tbuckley/cabot-search huggingface dataset:
Purification of Cardiomyocytes From Differentiating Pluripotent Stem Cells Using Molecular Beacons That Target Cardiomyocyte-Specific mRNA
Authors: KiwonBan, BrianWile, SangsungKim, Hun-JunPark, JaeminByun, Kyu-WonCho, TalibSaafir, Ming-KeSong, Shan PingYu, MaryWagner, GangBao, Young-SupYoon
Journal: Circulation (2013)

Background—Although methods for generating cardiomyocytes from pluripotent stem cells have been reported, current methods produce heterogeneous mixtures of cardiomyocytes and noncardiomyocyte cells. Here, we report an entirely novel system in which pluripotent stem cell–derived cardiomyocytes are purified by cardiomyocyte-specific molecular beacons (MBs). MBs are nanoscale probes that emit a fluorescence signal when hybridized to target mRNAs. Method and Results—Five MBs targeting mRNAs of either cardiac troponin T or myosin heavy chain 6/7 were generated. Among 5 MBs, an MB that targeted myosin heavy chain 6/7 mRNA (MHC1-MB) identified up to 99% of HL-1 cardiomyocytes, a mouse cardiomyocyte cell line, but <3% of 4 noncardiomyocyte cell types in flow cytometry analysis, which indicates that MHC1-MB is specific for identifying cardiomyocytes. We delivered MHC1-MB into cardiomyogenically differentiated pluripotent stem cells through nucleofection. The detection rate of cardiomyocytes was similar to the perc...
Left Ventricular Activation Time in Normal Men
Authors: Takashiwada
Journal: Circulation (1959)

Simultaneous recordings from right and left precordial leads in 50 normal individuals were obtained. The duration of rS in lead V1, was always equal to or greater than the duration of qR in lead V7. Evidence is presented to support the thesis that the duration of rS in lead V1, is a more accurate index of left ventricular activation time than the duration of qR in the left precordial leads.
Safety and Efficacy of Atorvastatin for Chronic Subdural Hematoma in Chinese Patients
Authors: Rongcai Jiang, Shiguang Zhao, Renzhi Wang, Hua Feng, Jianmin Zhang, Xingang Li, Ying Mao, Xianrui Yuan, Zhou Fei, Yuanli Zhao, Xinguang Yu, Wai Sang Poon, Xide Zhu, Ning Liu, Dezhi Kang, Tao Sun, Baohua Jiao, Xianzhi Liu, Rutong Yu, Junyi Zhang, Guodong Gao, Jiehe Hao, Ning Su, Gangfeng Yin, Xingen Zhu, Yicheng Lu, Junji Wei, Jin Hu, Rong Hu, Jianrong Li, Dong Wang, Huijie Wei, Ye Tian, Ping Lei, Jing-fei Dong, Jianning Zhang
Journal: JAMA Neurology (2018)

