tbuckley/cabot-search huggingface dataset:
Abstract 20657: Plasma MicroRNAs Correlate With Platelet Reactivity in Patients With Acute Coronary Syndrome: Association With Platelet Function
Authors: Manuel Mayr, Dorothee Kaudewitz, Philipp Skroblin, Peter Willeit, Anna Zampetaki, Allison C Morton, Robert F Storey
Journal: Circulation (2014)

Introduction: Platelets contribute plasma microRNAs (miRNAs). Levels of platelet-related miRNAs change in plasma in response to platelet inhibition. Hypothesis: It is currently unclear how plasma miRNAs correlate to platelet function in patients with acute coronary syndrome (ACS). Methods: We measured plasma miRNAs in 125 patients with a history of ACS (STEMI, NSTEMI or unstable angina) who have undergone detailed assessment of platelet function 30 days after the acute event. Results: Using custom-made quantitative real-time polymerase chain reaction plates, 92 miRNAs were assessed in patients on different anti-platelet therapies (clopidogrel, prasugrel, aspirin). Key platelet-related miRNAs were correlated with platelet function tests, including optical aggregometry using the agonists ADP and arachidonic acid, VerifyNow P2Y12 assay and vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay. Significant associations were obtained for miR-126 with the VerifyNow (rp=0.347, n=39, P=0.033) and VASP assay (rp=0.224, n=125, P=0.013). Other abundant platelet miRNAs also showed strong correlations with the VASP assay: miR-223 (rp =0.231, P=0.003), miR-191 (rp =0.243, P=0.007), miR-24 (rp =0.246, P=0.006), miR-197 (rp=0.293, P=0.008), miR-30b (rp=0.230, P=0.010) and miR-20b (rp=0.231 , P=0.010). Conclusions: Levels of platelet-related plasma miRNAs correlate with platelet function tests in ACS patients. Our findings reinforce the concept that platelets are an important contributor to the plasma miRNA pool.
Abstract 16169: Individual and Regional Determinants of Time in Therapeutic Range Among Patients Randomized to Warfarin in the ROCKET AF Trial of Rivaroxaban
Authors: Daniel E Singer, Anne S Hellkamp, Jonathan L Halperin, Kenneth W Mahaffey, Richard C Becker, Gunter Breithardt, Graeme J Hankey, Werner Hacke, Manesh R Patel, Robert M Califf, Keith A Fox
Journal: Circulation (2011)

Background: Time in the therapeutic range (TTR) of INR 2-3 is a common measure of warfarin anticoagulation quality. We explored individual and regional determinants of TTR among patients randomly a...
Abstract 2878: Modulation of Autonomic Function in Patients Undergoing Circumferential or Segmental Pulmonary Vein Ablation for Paroxysmal Atrial Fibrillation
Authors: Axel Bauer, Isabel Deisenhofer, Raphael Schneider, Petra Barthel, Bernhard Zrenner, Claus Schmitt, Georg Schmidt
Journal: Circulation (2006)

Background: Circumferential and segmental pulmonary vein ablation (CPVA and SPVA) are two established interventional treatment strategies for ablation of atrial fibrillation. Both techniques requir...
Molecular and functional analysis of the SLIT2 gene in breast cancer
Authors: Rachel E. Dickinson, Ashraf Dallol, Eammon R. Maher, Farida Latif
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

2799 

The SLIT2 gene encodes a secreted glycoprotein that acts as a ligand for the ROBO transmembrane receptors. Studies suggest that the SLIT2-ROBO1 interaction plays an important role in migration of cells in both the nervous and immune system. SLIT2 also seems to be involved in human cancer development. In several types of cancer loss of heterozygosity (LOH) at the SLIT2 (4p15.2) locus was shown. We have previously demonstrated that the CpG island of the SLIT2 gene is frequently hypermethylated in breast, lung, colorectal and glioma primary tumours. Recently we detected methylation of the SLIT2 promoter region in DCIS (ductal carcinoma in situ ) lesions indicating that inactivation of this gene may play a role in early stages of breast cancer. We also found hypermethylation of the SLIT3 promoter region in breast and colorectal tumours albeit to a lesser degree than SLIT2. In addition we have shown that secreted SLIT2 has the ability to induce apoptosis in colorectal tumour cell lines. Colony formation and soft agar assays have also demonstrated that exogenous expression of SLIT2 can significantly suppress growth of breast tumour cell lines. SLIT2 expressing stable clones, generated from a breast tumour cell line that does not normally express this gene, were used for gene target identification. Expression microarray analysis identified 60 genes differentially regulated by SLIT2 that are now being confirmed by quantitative real-time RT-PCR. Among these targets are genes involved in cell cycle, apoptosis, cell adhesion, signalling, protein synthesis and transcription. We have also used siRNA to successfully knock down endogenous SLIT2 in a breast tumour cell line. We will investigate the properties of these cells by analysing their cell cycle profile along with carrying out apoptosis, cell migration and growth suppression assays. Overall there is increasing evidence supporting a role for SLIT2 as a tumour suppressor gene involved in breast cancer development.
Abstract 9407: Overexpression of R120g {alpha}{beta} -Crystallin Causes Cardiac Arrhythmias, Reduced Heart Rate Variability, Alteration in the Expression Of Ca2+ Handling Proteins and Er Stress in Mice
Authors: Qibin Jiao, Atsushi Sanbe, Susumu Minamisawa
Journal: Circulation (2011)

