tbuckley/cabot-search huggingface dataset:
TRPC1 Is Essential for In Vivo Angiogenesis in Zebrafish
Authors: Peng-chunYu, Shan-yeGu, Ji-wenBu, Jiu-linDu
Journal: Circulation Research (2010)

Rationale: Wiring vascular and neural networks are known to share common molecular signaling pathways. Activation of transient receptor potential type C channels (TRPCs) has recently been shown to underlie chemotropic guidance of neural axons. It is thus of interest to examine whether TRPCs are also involved in vascular development. Objective: To determine the role of TRPC1 in angiogenesis in vivo during zebrafish development. Methods and Results: Knockdown of zebrafish trpc1 by antisense morpholino oligonucleotides severely disrupted angiogenic sprouting of intersegmental vessels (ISVs) in zebrafish larvae. This angiogenic defect was prevented by overexpression of a morpholino oligonucleotide–resistant form of zebrafish trpc1 mRNA. Cell transplantation analysis showed that this requirement of Trpc1 for ISV growth was endothelial cell–autonomous. In vivo time-lapse imaging further revealed that the angiogenic defect was attributable to impairment of filopodia extension, migration, and proliferation of ISV...
Newer Aspects of Echocardiography
Authors: Harveyfeigenbaum
Journal: Circulation (1973)

The recent increase in interest in echocardiography is partially due to the feasibility of using this technic to evaluate left ventricular performance in a noninvasive manner. It has been demonstrated that one can obtain an internal dimension of the left ventricular cavity and that this dimension is closely related to the corresponding volumes in uniformly contracting ventricles. Thus in patients with valvular heart disease, congenital heart disease, or cardiomyopathy, echocardiography provides an excellent noninvasive means of estimating diastolic volume, systolic volume, stroke volume, ejection fraction, and mean rate of circumferential shortening. In patients with segmental left ventricular disease, such as with coronary artery disease, these dimensions may not be true reflectors of the corresponding volumes. In such ventricles one probably should use echocardiography to evaluate the motion of individual segments of the chamber. To evaluate overall left ventricular function, one could use the mitral va...
Clinical utility of novel ultrathin single-balloon enteroscopy: a feasibility study
Authors: Kaoru Takabayashi, Naoki Hosoe, Ryoichi Miyanaga, Seiichiro Fukuhara, Kayoko Kimura, Shinta Mizuno, Makoto Naganuma, Naohisa Yahagi, Haruhiko Ogata, Takanori Kanai
Journal: Endoscopy (2018)

The advent of balloon-assisted enteroscopy (BAE) has facilitated the examination of the entire digestive tract. However, using a rigid sliding tube during the procedure reduces patient acceptance. This study evaluated the clinical application of a newly developed ultrathin single-balloon enteroscope for BAE.28 outpatients underwent enteroscopy with a novel ultrathin single-balloon enteroscope. None of the subjects required therapeutic procedures, such as balloon dilation or hemostasis. The insertability, efficacy, and safety of the ultrathin single-balloon endoscope were evaluated retrospectively.7 patients underwent transoral enteroscopy and 21 patients underwent transanal enteroscopy under conscious sedation. No adverse events related to the procedure were reported in any patients. Targeted observation and/or targeted biopsy were achieved in all procedures. All transoral procedures allowed evaluation of the jejunum beyond the ligament of Treitz. All transanal procedures allowed intubation of the terminal ileum, despite several patients having severe stenosis of the colon and ileum.A novel ultrathin single-balloon enteroscope showed adequate insertability and safety for outpatient surveillance enteroscopy under conscious sedation.
Differential Diagnosis of the Taussig-Bing Heart from Complete Transposition of the Great Vessels with a Posteriorly Overriding Pulmonary Artery
Authors: Aloisbeuren
Journal: Circulation (1960)

The Taussig-Bing transposition bears the name of the authors who described for the first time the clinical, physiologic, and anatomic findings. It has been recognized that the malformation is physiologically not so distinct as it is anatomically and that a transposition with the same physiologic pattern but different anatomy has been observed. Several case reports have appeared in the literature in which no clear differentiation was made in regard to the second type of transposition with overriding pulmonary artery. In the latter instance there is a complete transposition of both great vessels with a posteriorly placed overriding pulmonary artery in contrast to the original Taussig-Bing heart in which the 2 vessels are side by side, the pulmonary artery being in its normal place. Following the original case report, 14 cases were seen in this clinic in which the diagnosis was established either by catheterization, angiocardiography, or autopsy. In 4 other cases, the diagnosis of a transposition with a post...
Abstract 4000: Hepatitis B virus X gene accelerates the development of HBV-related hepatocellular carcinoma
Authors: Yu ZHANG, Qian YAN, Dandan YU, Xinyuan GUAN
Journal: Cancer Research (2018)

