tbuckley/cabot-search huggingface dataset:
Vascular Smooth Muscle Cell–Directed Overexpression of Heme Oxygenase-1 Elevates Blood Pressure Through Attenuation of Nitric Oxide–Induced Vasodilation in Mice
Authors: TomihikoImai, ToshisukeMorita, TakayukiShindo, RyozoNagai, YoshioYazaki, HirokiKurihara, MakotoSuematsu, ShigehiroKatayama
Journal: Circulation Research (2001)

Abstract—To elucidate pathophysiological roles of heme oxygenase (HO)-1 in regulation of vascular tone in vivo, we have developed and characterized transgenic (Tg) mice that overexpress HO-1 site specifically in vascular smooth muscle cells (VSMCs). The Tg mice were generated by use of human HO-1 cDNA under the control of SM22-α promoter. The HO-1 gene overexpression was demonstrated by Northern blot analysis and coincided with increases in the protein expression in VSMCs and total HO activities. Tg mice exhibited a significant increase in arterial pressure at various ages and displayed impaired nitrovasodilatory responses in isolated aortic segments versus nontransgenic littermates while enhancing their nitric oxide (NO) production. The pressure of Tg mice was unchanged by systemic administration of either Nω-nitro-l-arginine or SNP. Furthermore, the isolated aorta in these mice exhibited lesser extents of NO-elicited cGMP elevation via soluble guanylate cyclase (sGC), while exhibiting no notable downreg...
Hybrid endoscopic submucosal dissection using a full-thickness resection device allows en bloc resection of a large adenoma deeply invading the appendix
Authors: Alexandru Lupu, Jérémie Jacques, Jérôme Rivory, Jean-Christophe Saurin, Florian Rostain, Thierry Ponchon, Mathieu Pioche
Journal: Endoscopy (2018)

Endoscopic full-thickness resection using a full-thickness resection device (FTRD) (Ovesco; Tübingen, Germany) was introduced in 2014 and is mainly used for small colonic laterally spreading tumors (LSTs) with important fibrotic component, non-lifting after submucosal injection, or superficial recurrent lesions located at or near a surgical anastomosis. It has an 81 % R0 resection rate for lesions ≤ 2 cm, with a 10 % rate of adverse events [1] [2]. The main limitations are large tumor size and proximal colonic lesions, as the FTRD cap is 23 mm in length, which sometimes makes cecal intubation difficult. The most important risks are bleeding, trapping of pericolonic organs when sucking the lesions into the cap, and luminal stenosis due to the clip [3].
Abstract 9825: Cardiac Strain in a Swine Model of Regional Hibernating Myocardium: Effects of Bypass Surgery on Contractile Reserve
Authors: Rosemary F Kelly, Laura Hocum Stone, Christopher T Holley, Corey Swingen, Melanie Crampton, Herbert B Ward, Edward O McFalls
Journal: Circulation (2015)

Background: Clinical studies have suggested that functional recovery of hibernating myocardium may be delayed following coronary artery bypass graft (CABG) surgery. We have shown in a swine model of hibernating myocardium, that recovery of regional function and oxygen consumption during an infusion of high dose catecholamine is sub-maximal at 4-weeks following CABG. Using the same swine model of hibernating hearts along with MRI estimates of circumferential strain (ECC), we tested whether contractile reserve within hibernating myocardial regions during a low dose infusion of dobutamine improves post-CABG. Methods. Ten pigs underwent thoracotomy with placement of a constrictor around the LAD artery. At 12 weeks, MRI imaging was performed prior to CABG and repeated 4-weeks following off-pump revascularization with a left internal mammary artery graft to the LAD artery. MRI studies were performed at baseline and during an infusion of low dose dobutamine (5 μg/kg/min). Results: MRI studies prior to CABG showed that circumferential strain in the Hibernating (LAD) Region was lower than the Remote Region at rest (-14.5±0.7 versus -15.1±0.7 respectively; P&lt;0.05) and did not improve during dobutamine (-14.7±0.8 versus -16.7±0.8 respectively; P&lt;0.05). Following CABG, strain measurements in the hibernating LAD region remained lower than remote regions at rest, but improved during the same dose of dobutamine (Figure). Summary: Baseline function in hibernating myocardium does not fully recover at 4 weeks post-CABG but contractile reserve during an infusion of low dose dobutamine does improve compared with estimates of strain obtained prior to surgery. Future studies should address the time course of recovery of regional function post-CABG and test whether additional interventions might facilitate earlier recovery of contractile reserve.
Endothelial Progenitor Cells
Authors: CarmenUrbich, StefanieDimmeler
Journal: Circulation Research (2004)

