tbuckley/cabot-search huggingface dataset:
Abstract 12513: Comparison of Global Myocardial Function With 2 Types of Pressure-Overload Left Ventricular Hypertrophy Using Two-Dimentional Speckle-Tracking Echocardiography
Authors: Yoshikazu Ohara, Yuki Tsuda, Yohko Fukuoka, Atsuko Furukawa, Shingo Hosogi, Katsuhito Yamamoto
Journal: Circulation (2016)

Introduction: Left ventricular hypertrophy (LVH) secondary to hypertension and aortic stenosis (AS) are often considered together to be pressure overload hypertrophy. Comparisons of myocardial function by the 2 most common causes of LVH are limited. The global LV afterload that may be assessed by valvuloarterial impedance plays a detrimental effect on LV systolic function. Hypothesis: We hypothesized that important differences may exist in the myocardial function with these 2 origins of pressure-overload LVH. Methods: Global LV longitudinal strain (GLS) were measured using speckle-tracking echocardiography in 38 hypertensive LVH (H-LVH) patients and 36 patients with severe AS and preserved LV ejection fraction. To estimate the global LV afterload, we calculated the valvuloarterial impedance (Z va ) as the sum of the systolic arterial pressure and the mean transvalvular pressure gradient divided by the stroke volume index. Results: The patients were divided into two groups according to the level of Z va : low Z va (Z va &lt;3mmHg ml/m 2 , n=25) and high Z va (Z va ≥3mmHg ml/m 2 , n=49). GLS was reduced in the high Z va group (p&lt;0.05). The patients in the high Z va group were divided into two subgroups: AS group (n=28) and H-LVH group (n=21). Systolic blood pressure was higher in the H-LVH group than in the AS group (p&lt;0.0001). However, LV mass index and LV ejection fraction were not significantly differences. GLS was significantly reduced in the AS group (p&lt;0.0001). In the AS group, GLS was significantly correlated with Zva (r=0.44). However, there was no correlation between GLS and mean transaortic pressure gradient. Conclusions: Despite of similar global LV afterload and LV hypertrophy, myocardial LV longitudinal systolic function is impaired in patients with severe AS compared with H-LVH patients. However, there is no correlation between AS severity and LV longitudinal deformation. The magnitude of the global LV afterload as reflected by Z va is a powerful determinant of altered LV longitudinal deformation in severe AS patinets with preserved LV ejection fraction.
Abstract 4214: Characteristics of carcinoembryonic antigen-producing colorectal cancers: A population based study
Authors: Sarah Groover, Pragatheeshwar Thirunavukarasu, Mark E. Payton, Asha Karippot, Rashmi Kaul
Journal: Cancer Research (2018)

Abstract Serum Carcinoembryonic Antigen (CEA) is a tumor marker often found to be elevated in colorectal cancer patients. Elevated CEA has been strongly associated with poor prognosis. However, not all colon cancer tumors produce CEA, and little is known about the patient and tumor characteristics between CEA-producing and non-CEA-producing tumors. We performed a retrospective analysis of all patients (n=120,571) diagnosed with colorectal adenocarcinoma from 2010 to 2014 in the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) database. All patients were designated as either positive/elevated (C1) or negative/normal (C0) based on the pretreatment serum CEA level. We performed univariate and multivariate analyses to identify variables associated with CEA-producing tumors. Of the 68,856 (57.1%) with available CEA information, 33,426 (48.5%) were C1. Median age was 65 years and 36,479 (53.0%) were male. Compared to C0 cancers, C1 cancers were significantly more likely (P&amp;lt;0.001) to be female (49.3%% vs. 47.9%), black (58.4%), separated or never married (55.0% and 54.8%, respectively), higher grade (39.0%, 46.2%, 51.1% and 52.3% of well, moderately, poorly, and undifferentiated cancers, respectively), and of signet ring cell histology (61.1%). Multivariate analysis showed age, sex, race, marital status, and TNM stage to be independent prognostic factors associated with the diagnosis of CEA-producing tumors. This is the first report to describe differences in patient and tumor characteristics between CEA-producing and non-CEA-producing tumors in a large American population. About half of all colorectal adenocarcinomas are associated with elevated pre-treatment serum CEA levels. CEA-producing tumors are associated with female gender, non-Caucasian race, separated or never married marital status at diagnosis, and more extensive local, regional and metastatic disease. Citation Format: Sarah Groover, Pragatheeshwar Thirunavukarasu, Mark E. Payton, Asha Karippot, Rashmi Kaul. Characteristics of carcinoembryonic antigen-producing colorectal cancers: A population based study [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 4214.
Factors Affecting Vaccination in Children and Their Siblings After Autism Spectrum Disorder Diagnosis
Authors: Sarah Qin, Shari King, Sarabeth Broder-Fingert
Journal: JAMA Pediatrics (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Amiodarone Inhibits Production of Tumor Necrosis Factor-α by Human Mononuclear Cells
Authors: AkiraMatsumori, KohOno, RyosukeNishio, YoshisukeNose, ShigetakeSasayama
Journal: Circulation (1997)

