tbuckley/cabot-search huggingface dataset:
Abstract 19274: Coronary Artery Ectasia Are Frequently Observed in Patients With Bicuspid Aortic Valves With and Without Aneurysm of the Ascending Aorta
Authors: Christine Meindl, Birgit Achatz, Deborah Huber, Ute Hubauer, Stefan Buchner, Kurt Debl, Sabine Fenk, Christina Strack, Christian Hengstenberg, Heribert Schunkert, Christa Meisinger, Lars Maier, Andrea Baessler, Marcus Fischer
Journal: Circulation (2014)

Background: The exact etiology and prognostic significance of coronary artery ectasia (CAE) is still unknown. The presence of CAE is influenced by genetic factors and related to the presence of aneurysms in other vascular beds. Bicuspid aortic valve (BAV) disease is frequently accompanied by ascending aortic aneurysm. Since the aortic valve, the ascending aorta, and the proximal parts of the coronary arteries share a common embryonic origin, we hypothesized that CAE is associated with BAV disease. Methods: 181 patients with suspected aortic valve disease (n=101 BAV) underwent both cardiac magnetic resonance (CMR) imaging and coronary angiography. Eighty subjects with tricuspid aortic valve (TAV) disease were similarly studied and served as controls. The readers of the angiograms were blinded to valve type and clinical data. In order to confirm the association of CAE with BAV, the frequency of CAE was evaluated in an in-house BAV registry (n=500) and compared to the frequency of CAE in the German MI family study, in which the heritability of CAE was formerly established (899 with available coronary angiograms), as well as in an observational registry of “real-life patients” undergoing coronary angiography for clinically indicated reasons (n=3471). Furthermore the frequency of CAE was investigated in a subgroup of the KORA MI study, which is a population-based registry that comprises all hospitalized cases of acute non-fatal MI and coronary deaths occurring in inhabitants of a defined study region (n=403). Results: Compared to TAV disease, CAE occured twice as frequently in CMR confirmed BAV disease, (17.5% vs. 41.6%, p=0.0005). Ascending aortic aneurysm or ectasia was diagnosed in 60 subjects with BAV disease (59.4%), but CAE occurred similarly between subjects with (59.5%) and without (40.5%) ascending aortic pathology. The common appearance of CAE in patients with BAV could be independently confirmed in the BAV registry (38.9%), whereas CAE was found less frequently in family history positive MI patients (21.2%), and rarely in unrelated “real-life” catheterization patients (5.2%). Conclusion: To our knowledge, our data show for the first time that ectatic coronary artery disease is a common appearance of BAV disease with and without ascending aortic aneurysm.
Proteasome regulation of ERBB2 chaperone association, intracellular trafficking and overexpressed membrane receptor levels
Authors: Corina Marx, Surita Banwait, Christopher Benz
Journal: Cancer Research (2007)

