tbuckley/cabot-search huggingface dataset:
Abstract 1120: Akt Modified MSCs Secrete a Novel Stem Cell Paracrine Factor that Protects Injured Heart, Activates Cyclin Dependent Kinase and Phosphorylates/Activates Akt Signaling Pathway in Adult Rat Cardiomyocytes
Authors: Jian Guo, Maria Mirotsou, Jing Huang, Hui Mu, Lunan Zhang, David Loiselle, Zhiping Zhang, Richard E Pratt, Timothy Haystead, Victor J Dzau
Journal: Circulation (2007)

Previously, we have shown that intracardiac injection of mesenchymal stem cell (MSC) overexpressing Akt (Akt-MSCs) could dramatically reduced infarct size and restored cardiac function in a paracrine manner. Microarray analysis of Akt-MSCs led to the identification of a novel transcript encoding a secreted protein. Cloning of the cDNA encoding this candidate gene into pET15b allowed the purification as a 6×His tagged recombinant protein. Interestingly, a 30 minute pre-incubation of the H9C2 myocytes with this protein (10nM) reduced H 2 O 2 induced apoptosis by 50% as measured by annexin V/PI staining on flow cytometry (n = 3, p&lt;0.001). Moreover, this protein significantly prevent H 2 O 2 induced DNA fragmentation and inhibited Caspase 9 and Caspase 3/7 activities in adult rat cardiomyocytes by ~36% and ~42%, respectively (n=3, p&lt;0.01). Furthermore, this protein dramatically inhibited the mitochondrial release of Cytochrome C and maintained mitochondrial Bcl-2 protein level. Intramyocardial injection of 1 μg of this novel protein dramatically reduced infarct size (−58%, n=10, p&lt;0.001) and TUNEL positive nuclei (−69%, n=10, p&lt;0.001) in a 30 min ischemia/24h reperfusion rat model. Fibrosis evidenced by collagen deposition was greatly reduced (−61%, n=8, p&lt;0.001) 4 weeks after ischemia/reperfusion injury. Signaling studies demonstrated that this novel protein phosphorylated rat adult cardiomyocytes Akt Thr308 but not Akt Ser473 in a time-depended manner peaking at 30 min. Consequently, downstream Akt substrates, GSK3ß Ser9 and Bad Ser128 , are also phosphorylated at 30 min or at a later time point. In contrast to the traditional concept that PDK1 phosphorylates both Akt Thr308 and Akt Ser473 , our mass-spec and in vitro enzymatic analysis of rat cardiomyocytes stimulated with this factor suggests cyclin-dependent kinase 7 as being responsible for phosphorylation of Akt specifically at Thr 308 position. Further studies would be of great interest to interrogate whether this novel factor could activate other cyclin dependent kinase(s) and render the cardiomyocytes re-entering cell cycle. In conclusion, we have identified a novel paracrine factor from Akt-MSCs that mediates cardioprotective effects through activation of novel pathways involving Akt.
Abstract 699: Intracoronary Infusion Of Bone Marrow-derived Progenitor Cells In Patients With Non-ischemic Dilated Cardiomyopathy Is Associated With An Increase Of Coronary Blood Flow In The Target Vessel
Authors: Ulrich Fischer-Rasokat, Birgit Assmus, Florian Seeger, Joerg Honold, Volker Schaechinger, Stephan Fichtlscherer, Hans Martin, Stefanie Dimmeler, Andreas M. Zeiher
Journal: Circulation (2007)

