tbuckley/cabot-search huggingface dataset:
Abstract P271: Relationship among Dietary Patterns, Apolipoproteins, C Reactive Protein and Other Lipids in Adult Populations in Four Cities of the Southern Cone of Latin America
Authors: RosanaPoggio, NataliaElorriaga, LauraGutierrez, VilmaIrazola, AdolfoRubinstein
Journal: Circulation (2014)

Background: In the last decades, the nutrition transition in Latin America turned to diets with higher total caloric intake and lower consumption of vegetables, cereals and fruits. An unhealthy dietary pattern affects plasma levels of apolipoprotein (Apo) AI, Apo B and C-reactive protein (CRP) which are independently associated with the incidence of coronary heart disease and stroke). There is no data regarding these biomarkers in relation to dietary patterns from the Southern Cone of Latin America. Therefore the objective of this study is to analyze these biomarkers in relation to our traditional dietary patterns. Methods: CESCAS I study is an observational prospective cohort study with a multistage probabilistic sample of 7,600 participants from general population of 4 sites in Argentina, Chile and Uruguay. We conducted a cross-sectional analysis in a randomly selected subsample of 988 subjects. Subjects with previous cardiovascular event or under lipid lowering agents were excluded. Diet was assessed u...
Angiotensin II Type 1A Receptor Knockout Mice Display Less Left Ventricular Remodeling and Improved Survival After Myocardial Infarction
Authors: KoichiroHarada, TakeshiSugaya, KazuoMurakami, YoshioYazaki, IsseiKomuro
Journal: Circulation (1999)

Background—Angiotensin II (Ang II) has been implicated in ventricular remodeling after myocardial infarction (MI), which is an important determinant for prognosis after MI. The aim of this study was to determine whether Ang II type 1A receptor (AT1A)–mediated Ang II signals are critically involved in the mortality and LV remodeling after MI. Methods and Results—We examined survival, cardiac geometry and function, cardiac fibrosis, and gene expression of AT1A knockout (KO) mice and wild-type (WT) mice at 1 and 4 weeks after large MI. The survival rate was higher in KO mice than in WT mice at 4 weeks after MI. All WT survivors showed severe heart failure, detected by marked increases in both RV weight and lung weight. LV remodeling, such as the development of LV dilatation, LV dysfunction, and cardiac fibrosis at the noninfarcted area, were comparable in both kinds of mice at 1 week after MI. At 4 weeks after MI, however, WT mice showed more marked remodeling than KO mice. mRNA levels of AT1 at the noninfar...
Abstract 19048: Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes Reveals Hypokalemia Induced Exacerbation of Ventricular Arrhythmogenicity of Antiarrhythmic Drugs
Authors: Praveen Shukla, Chi Keung Lam, Jared Churko, Elena Matsa, Ningyi Shao, Oscar J Abilez, Joseph C Wu
Journal: Circulation (2016)

Hypokalemia is an independent risk factor associated with an increased risk of arrhythmia and all-cause mortality in patients with cardiovascular disease and exacerbates the cardiac arrhythmia (i.e...
Cardiovascular and Sympathetic Effects of Nitric Oxide Inhibition at Rest and During Static Exercise in Humans
Authors: RezaOwlya, LaurentVollenweider, LionelTrueb, ClaudioSartori, MattiaLepori, PascalNicod, UrsScherrer
Journal: Circulation (1997)

