 patients (62±7 years, 16 male) undergoing catheter ablation of paroxysmal (n=10) or persistent (n=13) AF, we intraprocedurally performed rotational angiography enhanced by contrast agent applied to the pulmonary artery with offline segmentation of left atrium (LA) and pulmonary veins (PV). Fig 1 depicts reconstructed LA and PV-anatomy directly importet into CARTOMerge. Distances between the 2 modalities were analyzed. Direct image integration of prereconstructed 3D-anatomy was feasible in all patients. Procedure time was 156 ± 24 minutes including 11 ± 3 minutes for DynaCT Cardiac registration and segmentation. 132 ± 74 mapping points were taken. Mapping points deviated to intraprocedural DynaCT Cardiac 3D-reconstructions by 2.2 ± 0.4 mm (2.3 ± 0.5 mm in patients suffering from paroxysmal atrial fibrillation (AF) vs. 2.1 ± 0.40 mm persistent AF, n.s.). No complications occured. Integration of intraprocedural Dyna CT Cardiac into EAM was feasible and fast. The work-flow seemed to be improved by avoiding additional preprocedural imaging. The novel modality is highly accurate in comparison to EAM.
Abstract 3795: Readjusting The Catabolic-anabolic Balance In Heart Failure: Beneficial Effects Of Physical Exercise On Protein Catabolism In The Skeletal Muscle
Authors: Stephan Gielen, Marcus Sandri, Volker Adams, Norman Mangner, Sandra Erbs, Axel Linke, Rainer Hambrecht, Gerhard Schuler
Journal: Circulation (2007)

Background: Progressive muscle wasting frequently occurs in the course of chronic heart failure (CHF) and has recently been identified as independent predictor of mortality in clincal studies. However, the molecular mechanisms that mediate muscle catabolism are still largely unknown and no specific pharmacological agents are available to antagonize the loss of muscle mass. We therefore tested the potential of an established anabolic intervention, i.e. exercise training, to prevent cytokine-induced ubiquitin-proteasome-mediated protein degradation in the skeletal muscle of stable patients with advanced CHF. Methods: 43 CHF-patients and 41 healthy subjects (HS) were prospectively randomized to 4 weeks of supervised bicycle ergometer training at 70% of the heart rate reserve 4 times 20 min/day or to a control group (C). Before and after the intervention a spiroergometry, echocardiography, and skeletal muscle biopsy from the vastus lateralis muscle were performed. Expression of TNF-alpha and the E3 ligase Murf-1, which tags proteins for degradation via the ubiquitin-proteasome system, were quantified by real-time PCR standardized for 18S-rRNA. Results: In CHF patients (age 60.3 ± 2.9 years, BMI 28.9 ± 1.7, LV-EF 27.4 ± 1.7%): training increased VO2max from 14.9 ± 3.3 to 18.1 ± 4.7 mL/min/kg (p&lt;0.01 vs. C), and LV-EF from 26.8 ± 4.6 to 33.1 ± 5.5% (p=0.001 vs. C). At baseline Murf-1 expression was significantly higher as compared to HS. Training decreased Murf-1 expression from 0.49 ± 0.21 to 0.22 ± 0.07 rel. units (p&lt;0.05) and TNF-alpha expression from 79 ± 7.1 to 44.7 ± 5.9 rel. units (p&lt;0.001). In HS (age 64.7 ± 2.7 years, BMI 26.2 ± 0.5, LV-EF 63 ± 0.8%) training increased VO2 max from 20.3 ± 2.1 to 27.9.2 ± 1.3 mL/kg min (p=0.01 vs. C). Murf-1 and TNF-alpha expression remained unchanged versus untrained HS. Conclusions: CHF is associated with local inflammatory and catabolic activation in the skeletal muscle as indicated by higher baseline TNF-alpha and Murf-1 levels. Training cuts the elevated TNF-alpha and E3-ligase expressions by half within only four weeks of intervention. These findings emphasize the role of training for the prevention of muscle atrophy and may provide a novel explanation for the prognostic benefits of exercise in CHF.