We recently could demonstrate that intracoronary administration of bonemarrow-derived progenitor cells (BMC) is associated with improved target area contractility and enhanced cardiac function in patients (pts) with nonischemic dilated cardiomyopathy (DCM). The influence of coronary microvascular dysfunction on development and progression of DCM in the absence of epicardial artery atherosclerosis has been demonstrated in experimental studies. Therefore, to get insights into potential mechanisms of BMC therapy in pts with DCM, we performed a substudy of the TOPCARE-DCM trial, assessing coronary blood flow (CBF) by intracoronary Doppler measurements. Methods 13 pts (age 31 to 64 yrs; ejection fraction 28 ± 14 %) were included. A mean number of 353 ± 119 * 10 6 BMC were infused into the left anterior descending (LAD) artery using the stop-flow technique. Doppler-derived CBF velocities in the target (LAD) as well as in a reference vessel (left circumflex artery, ref) were obtained at baseline prior to BMC administration and at 3 months’ angiographic follow up (FU). Results Heart rate, blood pressure and coronary artery lumen diameter did not differ between initial and FU measurements. Basal coronary vascular resistance (VR) decreased after 3 months in the target and in the ref vessel (target 6.32 ± 2.43 vs 5.43 ± 2.28, p &lt; 0.01; ref 6.72 ± 2.15 vs 5.41 ± 1.94 mmHg*s/cm, p = 0.03). In contrast, adenosine-induced minimal VR decreased only in the target vessel but not in the ref vessel (target 1.53 ± 0.60 vs 1.31 ± 0.65, p &lt; 0.01; ref 1.60 ± 0.45 vs 1.49 ± 0.45 mmHg*s/cm, p = ns). Due to the selective decrease in adenosine-induced minimal VR of the target vessel, the coronary flow reserve normalized for the ref vessel increased from 1.0 ± 0.2 to 1.2 ± 0.3 (p &lt; 0.05). Likewise, the CBF increased in the target vessel (from 48 ± 18 to 62 ± 25 ml/min, p = 0.02), but remained unchanged in the ref vessel (from 40 ± 21 to 48 ± 18 ml/min, p = ns). Conclusions In pts with nonischemic DCM, intracoronary BMC infusion is associated with a significant improvement in microvascular function of the target area. Whether improved microvascular function as a potential mechanism underlying the beneficial effects of BMC is causally linked to an improved cardiac contractile function has to be analysed in larger studies.
Abstract 3442: Normal Circadian Rhythms In Calcineurin-dependent Signaling And Protein Phosphorylation Are Disrupted In Heart Failure
Authors: Asim Dey, Nita Sachan, Misook Oh, Joseph A Hill, Beverly A Rothermel
Journal: Circulation (2008)

Many important cardiovascular factors, including metabolism, heart rate, blood pressure, and hormone release, oscillate over a 24-hour period. In humans, the incidents of adverse cardiac events, such as myocardial infarction, and ventricular tachycardia vary according to the time of the day. Despite overwhelming evidence of the importance of circadian rhythms in cardiovascular health and disease, little is known regarding the circadian regulation of intracellular signaling pathways involved in normal cardiac function and heart failure. Here we show that there are large circadian oscillations in calcineurin-dependent activities in normal, healthy mouse hearts. This finding is remarkable because activation of the protein phosphatase calcineurin has primarily been thought of as a pathological process driving cardiac hypertrophy and failure. In the hearts of wild type C57BL6 mice there was a 17-fold change in mRNA levels for the calcineurin/NFAT target gene RCAN1.4 that peaked in the early morning at the beginning of the animal’s sedentary phase. Nuclear occupancy of calcineurin-regulated transcription factor NFAT coincided with the changes in mRNA suggesting that circadian changes in calcineurin activity underlie these oscillations. Phosphorylation of the protein phosphatase 1 inhibitor 1 (I-1), a direct calcineurin substrate, and phospholamban (PLB), an indirect target, oscillated directly out of phase with calcineurin-dependent signaling. We propose that temporal separation of peak kinase and phosphatase activities form interdependent feedback loops helping coordinate cardiac function. In pressure overload-induced failing hearts, oscillations in calcineurin-dependent transcription persisted, however both the peak and trough activities were markedly elevated compared to control hearts. In contrast, oscillations in PLB and I-1 phosphorylation were largely lost in failing hearts where phosphorylation of I-1 could no longer be detected and PLB phosphorylation remained elevated throughout. Together, our results suggest that the normal relationships between circadian oscillations in protein phosphorylation and dephosphorylation are disrupted in heart failure. This research has received full or partial funding support from the American Heart Association, AHA South Central Affiliate (Arkansas, New Mexico, Oklahoma &amp; Texas).
Abstract 14648: The Small Dense LDL phenotype and the Progression of Aortic Stenosis : a substudy of the ASTRONOMER trial
Authors: Romain Capoulade, Marie-Annick Clavel, Jean G Dumesnil, Kwan L Chan, Koon K Teo, James W Tam, Patrick Mathieu, Jean-Pierre Despres, Philippe Pibarot
Journal: Circulation (2010)