Infusion of different hematopoietic stem cell populations and ex vivo expanded endothelial progenitor cells augments neovascularization of tissue after ischemia and contributes to reendothelialization after endothelial injury, thereby, providing a novel therapeutic option. However, controversy exists with respect to the identification and the origin of endothelial progenitor cells. Overall, there is consensus that endothelial progenitor cells can derive from the bone marrow and that CD133/VEGFR2 cells represent a population with endothelial progenitor capacity. However, increasing evidence suggests that there are additional bone marrow-derived cell populations (eg, myeloid cells, “side population” cells, and mesenchymal cells) and non-bone marrow-derived cells, which also can give rise to endothelial cells. The characterization of the different progenitor cell populations and their functional properties are discussed. Mobilization and endothelial progenitor cell-mediated neovascularization is critically r...
Physiological Roles of the Permeability Transition Pore
Authors: CatherineBrenner, MarylineMoulin
Journal: Circulation Research (2012)

Mitochondria are implicated in many important cellular functions covering the whole life cycle from mitochondrial biogenesis to cell death. Mitochondrial homeostasis is tightly regulated, and mitochondrial dysfunction is frequently associated with severe human pathologies (eg, cardiovascular diseases, cancer, and neurodegeneration). The permeability transition pore (PTP) is an unselective voltage-dependent mitochondrial channel. Despite the extensive use of electrophysiology, biochemistry, pharmacology, and genetic invalidation in mice, the molecular identity of PTP is still unknown. Nevertheless, PTP is central to mitochondrial vital functions and can play a lethal role in many pathophysiological conditions. This review recapitulates the current knowledge of the various modes of conductance of the PTP channel and discusses their implication in the physiological roles of PTP and their regulation. Based on its involvement in normal physiology and human pathology, a better understanding of this channel and ...
Hyperinsulinemia Predicts Coronary Heart Disease Risk in Healthy Middle-aged Men
Authors: MarjaPyörälä, HeikkiMiettinen, MarkkuLaakso, KaleviPyörälä
Journal: Circulation (1998)

Background—The Helsinki Policemen Study is one of the first prospective epidemiological studies demonstrating an association of hyperinsulinemia to the risk of coronary heart disease (CHD). The aim of the present study was to investigate the predictive value of hyperinsulinemia with regard to CHD risk during a 22-year follow-up of the Helsinki Policemen Study population. Methods and Results—The study was based on a cohort of 970 men who were 34 to 64 years of age and free of CHD, other cardiovascular disease, and diabetes. Risk factor measurements at baseline examination included an oral glucose tolerance test (OGTT) with blood glucose and plasma insulin measurements at 0, 1, and 2 hours. Area under the plasma insulin response curve (AUC insulin) during OGTT was used as a composite variable reflecting plasma insulin levels. During the 22-year follow-up, 164 men had a major CHD event (CHD death or nonfatal myocardial infarction). Age-adjusted hazard ratios for a major CHD event comparing men in the highest...
Abstract 12003: Bioprosthetic Valves Have a Higher Longevity in Blood Group a Recipients
Authors: Olivier Schussler, Nermine Lila, Thomas V Pernerger, Parmeseeven Mootoosamy, Marc Ruel, Anne François, Afksendiyos Kalangos, Alain Carpentier
Journal: Circulation (2014)

BACKGROUND: Pigs share with humans some of the antigens present on cardiac valves. Two such antigens are the major xenogenic Ag, “αGal” which mimics the human B antigen of ABO blood group system an...
Abstract CT039: Cyclin E1 (<i>CCNE1)</i> expression associates with benefit from palbociclib in metastatic breast cancer (MBC) in the PALOMA3 trial
Authors: Nicholas C. Turner, Yuan Liu, Zhou Zhu, Sherene Loi, Marco Colleoni, Sibylle Loibl, Angela DeMichele, Nadia Harbeck, Fabrice André, Zhe Zhang, Carla Giorgetti, Cynthia Huang Bartlett, Massimo Cristofanilli
Journal: Cancer Research (2018)

