tbuckley/cabot-search huggingface dataset:
Abstract 15274: Post-stenting Changes in the Coronary Geometry and In-stent Restenosis in Angulated Coronary Lesions: Comparison Between Platinum Chromium and Cobalt Chromium Everolimus-eluting Stents
Authors: Toshiyuki Kimura, Nozomi Watanabe, Nehiro Kuriyama, Yoshisato Shibata
Journal: Circulation (2015)

Purpose: Geometric changes in the coronary arteries at the site of coronary stent implantation can lead wall shear stress reduction with decreased coronary flow, which affect the clinical outcome after coronary intervention. Newly developed Platinum Chromium (PtCr)-Everolimus-eluting stent (EES) is expected to improve vessel conformability and restore the natural shape of the vessel with its modified scaffold design, using the same durable polymer and antiproliferative drug as the Cobalt Chromium (CoCr)-EES. The aim of this study was to investigate the long-term effect of PtCr-EES implantation on in-stent restenosis in angulated coronary lesions, comparing with CoCr-EES. Methods: This retrospective study included 250 lesions with CoCr-EES implantation and 217 lesions with PtCr-EES implantation for de novo angulated lesions (&gt;45-degree by quantitative coronary angiography). The angle of the lesions was measured in diatole and systole, and cyclic changes in the coronary angle &gt;20 degree was defined as hinge-like motion. Long-term coronary in-stent restenosis was defined as &gt;50% angiographic stenosis in 8 month after the procedure. Results: Changes in maximum coronary angle at the site of stent implantation were significantly smaller in PtCr-EES group than in CoCr-EES group compared with original angle (20.65±15.42 vs. 26.25±18.36 degree, p &lt;0.01). There were no significant differences in the occurrence of significant in-stent restenosis between PtCr-EES and CoCr-EES (6.7% vs 10.1%, p=0.32). CoCr-EES tended to show more restenosis than PtCr-EES (12.9% vs. 0.0%, p=0.07) in extremely angulated lesions (&gt;100-degree). Interestingly, in the lesions with hinge-like motion, PtCr-EES group showed significantly higher rate of restenosis compared with CoCr-EES group (26.3% vs 7.7%, p= 0.04). Conclusions: In comparison with CoCr-EES, PtCr-EES tended to restore the original curvature of the coronary vessels, and this may lead less restenosis rate in extremely angulated lesions. However, PrCr-EES might have adverse effect on long-term result after coronary stenting in the lesion with hinge-like cyclic motion.
In Vivo Quantitative Tissue Characterization of Human Coronary Arterial Plaques by Use of Integrated Backscatter Intravascular Ultrasound and Comparison With Angioscopic Findings
Authors: MasanoriKawasaki, HisatoTakatsu, ToshiyukiNoda, KeijiSano, YokoIto, KenjiHayakawa, KunihikoTsuchiya, MasazumiArai, KazuhikoNishigaki, GenzouTakemura, ShinyaMinatoguchi, TakakoFujiwara, HisayoshiFujiwara
Journal: Circulation (2002)

Background— The purpose of the present study was to define whether integrated backscatter (IB) combined with conventional intravascular ultrasound (IVUS) makes tissue characterization of coronary arterial plaques possible. Methods and Results— IB-IVUS was performed in coronary arteries (total 18 segments) of 9 patients at autopsy, and the findings were compared with the histology. RF signals, which were digitized at 2 GHz in 8-bit resolution, were obtained with an IVUS system with a 40-MHz catheter. IB values of the RF signal from the region of interest (ROI) (100-μm depth, 1.4° per line) were calculated by use of a personal computer. IB values on the ROIs were divided into 5 categories, compared with each of the plaque histologies: category 1 (thrombus), −88 < IB ≤ −80; category 2 (intimal hyperplasia or lipid core), −73 < IB ≤ −63; category 3 (fibrous tissue), −63 < IB ≤ −55; category 4 (mixed lesions), −55 < IB ≤ −30; and category 5 (calcification), −30 < IB ≤ −23. On the basis of these categories, we ...
Sildenafil Prevents Change in RhoA Expression Induced by Chronic Hypoxia in Rat Pulmonary Artery
Authors: VincentSauzeau, MalvyneRolli-Derkinderen, StéphanieLehoux, GervaiseLoirand, PierrePacaud
Journal: Circulation Research (2003)