3761   To better understand ERBB2 receptor mechanisms subject to therapeutic modulation, we investigated the proteasome dependence of ERBB2 receptor chaperone formation, trafficking, perinuclear accumulation and intracellular degradation using two  ERBB2  amplified and overexpressing human breast cancer cell lines, SKBR3 and BT474. Following culture treatment with a 20S proteasome-inhibiting dose of PS341/bortezomib (5-25 nM), these cancer cells demonstrate growth inhibition (SRB assay) and apoptosis induction (p85 PARP formation) along with marked loss of phospho-ERBB2 and total ERBB2 protein levels by 48-72 h. Within the first 24 h of proteasome inhibition, treated cells show an early shift in the association of 185 kDa ERBB2 protein with molecular chaperones, from one that stabilizes (Hsp90) to one that targets the receptor for degradation (Hsp70). Altered chaperone binding occurs in conjunction with ERBB2 protein ubiquitination and before significant loss in receptor content; and both the altered chaperone binding and receptor ubiquitination are associated with relocalization of immunoreactive ERBB2 from the cell surface to a perinuclear compartment that co-localizes with an immunoreactive lysosomal protein, LAMP1. The bortezomib induced perinuclear relocalization of ERBB2 can be prevented by co-treatment of these cells with the protein synthesis inhibitor cycloheximide. As well, co-treatment with a non-toxic dose of the lysosomal processing inhibitor, chloroquine, prevents bortezomib induced ERBB2 decay in these ERBB2-positive cells. In summary, early effects following proteasome inhibition appear to include altered chaperone binding and the perinuclear sequestration of ubiquitinated ERBB2 that is newly synthesized or endocytosed, followed by lysosomal degradation of receptor protein and loss of the critical receptor signals needed for proliferation and survival of these ERBB2-positive cancer cells. Apart from shedding light on the increased cytotoxic sensitivity of ERBB2-positive cancer cells to proteasome inhibitors like bortezomib, these findings suggest that the proteasome system plays a critical role in maintaining intracellular trafficking, chaperone recruitment, and appropriate cell surface localization of ERBB2 receptors, at least in epithelial cells transformed by  ERBB2  amplification and overexpression.
Abstract 12460: Deletion of the Angiotensin II Type 1a Receptor Prevents Atherosclerotic Plaque Rupture
Authors: Jun Aono, Jun Suzuki, Akiyoshi Ogimoto, Hideki Okayama, Masaru Iwai, Masatsugu Horiuchi, Jitsuo Higaki
Journal: Circulation (2010)

Background: Atherosclerotic plaque rupture and subsequent thrombus formation can trigger acute coronary syndrome. Angiotensin II, a principal vasoactive substance of the renin-angiotensin system, i...
Abstract 18260: Local Interleukin-6 and Pericardial Drainage Volume are Associated with Atrial Fibrillation After Coronary Artery Bypass Grafting
Authors: Tao Wenyan, Wu Fangqin, Tang Hongyuan, Shen Dongyan, Zhang Haibyong, Zhao Haibo, Wu Ying
Journal: Circulation (2011)

Objective. To examine the relationship between IL-6, WBC, CRP levels and volume of pericardial drainage in patients with AF following CABG. Method. In 124 patients with sinus rhythm (SR) undergoing elective isolated CABG, IL-6, WBC count and CRP levels were measured in pericardial drainage and peripheral blood at six, 12, and 18 hours (hrs) postoperatively. The volume of pericardial drainage was also recorded at the same time interval. Two-factor ANOVA for repeated measures was used to test the trends of the above parameters and their relationship with postoperative AF (POAF). Results. AF occurred in 44 (35.5%) patients and IL-6 levels in pericardial drainage increased over time in this group (from 1353.9 pg/ml at six hours to 2189.2 pg/ml at 18 hrs), while it was peaked at 12 hrs and declined thereafter in the SR group (1541.5 pg/ml at six hours, 1906.3pg/ml at 12 hrs, and 1876.2 pg/ml at 18 hrs). Two-factor ANOVA for repeated measures showed that the change of mean IL-6 levels in drainage over time between the two groups was significantly different ( P = 0.016). The postoperative levels of IL-6 in peripheral blood declined slowly over 18 hours in both groups (from 71.61 pg/ml to 62.90 pg/ml and 85.56 pg/ml to 75.92 pg/ml, respectively). Interestingly, IL-6 levels in drainage were 28 and 22 times higher in drainage than those in blood in the AF and SR groups, while the difference of IL-6 levels in drainage and blood in the AF group was six times higher than in the SR group ( P = 0.014). Although the volume of drainage decreased over time in both groups, logistic regression showed that age adjusted total drainage of ≥ 430 ml during the first 18 hours post-op was an independent predictor of POAF (OR 3.91, 95%CI 1.55-10.27). CRP levels in the drainage of the AF and SR groups increased noticeably from 3.74 and 3.08 mg/L at six hours, to 16.76 and 15.45 mg/L at 18 hrs after surgery, and in blood from 9.95 and 9.82 mg/L to 41.70 and 41.36 mg/L, respectively. CRP levels in blood were higher than in drainage for both groups ( P &lt; 0.001). There was no association between the occurrence of POAF and CRP levels or WBC in either drainage, or blood. Conclusion. IL-6 may be produced locally after CABG, and the levels of IL-6 in, as well as the volumes of pericardial drainage were associated with POAF.
Abstract 4537: Relationship Between Procedure Indications and Outcomes of Carotid Artery Stenting: Preliminary Results from the CARE Registry
Authors: K A Rosenfield, C J White, P G Jones, J A Spertus, C U Cates, K K Ho, M R Jaff, W J Koroshetz, S P Caldwell, R G Brindis, H V Anderson
Journal: Circulation (2008)