Chronic subdural hematoma (CSDH) is a trauma-associated condition commonly found in elderly patients. Surgery is currently the treatment of choice, but it carries a significant risk of recurrence and death. Nonsurgical treatments remain limited and ineffective. Our recent studies suggest that atorvastatin reduces hematomas and improves the clinical outcomes of patients with CSDH.To investigate the safety and therapeutic efficacy of atorvastatin to nonsurgically treat patients with CSDH.The Effect of Atorvastatin on Chronic Subdural Hematoma (ATOCH) randomized, placebo-controlled, double-blind phase II clinical trial was conducted in multiple centers in China from February 2014 to November 2015. For this trial, we approached 254 patients with CSDH who received a diagnosis via a computed tomography scan; of these, 200 (78.7%) were enrolled because 23 patients (9.1%) refused to participate and 31 (12.2%) were disqualified.Patients were randomly assigned to receive either 20 mg of atorvastatin or placebo daily for 8 weeks and were followed up for an additional 16 weeks.The primary outcome was change in hematoma volume (HV) by computed tomography after 8 weeks of treatment. The secondary outcomes included HV measured at the 4th, 12th, and 24th weeks and neurological function that was evaluated using the Markwalder grading scale/Glasgow Coma Scale and the Barthel Index at the 8th week.One hundred ninety-six patients received treatment (169 men [86.2%]; median [SD] age, 63.6 [14.2] years). The baseline HV and clinical presentations were similar between patients who were taking atorvastatin (98 [50%]) and the placebo (98 [50%]). After 8 weeks, the HV reduction in patients who were taking atorvastatin was 12.55 mL more than those taking the placebo (95% CI, 0.9-23.9 mL; P = .003). Forty-five patients (45.9%) who were taking atorvastatin significantly improved their neurological function, but only 28 (28.6%) who were taking the placebo did, resulting in an adjusted odds ratio of 1.957 for clinical improvements (95% CI, 1.07-3.58; P = .03). Eleven patients (11.2%) who were taking atorvastatin and 23 (23.5%) who were taking the placebo underwent surgery during the trial for an enlarging hematoma and/or a deteriorating clinical condition (hazard ratio, 0.47; 95% CI, 0.24-0.92; P = .03). No significant adverse events were reported.Atorvastatin may be a safe and efficacious nonsurgical alternative for treating patients with CSDH.ClinicalTrials.gov Identifier: NCT02024373.
Mechanical and Electrophysiological Substrate for Recurrent Atrial Flutter Detected by Right Atrial Speckle Tracking Echocardiography and Electroanatomic Mapping in Myotonic Dystrophy Type 1
Authors: PiercarloBallo, MarziaGiaccardi, AndreaColella, FabrizioCellerini, FabrizioBandini, LeandroChiodi, AlfredoZuppiroli
Journal: Circulation (2013)
Left Ventricular Entropy Is a Novel Predictor of Arrhythmic Events in Patients With Dilated Cardiomyopathy Receiving Defibrillators for Primary Prevention
Authors: Rahul G. Muthalaly, Raymond Y. Kwong, Roy M. John, Rob J. van der Geest, Qian Tao, Benjamin Schaeffer, Shinichi Tanigawa, Tomofumi Nakamura, Kyoichi Kaneko, Usha B. Tedrow, William G. Stevenson, Laurence M. Epstein, Sunil Kapur, Paul C. Zei, Bruce A. Koplan
Journal: JACC. Cardiovascular imaging (2018)
Abstract 16875: Measurement of Atherosclerotic Inflammation with FDG-PET Imaging Improves Cardiovascular Risk Stratification
Authors: Amparo L Figueroa, Amr Abdelbaky, Erin M Corsini, Meredith A Lawler, Gagandeep Gurm, Shanmugam Uthamalingam, Sharath Subramanian, Jayanthi Vijayakumar, Thomas J Brady, Udo Hoffmann, Ahmed Tawakol
Journal: Circulation (2011)

Background: FDG uptake correlates with cardiovascular (CV) events. Here we test the hypothesis that aortic inflammation measured with FDG-PET-CT imaging provides added value to Framingham risk score (FRS). Methods: We screened consecutive clinical data (n= 6,109) for patients with no prior CVD, active cancer, or chronic inflammatory conditions who had clinical follow-up data for up to 5 years after an index FDG-PET. From the 229 (median age[IQR],60[47,68], 38% males) meeting these criteria, 42 had CV events (incident ischemic stroke, TIA, ACS, carotid or coronary revascularization) and 187 did not during the follow-up. FRS 10 year % probability of CHD was calculated. FDG uptake was measured (ascending aorta) and reported as target-to-background ratio (TBR) while blinded to clinical data. Net Reclassification Improvement (NRI) and Integrated Discrimination Improvement (IDI) were used to compare FRS with and without TBR for CV event prediction. Results: Patients in the highest TBR tertile were substantially more likely to experience CV events (HR[95%CI], 4.85[1.89,12], p=0.001) compared to the lowest tertile after adjusting for FRS, BMI, statin, and diabetes. Further, addition of TBR (tertiles) to FRS variables resulted in an improvement in patient net reclassification, (NRI[95% CI]=26.89%[10%, 47%) across risk categories (&lt;10, 10-20, &gt;20) compared to their initially calculated risk. Adding TBR (tertiles) to FRS variables further improved discrimination of CV risk, (IDI=5.56%[0.27%, 11%]). Conclusions: FDG-PET measured aortic plaque inflammation improves risk discrimination and reclassification. These preliminary data support prospective follow-up studies to evaluate imaging plaque inflammation for CVD risk assessment.
Effect of Ganglion-Blocking Agents on Renin Release in Hypertensive Patients
Authors: Yoshihirokaneko, Tadanaotakeda, Takaoikeda, Hitoshitagawa, Masaoishii, Yutakatakabatake, Hideoueda
Journal: Circulation Research (1970)