Background Nitric oxide (NO) regulates vascular tone and blood pressure, and studies in animals suggest that it does so, at least in part, by modulating sympathetic neural outflow. Loss of NO-induced vasodilator tone and restraint on sympathetic vasoconstrictor outflow could lead to exaggerated vasoconstrictor and pressor responses to physical stress in humans. Methods and Results To determine the role of NO in the modulation of central sympathetic outflow and vascular tone at rest and during a physical stress, we tested effects of systemic inhibition of NO synthase by NG-monomethyl-l-arginine (L-NMMA) infusion (a stereospecific inhibitor of NO synthase) on sympathetic nerve activity (microneurography), regional vascular resistance, and blood pressure at rest and during static handgrip. The major new findings are that (1) under resting conditions, L-NMMA infusion, which increased mean arterial pressure by ≈10%, did not have any detectable effect on muscle sympathetic nerve activity, whereas a similar incr...
Sexually dimorphic behavior, neuronal activity, and gene expression in Chd8-mutant mice
Authors: Hwajin Jung, Haram Park, Yeonsoo Choi, Hyojin Kang, Eunee Lee, Hanseul Kweon, Junyeop Daniel Roh, Jacob Ellegood, Woochul Choi, Jaeseung Kang, Issac Rhim, Su-Yeon Choi, Mihyun Bae, Sun-Gyun Kim, Jiseok Lee, Changuk Chung, Taesun Yoo, Hanwool Park, Yangsik Kim, Seungmin Ha, Seung Min Um, Seojung Mo, Yonghan Kwon, Won Mah, Yong Chul Bae, Hyun Kim, Jason P Lerch, Se-Bum Paik, Eunjoon Kim
Journal: Nature Neuroscience (2018)
Bach1 Represses Wnt/β-Catenin Signaling and Angiogenesis
Authors: LiJiang, MengYin, XiangxiangWei, JunxuLiu, XinhongWang, CongNiu, XuelingKang, JieXu, ZhongweiZhou, ShaoyangSun, XuWang, XiaojunZheng, ShengzhongDuan, KangYao, RuizheQian, NingSun, AlexChen, RuiWang, JianyiZhang, SifengChen, DanMeng
Journal: Circulation Research (2015)

Rationale:Wnt/β-catenin signaling has an important role in the angiogenic activity of endothelial cells (ECs). Bach1 is a transcription factor and is expressed in ECs, but whether Bach1 regulates angiogenesis is unknown. Objective:This study evaluated the role of Bach1 in angiogenesis and Wnt/β-catenin signaling. Methods and Results:Hind-limb ischemia was surgically induced in Bach1–/– mice and their wild-type littermates and in C57BL/6J mice treated with adenoviruses coding for Bach1 or GFP. Lack of Bach1 expression was associated with significant increases in perfusion and vascular density and in the expression of proangiogenic cytokines in the ischemic hindlimb of mice, with enhancement of the angiogenic activity of ECs (eg, tube formation, migration, and proliferation). Bach1 overexpression impaired angiogenesis in mice with hind-limb ischemia and inhibited Wnt3a-stimulated angiogenic response and the expression of Wnt/β-catenin target genes, such as interleukin-8 and vascular endothelial growth facto...
Patent Foramen Ovale Is an Important Predictor of Adverse Outcome in Patients With Major Pulmonary Embolism
Authors: StavrosKonstantinides, AnnetteGeibel, WolfgangKasper, ManfredOlschewski, LianeBlümel, HanjörgJust
Journal: Circulation (1998)

Background—Right-to-left shunt through a patent foramen ovale is frequently diagnosed by contrast echocardiography and can be particularly prominent in the presence of elevated pressures in the right side of the heart. Its prognostic significance in patients with pulmonary thromboembolism, however, is unknown. Methods and Results—The present prospective study included 139 consecutive patients with major pulmonary embolism diagnosed on the basis of clinical, echocardiographic, and cardiac catheterization criteria. All patients underwent contrast echocardiography at presentation. The end points of the study were overall mortality and complicated clinical course during the hospital stay defined as death, cerebral or peripheral arterial thromboembolism, major bleeding, or need for endotracheal intubation or cardiopulmonary resuscitation. Patent foramen ovale was diagnosed in 48 patients (35%). These patients had a death rate of 33% as opposed to 14% in patients with a negative echo-contrast examination (P=.01...
Oestrogen versus androgen in hormone-replacement therapy for complete androgen insensitivity syndrome: a multicentre, randomised, double-dummy, double-blind crossover trial
Authors: Wiebke Birnbaum, Louise Marshall, Ralf Werner, Alexandra Kulle, Paul-Martin Holterhus, Katharina Rall, Birgit Köhler, Annette Richter-Unruh, Michaela F Hartmann, Stefan A Wudy, Matthias K Auer, Anke Lux, Siegfried Kropf, Olaf Hiort
Journal: The Lancet Diabetes & Endocrinology (2018)
Echocardiographic Diagnosis of Mitral Regurgitation due to Ruptured Chordae Tendineae
Authors: Thomassweatman, Arthurselzer, Masanobukamagaki, Keithcohn, JudithBasford
Journal: Circulation (1972)