Abstract Epidemic studies have shown hepatocellular carcinoma (HCC) is highly associated with chronic HBV infection. However, the underlying mechanism of how HBV integration leading to HCC remains elusive. We applied the ViralFusionSeq algorithm to aid our analysis of the raw whole-genome sequencing data from TCGA database and found HBX “re-integration” in tumor cells showed a relatively consistent pattern compared with the adjacent normal liver tissue. In order to further elucidate the oncogenic role of truncated HBX gene in HCC, full-length and two COOH-terminal truncated HBX (X120 and X134) genes were stably transfected into HCC cell lines to investigate its function. Results showed that both truncated forms (X120 and X134) overexpression increased HCC cell proliferation rate, the ability of foci formation and colony formation in soft agar, as well as migration and invasion, while full-length HBX showed the opposite effect, both in vitro and vivo. Furthermore, RNA-sequencing of HBX overexpression HCC cells revealed key cancer-related signaling pathways were altered compared with control cells. Here our findings give a novel insight into the HBV integration pattern in the host genome which contributes to HCC. Citation Format: Yu ZHANG, Qian YAN, Dandan YU, Xinyuan GUAN. Hepatitis B virus X gene accelerates the development of HBV-related hepatocellular carcinoma [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 4000.
Abstract 4019: The chronic intermittent hypoxia enhances cancer progression in lung cancer mouse model
Authors: SangHaak Lee, In Kyoung Kim, Hyeon Hui Kang, Hee Young Kwon, Hye Sun Kang, Chang Dong Yeo
Journal: Cancer Research (2018)

Abstract Background: Obstructive sleep apnoea (OSA) is a very prevalent disorder charaterized by chronic intermittent hypoxia (CIH) and some reports suggested that OSA is related to increased incidence of cancer as well as cancer progression. The purpose of this study was to evaluate whether intermittent hypoxia with a time course similar to that found in OSA influence lung cancer development and progression in metastatic lung cancer animal model. Methods: C57/BL6 mice were divided into two groups; control condition (room air) or CIH. The mice of CIH group were exposed to IH for 2 weeks before and immediately for 2 weeks after tumour induction by tail vein injection of carcinoma cells. At day 14, the mice were sacrificed and measured cancer growth. Hypoxia inducible factor (HIF-1α), vascular endothelial growth factor (VEGF) and metastasis related matrix metalloproteinases (MMP) were measured by ELISA and gelatin zymography in lung tissue and serum, respectively. The mRNA expressions of epithelial mesenchymal transition markers were measured by real-time PCR in lung tissue. Results: The marked increase in tumor number and volume was found in CIH group (p &amp;lt; 0.05). The accumulation of total cell and neutrophils in BAL fluids and the activation of MMP -2 and -9 in serum were also increased by CIH. The level of HIF-1α in the nuclear fraction of pneumocytes and the expression of VEGF were increased significantly in CIH group compared to the control (p &amp;lt; 0.05). The mRNA expression of E-cadherin was decreased in CIH group compared to the control group while vimentin was increased. Conclusions: Our data shows that CIH is associated with enhanced proliferative and migratory properties of cancer. These results suggest evidence for the causal link between OSA and lung cancer progression. Key words: chronic intermittent hypoxia, obstructive sleep apnea, lung cancer Citation Format: SangHaak Lee, In Kyoung Kim, Hyeon Hui Kang, Hee Young Kwon, Hye Sun Kang, Chang Dong Yeo. The chronic intermittent hypoxia enhances cancer progression in lung cancer mouse model [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 4019.
Mechanism of Syncope in Patients With Heart Disease and Negative Electrophysiologic Test
Authors: CarloMenozzi, MicheleBrignole, RobertoGarcia-Civera, AngelMoya, GianlucaBotto, LuisTercedor, RobertaMigliorini, XavierNavarro
Journal: Circulation (2002)