Background Recent studies suggest that cytokines such as tumor necrosis factor (TNF)-α and interleukins (ILs) are capable of modulating cardiovascular function and that drugs used in the treatment of heart failure have various modulatory effects on the production of cytokines. This study was performed to examine the effects of amiodarone (a drug shown to be beneficial in some patients suffering from heart failure) versus other antiarrhythmic agents on the production of cytokines in vitro. Methods and Results Human peripheral blood mononuclear cells (PBMC) were obtained from healthy volunteers. PBMC were cultured with 0.1, 1, and 10 μmol/L of amiodarone, quinidine, disopyramide, and lidocaine in the presence of lipopolysaccharide. After 24 hours’ incubation, TNF-α, IL-1β, and IL-6 were measured in the culture supernatants by an enzyme-linked immunosorbent assay. TNF-α production was inhibited by amiodarone but stimulated by quinidine in a concentration-dependent manner. Disopyramide and lidocaine tended to...
Abstract 14779: Lack of Adiponectin Receptor 1 Impairs Mitochondrial Function in the Heart
Authors: Alexandra König, Katharina Pfeil, Maria C Cimolai, Michael M Hoffmann, Christoph Bode, Heiko Bugger
Journal: Circulation (2012)

In Type 2 diabetic rodent models, myocardial mitochondrial dysfunction and downregulation of electron transport chain (ETC) proteins is associated with reduced expression of adiponectin receptors, ...
Abstract 15915: Combined Methylglyoxal Scavenger and Collagen Hydrogel Therapy Improves Function of the Infarcted Heart
Authors: Cagla Eren-Cimenci, Nick J Blackburn, Manuel Ahumada, Brian McNeill, Emilio I Alarcon, Erik J Suuronen
Journal: Circulation (2017)

Introduction and Hypothesis: We recently found that myocardial infarction (MI) stimulates production of the toxic metabolite methylglyoxal (MG), and that its accumulation post-MI contributes to red...
Corrections to “Final analysis of the prospective WSG-AGO EC-Doc versus FEC phase III trial in intermediate-risk (pN1) early breast cancer: efficacy and predictive value of Ki67 expression”
Authors: U Nitz, O Gluz, J Huober, H H Kreipe, R E Kates, A Hartmann, R Erber, Z Moustafa, M Scholz, B Lisboa, S Mohrmann, V Möbus, D Augustin, G Hoffmann, E Weiss, S Böhmer, R Kreienberg, A Du Bois, D Sattler, C Thomssen, M Kiechle, F Jänicke, D Wallwiener, N Harbeck, W Kuhn
Journal: Annals of Oncology (2016)
Serum Cholesterol and Relative Body Weight of Coronary Patients in Different Populations
Authors: Ancelkeys, Flaminiofidanza
Journal: Circulation (1960)

Men under 66 years of age suffering from unequivocal coronary heart disease in the Twin Cities of Minnesota and in Naples, Italy, were compared with clinically healthy men matched in place of residence, age, type of occupation, and socioeconomic status. The Twin Cities patients (N = 72) did not differ in relative body weight from their controls (N = 338) and the average relative weight of both groups was less than either of the 2 Naples coronary groups and the upper class Naples control subjects. The average relative body weight of the upper class Naples coronary patients (N = 54) was insignificantly greater than that of their controls (N = 89). The Naples working class coronary patients (N = 54) had a significant tendency to be more often overweight than their controls (N = 144). The serum total cholesterol concentration was significantly higher in each of the 3 groups of coronary patients than in their corresponding controls and the 3 groups, control and coronary, formed a sharp progression from high to...
Abstract 360: The role of polybromo1 in stress response
Authors: Elizabeth G. Porter, Emily C. Dykhuizen
Journal: Cancer Research (2018)