The echocardiographic findings from six patients with ruptured chordae tendineae from the posterial mitral valve leaflet and three with ruptured chordae from the anterior leaflet are reported; in all cases the diagnosis was later proven by open-heart surgery. The constellation of echocardiographic findings suggesting ruptured chordae tendineae to the posterior leaflet are: (1) The appearance of echoes within the left atrial chamber, representing prolapse of the posterior leaflet and flail chordae tendineae. This finding, although not consistently observed, is the most pathog-nomonic echocardiographic sign. (2) Increased amplitude of systolic excursion of the left atrial wall, in most cases associated with normal or only mildly increased left atrial diameter. (3) Recognition of thin, low-intensity (noncalcified) mitral valve leaflets. (4) The anterior leaflet may also manifest increased amplitude of motion, and may not coapt normally with the posterior leaflet in systole. (5) Increased amplitude of motion ...
Use of user-centered design to create a smartphone application for patient-reported outcomes in atopic dermatitis
Authors: Lia E. Gracey, Shiyi Zan, Joseph Gracz, John J. Miner, Jacqueline F. Moreau, Jodi Sperber, Kamal Jethwani, Timothy M. Hale, Joseph C. Kvedar
Journal: npj Digital Medicine (2018)

The ubiquity and convenience of smartphones carries great potential for collecting patient-reported data to address many gaps in research, especially those that rely on ongoing, real-time data collection. Health care apps have often suffered from low utility due to lack of consideration of the needs of multiple stakeholders. We employed an iterative user-centered design approach to create the myEczema smartphone application (app) to study the burden of disease of atopic dermatitis. We outline below the steps we took for developing myEczema for multiple stakeholders, including patients, clinicians, and researchers.
Androgen Receptor Enhances Hepatic Telomerase Reverse Transcriptase Gene Transcription After Hepatitis B Virus Integration or Point Mutation in Promoter Region
Authors: Chiao‐Ling Li, Chen‐Yu Li, You‐Yu Lin, Ming‐Chih Ho, Ding‐Shinn Chen, Pei‐Jer Chen, Shiou‐Hwei Yeh
Journal: Hepatology (2018)