Upregulation of αβ-crystallin (Cryαβ), a small heat shock protein, is associated with a variety of diseases, including desmin-related myopathies. Cryαβ, which binds to both desmin and cytoplasmic a...
Abstract 75: Body Weight-Related Adjustments to Chest Compression Depth by EMS Providers During Out-of-Hospital Cardiac Arrest
Authors: Jason R Roosa, Daniel W Spaite, Ashish R Panchal, Uwe Stolz, Tyler F Vadeboncoeur, Annemarie Silver, Karl B Kern, Bentley J Bobrow, Gordon A Ewy
Journal: Circulation (2011)

Background: The 2010 AHA Guidelines state rescuers should perform chest compressions (CCs) of at least 2 inches in depth for adult cardiac arrest patients. Although the pediatric guidelines recommend adjustment of CC depth based upon anteroposterior chest dimension, there is no such recommendation for adults. Purpose: To determine 1) whether prehospital providers intuitively vary CC depth in adults according to patient size and 2) whether implementation of real-time audiovisual CPR feedback (RTAVF) impacts weight/CC depth variation. Methods: CC quality data were prospectively collected prior to (9/08-4/10; Pre-feedback) and after (5/10-12/10; Post-feedback) implementation of an RTAVF system (ZOLL Medical, Chelmsford MA) from 3 EMS agencies. The RTAVF includes a visual display of absolute CC depth and gives audio prompts when depth is outside of the Guideline-recommended range. Among 363 cases of adult, non-traumatic out-of-hospital cardiac arrest (OHCA), body weight was estimated by EMS in 249 patients (study group; 66%). CPR quality data were available for all cases via code review software. Results: 168 Pre-feedback and 81 Post-feedback study group cases (mean 64±16 years, 68% male). Mean estimated body weight was 201 lbs (quartiles 161, 231; range 70-451) and was not different between groups. CC depth increased significantly with RTAVF use (Pre-feedback = 1.77, 95% confidence interval [CI]:1.71-1.83 in.; Post-feedback = 2.10, CI: 2.04-2.15 in.; p&lt;0.001). CC depth did not vary significantly by patient gender or age (p&gt;0.4). Multivariate linear regression (r 2 =0.23, p&lt;0.001 for model) revealed a significant increase in CC depth with estimated weight in both periods (0.07in/50lbs, p&lt;0.001) after controlling for the presence of RTAVF. RTAVF was not an effect-modifier of the relationship between estimated weight and CC depth (p-value for interaction term=0.4). Conclusion: Although not specifically recommended in the 2010 AHA Guidelines for adults, rescuers may instinctively and/or intentionally adjust CC depth according to patient size. In this setting, weight/CC depth adjustments occurred both without and with real-time feedback. Follow-up studies are needed to determine the potential effect of size-adjusted CC depth on patient outcome.
Atrial Tachycardia After Circumferential Pulmonary Vein Ablation of Atrial Fibrillation
Authors: Sanders Chae, Hakan Oral, Eric Good, Sujoya Dey, Alan Wimmer, Thomas Crawford, Darryl Wells, Jean-Francois Sarrazin, Nagib Chalfoun, Michael Kuhne, Jackie Fortino, Elizabeth Huether, Tammy Lemerand, Frank Pelosi, Frank Bogun, Fred Morady, Aman Chugh
Journal: Journal of the American College of Cardiology (2007)
Abstract 504: Tie2-Mediated Loss of Peroxisome Proliferator-Activated Receptor-{gamma} in Transgenic Mice Increases Platelet Derived Growth Factor-Receptor {beta} and Pulmonary Arterial Muscularization
Authors: Christophe Guignabert, Cristina M Alvira, Tero-Pekka Alastalo, Hirofumi Sawada, Vinicio De Jesus Perrez, Georg Hansmann, Mingming Zhao, Lingli Wang, Nesrine El-Bizri, Marlene Rabinovitch
Journal: Circulation (2008)