Abstract Polybromo1 (PBRM1) is mutated in 3.5% of human cancers with the highest incident in renal clear cell carcinoma (40%). PBRM1 is a member of the PBRM1-Brg-Associating Factors (PBAF) chromatin remodeling complex and is characterized by six tandem bromodomains. PBRM1 acts as a tumor suppressor and when deleted along with VHL, the most frequently mutated gene in RCCC, tumors develop in mice. We have previously shown that PBRM1 regulates the expression of genes involved in cell adhesion, apoptosis, and negative cell proliferation in a RCCC cell line. Additionally, we have demonstrated that four of the six bromodomains work together to regulate binding of the complex to chromatin, gene expression, and tumor suppression in RCCC, which correlates with pattern of PBRM1 missense mutations found in RCCC patient tumors. Through this work we identified histone 3 lysine 14 acetylation (H3K14Ac) as the chromatin mark essential for PBRM1 binding. While H3K14Ac is generally found at active promoters, it is also induced at the promoters of stress genes when cells experience stressors such as metabolic stress, osmotic stress, ER stress, or reactive oxygen species (ROS) stress. Knockdown of PBRM1 in normal epithelial cells leads to an increase in proliferation and a partial epithelial to mesenchymal transition (EMT), consistent with low grade ROS. RNA-seq analysis further confirmed a role for PBRM1 in regulating stress response genes. Although loss of PBRM1 increases proliferation in epithelial cells, it also increases cell vulnerability to high levels of ROS. Together this suggests that PBRM1 can be growth promoting or growth inhibiting to cells depending on the cells environment and stress response needs. Citation Format: Elizabeth G. Porter, Emily C. Dykhuizen. The role of polybromo1 in stress response [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 360.
Abstract CT019: ASN003, a novel highly selective BRAF and PI3K dual inhibitor: Phase I PK/PD results in patients with advanced solid tumors
Authors: Drew Rasco, Nehal Lakhani, Ryan Sullivan, Monica Mita, Jaimini Shah, Helen Usansky, Sanjeeva Reddy, Niranjan S. Rao, Sarper Toker, Louis Denis, Keith Flaherty, Anthony Tolcher
Journal: Cancer Research (2018)

Abstract Background RAS-RAF-MEK and PI3K-AKT-mTOR are two major pathways involved in tumor cell signaling and growth. Components of these pathways are frequently mutated in a broad range of tumors. ASN003 is a highly selective and potent (low nM IC50) inhibitor of BRAF and PI3K-α and -δ. ASN003 shows strong antitumor activity in tumor models harboring BRAF and PIK3CA mutations, and also in patient-derived xenograft (PDX) models that are resistant to selective BRAF and MEK inhibitors. Patients and Methods: Oral once-daily ASN003 is being evaluated for safety/tolerability and preliminary efficacy in eligible patients with advanced solid tumors using an accelerated dose titration design (Part A) and enrolling cohorts of patients diagnosed with melanoma, CRC, NSCLC and other solid tumors with a BRAF, PIK3CA mutations at MTD (Part B). Pharmacokinetic (PK) profile and the pharmacodynamic (PD) effects of ASN003 on tumor tissue biomarkers such as pERK and pS6 are being investigated in both parts of the study. Results: Patient accrual in Part A is ongoing. As of January 2018, fifteen eligible patients were enrolled in dose levels ranging from 10 - 400 mg QD and 400 mg BID. ASN003 has been well tolerated. Treatment-related adverse events (TRAEs) were mostly mild (G1) to moderate (G2). TRAEs include, rash (G3), hypersensitivity (G3) (n=1), diarrhea (G2) (n=1), hyperglycemia (G2) (n=1), rash maculo-papular (G2) (n=1), vomiting (G1) (n=3), nausea (G1) (n=2), hyperglycemia (G1) (n=2), and dry mouth/lips/skin, transient blurred vision, rash acneiform, ALT increase, cognitive disturbance and hyperkalemia. The PK profile showed dose-dependent increase in systemic exposure at steady state (Cmax up to 5,990 ng/mL, AUC0-T up to 110,000 ng.h/mL) and a half-life of 14-25 hours in general. Early evidence of biomarker changes in repeat biopsies, and clinical disease control have been observed. Conclusions: ASN003 is a novel small molecule, with uniquely selective and potent inhibition of BRAF, PI3K-α and -δ kinases. To date, ASN003 was well tolerated at doses up to 400 mg QD/BID and achieved good systemic exposure. Updated and detailed clinical safety/efficacy and PK/PD results will be presented. Citation Format: Drew Rasco, Nehal Lakhani, Ryan Sullivan, Monica Mita, Jaimini Shah, Helen Usansky, Sanjeeva Reddy, Niranjan S. Rao, Sarper Toker, Louis Denis, Keith Flaherty, Anthony Tolcher. ASN003, a novel highly selective BRAF and PI3K dual inhibitor: Phase I PK/PD results in patients with advanced solid tumors [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 CT019.
Myc Regulates Embryonic Vascular Permeability and Remodeling
Authors: EniköKokai, FlorianVoss, FrankFleischer, SybilleKempe, DraganMarinkovic, HartwigWolburg, FrankLeithäuser, VolkerSchmidt, UrbanDeutsch, ThomasWirth
Journal: Circulation Research (2009)