Exposure to chronic hypoxia (CH) induces a sustained pulmonary hypertension associated with structural and functional changes in the pulmonary arterial bed, including alterations of contractile properties. The small G-protein RhoA and its effector Rho kinase play a major role in the sustained rise in tension induced by vasoconstrictors. The aim of this study was to analyze the effect of CH on the RhoA/Rho kinase signaling pathway in the rat pulmonary artery. Maximal contraction of pulmonary artery rings to endothelin-1, noradrenaline, and the thromboxane A2 analog U46619 was markedly decreased in rats exposed to CH (10% O2, 2 weeks). This CH-induced decrease response to agonists was attributable to the abolition of RhoA-mediated Ca2+ sensitization of the contraction. Real-time reverse transcriptase–polymerase chain reaction and Western blot analysis revealed a decrease in RhoA mRNA (79.4±6.0%, n=4) and RhoA (81.1±8.0%, n=4) expression in the main pulmonary artery from CH rats, whereas RhoA expression was ...
Abstract 2301: Dual targeting of CDK4/6 and MET in metastatic uveal melanoma
Authors: Masahiro Ohara, Kengo Saito, Ken Kageyama, Mizue Terai, Hanyin Cheng, Andrew E. Aplin, Takami Sato
Journal: Cancer Research (2018)

Abstract Uveal melanoma (UM) is the most common cancer of the eye in adults. Up to 50% of UM patients subsequently develop metastases, especially in the liver, for which no effective treatment has been identified. It has been reported that the retinoblastoma (RB) pathway is deregulated in more than 90% of UM despite the rarity of mutations in the RB1 gene itself. Cyclin D1 over-expression and inactivation of p16INK4a in UM are frequently present and make the RB protein constitutively hyperphosphorylated and functionally inactivated; therefore, CDK4/6 inhibition (CDK4/6i) is a rational strategy for treatment of UM. In this report, we investigated the antiproliferative activity of a selective CDK4/6 inhibitor on metastatic UM. A CDK4/6 inhibitor induced G0-G1 arrest in all three metastatic UM cell lines and suppressed their growth in in vitro and in vivo experiments. Interestingly, hepatocyte growth factor (HGF) decreased the effect of CDK4/6 inhibitor on metastatic UM cell lines and protected the metastatic UM cells from CDK4/6 inhibitor-induced cellular senescence. When CDK4/6i was combined with MET inhibitor, enhanced growth suppression was observed in metastatic UM tumors grown in human-HGF knock-in xenograft mouse models. HGF is enriched in the liver and the majority of liver metastases from UM express activated forms of MET; therefore, signaling through MET could contribute to the resistance mechanisms against CDK4/6i, especially in UM patients with hepatic metastasis. Together, these results provide a rationale for the use of MET inhibitor in combination with a CDK4/6 inhibitor for the treatment of metastatic UM. Citation Format: Masahiro Ohara, Kengo Saito, Ken Kageyama, Mizue Terai, Hanyin Cheng, Andrew E. Aplin, Takami Sato. Dual targeting of CDK4/6 and MET in metastatic uveal melanoma [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 2301.
Abstract 969: Tunneling nanotubes, a novel mode of tumor cell-macrophage communication in tumor cell invasion
Authors: Samer Hanna, Kessler McCoy-Simandle, Edison Leung, John Condeelis, Dianne Cox
Journal: Cancer Research (2018)

Abstract The interaction between tumor cells and macrophages is crucial in promoting tumor invasion and metastasis. These two cell types are engaged in a mutual interaction in which tumor-associated macrophages produce epidermal growth factor (EGF) to activate tumor cells. In turn, tumor cells produce colony-stimulating factor-1 (CSF-1) that stimulates macrophages. The tumor cell - macrophage pairs formed in response to this paracrine signaling are then attracted toward blood vessels under an endothelial cell produced HGF gradient. This mutual signaling interaction leads to the co-migration and invasion of both cell types as imaged both in vitro and in vivo. . Recent studies have revealed an additional novel mechanism of intercellular communication between macrophages that can transmit signals over long distances through membranous actin-based tunneling nanotubes (TNTs). Our data demonstrates that heterotypic TNTs form between macrophages and tumor cells in co-culture. This novel interaction induced changes in tumor cell morphology consistent with a more invasive phenotype which was dependent on EGF-EGFR signaling. Moreover, the presence of these heterotypic TNTs was important for tumor cell invasion in an in vitro 3D invasion assay. Furthermore, reduction of M-Sec (TNFAIP2) in macrophages, a protein involved in TNT formation, inhibited tumor cell elongation and blocked the ability of tumor cells to invade. Using a modified 1D assay that mimics macrophage-dependent tumor cell streaming observed in vivo, we show a significant increase in long distance directional migration of tumor cells towards an endothelial-coated bead in a TNT dependent manner. We also employed an in vivo zebrafish model that recreates macrophage mediated tumor cell invasion in a more physiological fashion. The presence of macrophages increased tumor spread from the injection site, number of metastatic foci, and the distance of metastatic spread in a macrophage TNT-dependent manner. Overall, our studies support a role for TNTs as a novel means of interaction between tumor cells and macrophages that may lead to tumor progression and metastasis. Citation Format: Samer Hanna, Kessler McCoy-Simandle, Edison Leung, John Condeelis, Dianne Cox. Tunneling nanotubes, a novel mode of tumor cell-macrophage communication in tumor cell invasion [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 969.
C-Reactive Protein Is an Independent Predictor of the Rate of Increase in Early Carotid Atherosclerosis
Authors: HiroyukiHashimoto, KazuoKitagawa, HidetakaHougaku, YoshiomiShimizu, ManabuSakaguchi, YojiNagai, ShigeruIyama, HachiroYamanishi, MasayasuMatsumoto, MasatsuguHori
Journal: Circulation (2001)