Abstract BACKGROUND: The CDK4/6 inhibitor palbociclib in combination with fulvestrant (F) improved progression-free survival (PFS) vs F alone in previously-treated MBC. Prior pre-clinical research, and the NeoPalAna window study, identified high CCNE1 expression as a potential palbociclib resistance marker. We conducted large panel gene expression analysis of baseline tumor tissue to identify biomarkers (BMs) that predicted the relative benefit of palbociclib. METHODS: The PALOMA3 trial randomized 521 patients (pts) with endocrine-pretreated MBC to receive palbociclib + F or placebo (PBO) + F. All pts, except bone only or early relapse, provided FFPE tissue taken from recurrent disease. EdgeSeq Oncology BM Panel (HTG Molecular Diagnostics) was used for mRNA profiling, assessing 2534 cancer related genes. Primary objective was to evaluate the association of cell cycle pathway with palbociclib + F vs F alone treatment effect by using gene expression as a continuous variable or dichotomization by median level with Cox regression analysis. RESULTS: 302 pts had tumor tissue analyzed (194/347 [56%] palbociclib + F; 108/174 [62%] PBO+F). The BM and overall populations had similar treatment effect. Benefit from palbociclib was greater in patients with low tumor CCNE1 expression (median PFS: palbociclib + F 14.1 mo vs PBO+F 4.8 mo, HR 0.32) than high tumor CCNE1 expression (palbociclib + F 7.6 mo vs PBO+F 4.0 mo; HR 0.85) (interaction p=0.0024). Similar results were observed with CCNE1 as a continuous variable (interaction p=0.0008). Expression levels of CDK4, CDK6, cyclin D1 and RB1 did not associate with benefit from palbociclib, and both luminal A and B tumors derived benefit from palbociclib. In exploratory analysis, high E2F-regulon expression predicted for relative resistance to palbociclib. CONCLUSION: Higher expression of CCNE1 was associated with relative resistance to palbociclib, although all biomarker groups derived benefit from treatment. This data supports CDK2 as the key bypass kinase of CDK4/6 inhibition, and potential to target CDK2 to subvert resistance. Sponsor: Pfizer Citation Format: Nicholas C. Turner, Yuan Liu, Zhou Zhu, Sherene Loi, Marco Colleoni, Sibylle Loibl, Angela DeMichele, Nadia Harbeck, Fabrice André, Zhe Zhang, Carla Giorgetti, Cynthia Huang Bartlett, Massimo Cristofanilli. Cyclin E1 (CCNE1) expression associates with benefit from palbociclib in metastatic breast cancer (MBC) in the PALOMA3 trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT039.
Abstract 12683: Combined Assessment of High-Sensitive Troponin I and N-Terminal Pro-B-Type Natriuretic Peptide Levels Improves the Prediction of Future Admission for Heart Failure in Outpatients With Chronic Kidney Disease
Authors: JunnichiIshii, HiroshiTakahashi, MidoriHasegawa, RyuunosukeOkuyama, HidekiKawai, TakashiMuramatsu, HiroyukiNaruse, SadakoMotoyama, ShigeruMatsui, HideoIzawa, YukioYuzawa, YukioOzaki
Journal: Circulation (2014)

Background: Heart failure (HF) is a common consequence of chronic kidney disease (CKD), and it portends high risk for mortality. We prospectively investigated the predictive value of a combination of high-sensitive troponin I (hsTnI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) for HF admission in outpatients with CKD. Methods: Baseline hsTnI and NT-proBNP levels were measured in 451 stable outpatients with CKD (estimated GFR < 60 mL/min/1.73 m2) on not dialysis (mean age, 69.7 years). Using echocardiography with tissue Doppler imaging, left ventricular ejection fraction (EF) and E/e’ ratio were estimated. Among these patients, 41% had a history of cardiovascular disease, and 48% had a history of diabetes. Results: During a mean follow-up period of 924 days, there were 70 HF admissions. Patients who admitted for HF had higher hsTnI levels (22.4 vs. 10.5 pg/mL, p < 0.0001), NT-proBNP levels (1726 vs. 310 pg/mL, p < 0.0001), and E/e’ ratio (15.3 vs. 10.3, p < 0.0001), and displayed lower values...
Abstract 5131: Obese conditions induce changes in stromal fibroblast phenotype
Authors: Brittany Harlow, Albert Davalos, Andrew Brenner, Christopher Jolly, Stephen Hursting, Linda deGraffenried
Journal: Cancer Research (2018)