Previous work has shown that c-Myc is required for adequate vasculogenesis and angiogenesis. To further investigate the contribution of Myc to these processes, we conditionally expressed c-Myc in embryonic endothelial cells using a tetracycline-regulated system. Endothelial Myc overexpression resulted in severe defects in the embryonic vascular system. Myc-expressing embryos undergo widespread edema formation and multiple hemorrhagic lesions. They die between embryonic days 14.5 and 17.5. The changes in vascular permeability are not caused by deficiencies in vascular basement membrane composition or pericyte coverage. However, the overall turnover of endothelial cells is elevated as is revealed by increased levels of both proliferation and apoptosis. Whole-mount immunohistochemical analysis revealed alterations in the architecture of capillary networks. The dermal vasculature of Myc-expressing embryos is characterized by a reduction in vessel branching, which occurs despite upregulation of the proangiogen...
Targeting the MTF2–MDM2 Axis Sensitizes Refractory Acute Myeloid Leukemia to Chemotherapy
Authors: Harinad B. Maganti, Hani Jrade, Christopher Cafariello, Janet L. Manias Rothberg, Christopher J. Porter, Julien Yockell-Lelièvre, Hannah L. Battaion, Safwat T. Khan, Joel P. Howard, Yuefeng Li, Adrian T. Grzybowski, Elham Sabri, Alexander J. Ruthenburg, F. Jeffrey Dilworth, Theodore J. Perkins, Mitchell Sabloff, Caryn Y. Ito, William L. Stanford
Journal: Cancer Discovery (2018)

Abstract Deep sequencing has revealed that epigenetic modifiers are the most mutated genes in acute myeloid leukemia (AML). Thus, elucidating epigenetic dysregulation in AML is crucial to understand disease mechanisms. Here, we demonstrate that metal response element binding transcription factor 2/polycomblike 2 (MTF2/PCL2) plays a fundamental role in the polycomb repressive complex 2 (PRC2) and that its loss elicits an altered epigenetic state underlying refractory AML. Unbiased systems analyses identified the loss of MTF2–PRC2 repression of MDM2 as central to, and therefore a biomarker for, refractory AML. Thus, immature MTF2-deficient CD34+CD38− cells overexpress MDM2, thereby inhibiting p53 that leads to chemoresistance due to defects in cell-cycle regulation and apoptosis. Targeting this dysregulated signaling pathway by MTF2 overexpression or MDM2 inhibitors sensitized refractory patient leukemic cells to induction chemotherapeutics and prevented relapse in AML patient-derived xenograft mice. Therefore, we have uncovered a direct epigenetic mechanism by which MTF2 functions as a tumor suppressor required for AML chemotherapeutic sensitivity and identified a potential therapeutic strategy to treat refractory AML. Significance: MTF2 deficiency predicts refractory AML at diagnosis. MTF2 represses MDM2 in hematopoietic cells and its loss in AML results in chemoresistance. Inhibiting p53 degradation by overexpressing MTF2 in vitro or by using MDM2 inhibitors in vivo sensitizes MTF2-deficient refractory AML cells to a standard induction-chemotherapy regimen. Cancer Discov; 8(11); 1376–89. ©2018 AACR. See related commentary by Duy and Melnick, p. 1348. This article is highlighted in the In This Issue feature, p. 1333
The Multiple Phases and Faces of Wnt Signaling During Cardiac Differentiation and Development
Authors: SusanneGessert, MichaelKühl
Journal: Circulation Research (2010)