Background: In 2007 a consortium of specialty societies developed and published a clinical expert consensus document (CECD) on carotid artery stenting (CAS). This CECD listed suggested indications for CAS based on the presence of symptoms, stenosis severity, and the presence of features that increase the surgical risk of carotid endarterectomy. The National Cardiovascular Data Registry, in conjunction with multiple specialty societies, established the CARE (Carotid Artery Revascularization and Endarterectomy) Registry to provide a comprehensive national database characterizing both forms of carotid revascularization. Methods: CARE employs written definitions, a data dictionary, standardized data collection tools, and quality control checks. We constructed an algorithm that categorized each procedure as conforming to a Recommended Indication (RECC) if it met the indications criteria in the CECD, or as not recommended (NOTRECC) if it didn’t. Patient characteristics and outcomes of these 2 groups were compared. Results: There were 3118 CAS procedures submitted from 107 participating centers for the period 01/2007 through 03/2008. Of these, 2397 (77%) were RECC, while 721 (23%) were NOTRECC. Clinical profiles in the NOTRECC group were more favorable, but overall outcomes were similar. (See Table ) Conclusions: CAS procedures categorized as NOTRECC by CECD criteria accounted for approximately one-fourth of submissions to the CARE Registry. Clinical profiles were different. Outcomes were similar.
Abstract 658: Lentiviral Blockade of the SDF-1/CXCR4 Pathway in Leukocytes Aggravates Atherosclerotic Lesion Development
Authors: Ilze Bot, Alma Zernecke, Theo J Van Berkel, Christian Weber, Erik A Biessen
Journal: Circulation (2006)

The chemokine SDF-1α and its receptor CXCR4 have been shown to be highly expressed in advanced atherosclerotic lesions. To delineate the effect of blockade of the SDF-1α/CXCR4 pathway in leukocytes...
腰痛与锻炼的随机对照试验：临床效果,费用和患者的？…
Authors: Moff., Jk, 陆少磊
Journal: BMJ (2000)

目的：评价在社会进行、旨在鼓励腰痛患者恢复正常活动的一项锻炼方法的有效性。设计：随机对照的渐进的锻炼方法与通常的初级保健治疗进行比较。分组时先了解患者的选择倾向。参加者：１８７例患者，１８～６０岁，力学性腰痛持续４周～６个月。干预：锻炼课程由同一位理疗医师指导。内容包括所有肌群的力量锻炼、放松阶段和简单的背部保养方法。使用了认知－行为疗法。主要结果的评价指标：全面地评价了干预前后及干预后６个月、１
Abstract MP013: Strong Inverse Relation between Physical Activity and Incidence of Cardiovascular Disease in African Americans: the Atherosclerosis Risk in Communities Study
Authors: Elizabeth J Bell
Journal: Circulation (2012)