Background: We previously reported that metabolic syndrome (MetS) which represents a cluster of metabolic abnormalities including insulin resistance, is associated with faster progression of AS. A ...
Clinical benefit of lapatinib-based therapy in patients with HER2-positive breast tumors expressing p95HER2
Authors: L. Prudkin, C. M. Aura, J. Jimenez, M. Scaltriti, C. Ellis, R. Gagnon, M. Arbushites, Y. Liu, M. Koehler, J. Baselga
Journal: Journal of Clinical Oncology (2009)

1048 Background: Approximately 25% of HER2 overexpressing breast tumors express a truncated form of the receptor (p95HER2) that lacks the extracellular domain but retains kinase activity. p95HER2-positive tumors are associated with a worse prognosis and resistant to trastuzumab therapy. In preclinical models, lapatinib (L), a tyrosine kinase inhibitor of EGFR and HER2, is active in p95HER2 expressing tumors. The aim of this analysis was to test the hypothesis that benefit from L-based therapy is independent of p95HER2 expression in 2 clinical trials in patients (pts) with HER2-positive tumors treated with either L monotherapy (Study EGF20009 ) or L in combination with capecitabine (Study EGF100151). Methods: Pre-treatment tumor tissue from both trials (N=201) was analyzed for p95HER2 expression by immunofluorescence as previously described (Scaltriti M. et al, JNCI 2007). Expression of p95HER2 was correlated with clinical benefit rate (CBR: complete response [CR] + partial response [PR] + stable disease [SD] ≥ 24 weeks) and progression-free survival (PFS) using logistic regression and Cox-proportional hazard models. Results: 68/105 and an initial 72/96 tissue samples were evaluable for p95HER2 expression from studies EGF20009 and EGF100151, respectively. The Table summarizes the results from the L treated pts. The CBR and PFS in L treated pts were not significantly different between the p95HER2 subgroups. Expanded data for p95HER2 expression in additional EGF100151 tumor samples will be presented. Conclusions: L as a monotherapy or in combination with capecitabine has similar response activity in pts with p95HER2-positive and p95HER2-negative HER2-positive breast tumors. [Table: see text] [Table: see text]
Factor V Inhibitor after Injection of Human Thrombin (Tissucol) into a Bleeding Peptic Ulcer
Authors: Jo Caers, An Reekmans, Kristin Jochmans, Serge Naegels, Fazia Mana, Daniel Urbain, Hendrik Reynaert
Journal: Endoscopy (2003)

Endoscopic injection of fibrin glue into a bleeding peptic ulcer is an effective and safe treatment modality. The present report describes a patient who developed rectal bleeding from an arteriovenous malformation after endoscopic injection of fibrin glue containing human thrombin into a gastric ulcer. Additional laboratory investigations revealed the presence of an inhibitor against coagulation factor V, which resulted in severe coagulopathy, triggering the bleeding. Acquired factor V inhibitors have frequently been reported with the use of bovine thrombin, but to our knowledge, they have never been documented in patients exposed to human thrombin. Endoscopists should be aware of this rare, but potentially serious, complication.
Some Examples of Gene-Controlled Functional Disturbances in the Mouse&lt;xref ref-type="fn" rid="fn1"&gt;1&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: Herman B. Chase
Journal: JNCI Journal of the National Cancer Institute (1954)