Background— In patients with syncope and structural heart disease, syncope is suspected to be attributable to a primary cardiac arrhythmia, but little is known of its mechanism when electrophysiologic study is unremarkable. Methods and Results— We applied an implantable loop recorder in 35 patients with overt heart disease at risk of ventricular arrhythmia, because these were patients with previous myocardial infarction or cardiomyopathy with depressed ejection fraction or nonsustained ventricular tachycardia in whom an electrophysiologic study was unremarkable. During a follow-up of 3 to 15 months, syncope recurred in 6 patients (17%) after a mean of 6±5 months; in 3 patients, the mechanism of syncope was bradycardia with long pauses (sudden-onset AV block in 2 cases and sinus arrest in 1 case); in 1 patient, there was stable sinus tachycardia; and in 2 patients, who had chronic atrial fibrillation, there was an increase in ventricular rate. A total of 23 episodes of presyncope were documented in 8 patie...
Regulation of Ion Channel Expression
Authors: BarbaraRosati, DavidMcKinnon
Journal: Circulation Research (2004)

A potentially important mechanism controlling ion channel expression is homeostatic regulation, which can act to maintain a stable electrophysiological phenotype in cardiac myocytes as well as to provide plasticity in response to genetic, pathological, or pharmacological insults. The capabilities and limitations of the homeostatic regulatory mechanisms that contribute to the control of cardiac ion channel expression are the primary topic of this review.
Abstract 21062: Association Between High-Density Lipoprotein Cholesterol With All-Cause Death and Cardiovascular Events in a Primary Prevention Population
Authors: Neha J Pagidipati, Matthew Phelan, Ann Marie Navar, Michael Pencina, Eric Peterson
Journal: Circulation (2017)

Introduction: Higher levels of high density lipoprotein cholesterol (HDL-C) are associated with reduced risk of cardiovascular disease (CVD). However, observational data suggest very high HDL-C may be associated with increased all-cause mortality. We aimed to investigate the relationship between HDL-C and CV mortality and morbidity. Methods: Using data from adults without prior CVD from 5 large U.S.-based cohorts available through NIH BioLINCC (Framingham Cohort Study, Framingham Offspring, Multi-ethnic Study of Atherosclerosis, Atherosclerosis Risk in Communities, and Cardiovascular Health Study), we assessed the association between HDL-C and all-cause death and CVD composite events (CV death, myocardial infarction, angina, or stroke) using Cox proportional hazards models, modeling HDL-C with restricted cubic splines to allow for non-linearity. Adjustment factors included age, race, systolic blood pressure, antihypertensive medications, diabetes, body-mass index, smoking status, low-density lipoprotein cholesterol, and weekly alcohol use. Results: Among 22,569 individuals (median age 56 years, 55% women), median (IQR) HDL-C was 50 mg/dL (41, 62). Those with HDL-C&gt;50 mg/dL were more frequently female, non-smokers, and less obese. Over median follow up of 19.5 years, 6,539 deaths occurred (31% CV deaths). After adjustment for clinical factors, there was a U-shaped association between HDL-C and all-cause death in men, and to a lesser degree in women (Figure). As compared with a reference point of 50 mg/dL, lower HDL-C was associated with higher CVD composite events in both men and women, but higher HDL-C was not associated with increased CVD composite risk in either sex. Conclusions: In this large, U.S.-based study of well-characterized clinical cohorts and long-term follow-up, HDL-C displayed a U-shaped relationship with all-cause death. Low, but not high, HDL-C is associated with higher CVD composite events in both men and women.
Comparative Evaluation of Left and Right Ventricular Endomyocardial Biopsy
Authors: AliYilmaz, IngridKindermann, MichaelKindermann, FelixMahfoud, ChristianUkena, AnastasiosAthanasiadis, StephanHill, HeikoMahrholdt, MatthiasVoehringer, MichaelSchieber, KarinKlingel, ReinhardKandolf, MichaelBöhm, UdoSechtem
Journal: Circulation (2010)

Background— Endomyocardial biopsy (EMB) represents the gold standard for diagnosing myocarditis and nonischemic cardiomyopathies. This study focuses on the risk of complications and the respective diagnostic performance of left ventricular (LV), right ventricular (RV), or biventricular EMB in patients with suspected myocarditis and/or cardiomyopathy of unknown origin. Methods and Results— In this 2-center study, 755 patients with clinically suspected myocarditis (n=481) and/or cardiomyopathy of nonischemic origin including those with infiltrative or connective tissue disease (n=274) underwent either selective LV-EMB (n=265; 35.1%), selective RV-EMB (n=133; 17.6%), or biventricular EMB (n=357; 47.3%) after coronary angiography and exclusion of significant coronary artery disease. Cardiovascular magnetic resonance, including late gadolinium enhancement, imaging was performed in 540 patients (71.5%). The major complication rate for LV-EMB was 0.64% and for RV-EMB, 0.82%. Considering postprocedural pericardia...
Abstract 3581: Convergence of the specificity and cross-reactivity of multiple T cell receptors isolated against a single cancer peptide/HLA complex
Authors: Preeti Sharma, Daniel T. Harris, Marlies V. Hager, David M. Kranz
Journal: Cancer Research (2018)