Abstract Background: Over 40% of American women present a BMI ≥30, which is particularly alarming since obesity confers a worse prognosis for both pre- and postmenopausal breast cancer patients. Although the molecular mechanisms behind this remain unclear, obese conditions have been shown to upregulate certain components of the cancer-associated fibroblast (CAF) secretome and senescence associated secretory phenotype (SASP), both directly correlated with tumorigenesis. However, studies have yet to determine whether obesity induces a cohesive SASP or CAF-like phenotype from any one cell type of the breast tumor microenvironment. Because fibroblasts represent the most common breast tumor cell type, it is of particular importance to investigate obesity-induced changes in this cellular compartment and their effects on cancer cell behavior. Methods: Direct effects of obesity were examined by exposing IMR-90 and HCA2 human fibroblasts to media supplemented with 2% sera from obese women and measuring changes in gene and protein expression, while indirect effects were evaluated by exposing the fibroblasts to conditioned media (CM) from obesity-stimulated MCF-7 and T47D cells and assessing changes in expression of proinflammatory cytokines. Breast cancer cells were also exposed to CM from obesity-stimulated fibroblasts and measured for changes in proliferation, survival, motility, and invasion. Results and Conclusions: Obese conditions induced proinflammatory changes in fibroblasts both directly and indirectly and stimulated changes in the paracrine signaling between fibroblasts and breast cancer cells. These data contribute to the growing evidence implicating obesity in the promotion of breast cancer progression. Additionally, these findings provide a new line of research to develop potential therapeutic targets to improve outcome. Citation Format: Brittany Harlow, Albert Davalos, Andrew Brenner, Christopher Jolly, Stephen Hursting, Linda deGraffenried. Obese conditions induce changes in stromal fibroblast phenotype [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5131.
Abstract 10450: Prognostic Effect of Estimated Glomerular Filtration Rate in Patients With Cardiac Arrest Undergoing Extracorporeal Cardiopulmonary Resuscitation
Authors: Norihiro Kuroki, Daisuke Abe, Tooru Iwama, Kazuya Tateishi, Masakazu Kaneko, Tomohiko Harunari, Yoshiaki Yui, Takao Yuba, Kazuhiro Sugiyama, Akiko Akashi, Yuichi Hamabe, Akira Sato
Journal: Circulation (2015)

Introduction: Extracorporeal membrane oxygenation (ECMO) can provide immediate and adequate systemic circulation and oxygenation in patients with refractory cardiac arrest. Even mild renal dysfunction has been identified as an independent cardiovascular risk factor. We hypothesized that renal dysfunction influences resuscitation outcomes. The aim of this study was to elucidate the association between initial renal function just before implantation and clinical outcome in patients undergoing extracorporeal cardiopulmonary resuscitation (ECPR). Methods: A cohort of 298 patients who underwent ECMO at our hospital was registered from January 2005 to April 2015. After excluding 70 patients with non-cardiac arrest, we analyzed the clinical outcome which was defined as all-cause death at 30 days of the remaining 228 patients (58.4±14.8 years old, 81% male, 196 with cardiogenic events, 32 with non-cardiogenic events). The patients were divided into 2 groups according to initial estimated-glomerular filtration rate (eGFR). Non-CKD Group: eGFR ≥60ml/min/1.73m2 (n=70); CKD Group: eGFR &lt;60 (n=158). Results: The rate of out-of-hospital cardiac arrest was 40%. In baseline characteristics, Non-CKD group was significantly younger (52.7 vs. 61.3 years old), lower incidence of hypertension (28 vs.52 %) and known coronary artery disease (6 vs 21%) in past history and lower BUN (14.5 vs. 26.2 mg/dl, all p&lt;0.05) than CKD group. Incidence of all-cause death at 30 days was significantly lower in the non-CKD than CKD group (53 vs. 78%, p&lt;0.0001). CKD was an independent predictor of mortality after adjustment for multiple cofounders (OR: 4.49, 95% CI: 2.07-9.77, p&lt;0.001). Kaplan-Meier curve showed better outcome in the non-CKD versus CKD group (p&lt;0.01). Conclusions: Initial low e-GFR just before implantation provides worse clinical outcome in patients undergoing ECPR.
Abstract 21122: Contribution of <i>ABCA1</i> Genetic Variation to Plasma Lipid Levels in Non-Hispanic White Americans
Authors: Vipavee Niemsiri, Xingbin Wang, Zaheda H Radwan, Dilek Pirim, Indrani Halder, Steven E Reis, John E Hokanson, Richard F Hamman, M M Barmada, Eleanor Feingold, F Y Demirci, M I Kamboh
Journal: Circulation (2017)