Introduction: Although there is substantial evidence that physical activity reduces risk of cardiovascular disease (CVD), the few studies that included African Americans offer inconclusive evidence and did not study stroke and heart failure separately. Objective: We examined, in African Americans and Caucasians in the Atherosclerosis Risk in Communities study (ARIC), the association of physical activity with CVD incidence (n=1,039) and its major components - stroke (n=350), heart failure (n=633), and coronary heart disease (n=442) - over a follow-up period of 21 years. Methods: ARIC is a population-based biracial cohort study of 45– to 64-yr-old adults at the baseline visit in 1987–89. Physical activity was assessed using the modified Baecke physical activity questionnaire and categorized by the American Heart Association’s ideal CVD health guidelines: poor, intermediate, and ideal physical activity. An incident CVD event was defined as the first occurrence of 1) heart failure, 2) definite or probable stroke, or 3) coronary heart disease, defined as a definite or probable myocardial infarction or definite fatal coronary heart disease. Results: We included 3,707 African Americans and 10,018 Caucasians free of CVD at the baseline visit. After adjustment for age, sex, cigarette smoking, alcohol intake, hormone therapy use, education, and ‘Western’ and ‘Prudent’ dietary pattern scores, higher physical activity was inversely related to CVD, heart failure, and coronary heart disease incidence in African Americans and Caucasians (p-values for trend tests &lt;.0001), and with stroke in African Americans. Hazard ratios (95% confidence intervals) for CVD for intermediate and ideal physical activity, respectively, compared to poor, were similar by race: 0.65 (0.56, 0.75) and 0.59 (0.49, 0.71) for African Americans, and 0.74 (0.66, 0.83) and 0.67 (0.59, 0.75) for Caucasians (p-value for interaction = 0.38). Physical activity was also associated similarly in African Americans and Caucasians for each of the individual CVD outcomes (coronary heart disease, heart failure, and stroke), with an approximate one-third reduction in risk for intermediate and ideal physical activity versus poor physical activity- this reduction was statistically significant. Conclusions: In conclusion, our findings reinforce public health recommendations that regular physical activity is important for CVD risk reduction, including reductions in stroke and heart failure. They provide strong new evidence that this risk reduction applies to African Americans as well as Caucasians and support the idea that some physical activity is better than none.
Integrative Protein-Based Prognostic Model for Early-Stage Endometrioid Endometrial Cancer
Authors: Ji-Yeon Yang, Henrica M.J. Werner, Jie Li, Shannon N. Westin, Yiling Lu, Mari K. Halle, Jone Trovik, Helga B. Salvesen, Gordon B. Mills, Han Liang
Journal: Clinical Cancer Research (2015)

Endometrioid endometrial carcinoma (EEC) is the major histologic type of endometrial cancer, the most prevalent gynecologic malignancy in the United States. EEC recurrence or metastasis is associated with a poor prognosis. Early-stage EEC is generally curable, but a subset has high risk of recurrence or metastasis. Prognosis estimation for early-stage EEC mainly relies on clinicopathologic characteristics, but is unreliable. We aimed to identify patients with high-risk early-stage EEC who are most likely to benefit from more extensive surgery and adjuvant therapy by building a prognostic model that integrates clinical variables and protein markers.We used two large, independent early-stage EEC datasets as training (n = 183) and validation cohorts (n = 333), and generated the levels of 186 proteins and phosphoproteins using reverse-phase protein arrays. By applying an initial filtering and the elastic net to the training samples, we developed a prognostic model for overall survival containing two clinical variables and 18 protein markers and optimized the risk group classification.The Kaplan-Meier survival analyses in the validation cohort confirmed an improved discriminating power of our prognostic model for patients with early-stage EEC over key clinical variables (log-rank test, P = 0.565 for disease stage, 0.567 for tumor grade, and 1.3 × 10(-4) for the integrative model). Compared with clinical variables (stage, grade, and patient age), only the risk groups defined by the integrative model were consistently significant in both univariate and multivariate analyses across both cohorts.Our prognostic model is potentially of high clinical value for stratifying patients with early-stage EEC and improving their treatment strategies.
Three-Dimensional Speckle-Tracking Longitudinal-Strain Predicts Improvement of Left Ventricular Function After Acute Myocardial Infarction
Authors: E. Abate, G.E. Hoogslag, M.L. Antoni, G. Nucifora, V. Delgado, S.H. Ewe, D.P. Leong, M.J. Schalij, J.J. Bax, N.A. Marsan
Journal: Circulation (2011)
Integrated medicine
Authors: L. Rees
Journal: BMJ (2001)