Peroxisome Proliferator-Activated Receptor (PPAR)-γ is reduced in pulmonary arteries (PA) of PA hypertension (PAH) patients, and we reported that deletion of PPARγ in smooth muscle cells (SMCs) of ...
Abstract 1194: Lp-PLA2 is Weakly to Modestly Correlated with Insulin, Visceral Fat, and Lipids and Lipoproteins, but is Uncorrelated with C-Reactive Protein (hsCRP) and Blood Pressure: The HERITAGE Family Study
Authors: Gordon A Ewy, Jack H Wilmore, Tuomo Rankinen, Arthur S Leon, D.C. Rao, James S Skinner, Claude Bouchard
Journal: Circulation (2006)
Human B lymphoma cell lines and primary B cells actively secrete Granzyme B in response to IL-2 family cytokines
Authors: Magdalena Hagn, Thamara Beyer, Sue Blackwell, George Weiner, Thomas Simmet, Bernd Jahrsdorfer
Journal: Cancer Research (2008)

1032   It is widely believed that the main function of B cells is antibody secretion, but not cellular cytotoxicity. Recently we found that human B cells activated with interleukin 21 (IL-21) and antibodies to the B cell receptor (BCR) or immunostimulatory oligonucleotides (CpG ODN) develop a phenotype similar to that of cytotoxic T lymphocytes. B cells treated in such a way start to secrete large amounts of granzyme B (GrB) instead of antibodies and, as in the case of B-chronic lymphocytic leukemia (B-CLL), acquire the capability to induce apoptosis in bystander B-CLL cells in a GrB-dependent manner. Using FACS and ELISpot analyses we could now demonstrate that GrB is actively secreted by B cells in a time-dependent manner and that IL-21 is not the only cytokine that induces GrB in B cells. Also cytokine combinations such as IL-10 and IL-4 as well as IL-10 and IFN-alpha induce GrB in normal B cells and various B lymphoma cell lines including MEC-1 (CLL), ARH-77 (plasma cell leukemia), SU-DHL-5 (large cell lymphoma) and Namalwa (Burkitts lymphoma). We conclude that IL-21 and further cytokines can induce B cells to produce functional granzyme B. Further studies are required to elucidate the interactions with B lymphocytes of cells producing these cytokines such as CD4+ T cells, regulatory T cells, NKT cells and plasmacytoid dendritic cells. Our unexpected findings could have significant implications on our understanding of the role of B cells in cancer immunity, open new approaches to treat B cell malignancies and may add novel components to future immunotherapeutic strategies.
Risk factors for acanthamoeba keratitis
Authors: D. V Seal, J. Hay
Journal: BMJ (1995)

Population study is required to confirm results

EDITOR,--Cherry F Radford and colleagues' highly publicised paper concerning possible risk factors for acanthamoeba keratitis in contact lens users contains some potentially misleading comments.1 Their extrapolation of limited data into sweeping generalisations seems unhelpful in providing a rational approach to understanding of the multiplicity of factors associated with acquisition of this rare but potentially sight threatening condition. Frequent replacement of storage cases will not alone prevent acanthamoebal growth and replication if chlorine based disinfection is used, since these products do not generate sufficient active …
Sinusitis and rhinitis, or rhinosinusitis?
Authors: J. Rowe-Jones, I. Mackay
Journal: BMJ (1995)

excision or mastectomy for breast cancer is prob- ably at least 20%,2 and mild discomfort may be experienced even more commonly.The pain is usually a late onset phenomenon, developing any- thing from a few months to several years after treatment.This problem is frequently encountered in both hospital and general practice, and failure to recog- nise the syndrome can lead to much anxiety for the patient and often fruitless and unnecessary investigations.
Pharmacologic demethylation identifies UCHL1 as a tumor suppressor gene frequently silenced in nasopharyngeal and multiple other carcinomas
Authors: Ada Wong, Qian Tao, Jianming Ying, Xian Wang, Fion Sung, Andrew van Hasselt, Mu-Sheng Zeng, Wei Hua Jia, Yi-Xin Zeng, Anthony Chan
Journal: Cancer Research (2007)