Journal Article Some Examples of Gene-Controlled Functional Disturbances in the Mouse Get access Herman B. Chase Herman B. Chase Biology Department, Brown University, Providence, R. I. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 15, Issue 3, December 1954, Pages 655–664, https://doi.org/10.1093/jnci/15.3.655 Published: 01 December 1954
Abstract 21032: Ventricular Tachycardia and Atrial Fibrillation Complicating the Clinical Course of Tako-tsubo Cardiomyopathy: Results of the German Tako-tsubo Registry
Authors: Birke Schneider, Anastasios Athanasiadis, Wolfgang Pistner, Johannes Schwab, Uta Gottwald, Wolfgang Toepel, Ralph Schoeller, Klaus-Dieter Winter, Christoph Stellbrink, Udo Sechtem
Journal: Circulation (2010)

Background: Arrhythmias may complicate the clinical course of tako-tsubo cardiomyopathy (TTC). This study evaluated the incidence and clinical relevance of ventricular arrhythmias and atrial fibrillation (AF) in pts of the German TTC registry. Methods: From 37 hospitals, 324 pts (296 f, 28 m, age 68±12) were included in the registry. Seven pts (2.2%) died (cardiogenic shock n=4; myocardial rupture, stroke and asystole n=1 each); 209 pts were continuously monitored and had daily ECG recordings for evaluation of arrhythmias. Results: Ventricular tachycardia (VT) was documented in 17 pts (8%) and newly diagnosed AF in 32 pts (15%). TTC pts with and without arrhythmias were compared. In pts with VT, time from symptom onset to hospital admission was shorter (3.8±3.2 vs 8.7±7.3 hours, p<0.001). Pulmonary edema (29% vs 12%, p<0.05), need for intraaortic balloon pumping (6% vs 0.5%, p<0.05), resuscitation (18% vs 3%, p<0.002) and left ventricular thrombi (12% vs 3%, p=0.05) were seen more frequently. The QTc inte...
Abstract 11970: A Valid and Reliable Scale to Differentiate State and Trait Hopelessness in Patients with Coronary Heart Disease
Authors: Nathan Tintle, Grace Olamijulo, Heather Fuglseth, Theresa Holden, Lien Brusselmans-Swieringa, Michael Sit, Susan L Dunn
Journal: Circulation (2012)

Introduction: Coronary heart disease (CHD) and depression are highly prevalent, comorbid health problems associated with increased morbidity and mortality. Hopelessness is a factor related to depre...
Abstract 21009: Mid-term outcomes of Medtronic-Corevalve Transcatheter Aortic Valve Implantation: Follow-up to 4 years
Authors: Hasan Jilaihawi, Anita Asgar, Anique Ducharme, Jean-Benoit le Polain de Waroux, Raymond Cartier, Reda Ibrahim, Arsene Basmadijan, Philippe Demers, Raoul Bonan
Journal: Circulation (2010)

Background: Transcatheter Aortic Valve Implantation(TAVI) has yielded favourable outcomes at 1 year follow-up in multicenter series. Limited data exists for results beyond this time-frame. Methods:...
Abstract 1234: Proteomic Analysis Provides Insights into Molecular Mechanisms of Atrial Profibrillatory Remodeling in Congestive Heart Failure
Authors: Ayesha I De Souza, Sophie Cardin, Robin Wait, Nina Patel, Akiko Shiroshita-Takeshita, A. John Camm, Stanley Nattel
Journal: Circulation (2007)

Congestive heart failure (CHF) leads to atrial structural remodeling and increased susceptibility to sustained atrial fibrillation (AF). The underlying molecular mechanisms are poorly understood. O...
Abstract 4066: Response to Symptom Management Intervention among Functionally Impaired Older Adults Following Coronary Artery Bypass Surgery (CABS)
Authors: Susan A Barnason, Lani Zimmerman, Paula Schulz
Journal: Circulation (2008)