Integrated medicine (or integrative medicine as it is referred to in the United States) is practising medicine in a way that selectively incorporates elements of complementary and alternative medicine into comprehensive treatment plans alongside solidly orthodox methods of diagnosis and treatment. The concept is better recognised in the US than in the United Kingdom, but a conference in London next week, organised by the Royal College of Physicians and the US National Center for Complementary and Alternative Medicine, may help to raise its profile in the UK.

Integrated medicine is not simply a synonym for complementary medicine. Complementary medicine refers to treatments that may be used as adjuncts to conventional treatment and are not usually taught in medical schools. Integrated medicine has a larger meaning and mission, its focus being on health and healing rather than disease and treatment. It views patients as whole people with minds and spirits as well as bodies and includes these dimensions into diagnosis and treatment. It also involves patients and doctors working to maintain health by paying attention to lifestyle factors such as diet, exercise, quality of rest …
Phase I/II study of arsenic trioxide (ATO) in combination with cytosine arabinoside (ARA-C) in patients with myelodysplastic syndromes (MDS)
Authors: W. M. Batista, L. Hineman, L. Seneviratne, B. Bagdasarian, J. K. Wada, D. Aboulafia, T. Malpass, C. H. Gota
Journal: Journal of Clinical Oncology (2006)

16525 Background: MDS is a group of myeloid disorders characterized by ineffective erythropoeisis with peripheral pancytopenia. We studied the efficacy and safety of ATO with/without ARA-C. Methods: We enrolled 10 patients with biopsy proven MDS per original FAB classification. See table for treatment design. Response was as follows: for CR the blast count in the BM should be &lt;5% with normal maturation of all cell lines without evidence of dysplasia and PB values of Hemoglobin &gt;11 g/dL, Neutrophils ≥1500/mm 3 , Platelets ≥100,000/mm 3 lasting 2 months without transfusion support. PR was all of CR criteria except blasts decreased by &gt; 50% over pretreatment or a less advanced MDS FAB classification than pretreatment. SD was failure to achieve at least a PR but without evidence of progression for at least 2 months. Results: 3 of 10 patients completed the study. 7 did not complete due to: 1 death from unrelated causes, 1 death from PD, 2 subjects withdrew, 2 were withdrawn at physician’s discretion, 1 withdrawal from toxicity. Of the 3 patients who completed study, 2 had SD and 1 had PR. 1 SD patient is alive 2 years later with transfusion support and another patient lasted 6 months before requiring transfusion. PR patient succumbed to acute myelogenous leukemia 12 months post-treatment. Conclusions: ATO with ARA-C appears to be an active regimen for patients with high risk MDS. Additional studies are warranted to confirm these findings. [Table: see text] [Table: see text]
Abstract 14567: Caveolin-1 Deficiency Exacerbates Cardiac Dysfunction and Reduces Survival in Mice with Myocardial Infarction
Authors: Jean-Francois Jasmin, Giuseppe Rengo, Anastasios Lymperopoulos, Ratika Gupta, Gregory J Eaton, Kevin Quann, Donna M Gonzales, Isabelle Mercier, Walter J Koch, Michael P Lisanti
Journal: Circulation (2010)