Background—An elevated plasma concentration of high-sensitivity C-reactive protein (hs-CRP) is a strong predictor of cardiovascular events. However, there have been no longitudinal studies of the relations between development of atherosclerotic lesions and hs-CRP concentrations. Furthermore, it remains unknown whether increased hs-CRP concentrations result in the development of atherosclerosis. Methods and Results—The study included 179 outpatients 40 to 79 years of age who were treated at our institute for traditional risk factors for cardiovascular disease. The patients had no evidence of advanced carotid atherosclerosis at the time of baseline examination. Patients underwent repeated ultrasonographic evaluation of the carotid arteries for 35±10 months. Blood samples were collected for hs-CRP measurements. Based on focal intima-media thickening ≥1.1 mm representing plaque, plaque number (PN) and plaque score (PS; the sum of all plaque thicknesses) were calculated. The development of atherosclerosis was ...
Abstract 17832: Model for Predicting Amputation and Death in Patients With Critical Limb Ischemia Following Endovascular Treatment
Authors: Robert K Rogers, Kevin Josey, Diana Brostow, David Magid, Anna E Barón, Thomas F Rehring, Omid Jazaeri, Rajan Gupta, Schuyler Jones, Manesh Patel, Alan S Go, Robert W Chang, Bradley Hill, Michael Ho, Thomas Tsai
Journal: Circulation (2016)

Introduction: Patients with critical limb ischemia (CLI) are at high risk for amputation and death. However, there is sparse data on predictors of amputation and death among CLI patients who have u...
Abstract 21191: Low Diastolic Blood Pressure (DBP) and Outcomes in Patients With Heart Failure and Preserved Ejection Fraction (HFpEF) and Hypertension (HTN): Findings From Medicare-Linked OPTIMIZE-HF Registry
Authors: Phillip H Lam, Daniel J Dooley, Gregg C Fonarow, Ali Ahmed
Journal: Circulation (2017)

Background: According to the 2017 update of the 2013 ACCF/AHA HF guideline, systolic BP (SBP) should be lowered to &lt;130 mmHg in euvolemic patients (pts) with HFpEF and persistent HTN. However, little is known about the role of low DBP on outcomes in these patients. Methods: Of the 10482 hospitalized pts with decompensated HFpEF (EF &gt;40%) discharged alive, 5514 had HTN, defined as SBP ≥140 or DBP ≥90 mmHg on both admission and discharge, or if BP was normal (SBP &lt;140 and DBP &lt;90 mmHg), by use of anti-HTN drugs (CCBs, hydralazine, or both ACEI/ARBs and beta-blockers) both on admission and discharge. To minimize confounding by low SBP, we excluded 1810 pts with discharge SBP &lt;130 mmHg. Of the remaining 3704 pts, 1571 had a discharge DBP &lt;70 mmHg. Propensity scores for DBP &lt;70 mmHg, estimated for each of the 3704 pts, were used to assemble a cohort of 1238 pairs of pts, with a discharge DBP &lt;70 vs ≥70 mmHg, balanced on 40 baseline characteristics including discharge SBP. The 2476 matched pts (66% women, 10% African American) had mean (±SD) age of 78 (±10) years, EF of 57 (±8) %, and discharge DBP of 70 (±11) mmHg. Results: During 6 (median, 3) years of follow-up, all-cause mortality occurred in 69% and 65% of matched pts with a discharge DBP &lt;70 vs ≥70 mmHg, resp. (HR, 1.11; 95% CI, 1.004-1.22; p=0.042; Figure). HF readmission occurred in 50% and 47% of matched pts with DBP &lt;70 vs ≥70 mmHg, resp. (HR, 1.17; 95% CI, 1.05-1.31; p=0.007). There was no association with all-cause readmission (HR, 1.05; 95% CI, 0.96-1.14). Conclusions: In patients with HFpEF and HTN with SBP≥130 mmHg, a discharge DBP of &lt;70 mmHg was associated with higher risk of mortality or morbidity.
Improvement of von Willebrand Factor Proteolysis After Prostacyclin Infusion in Severe Pulmonary Arterial Hypertension
Authors: AgnèsVeyradier, ToshiyaNishikubo, MarcHumbert, MartineWolf, OlivierSitbon, GéraldSimonneau, Jean-PierreGirma, DominiqueMeyer
Journal: Circulation (2000)