Abstract Adoptive T cell therapy using T cell receptors (TCRs) or chimeric antigen receptors (CARs) requires careful selection of the receptor so as to target only the specific cancer antigen, without cross-reactivity toward structurally similar antigens. In this study, we used two TCRs (T1 and RD1) that bind to the HLA-A2 restricted melanoma antigen MART-1 (ELAGIGILTV). TCR-T1 was initially isolated from a melanoma-reactive T cell line specific for MART-1 whereas TCR-RD1 was derived completely by in vitro engineering, switching the specificity of the well-studied A6 TCR from its cognate viral peptide (Tax) to MART-1 by directed evolution. Despite their distinct origins, engineered high-affinity forms of both TCRs had remarkably similar fine-specificities as determined using a panel of MART-1 variant peptides. This binding signature allowed us to conduct a bioinformatic scan of the human and mouse proteomes for peptides that were homologous to MART-1. Our analysis resulted in identification of a self-peptide (TM74B: IIAGLGILTV) that also bound to both T1 and RD1 TCRs. T1-transduced T cells (CD4+) from HLA-A2/Db transgenic (AAD) mice were potently activated by MART-1, and cross-reacted (at 1000-fold higher doses) with the TM74B peptide. CD8+ T cells transduced with the T1 TCR were activated by AAD+ antigen presenting cells, indicating recognition of an endogenous peptide, possibly TM74B. To extend these studies, we have shown that T1-transduced AAD T cells (CD4+) are also stimulated by murine MART-1 (EAAGIGILIV) and that transfer of T1-transduced T cells into AAD mice did not result in overt toxicity. Thus, the AAD mouse could be used to study efficacy and toxicity of T1 TCR in syngeneic models. We are currently developing a B16/AAD tumor model to compare recognition of B16 melanoma by MART-1 directed TCRs and CARs. In summary, the convergence of specificity of T1 and RD1 suggests that TCRs against a cancer peptide antigen are focused on the same exposed features of the peptide. Furthermore, the results with RD1 suggest that it is possible to engineer TCRs completely in vitro, and that these TCRs can recapitulate the fine-specificities of conventional TCRs isolated from T cell clones. Citation Format: Preeti Sharma, Daniel T. Harris, Marlies V. Hager, David M. Kranz. Convergence of the specificity and cross-reactivity of multiple T cell receptors isolated against a single cancer peptide/HLA 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 3581.
Abstract 13524: Examining Variation in Interstage Mortality Rates Across the National Pediatric Cardiology Quality Improvement Collaborative: Do Lower Mortality Centers Have Lower Risk Patients?
Authors: Katherine E Bates, Sara K Pasquali, David W Brown, Peter B Manning, Karen Uzark
Journal: Circulation (2016)

Introduction: Although overall interstage mortality for infants with hypoplastic left heart syndrome has declined within the National Pediatric Cardiology Quality Improvement Collaborative (NPC-QIC), variation in outcomes across centers persists. It remains unclear whether centers with lower mortality rates have lower risk interstage patients or whether differences in the type of interstage care provided may explain this variation. We examined previously established patient risk factors across NPC-QIC centers with higher and lower interstage mortality rates. Methods: Lower mortality NPC-QIC centers were defined as those with &gt;25 consecutive interstage survivors, and included 7 centers. Higher mortality centers were defined as those with cumulative interstage mortality rates greater than the NPC-QIC historic baseline rate (&gt;10%), and included 4 centers. Patient risk factors were compared between lower and higher mortality centers, accounting for within center clustering. Results: The 7 lower mortality centers (n=331 patients) had a lower interstage mortality rate of 2.7% compared to 13.3% in the 4 higher mortality centers (n=173 patients); p&lt;0.0001. Post-natal diagnosis was the only risk factor less prevalent in the lower mortality centers (Figure) compared to higher mortality centers (18.4% vs. 31.8%, p=0.04). All other risk factors examined were either similar between the lower and higher mortality centers (including gestational age, anatomic diagnoses, birth weight), or more prevalent in the lower mortality centers (major syndrome- 6.9% vs. 4.0%, p=0.03; major anomalies- 7.3% vs. 4%, p=0.047). Conclusions: Differences in interstage mortality rates among NPC-QIC centers do not appear to be explained by a lower rate of patient risk factors in lower mortality centers. Further study is necessary to evaluate differences in interstage care practices across centers in order to identify targets for efforts to reduce variation and improve outcomes.
Abstract 362: Restoring Diabetes-induced Autophagic Flux Arrestment in Ischemic/Reperfused Heart by Adiponectin Receptor Activation Involves Both AMPK-Dependent and AMPK-Independent Signaling
Authors: Yajing Wang, Wayne Lau, Bernard Lopez, Theodore Christopher, Erhe Gao, Walter Koch, Xinliang (Xin) Ma
Journal: Circulation Research (2017)