The gender disparity of hepatocellular carcinoma (HCC) is most striking in hepatitis B virus (HBV)-related cases. The majority of such HCC cases contain integrated HBV, and some hotspot integrations, such as those in the telomerase reverse transcriptase gene (TERT) promoter, activate gene expression to drive carcinogenesis. As the HBV genome contains both androgen-responsive and estrogen-responsive motifs, we hypothesized that the integrated HBV DNA renders a similar regulation for downstream gene expression and thus contributes to male susceptibility to HCC. To test this hypothesis, the HBV integration sites and the common mutations in the TERT promoter and tumor protein P53 (TP53) coding region were analyzed in 101 HBV-related HCC cases using a capture-next-generation sequencing platform. The results showed that both HBV integration and -124G>A mutation in the TERT promoter region, occurring in a mutually exclusive manner, were more frequent in male than in female patients with HCC (integration: 22/58 male patients with HCC, 6/36 female patients with HCC, P = 0.0285; -124G>A: 17/62 male patients with HCC, 3/39 female patients with HCC, P = 0.0201; in combination, 39/62 male patients with HCC, 9/39 female patients with HCC, P < 0.0001). The effects of sex hormone pathways on the expression of TERT with both genetic changes were investigated using a reporter assay. HBV integration in the TERT promoter rendered the TERT transcription responsive to sex hormones, with enhancement by androgen receptor (AR) but suppression by estrogen receptor, both of which were dependent on hepatocyte nuclear factor 4 alpha. Besides, AR also increased TERT expression by targeting TERT promoter mutations in a GA binding protein transcription factor subunit alpha-dependent manner. Conclusion: TERT elevation by AR through integrated HBV and point mutation at the TERT promoter region was identified as a mechanism for the male dominance of HBV-related HCCs; telomerase and AR thus may be targets for intervention of HCC.
Bone Marrow–Derived Regenerated Cardiomyocytes (CMG Cells) Express Functional Adrenergic and Muscarinic Receptors
Authors: DaihikoHakuno, KeiichiFukuda, ShinjiMakino, FusakoKonishi, YuichiTomita, TomohiroManabe, YusukeSuzuki, AkihiroUmezawa, SatoshiOgawa
Journal: Circulation (2002)

Background— We recently reported that cardiomyocytes could be differentiated from bone marrow mesenchymal stem cells in vitro by 5-azacytidine treatment. In native cardiomyocytes, adrenergic and muscarinic receptors play crucial roles in mediating heart rate, conduction velocity, contractility, and cardiac hypertrophy. We investigated whether these receptors are expressed in differentiated CMG cells, and if so, whether they have downstream signaling systems. Methods and Results— Reverse transcription–polymerase chain reaction revealed that CMG cells had already expressed α1A-, α1B-, and α1D-adrenergic receptor mRNA before 5-azacytidine treatment, whereas expression of β1-, β2-adrenergic and M1-, M2-muscarinic receptors was first detected at 1 day. Phenylephrine dose-dependently induced phosphorylation of ERK1/2, which was completely inhibited by prazosin, and significantly increased cell size. Isoproterenol augmented cAMP by 38-fold, which was fully inhibited by propranolol. Isoproterenol (10−7 mol/L) inc...
Left Ventricular Performance in Patients With Severe Acute Respiratory Syndrome
Authors: Steven Siu-lungLi, Cheung-wahCheng, Chiu-laiFu, Yiu-hanChan, Man-poLee, Johnny Wai-manChan, Siu-fungYiu
Journal: Circulation (2003)

Background— Severe acute respiratory syndrome (SARS) is characterized by an overaggressive immune response. Myocardial performance may be impaired in cytokine-mediated immune reactions. Methods and Results— Forty-six patients with established clinical diagnosis of SARS were studied prospectively. Transthoracic echocardiographic examinations were done at the acute stage of infection and 30 days later. Among them, 14 patients required mechanical ventilation. The clinical course, laboratory data, SARS-CoV antibody titers, and results of reverse transcriptase–polymerase chain reaction were studied. Significantly higher left ventricular index of myocardial performance (IMP) (0.42±0.13 versus 0.33±0.09, P<0.001), longer isovolumic relaxation time (102.9±15.7 versus 81.6±14.7 ms, P<0.001), lower flow propagation velocity (69.6±15.7 versus 83.8±19.7 cm/s, P=0.011), and Doppler-derived cardiac output (4.69±1.01 versus 5.49±1.04 L/min, P<0.001) were observed during acute infection when compared with those at 30 day...
Abstract 5772: Engineered lectins to treat cancer
Authors: Thomas Murarasu, Ludger Johannes
Journal: Cancer Research (2018)