Background—The presence of dysfunctional von Willebrand factor (vWF) in pulmonary arterial hypertension (PAH) was suggested to be related to increased proteolysis. Methods and Results—In 10 patients with severe PAH, we studied the proteolysis of plasma vWF (vWF levels, multimeric distribution, proteolytic pattern, and cleaving protease activity) and hemodynamic variables (mean pulmonary artery pressure, cardiac index, and total pulmonary vascular resistance) at baseline and 30 days after initiation of continuous prostacyclin infusion. At baseline, vWF levels were significantly increased, vWF proteolysis was excessive, and vWF-cleaving protease activity remained normal. These biological abnormalities were reversible and paralleled the improvement of hemodynamics under vasodilator treatment with prostacyclin. Conclusions—The excessive proteolysis of vWF in PAH is likely to be related to an increased susceptibility of vWF to proteases induced by high shear rates rather than to an enhanced release of enzymes.
Spontaneous Left Atrial Dissection Presenting as Pulmonary Edema
Authors: Jung-HyunChoi, Jun-KyuKang, Kyung-JooPark, Jo-WonJung, So-YeonChoi, Myeong-HoYoon, Gyo-SeungHwang, Seung-JeaTahk, Joon-HanShin
Journal: Circulation (2005)
Abstract LB-174: Novel AC electrokinetic platform for rapid isolation and characterization of extracellular vesicles from NSCLC patients
Authors: Rajaram Krishnan, Juan P. Hinestrosa, David Searson, Robert Turner, Robert Kovelman, Heath Balcer, James Madsen, David Bodkin
Journal: Cancer Research (2018)

Abstract We have developed a novel Alternating Current Electrokinetics (ACE) platform to isolate macromolecules such as circulating cell-free DNA (ccfDNA) and nanoparticles, including cell-derived extracellular vesicles (EVs). ccfDNA and EV isolation, and antibody staining using the platform required less than two hours to complete. EVs isolated by ultracentrifugation from the pancreatic cancer cell line ASPC-1 were used to validate the ACE platform's performance. EVs from pancreatic cancer ASPC-1 cells were detected using an anti-CD63 antibody and an antibody to the pancreatic cancer specific membrane protein Glypican-1, confirming that the ACE platform could isolate EVs and identify membrane-bound proteins. Recovered EVs were isolated and EV-associated RNA was amplified by RT-PCR. EVs from isolated from NSCLC patient plasma on the ACE platform contained higher levels of PD-L1 compared to healthy individuals (p&amp;lt;0.001). In parallel on the ACE platform, ccfDNA was isolated and quantified from the same samples, with increased levels measured in cancer patients. Improved differentiation between the NSCLC patients and the healthy normals was achieved when both markers were included in the analysis. Therefore, we believe the ACE platform has the potential to become a multimodal analytics tool for cancer diagnostics and treatment monitoring. Citation Format: Rajaram Krishnan, Juan P. Hinestrosa, David Searson, Robert Turner, Robert Kovelman, Heath Balcer, James Madsen, David Bodkin. Novel AC electrokinetic platform for rapid isolation and characterization of extracellular vesicles from NSCLC patients [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 LB-174.
Abstract 16254: Heart Rate as a Prognostic Marker in Patients With Heart Failure With Preserved Ejection Fraction
Authors: Ozlem Bilen, Sarah Marks, Lisa M Wruck, Umair Khalid, Salim S Virani, Vijay Nambi, Hani Jneid, Luke Cunningham, Patciria Chang, Biykem Bozkurt, Anita Deswal
Journal: Circulation (2015)