In 18 patients with benign essential hypertension, renin release during reduction of arterial pressure due to sodium nitroprusside infusion was measured before and after administration of ganglion-blocking agents (pentolinium or trimethaphan). In 12 patients, renin release induced by reduction in pressure was significantly reduced but not abolished by ganglion blockade. Simultaneously, ganglion blockade significantly reduced renal vascular resistance (RVR) and almost abolished a decrease in renal blood flow (RBF) due to hypotension. In 6 other patients in whom no significant renin release resulted from hypotension, ganglion blockade caused little changes in renin release, RVR or RBF. The results support the hypothesis that renal sympathetic nerve activity is a factor in variations in renin release in patients with essential hypertension. Following ganglion blockade in the responsive patients, the significant reciprocal correlation between renal venous renin activity and sodium excretion rate shifted but s...
Adult Patient With Isolated Noncompaction of Ventricular Myocardium
Authors: TomoyaKaneda, MasamiShimizu, HidekazuIno, HidenobuTerai, NoboruFujino, KatsuharuUchiyama, TomohitoMabuchi, TetsuoKonno, TakashiFujita, EichiMasuda, HiromasaKato, AkiraFunada, HiroshiMabuchi, HirokoIkeda
Journal: Circulation (2005)
Abstract 349: Regulation Of Key Metabolic Enzymes By Tristetraprolin
Authors: MarinaBayeva, KonradSawicki, HosseinArdehali
Journal: Circulation Research (2013)

Introduction: Heart disease and stroke are the primary causes of death in adults with type-2 diabetes thus strict metabolic control is essential in these patients. Here, we show that tristetraprolin (TTP), a protein involved in regulation of inflammation and iron homeostasis via mRNA degradation, may alleviate diabetic phenotype through modulation of key enzymes involved in gluconeogenesis and fatty acid (FA) metabolism in insulin-sensitive tissues. Results: TTP protein content was significantly reduced in livers of diabetic mice fed high-fat diet compared to control, suggesting that mRNA targets of TTP may be stabilized in diabetes. We then assessed the effects of TTP knockdown using siRNA in HepG2 liver cells on the expression of enzymes in four major metabolic pathways: glycolysis, gluconeogenesis, FA oxidation and synthesis. Consistent with reduced TTP, we found increased expression of a key gluconeogenic regulator - pyruvate dehydrogenase kinase 4 (PDK4). In silico analysis of the 3’ untranslated reg...
Abstract 1151: A unique layered 3D stromal tissue model for in vitro evaluation of immunologic agents and immune cell infiltration into cancer microenvironment
Authors: Rii Morimura, Kei Tsukamoto, Shiro Kitano, Eiji Shinozaki
Journal: Cancer Research (2018)

Abstract Background; The modulation of the immune system is a proven key target for cancer therapy, however, the complex interplay between immune cells and cancer cells in cancer microenvironment remains only partially understood. In addition, the currently available in vitro cancer microenvironment models are not designed to study the immunologic agents and a role of immune cells. Here, we developed a unique layered 3D stromal tissue model comprising an allogeneic immune, stromal and cancer cells. Method; Human umbilical vein endothelial cells (HUVEC) and normal human dermal fibroblasts (NHDF) were coated with collagen and heparin to construct Extracellular matrix (ECM) nanofilm and cultured to form multi-layers. Lung cancer cells were placed between stromal cells. Furthermore, we added Peripheral Blood Mononuclear Cell (PBMC) and Programmed cell death 1 (PD-1) blockade with Nivolumab and evaluated cytotoxic effects of immune cells on cancer cells and immune cell infiltration by immunohistochemistry. Result; The co-cultured stromal tissues were multi-layered (approximately 20 layers), and the presence of lung cancer cells between stromal cells was observed. Immunohistochemistry revealed CD8 positive immune cell infiltration into the fibroblast layers. PBMC with Nivolumab treatment significantly decreased the viability of lung cancer cells in this 3D co-culture compared with the results in 2D mono-culture. High level of programmed cell death ligand 1 (PD-L1) expression on lung cancer cell lines correlated with a higher response to PD-1 blockade in vitro as well as clinical trials. Conclusion; In summary, we present a unique 3D cell culture system based on an allogeneic stromal/cancer/immune cell setting to study immunologic agents and immune cell infiltration in cancer microenvironment. This 3D model has the ability to reflect in vivo conditions closer than 2D model and provide a tool for in vitro immunologic agent testing. Citation Format: Rii Morimura, Kei Tsukamoto, Shiro Kitano, Eiji Shinozaki. A unique layered 3D stromal tissue model for in vitro evaluation of immunologic agents and immune cell infiltration into cancer microenvironment [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 1151.
Long-Term (&gt;10 Years) Clinical Outcomes of First-in-Human Biodegradable Poly- <i>l</i> -Lactic Acid Coronary Stents
Authors: Soji Nishio, Kunihiko Kosuga, Keiji Igaki, Masaharu Okada, Eisho Kyo, Takafumi Tsuji, Eiji Takeuchi, Yasutaka Inuzuka, Shinsaku Takeda, Tatsuhiko Hata, Yuzo Takeuchi, Yoshitaka Kawada, Takeshi Harita, Junya Seki, Shunji Akamatsu, Shinichi Hasegawa, Nico Bruining, Salvatore Brugaletta, Sebastiaan de Winter, Takashi Muramatsu, Yoshinobu Onuma, Patrick W. Serruys, Shigeru Ikeguchi
Journal: Circulation (2012)