Abstract: Understanding heart development on a molecular level is a prerequisite for uncovering the causes of congenital heart diseases. Therapeutic approaches that try to enhance cardiac regeneration or that involve the differentiation of resident cardiac progenitor cells or patient-specific induced pluripotent stem cells will also benefit tremendously from this knowledge. Wnt proteins have been shown to play multiple roles during cardiac differentiation and development. They are extracellular growth factors that activate different intracellular signaling branches. Here, we summarize our current understanding of how these factors affect different aspects of cardiogenesis, starting from early specification of cardiac progenitors and continuing on to later developmental steps, such as morphogenetic processes, valve formation, and establishment of the conduction system.
Abstract 17971: Overexpression of Nicotinamide Phosphoribosyltransferase (NAMPT) Negatively Regulates Cardiac Function in Response to Pressure Overload in Mice
Authors: Jaemin Byun, Peiyong Zhai, Yoshiyuki Ikeda, Shinichi Oka, Junichi Sadoshima
Journal: Circulation (2017)

Nicotinamide phosphoribosyltransferase (NAMPT) is a rate-limiting enzyme in the salvage pathway of NAD+ synthesis. Besides respiration and oxidative phosphorylation, NAD+ is required as a cofactor ...
Point Mutation in the HCN4 Cardiac Ion Channel Pore Affecting Synthesis, Trafficking, and Functional Expression Is Associated With Familial Asymptomatic Sinus Bradycardia
Authors: EyalNof, DavidLuria, DovratBrass, DinaMarek, HadasLahat, HayaReznik-Wolf, ElonPras, NathanDascal, MichaelEldar, MichaelGlikson
Journal: Circulation (2007)

Background— The hyperpolarization-activated nucleotide-gated channel-HCN4 plays a major role in the diastolic depolarization of sinus atrial node cells. Mutant HCN4 channels have been found to be associated with inherited sinus bradycardia. Methods and Results— Sixteen members of a family with sinus bradycardia were evaluated. Evaluation included a clinical questionnaire, 12-lead ECGs, Holter monitoring, echocardiography, and treadmill exercise testing. Eight family members (5 males) were classified as affected. All affected family members were asymptomatic with normal exercise capacity during long-term follow-up. Electrophysiological testing performed on 2 affected family members confirmed significant isolated sinus node dysfunction. Segregation analysis suggested autosomal-dominant inheritance. Direct sequencing of the exons encoding HCN4 revealed a missense mutation, G480R, in the ion channel pore domain in all affected family members. Function analysis, including expression of HCN4 wild-type and G480R...
Infectious events and associated risk factors in mycosis fungoides/Sézary syndrome: a retrospective cohort study
Authors: R. Blaizot, E. Ouattara, A. Fauconneau, M. Beylot-Barry, A. Pham-Ledard
Journal: British Journal of Dermatology (2018)

Infections are one of the major causes of death in patients with advanced-stage mycosis fungoides (MF) or Sézary syndrome (SS). However, few recent data are available on the characteristics and risk factors of these infectious events.To describe infectious events occurring in a cohort of patients with MF/SS, and to identify associated clinical and biological risk factors.A retrospective cohort study was performed to investigate infectious events and associated factors in patients diagnosed with MF (stage IB and beyond) or SS followed from May 2011 to May 2016 at the University Hospital of Bordeaux, France.Seventy-one patients with complete follow-up were included. Eighty infectious events were recorded in 40 patients, including 28 skin and soft tissue infections and 25 cases of pneumonia. Opportunistic infections, which are usually associated with depleted cell-mediated immunity, were scarce (9%). In multivariate analysis, cardiac, renal or lung comorbidities [odds ratio (OR) 7·2, 95% confidence interval (CI) 3·3-15·9; P = 0·002], SS (OR 8·8, 95% CI 7·7-10·2; P = 0·037) and lymphocyte count < 0·5 × 109 cells L-1 (OR 6·4, 95% CI 1·5-27·4; P = 0·004) were significantly associated with a higher risk of infection.Opportunistic germs were rarely recorded, but their incidence was probably prevented by adequate prophylaxis (ongoing in 28% of patients). As in patients living with AIDS, pneumonias were frequent. On the other hand, bacterial cutaneous infections represent a specific pattern in patients with MF/SS. Patients with chronic organ failure, lymphocytopenia and SS should be considered as being at high risk for infectious events. Pneumococcal vaccination should be systematically recommended, and prophylaxis with co-trimoxazole and valaciclovir when the CD4 count is < 0·2 × 109 cells L-1 .
Idiopathic pulmonary fibrosis: time for greater expectations?
Authors: Wim Wuyts, Vincent Cottin
Journal: European Respiratory Journal (2018)

<b>Based on two studies published in the <i>ERJ</i>, maybe the time has come to raise the bar and target larger goals for IPF treatment when designing new treatment approaches, goals that might better fit patients’ expectations</b>http://ow.ly/MsJR30kZtPf