Older adults with poor functioning preoperatively are at risk for delayed recovery following CABS. The purpose of this study was to determine if a symptom management (SM) telehealth intervention was effective in improving early recovery outcomes (physical activity, physiological and psychological functioning) for older adults with impaired functioning prior to CABS. A descriptive, repeated measures design was used in this subanalysis of a larger RCT. Subjects in the parent study (N=232), who met the preoperative impaired functioning criteria [physical component score of Medical Outcomes Study Short-form 36 (MOS SF-36) &lt;50 and a RISKO score of ≥ 6], were included in either the SM intervention group (n=23) or the usual care group (n=31). Methods : Physical activity was measured at baseline using the Modified 7-Day Activity Interview; and at follow-up times by the RT3® accelerometer and an Activity Diary. Physiological and psychosocial functioning was measured by the MOS SF-36. Data was gathered prior to hospital discharge, at 3- and 6-weeks and 3-months after hospital discharge. Findings : Subjects ranged in age from 65– 85 years, with a mean of 71.6 (± 5.1) years. Analysis of covariance with repeated measures was used on physical activity and functioning measures, with preoperative levels used as covariates. There were significant group by time effects, with the SM intervention group as compared to the usual care group having higher levels of physical activity over time for: average daily activity counts [F (3,37)=3.55, p&lt;.05]; levels of estimated energy expenditure (average kcal/kg/day expended) as measured by both the RT3® [F (3,37)=2.89, p&lt;.05] and Activity Diary [F (3,42)=3.01, p&lt;.05]; and average minutes/day in moderate or higher levels of activity [F (3,42)=3.18, p&lt;.05]. Both groups had significantly (p&lt;.05) increased role-physical, mental and social functioning over time. Conclusions : Study findings demonstrated the responsiveness of a subgroup of CABS subjects with impaired preoperative functioning to a SM intervention for older adults. Subjects’ improvements in physical activity functioning can help to decrease their risk for morbidity and mortality that can be associated with poor functioning after cardiac events.
Abstract 16347: Peripartum Cardiomyopathy-Associated Sequence Variant at the PTHLH Locus is Not Predictive of Idiopathic or Ischemic Cardiomyopathy
Authors: Benjamin D Horne, Kismet D Rasmusson, Rami Alharethi, Deborah Budge, Kimberly D Brunisholz, John F Carlquist, John A Huntinghouse, Jenny J Connolly, T. Flint Porter, Josef Stehlik, Joseph B Muhlestein, Heidi T May, Stacey Knight, Jeffrey L Anderson, Abdallah G Kfoury
Journal: Circulation (2011)

Background: A rare diagnosis with undescribed etiology, Peripartum (PP) cardiomyopathy (CM) occurs near the end of pregnancy or during the early postpartum period. A single nucleotide polymorphism ...
Bull Riderʼs Myositis
Authors: Kathy Tieu, Eugene D. Silverman, Richard L. Cole
Journal: Clinical Nuclear Medicine (2004)

A 21-year-old man was evaluated for acute hip pain with skeletal scintigraphy to exclude femoral neck stress fracture. The bone scan revealed extraosseous tracer uptake in the adductor muscles of the thighs bilaterally. History revealed multiple episodes of mechanical bull riding within the previous week. Muscle uptake of bone scanning agents may occur in a variety of conditions including overexertion and direct trauma to muscle.
Sources of Toxoplasma gondii infection in pregnancy
Authors: J P Dubey
Journal: BMJ (2000)

topical use are substantially higher than those achieved by using other forms of administration, and thus there is a good chance of eradicating the infection.If ciprofloxacin or ofloxacin fails, parenteral treatment with ceftazidime or imipenem can be used. 12ntil topical ciprofloxacin is commercially available its use will remain restricted in the United Kingdom.Guidelines should be issued for the appropriate use of the drug in chronic otitis media with perforated eardrums, and its introduction for treating chronic otitis externa as well as its use in children should also be considered.
The prognosis of Hodgkin's disease in older adults.
Authors: V F Guinee, G G Giacco, M Durand, J W van den Blink, A Gustavsson, J G McVie, R Zewuster, S Dische, T Fahey, W Lane
Journal: Journal of Clinical Oncology (1991)