257   Nasopharyngeal carcinoma (NPC) is a common tumor in Southern China and Southeast Asia with remarkable racial and geographic distribution. Aberrant CpG methylation associated with transcriptional silencing of tumor suppressor genes (TSGs) is known to be involved in its pathogenesis. To elucidate more the molecular mechanism of NPC pathogenesis and identify more epigenetic biomarkers, we performed microarray expression analysis to screen for upregulated genes in NPC cells after the demethylating treatment with 5-aza-29-deoxycitidine (Aza). Among a few upregulated genes identified was  UCHL1 (or PGP9.5) , a member of the carboxyl-terminal ubiquitin hydrolase family involved in carcinogenesis. A typical CpG island (CGI) in its promoter was heavily methylated in all NPC cell lines with downregulated or silenced expression, while both methylated and unmethylated alleles are detected in an immortalized nasopharyngeal epithelial cell line NP69, which expresses  UCHL1 . Aza treatment or genetic knock-out of DNA methyltranferases  DNMT1  and  DNMT3B  in tumor cells induced demethylation and restored  UCHL1  expression, indicating methylation directly-mediated silencing.  UCHL1  downregulation and methylation was also frequently observed in other common carcinoma cell lines, including colorectal, breast, cervical, hepatocellular, gastric and esophageal carcinomas, but its expression was ubiquitously detected in all normal tissues examined. Furthermore,  UCHL1  methylation was frequently detected in primary tumors. Ectopic expression of  UCHL1  inhibited the colony formation of tumor cells. Thus, these results demonstrated that  UCHL1  is a putative TSG epigenetically inactivated in NPC and multiple other tumors, and involved in multiple carcinogenesis (supported by RGC Grant CUHK4443/05M)
Prolactin in psychiatry
Authors: J R de la Fuente, A H Rosenbaum
Journal: American Journal of Psychiatry (1981)

Prolactin is a protein hormone synthesized and secreted by the anterior pituitary gland. Because the monoamines dopamine and serotonin are important in the control of its secretion, prolactin has been the subject of much psychoendocrine research in recent years. The authors review some of the implications of the main findings of such research as they relate to schizophrenia, affective disorders, premenstrual syndrome, and alcoholism and discuss its possible usefulness to clinicians. As a research strategy, prolactin studies have a good potential for identifying specific neurotransmitters involved in discrete psychopathologic entities.
P1191 : Increased IgG4 responses to multiple environmental antigens indicate a polyclonal expansion and differentiation of pre-existing B cells in autoimmune pancreatitis and IgG4 -related cholangitis
Authors: E.L. Culver, M. Makuch, E. Vermeulen, A. van Leeuwen, R. Sadler, T. Cargill, P. Klenerman, R.C. Aalberse, S.M. Van Ham, E. Barnes, T. Rispens
Journal: Journal of Hepatology (2015)
Differences in Fabry Cardiomyopathy Between Female and Male Patients
Authors: Markus Niemann, Sebastian Herrmann, Kai Hu, Frank Breunig, Jörg Strotmann, Meinrad Beer, Wolfram Machann, Wolfram Voelker, Georg Ertl, Christoph Wanner, Frank Weidemann
Journal: JACC. Cardiovascular imaging (2011)
Changes to the varicella and pertussis immunisation schedule in Germany 2009: Background, rationale and implementation
Authors: M Wiese-Posselt, W Hellenbrand
Journal: Eurosurveillance (2010)

In July 2009, the German Standing Committee on Vaccination (STIKO) modified its recommendations for varicella and pertussis vaccination, based on newly available data on disease epidemiology, vaccine effectiveness (VE) and safety, and an evaluation of the feasibility of the recommended immunisation strategy. The recommendation for varicella vaccine now includes a routine two-dose schedule with the administration of the first dose at the age of 11 to 14 months and the second dose at the age of 15 to 23 months, with a minimum interval of four weeks between these doses. Furthermore, STIKO recommended adding a one-time pertussis booster to the adult vaccination schedule to expand the cocoon strategy in place since 2004. The recommendation of a booster vaccination with an acellular pertussis vaccine every 10 years for persons employed in the care of pre-school children and for healthcare personnel in paediatric, gynaecologic and obstetric health facilities was extended to persons employed in schools and in other institutions caring for older children, and to all healthcare personnel. These recommendations were based on available epidemiological data showing an increase in incidence from 7-10 cases per 100,000 inhabitants in 2002-2004 to over 30 by 2007. Moreover, the high burden of pertussis in infants at 94 hospitalised cases per 100,000 infants in 2007 suggested that the previous cocoon strategy was insufficient.
Wound assessment
Authors: Joseph E Grey, Stuart Enoch, Keith G Harding
Journal: BMJ (2006)