Introduction: Dyslipidemia [i.e., elevated levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG); decreased level of high-density lipoprotein cholesterol (HDL-C)] is one of the risk factors for cardiovascular disease (CVD). Genetics play an important role in inter-individual variation of lipid levels. ATP-binding cassette A1 (ABCA1), a membrane transporter, mediates cellular phospholipid and cholesterol efflux. Mutations in ABCA1 gene cause Tangier’s disease (OMIM #205400) presented with HDL-C deficiency, as well as, increased risk for developing CVD. In this study, we aimed to identify both common [minor allele frequency (MAF)≥5%] and uncommon (MAF&lt;5%) variants of ABCA1 associated with inter-individual variation in major lipid traits. Methods: We resequenced 50 exons and exon-intron boundaries of ABCA1 in a selected set of 95 individuals with extreme HDL-C levels (≤10 th and ≥90 th %tile), and subsequently genotyped selected variants in the entire sample of 623 US Non-Hispanic Whites. With resequencing, we identified 404 variants, and for genotyping we selected 250 variants (216 from sequencing data, 34 from HapMap-CEU data). A total of 182 successfully genotyped and QC-passed bi-allelic variants were tested for association with plasma lipid levels. Results: Gene-based test showed evidence of association between ABCA1 and TG ( p =0.0108). Single-site association analyses demonstrated 26 common variants nominally associated ( p &lt;0.05) with at least one lipid trait. After multiple testing correction, two variants [rs4743763 with TC levels, p =0.0005; rs2066716 (Thr1427Thr) with TG levels, p =0.0016] remained significant. Furthermore, rs2066716 (Thr1427Thr) was among 11 out of 26 lipid-associated ABCA1 variants for which the replication data were available in an independent sample ( n =744) and it remained significantly associated with TG levels in the meta-analysis (meta- p =0.0088). Rare variant analyses revealed association of multiple sets of rare variants with lipid traits. Conclusions: Our findings support the genetic contribution of ABCA1 , both common and rare variants, to lipid levels in humans.
An Accurate, Clinically Practical System For Spatial Vectorcardiography
Authors: Ernestfrank
Journal: Circulation (1956)

This paper describes a news improved system of spatial vectorcardiography that is practical for clinical use. It represents an optimum compromise among such factors as soundness of theoretic basis, accuracy, reproducibility, signal-to-noise ratio, and speed of application. Some of its advantages over currently employed systems include a rational physical basis, corrections for torso shape, avoidance of left arm, insensitivity to individual variability of ventricle location, and accuracy comparable to applicability of 3-dimensional torso-model data to the human subject. Detailed description of electrode placement, practical procedures, and useful technics is included.
Abstract 5169: Novel target molecules for treatment of cancer of unknown primary
Authors: Yoshihiko Fujita, Kazuko Sakai, Marco De Velasco, Takayasu Kurata, Hidetoshi Hayashi, Kazuhiko Nakagawa, Kazuto Nishio
Journal: Cancer Research (2018)

Abstract We have previously been involved in a multicenter clinical study to predict the primary site of cancer of unknown primary site (CUP) for a site-specific therapy. Based on the microarray analysis of gene expression pattern, we not only predicted the primary site for each CUP patient but also extracted 44 up-regulated genes common to each CUP showing over 2.5-fold change compared to normal tissue (lymph node). To identify genes related to CUP development among these candidate genes, we performed cell-based siRNA screening and estimated to what extend A549 cells reduce the ability of migration, and found 4 genes, GRN, MIF, PRKDC, PSMB4. Konckdown of each of these genes suppressed metastasis of implanted cells from a footpad to a popliteal lymph node. Inhibitors for PRKDC (NU 7441) and PSMB4 (bortezomib) also suppressed the metastasis of parental A549 cells in vivo, suggesting the involvement of these genes in metastasis. As there is no standard treatment for CUP, drugs targeting immune checkpoints, such as PD-1 or IDO, may reveal promising antitumor activity for CUP. Recent studies suggest that expression levels of PD-L1 (a PD-1's ligand) or IDO may be a biomarker of patient response to anti-PD-1 or anti-IDO therapy, respectively. We analyzed the expression of PD-L1 and IDO for the CUP tissues and found several patients with high expression of either or both proteins who may be most likely respond to these novel immunotherapies. Citation Format: Yoshihiko Fujita, Kazuko Sakai, Marco De Velasco, Takayasu Kurata, Hidetoshi Hayashi, Kazuhiko Nakagawa, Kazuto Nishio. Novel target molecules for treatment of cancer of unknown primary [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5169.