Autophagy is increasingly recognized as an important regulator of myocardial ischemia-reperfusion (MI-R) injury. However, whether and how diabetes may alter autophagy in response to MI-R remains unknown. Deficiency of adiponectin (AdipoQ), a cardioprotective molecule, markedly increases MI-R injury. However, the role of diabetic hypoadiponectinemia in cardiac autophagy alteration after MI-R is unclear. Utilizing normal control (NC), high-fat-diet-induced diabetes, and Adipoq knockout ( adipoq -/- ) mice, we demonstrated that autophagosome formation was modestly inhibited and autophagosome clearance was markedly impaired in the diabetic heart subjected to MI-R. adipoq -/- largely reproduced the phenotypic alterations observed in the ischemic-reperfused diabetic heart. Treatment of diabetic and adipoq -/- mice with AdipoRon, a novel adiponectin receptor agonist, stimulated autophagosome formation, markedly increased autophagosome clearance, reduced infarct size, and improved cardiac function (P&lt;0.01 vs vehicle). Mechanistically, AdipoRon caused significant phosphorylation of AMPK-BECN1 (Ser93/Thr119)-PtdIns3K (Ser164) and enhanced lysosome protein LAMP2 expression both in vivo and in isolated adult cardiomyocytes. Pharmacologic AMPK inhibition or genetic AMPK alpha2 mutation abolished AdipoRon-induced BECN1 (Ser93/Thr119)-PtdIns3K (Ser164) phosphorylation and AdipoRon-stimulated autophagosome formation. However, AdipoRon-induced LAMP2 expression, AdipoRon-stimulated autophagosome clearance, and AdipoRon-suppressed superoxide generation were not affected by AMPK inhibition. Treatment with MnTMPyP (a superoxide scavenger) increased LAMP2 expression and stimulated autophagosome clearance in simulated ischemic-reperfused cardiomyocytes. However, no additive effect between AdipoRon and MnTMPyP was observed. Collectively, these results demonstrate that hypoadiponectinemia impairs autophagic flux, contributing to enhanced MI-R injury in the diabetic state. Adiponectin receptor activation restores AMPK-mediated autophagosome formation and antioxidant-mediated autophagosome clearance, representing a novel intervention effective against MI-R injury in diabetic conditions.
Abstract 13040: Repeated Social Defeat Stress Enhances Neutrophil Extracellular Traps Formation in vivo and in vitro: Implication in the Exaggerated Atherosclerosis in Chronic Social Stress-exposed Apoe-/- Mice
Authors: Keita Yamamoto, Hiroyuki Yamada, Kensuke Terada, Shinichiro Motoyama, Naotoshi Wada, Makoto Saburi, Masakazu Kikai, Noriyuki Wakana, Satoaki Matoba
Journal: Circulation (2016)

Introduction: Neutrophil extracellular traps (NETs) has been reported to promote atherosclerosis through induction of NETosis, a new type of neutrophil cell death; however, the role of NETosis in psychosocial stress-induced atherosclerosis remains undefined. Methods and Results: Eight-week-old male apoE-/- mice were exposed to the repeated social defeat (RSD) by housing with a larger CD-1 mice in a shared home cage with a clear perforated divider. They were repeatedly subjected to vigorous physical contact for 5-10 min each day on 10 consecutive days. Control mice were housed in the same gage without physical contact. After 6 weeks of high-cholesterol diet feeding, atherosclerotic lesion area of the aortic root was significantly increased in RSD mice compared with control mice (19.4% vs 13.9%, P < 0.05). There was no significant difference in body weight, food intake, mean blood pressure, and lipid profile between the 2 groups. Although both of Ly6G-positive and Mac3-positive area in immunofluorescent sta...
Influenza Vaccination Practices of Physicians and Caregivers of Children with Neurologic and Neurodevelopmental Conditions — United States, 2011–12 Influenza Season
Authors: Michael J. Smith, Deborah McFalls, Jennifer Hendricks, Janice Watkins, Cynthia Moore, Georgina Peacock, Adina de Coteau
Journal: MMWR Morbidity and Mortality Weekly Report (2013)