Most wounds, of whatever aetiology, heal without difficulty.Some wounds, however, are subject to factors that impede healing, although these do not prevent healing if the wounds are managed appropriately.A minority of wounds will become chronic and non-healing.In these cases the ultimate goal is to control the symptoms and prevent complications, rather than healing the wound.
Abstract 9613: Left Ventricular Dyssynchrony (LVD) in Children With End-Stage Renal Disease
Authors: Daisuke Kobayashi, Sheetal Patel, Tej Mattoo, Rudolph Valentini, Sanjeev Aggarwal
Journal: Circulation (2011)

Introduction: Left ventricular dyssynchrony (LVD) adversely affects systolic performance and regional myocardial perfusion and metabolism. The association between LVD and end-stage renal disease (ESRD) in children has not been previously investigated. Hypothesis: 1. LVD in children with ESRD would be significantly increased compared to controls 2. Children undergoing peritoneal (PD) and hemodialysis (HD) would have comparable LVD. Methods: Prospective observational study in which real-time 3-D echocardiographic data were acquired in 27 stable children with ESRD (13 PD and 14 HD) and 29 normal controls. For children with HD, data were acquired before and after a HD session. Dyssynchrony index (SDI) was defined as standard deviation of the time to reach minimum regional volume for 16, 12 and 6 segments. SDI was normalized to duration of cardiac cycle (SDIp). Left ventricular mass (LVM) was obtained from the short-axis view on M-mode echocardiography and was normalized to height 2.7 (LVM index). Means were compared by paired t test. Results: The mean age of children with ESRD was higher than that of controls (13.8 vs 11.3 years; p= 0.012) while gender distribution, height, weight and body surface areas were comparable. SV, ESV, SDI, SDIp, LVM and LVM index were significantly higher in those with ESRD (Table). Demographics and HR were comparable between HD and PD subgroups while EDV, ESV, SV, SDI 16 and 12 segments, SDIp 16 segments and LVM were significantly higher in the HD group (P &lt;0.05). SDI and SDIp 16 segments significantly improved after a HD session (p &lt;0.05); LVM and LVM index remained unchanged. There was no correlation between SDIp and LVM. Conclusions: Children with ESRD have significant LVD and increased LVM compared to controls. LVD and increased LVM in those undergoing HD and the improvement in synchrony following a HD session suggest that volume may modulate LVD. We speculate that LVD in children with ESRD may have pathogenic implications.
The actin filament associated protein (AFAP-110) is overexpressed and contributes to prostate carcinoma development by regulating PKC α-mediated fibronectin expression
Authors: Jing Zhang, Serk In Park, Marlene Artime, Justin Summy, Ami Shah, Daniel Flynn, Gary Gallick
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

2459 

The actin filament-associated protein, AFAP-110, first identified as a classic substrate of the non-receptor tyrosine kinase, Src, was subsequently implicated in protein kinase Cα (PKCα) signaling. Parallel with the important roles of several other Src substrates in human tumor development and progression, we demonstrate that AFAP-110 expression contributes to human prostate cancer growth. Using prostate tissue arrays, we found that AFAP-110 was absent or expressed at very low levels in normal prostatic epithelium and benign prostatic hyperplasia, but was significantly increased in prostate carcinomas. Additionally, the expression of AFAP-110 positively correlated with Gleason grades, indicating a potential role in prostate cancer progression. Down-regulation of AFAP-110 in PC3 prostate cancer cells resulted in decreased cell proliferation and anchorage-independent growth in vitro, as well as reduced tumor incidence and growth in orthotopic nude mouse models. Furthermore, down-modulation of AFAP-110 significantly decreased cell-matrix adhesion and migration, correlating with reduced focal adhesions. To further understand the underlying molecular mechanisms by which AFAP regulates prostate cancer growth, we utilized an extracellular matrix (ECM) and adhesion molecule mRNA microarray and identified a significant decrease in fibronectin expression in AFAP-110 down-regulated clones, accompanied by reduced protein level of major fibronectin receptor, integrin α5β1. In agreement with AFAP-110 affecting PKCα signaling, down-regulation of AFAP-110 decreased PKCα-mediated fibronectin expression. These data suggest that AFAP-110 regulates critical signaling pathways governing PKCα-mediated ECM protein expression in regulating prostate cancer cell adhesiveness and motility. Thus, AFAP-110 may be a novel prognostic marker for prostate cancer that functions, in part, by regulating cell-ECM interaction.