Abstract Targeted delivery of cytotoxic compounds to tumors has become one of the most dynamic areas of research and development in the cancer therapy field. In this context, glycosphingolipids (GSLs) represent a promising class of tumor markers. Indeed, cancer patients have altered GSL expression patterns on their tumoral cells compared to healthy tissue (Krengel et al., 2014). In a recent prioritization of cancer antigens by the National Cancer Institute at Rockville (USA), 4 out of 75 were GSLs (GD2, GD3, fucosyl-GM1, and GM3), with GD2 arriving already at the 12th position (Cheever et al., 2009). However, GSLs are only rarely addressed in the context of tumor targeting, obtaining GSL specific antibodies being a notorious difficult task. An exception is the anti-GD2 antibody, dinutuximab, which entered the market for the treatment of high-risk neuroblastoma patients, which is unfortunately associated to dose-limiting acute toxicity (Yu et al., 2010). This project aims at developing a novel class of therapeutic products for the delivery of therapeutic compounds by targeting tumor-specific GSLs. Our products are based on a naturally occurring GSL-binding lectin with intrinsic tumor targeting capacity. We will rely on a proprietary technology to derive products which are tuned to transport cytotoxic compounds specifically into cancer cells. As a proof of concept, we apply our technology to a tumor-specific GSL, GD2, to generate a therapeutic formulation against neuroblastoma, one of the most frequent cancer in children under 5 years old. Our technology has truly groundbreaking potential as, in principle, it can apply to any GSL to specifically target several common tumors. Citation Format: Thomas Murarasu, Ludger Johannes. Engineered lectins to treat cancer [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 5772.
Right-Sided Heart Failure Due to Compression of the Right Atrium by Remarkable Ascending Aortic Elongation
Authors: SatoshiAkagi, EijiTaguchi, KazuhiroDan, YokoIkeda, YusukeKawai, KenichiHisamatsu, MitsuruMunemasa, YoshihisaFujimoto, HiromiMatsubara, HiroshiMikouchi
Journal: Circulation (2005)
Abstract 1238: International comparison of cancer risks for Lynch syndrome
Authors: Mark A. Jenkins, Jeanette Reece, Grant Lee, Aung K. Win
Journal: Cancer Research (2018)

Abstract Aims: The International Mismatch Repair Consortium (IMRC) was formed in 2010 and comprises major worldwide consortia involved in the research and/or clinical treatment of Lynch syndrome (cancer predisposition caused by inherited mutations in mismatch repair (MMR) genes: MLH1, MSH2, MSH6, PMS2 and EPCAM); http://www.sphinx.org.au/imrc. The aim of this study was to determine cancer risks by geographic region. Methods: For each cancer, we estimated the age-specific cumulative risks (penetrance) and the hazard ratios compared to the average population risk. We used a modified segregation analysis and adjusted for any ascertainment of families given this is an analysis of prospective data. We estimated penetrance by: cancer sex, mismatch repair gene, type of mutation, and geographic region. Results: 43 investigators representing 53 different sites in 23 countries have submitted pedigree data. In total IMRC consists of 6,436 Lynch syndrome families (North America = 2,482, South America = 101, Europe = 3,307, Asia = 216, Australasia = 330). Of these, 2,214 were MLH1, 2,717 were MSH2, 1,118 were MSH6, 558 were PMS2, and 44 were EPCAM. The total number of distinct variants were 1,270 and the maximum size of families was 333 relatives. Of the distinct MMR variants submitted to the IMRC, 89% were classified as Class 4 (likely pathogenic) or 5 (pathogenic) by the InSiGHT Variant classification criteria (LOVD). Penetrance analyses were conducted only for the pathogenic or likely pathogenic variants. Preliminary analyses suggest that the risk of colorectal cancer to age 70 is highest for carriers in Australasia and North America and lowest for carriers in South America and Asia (Table 1). Conclusion: Preliminary results suggest that cancer risks for people with Lynch syndrome differ by geographic region, which is consistent with environmental modifiers for the disease and might justify region-specific screening guidelines. Risk (% to age 70) and hazard ratio (HR) of colorectal cancer by MMR gene and regionGeneRegionHR (95% CI)Risk MalesRisk FemalesMLH1Europe19 (14-26)50%32%MLH1Nth America32 (26-38)61%48%MLH1Australasia32 (22-46)68%55%MLH1Sth America6 (2-22)12%10%MLH1Asia7 (5-15)39%24%MSH2Europe14 (11-16)39%24%MSH2Nth America33 (28-40)61%50%MSH2Australasia36 (24-54)73%59%MSH2Sth America70 (10-490)82%75%MSH2Asia8 (5-17)21%15% Citation Format: Mark A. Jenkins, Jeanette Reece, Grant Lee, Aung K. Win, International Mismatch Repair Consortium. International comparison of cancer risks for Lynch syndrome [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 1238.
Abstract 4927: Plasma and CNS pharmacokinetics of the CHK-1 inhibitor prexasertib (LY-2606368) in mice bearing orthotopic group 3 medulloblastoma
Authors: Anil Maharaj, Abigail Davis, Bo Zhong, Martine F. Roussel, Clinton F. Stewart
Journal: Cancer Research (2018)