Background: Caveolin-1 (Cav-1), the principal protein of caveolar domains, has previously been involved in the pathogenesis of ischemic injuries. For instance, modulations of endogenous Cav-1 expression have been reported in animal models of ischemic acute renal failure, myocardial infarction and cerebral ischemia/reperfusion. Furthermore, ablation of the Cav-1 gene in mice was shown to increase the extent of ischemic injury in models of cerebral and hindlimb ischemia. Cav-1 was also recently suggested to be involved in myocardial ischemic preconditioning. However, the role of Cav-1 in myocardial ischemia (MI)-induced cardiac dysfunction still remains to be determined. Methods: Eight week-old wild-type (WT) and Cav-1 knockout (KO) FVB/N male mice were subjected to either sham surgery or permanent left anterior descending (LAD) coronary artery ligation for 24 hours. The progression of myocardial ischemic injury was monitored by transthoracic echocardiography, hemodynamic measurements, 2,3,5-triphenyltetraz...
Administration of a Tryptophan Metabolite, Indole-3-Carboxaldehyde, Reduces Graft Versus Host Disease Morbidity and Mortality and Enhances Gastrointestinal Barrier Function in a Murine Model of Allogeneic Bone Marrow Transplantation
Authors: Edmund K. Waller, Cynthia R. Giver, Sravanti Rangaraju, Alyson Swimm, Akshay Sharma, Muna Qayed, Zachariah Defilipp, Daniel Kalman
Journal: Blood (2014)
Abstract 9306: Site-Specific Reporter Gene Imaging of Stem Cell Transplantation: Early Engraftment Predicts Late Improvement in Cardiac Function
Authors: Kazim H Narsinh, Feng Lan, Junwei Liu, Robert C Robbins, Joseph C Wu
Journal: Circulation (2011)

Stable genetic modification of cardiac progenitor cells (CPCs) enables quantitative assessment of their engraftment and proliferation using reporter gene imaging. However, random lentiviral integration techniques carry the concomitant risk of introducing inadvertent mutations, including the unacceptable risk of proto-oncogene activation. Here, we demonstrate a safe, clinically applicable method for site-specific PET reporter gene imaging of transplanted CPCs. A triple fusion reporter gene was integrated specifically into chromosome 19 of Sca-1+ human CPCs using the ΦC31 integrase. Targeted integration into this genomic locus was confirmed using nested PCR and Southern blotting. Stably-integrated CPCs (1×10 6 ) were then transplanted into ischemic murine myocardium (n=40), and monitored noninvasively using PET, bioluminescence, cardiac MR, and echocardiography for four weeks. hCPC-treated hearts demonstrated a statistically significant improvement in fractional shortening (27.2±2.3% vs. 21.5±1.4%; P=0.04) as well as ejection fraction (48.3±2.6% vs. 42.2±1.7%; P=0.03) at day 14 post-transplant compared to PBS controls, as assessed by echocardiography and cardiac MRI, respectively. Initial PET signal intensity, as a surrogate marker of cellular engraftment, predicted the degree of functional improvement at week 2 (R 2 =0.73) in a “dose-effect” relationship. To investigate the mechanism of hCPC benefit on myocardial function, we isolated the transplanted cells from recipient myocardium by laser capture microdissection and found direct evidence for upregulated expression of the VEGF-α and CTGF pro-angiogenic growth factors in vivo. Here, we demonstrate the first use of site-specific reporter gene imaging to enable prognostic prediction of the ultimate success of CPC therapy. Given the encouraging but variable results of recent cell therapy trials, our results provide valuable insight into the determinants of successful cell therapy.
Abstract 15847: Krüppel-Like Factor 6 (KLF6) Regulates Obesity and Glucose Intolerance
Authors: Junichi Ishida, Toru Suzuki, Kenichi Aizawa, Daigo Sawaki, Takayoshi Matsumura, Scott L Friedman, Ryozo Nagai
Journal: Circulation (2011)

Introduction: Obesity and diabetes mellitus are regarded as major risk factors for cardiovascular disease. Kruppel-like zinc-finger transcription factors (KLFs) are important regulators of develop...