Background— The purpose of this study was to evaluate the long-term safety of the Igaki-Tamai stent, the first-in-human fully biodegradable coronary stent made of poly- l -lactic acid. Methods and Results— Between September 1998 and April 2000, 50 patients with 63 lesions were treated electively with 84 Igaki-Tamai stents. Overall clinical follow-up (&gt;10 years) of major adverse cardiac events and rates of scaffold thrombosis was analyzed together with the results of angiography and intravascular ultrasound. Major adverse cardiac events included all-cause death, nonfatal myocardial infarction, and target lesion revascularization/target vessel revascularization. During the overall clinical follow-up period (121±17 months), 2 patients were lost to follow-up. There were 1 cardiac death, 6 noncardiac deaths, and 4 myocardial infarctions. Survival rates free of all-cause death, cardiac death, and major adverse cardiac events at 10 years were 87%, 98%, and 50%, respectively. The cumulative rates of target lesion revascularization (target vessel revascularization) were 16% (16%) at 1 year, 18% (22%) at 5 years, and 28% (38%) at 10 years. Two definite scaffold thromboses (1 subacute, 1 very late) were recorded. The latter case was related to a sirolimus-eluting stent, which was implanted for a lesion proximal to an Igaki-Tamai stent. From the analysis of intravascular ultrasound data, the stent struts mostly disappeared within 3 years. The external elastic membrane area and stent area did not change. Conclusion— Acceptable major adverse cardiac events and scaffold thrombosis rates without stent recoil and vessel remodeling suggested the long-term safety of the Igaki-Tamai stent.
Abstract 5424: Improved anticancer activity of clotam as a copper-complex
Authors: Umesh T. Sankpal, Rafid Patel, Bianca Arechiga, Abigail Hunter, Jaya Chhabra, Deondra T. Brown, Raj K. Gurung, Alvin A. Holder, Riyaz M. Basha
Journal: Cancer Research (2018)

Abstract Clotam (tolfenamic acid or TA) is a nonsteroidal anti-inflammatory drug used to treat migraine headaches. Research from our laboratory and other groups has demonstrated that TA also acts as an anticancer agent in several adult and pediatric cancer models. It is well established that the anticancer activity of TA is partly mediated by its ability to downregulate the specificity protein (Sp) family of transcription factors and their downstream targets, notably the inhibitor of apoptosis protein family member survivin. Both Sp1 and survivin are upregulated in cancer cells and are associated with poor prognosis, making them ideal therapeutic targets. It was recently suggested that the therapeutic potential of TA could be enhanced by forming a complex with copper(II). In this study we synthesized a copper(II) complex of TA (Cu-TA) and tested its anticancer activity using cell lines representing various cancers such as breast, prostate, pancreatic, brain, colon, neuroblastoma, medulloblastoma, and sarcoma. The compound was synthesized and its purity was assessed by UV-visible spectrophotometry. Purified compound (&amp;gt;98%) was dissolved in DMSO and its antiproliferative activity was determined using the CellTiter-Glo cell viability assay kit. In our initial screening various cancer cells were treated with increasing concentration of Cu-TA or TA, and cell viability was assessed at 24 and 48h post-treatment. The effect of Cu-TA on expression of Sp1 and survivin was determined by Western blot analysis of lysates prepared using cells treated with Cu-TA or TA for 48h. We also studied the effect of Cu-TA on cell cycle and apoptosis using medulloblastoma cell lines. Both Cu-TA and TA decreased cell viability in a dose-dependent manner; however, Cu-TA consistently had lower IC50 values in all the cell lines tested, suggesting its higher efficacy compared to TA. In line with the viability results, Western blot analysis of survivin expression demonstrated that Cu-TA was more effective in inhibiting its expression compared to TA. Also, treatment of medulloblastoma cells with Cu-TA resulted in cell cycle arrest in G0/G1 phase accompanied by an increased apoptosis as determined by annexin-V staining. This preliminary screening demonstrates the potential of Cu-TA as an effective anticancer agent with the ability to target survivin. Further studies to delineate the mechanism of action of Cu-TA are under way. Citation Format: Umesh T. Sankpal, Rafid Patel, Bianca Arechiga, Abigail Hunter, Jaya Chhabra, Deondra T. Brown, Raj K. Gurung, Alvin A. Holder, Riyaz M. Basha. Improved anticancer activity of clotam as a copper-complex [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 5424.
Angiotensin II and Serum Differentially Regulate Expression of Cyclins, Activity of Cyclin-Dependent Kinases, and Phosphorylation of Retinoblastoma Gene Product in Neonatal Cardiac Myocytes
Authors: JunichiSadoshima, HirokiAoki, SeigoIzumo
Journal: Circulation Research (1997)