Abstract Many children with brain tumors have limited treatment options and poor long-term survival. A key protein kinase involved in activating and maintaining the S and G2/M checkpoints is CHK1, which when inhibited in the absence of p53 leads to loss of DNA damage checkpoints and can enhance the activity of many DNA-damaging agents. Prexasertib (LY-2606368), a potent and selective small molecule inhibitor of CHK1 protein kinase activity in vitro (IC50 &amp;lt;1 nM), is currently under clinical evaluation for treatment of pediatric malignancies. To evaluate prexasertib in preclinical efficacy studies for pediatric brain tumor models, the ratio of free drug concentrations between the central nervous system (CNS) and plasma (Kpu,u) is typically computed as a surrogate to measure CNS penetration. To facilitate the prospective determination of preclinical CNS Kpu,u values, we evaluated the plasma pharmacokinetic (PK) disposition of prexasertib in a murine model of medulloblastoma. A plasma PK study was performed using CD1 nude mice orthotopically implanted with group 3 medulloblastoma to obtain initial prexasertib PK parameters. Tumor growth was assessed by bioluminescence imaging (D-Luciferin) and mice were enrolled in the study once tumors reached 1x10~8-9 photons/second. Prexasertib mesylate monohydrate was reconstituted in 20% Captisol and administered subcutaneously at a dosage of 10 mg/kg (free base). A population based study design was used in which 3 samples per mouse were obtained. Plasma samples were prepared using a liquid-liquid extraction technique, and analyzed for prexasertib using a validated LC-MS/MS method (LLOQ = 0.2 µg/L). A two-compartment PK model was fit to the prexasertib concentration-time data using nonlinear mixed effects modeling (NONMEM 7.3, ICON Development Solutions). Plasma PK parameters from this model were used with the D-optimality criterion as implemented in ADAPT (D'Argenio, 1981) to derive a limited sampling model (LSM) for use in upcoming cerebral microdialysis studies. The results of our plasma PK studies showed a Cmax, terminal half-life, and AUC in CD1 nude mice bearing group 3 medulloblastoma of 1015 µg/L, 4.5 hours, and 1773 µg*hr/L, respectively. The LSM for plasma PK that will be used in the cerebral microdialysis studies include the time points of 0.25, 6.6, and 24 hours. Now that the plasma PK and a LSM are defined, we are poised to begin cerebral microdialysis studies in CD1 nude mice bearing group 3 medulloblastoma. Citation Format: Anil Maharaj, Abigail Davis, Bo Zhong, Martine F. Roussel, Clinton F. Stewart. Plasma and CNS pharmacokinetics of the CHK-1 inhibitor prexasertib (LY-2606368) in mice bearing orthotopic group 3 medulloblastoma [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 4927.