Introduction: Higher heart rate is associated with worse outcomes in patients with heart failure (HF) and reduced left ventricular ejection fraction (EF). This association is less certain in patients with HF and preserved EF (HFpEF). Methods: The Atherosclerosis Risk in Communities (ARIC) HF community surveillance study sampled HF hospitalizations from 2005-2010 identified by ICD discharge codes (for patients aged ≥ 55 years from 4 US communities). Patients with validated acute decompensated HF (ADHF) and EF ≥50% were categorized as HFpEF. We examined the association between quartiles of heart rate (HRt) at admission and 1-year mortality in HFpEF patients using multivariable Cox-proportional hazard models. Patients with atrial fibrillation, pacemakers and ICDs, and patients with missing covariates were excluded. Analyses were weighted to account for the stratified sampling design. Results: The final study sample included 874 HFpEF hospitalizations (weighted n=3934). Patients with lower HRt were more often male; more often had hypertension, less lung disease, had lower eGFR values and were more often on beta-blockers and diuretics. Unadjusted Kaplan Meier curves showed significant survival differences between the HRt quartiles (Fig). After adjusting for demographics, comorbidities, labs and medications (including beta blockers), compared to patients in the lowest HRt quartile, patients with HRt in the highest quartile had the highest risk of mortality (hazard ratio [95% CI] 2.07 [1.22-3.52]); patients in the 3rd and 2nd quartiles also had elevated risks (1.92 [1.22-3.04] and 1.44 [0.90-2.23]). Conclusions: There is a strong association between increasing HRt at admission and 1-year mortality in acute decompensated HFpEF.
Abstract 53: Pathogenic role of DNA Single Strand Break Accumulation in Heart Failure
Authors: TomoakiHigo, AtsuhikoNaito, YasushiSakata, IsseiKomuro
Journal: Circulation Research (2014)

Various environmental stress including reactive oxygen species (ROS) causes nuclear DNA damage. Increased production of ROS is observed in the failing heart and is considered as one of the causes of heart failure. Accumulating evidences suggest the presence of DNA damage in the failing heart, however, mechanistic link that connects DNA damage and heart failure remains elusive. Here, we show that DNA single strand break (SSB) accumulates in the failing heart and that SSB accumulation induces cell-autonomous inflammation through activation of DNA damage response (DDR) signaling pathway. Using alkaline- and neutral comet assay, we found that SSB is increased in the failing heart of pressure overload. Using in vitro model, we found that SSB accumulation activates ataxia talengiectasia mutated (ATM) kinase, which in turn induces nuclear translocation of NF-kB and increases the expression of inflammatory cytokines. Our findings suggest that SSB accumulation in cardiomyocytes plays an important role in the patho...
Antisense to Thyrotropin Releasing Hormone Receptor Reduces Arterial Blood Pressure in Spontaneously Hypertensive Rats
Authors: SatoshiSuzuki, PaulPilowsky, JaneMinson, LeonardArnolda, IdaLlewellyn-Smith, JohnChalmers
Journal: Circulation Research (1995)

Abstract We report in the present study the effect of intrathecal treatment with antisense oligonucleotides complementary to thyrotropin releasing hormone (TRH) receptor mRNA on the pressor response to intrathecal administration of TRH and on resting arterial blood pressure in Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). In 16-week-old male WKY rats, 18-base phosphodiester antisense or mismatch oligonucleotides to TRH receptor mRNA (100 μg per day) were injected intrathecally for 3 days. Twenty-four hours after the last injection, the magnitude of the pressor response to intrathecal TRH (10 μg) was significantly smaller in the antisense-treated group (n=7) compared with mismatch-treated controls (n=7) (change in mean arterial pressure, +20.3±3.0 versus +32.6±2.5 mm Hg, P<.01). No differences were observed in the pressor responses to injection of N-methyl-d-aspartic acid. Resting arterial blood pressure was unaffected by antisense treatment in WKY rats. In separate experiments, 16-wee...
Publisher Correction: Cold-induced epigenetic programming of the sperm enhances brown adipose tissue activity in the offspring
Authors: Wenfei Sun, Hua Dong, Anton S. Becker, Dianne H. Dapito, Salvatore Modica, Gerald Grandl, Lennart Opitz, Vissarion Efthymiou, Leon G. Straub, Gitalee Sarker, Miroslav Balaz, Lucia Balazova, Aliki Perdikari, Elke Kiehlmann, Sara Bacanovic, Caroline Zellweger, Daria Peleg-Raibstein, Pawel Pelczar, Wolf Reik, Irene A. Burger, Ferdinand von Meyenn, Christian Wolfrum
Journal: Nature Medicine (2018)