This investigation was undertaken to assess the apparent poor survival of older patients with Hodgkin's disease. The clinical course of Hodgkin's disease in 136 patients, 60 to 79 years of age, was compared with that of 223 patients, 40 to 59 years of age. The patients registered from November 1977 through December 1983 had not been previously treated, and were treated at eight cancer centers. When the prognosis of all patients was examined by age, a definite change in the pattern of survival first appeared in the 60- to 69-year-old cohort. The entire older group (60 to 79 years) experienced twice the risk of dying from Hodgkin's disease and four times the risk of dying from other causes than did the younger group. In both groups, stage of disease was the strongest factor in predicting adjusted survival. Delay in treatment and advanced stage at presentation were not characteristic of Hodgkin's disease in older patients as has been postulated. Older patients responded to therapy with a similar complete remission rate (84% v 88% in the younger group, P = .24). From this study, we conclude that (1) Hodgkin's disease in the older adult does not have a different natural history, its major risk factors are similar to those known in other age groups, and thus should be amenable to existing therapeutic approaches; and (2) the prognosis of older patients with Hodgkin's disease has been obscured in previous studies by the inclusion of deaths due to other causes in survival estimates.
Abstract 2708: Long-Term Outcome After Restrictive Annuloplasty and Coronary Revascularization in Ischemic Mitral Regurgitation
Authors: Nico R Van de Veire, Jerry Braun, Jos J Westenberg, Robert J Klautz, Michel I Versteegh, Eduard R Holman, Ernst E van der Wall, Robert A Dion, Jeroen J Bax
Journal: Circulation (2006)

Objectives Long-term follow-up data, including echocardiographic evaluation of reverse left ventricular (LV) remodeling, on combined coronary artery bypass grafting (CABG) and restrictive annulopla...
Low coverage of seasonal influenza vaccination in the elderly in many European countries
Authors: J Mereckiene, S Cotter, J T Weber, A Nicoll, D Lévy-Bruhl, A Ferro, G Tridente, G Zanoni, P Berra, S Salmaso, D O'Flanagan, Collective on behalf of the VENICE gatekeepers group
Journal: Eurosurveillance (2008)

In May 2003, the 56th World Health Assembly (WHA) recommended influenza vaccination for all people at high risk defined as the elderly and persons with underlying diseases [1]. The WHA countries, including all European Union (EU) Member States, also committed to the goal of attaining vaccination coverage of the elderly population of at least 50% by 2006 and 75% by 2010 and to having mechanisms for monitoring the uptake [1]. To date there has been no published survey on how successful European countries have been in implementing this WHA resolution.
Abstract 1132: Levels of Serum Soluble Lectin-like Oxidized LDL Receptor (sLOX-1) Predict Adverse Cardiovascular Outcomes in Patients With Stable Coronary Artery Disease
Authors: Marwa A Sabe, David A Morrow, Michelle O'Donoghue, Sarah Sloan, Eugene Braunwald, Marc S Sabatine
Journal: Circulation (2009)

Background: Oxidized LDL (oxLDL) has been proposed as an independent biomarker of risk for adverse cardiovascular (CV) outcomes. Lectin-like oxLDL receptor-1 (LOX-1) is expressed in advanced plaques and activated platelets and may play a role in plaque rupture; a soluble form (sLOX-1) can be measured in serum. We aimed to define the prognostic value of these biomarkers in patients with stable coronary artery disease (CAD). Methods: Levels of sLOX-1 and oxLDL [the latter using 2 different ELISAs: competitive (oxLDLc) and sandwich (oxLDLs)] were measured on baseline samples in 3791 patients enrolled in PEACE, a placebo-controlled trial of trandolapril vs placebo in patients w/stable CAD followed for 4.8 y for clinical outcomes. Multivariable Cox regression (limited access dataset, NHLBI) was used to adjust for age, sex, CV risk factors, lipid profile (apoB, apoA), lipid-lowering therapy, and treatment group. Results: The incidence of the composite of CV death, MI or stroke significantly increased across qua...
Improving the Quality of Coronary Bypass Surgery With Intraoperative Angiography
Authors: Nimesh D. Desai, Senri Miwa, David Kodama, Gideon Cohen, George T. Christakis, Bernard S. Goldman, Mark O. Baerlocher, Marc P. Pelletier, Stephen E. Fremes
Journal: Journal of the American College of Cardiology (2005)