The hypertrophic response in cardiac myocytes and the mitogenic response in other cell types share various early cellular responses. However, how the subsequent cell growth response, such as cell cycle machinery, is regulated in cardiac hypertrophy is not understood. Using cultured neonatal rat cardiac myocytes, we examined the effect of angiotensin II (Ang II), a hypertrophic stimulus, on mRNA and protein expression of cyclins and cyclin-dependent protein kinases (cdks), activity of cdks, and phosphorylation of retinoblastoma gene product (pRb). The effect of FCS, a stimulus that was previously reported to initiate both protein and DNA synthesis in cardiac myocytes, was also examined for comparison. Ang II activated cdk4 and caused phosphorylation of pRb, peaking at 12 hours, but subsequently downregulated cyclin D1, D3, and A expression and cdk2 activity. FCS increased the expression of G1-S cyclins, caused activation of cdk4, cdk2, and cdc2, and strongly phosphorylated pRb but failed to significantly s...
Role of Monocyte Chemoattractant Protein-1 in Cardiovascular Remodeling Induced by Chronic Blockade of Nitric Oxide Synthesis
Authors: MasamichiKoyanagi, KensukeEgashira, ShiroKitamoto, WeihuaNi, HiroakiShimokawa, MotohiroTakeya, TeizoYoshimura, AkiraTakeshita
Journal: Circulation (2000)

Background—Chronic inhibition of endothelial nitric oxide (NO) synthesis by the administration of Nω-nitro-l-arginine methyl ester (L-NAME) to rats induces early vascular inflammatory changes (monocyte infiltration into coronary vessels and monocyte chemoattractant protein-1 [MCP-1] expression) as well as subsequent arteriosclerosis (medial thickening and perivascular fibrosis) and cardiac fibrosis. However, the role of MCP-1 in this process is not known. Methods and Results—We investigated the effect of a specific monoclonal anti–MCP-1 neutralizing antibody in rats treated with L-NAME to determine the role of monocytes in the regulation of cardiovascular remodeling. We found increased expression of MCP-1 mRNA in vascular endothelial cells and monocytes in inflammatory lesions. Cotreatment with an anti–MCP-1 antibody, but not with control IgG, prevented the L-NAME–induced early inflammation and reduced late coronary vascular medial thickening. In contrast, the anti–MCP-1 antibody did not decrease the deve...
Toll-Like Receptor-2 Modulates Ventricular Remodeling After Myocardial Infarction
Authors: TetsuroShishido, NaokiNozaki, SeijiYamaguchi, YokoShibata, JojiNitobe, TakuyaMiyamoto, HirokiTakahashi, TakanoriArimoto, KunihikoMaeda, MitsunoriYamakawa, OsamuTakeuchi, ShizuoAkira, YasuchikaTakeishi, IsaoKubota
Journal: Circulation (2003)

Background— Toll-like receptors (TLRs) are members of the interleukin-1 receptor family and transduce similar signals as interleukin-1 receptor in response to exogenous pathogens. Recent studies have demonstrated that TLRs are activated by endogenous signals, such as heat shock proteins and oxidative stress, that may contribute to ventricular remodeling after myocardial infarction. In this study, we determined whether TLR-2 was involved in cardiac remodeling after myocardial infarction. Methods and Results— Myocardial infarction was induced by surgical left anterior descending coronary artery ligation on wild-type (WT) mice and TLR-2–knockout (KO) mice. The survival rate was significantly higher in KO mice than in WT mice 4 weeks after myocardial infarction (65% versus 43%, P<0.03). Infarct size and degree of inflammatory cell infiltration in infarct area were similar between WT and KO mice. However, myocardial fibrosis in the noninfarct area of KO mice was much less than in WT mice (P<0.01) and was accom...