tbuckley/cabot-search huggingface dataset:
Abstract LB-164: Aurora Kinase A as a target for sensitizing glioma cells to radiation treatment
Authors: Disha Patel, Nicolaus Gordon, Katsyuki Shirai, Arnab Chakravarti
Journal: Cancer Research (2010)

Abstract Purpose: Eukaryotic cells have a complex cell cycle process that is regulated by many factors. Tumors arise when cell cycle progression is deregulated. Mitosis is a well coordinated event and occurs only when proper signals allow the cell cycle machinery to proceed beyond the G2/M checkpoint. Aurora kinase A (AurKA) is a mitotic regulator involved in bipolar-spindle assembly and chromosome segregation, and also recruits other proteins and cofactors that are important for mitotic events. AurKA is upregulated in many cancers and has been shown to cause aneuploidy and induce oncogenic transformation. AurKA overexpression allows cells to surpass the G2/M checkpoint and enter mitosis prematurely, which leads to chromosomal abnormalities and genomic instability. Experimental Design: Here we are investigating AurKA in established (ATCC) and primary glioblastoma (GBM) cell lines. Assays measuring radiosensitivity were conducted using wild-type and AurKA knockdown GBM cells. These include the clonogenic survival assay, MTS proliferation assay, cell-cycle analysis, and Annexin V apoptosis assay. Protein profiles were used to investigate pro-apoptotic, anti-apoptotic, and other downstream and upstream signaling pathways after radiation treatment. Results and Discussion: Irradiation induces AurKA expression in both our established and primary GBM cell lines. Next we silenced AurKA using lentiviral mediated shRNA transduction. AurKA knockdown cells exhibit greater radiosensitivity when compared to cells transduced with a mock vector. AurKA and p53 interact at multiple levels. Preclinical data with AurKA inhibitors suggest p53-negative tumors may be more sensitive to AurKA inhibitors than p53-positive tumors. To investigate which subset of GBMs show greater response to AurKA silencing, we will conduct experiments using our panel of isogenic GBM cells lines. Our hypothesis is that AurKA knockdown cells will show reduced proliferation and increased apoptosis, thereby leading to cell death. The outcome of this preclinical study would be to evaluate AurKA as a potential therapeutic target for the treatment of GBM. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-164.
Serial volumetric (three-dimensional) intravascular ultrasound analysis of restenosis after directional coronary atherectomy
Authors: Evelyn A de Vrey, Gary S Mintz, Clemens von Birgelen, Takeshi Kimura, Masakiyo Noboyoshi, Jeffrey J Popma, Patrick W Serruys, Martin B Leon
Journal: Journal of the American College of Cardiology (1998)
TCT-4 Delayed Revascularization in High-Risk Non-ST Elevation Myocardial Infarction Patients Reflects a Clinical Decision not a Risk Score
Authors: Nevin C. Baker, Ricardo O. Escarcega, Michael J. Lipinski, Marco A. Magalhaes, Sa'ar Minha, Thibault Lhermusier, Hideaki Ota, lakshmana Pendyala, Wenjie Tian, Augusto Pichard, Lowell F. Satler, William O. Suddath, Rebecca Torguson, Ron Waksman
Journal: Journal of the American College of Cardiology (2014)
Comparisons of established risk prediction models for cardiovascular disease: systematic review
Authors: G. C. M. Siontis, I. Tzoulaki, K. C. Siontis, J. P. A. Ioannidis
Journal: BMJ (2012)

<b>Objective</b> To evaluate the evidence on comparisons of established cardiovascular risk prediction models and to collect comparative information on their relative prognostic performance. <b>Design</b> Systematic review of comparative predictive model studies. <b>Data sources</b> Medline and screening of citations and references. <b>Study selection</b> Studies examining the relative prognostic performance of at least two major risk models for cardiovascular disease in general populations. <b>Data extraction</b> Information on study design, assessed risk models, and outcomes. We examined the relative performance of the models (discrimination, calibration, and reclassification) and the potential for outcome selection and optimism biases favouring newly introduced models and models developed by the authors. <b>Results</b> 20 articles including 56 pairwise comparisons of eight models (two variants of the Framingham risk score, the assessing cardiovascular risk to Scottish Intercollegiate Guidelines Network to assign preventative treatment (ASSIGN) score, systematic coronary risk evaluation (SCORE) score, Prospective Cardiovascular Münster (PROCAM) score, QRESEARCH cardiovascular risk (QRISK1 and QRISK2) algorithms, Reynolds risk score) were eligible. Only 10 of 56 comparisons exceeded a 5% relative difference based on the area under the receiver operating characteristic curve. Use of other discrimination, calibration, and reclassification statistics was less consistent. In 32 comparisons, an outcome was used that had been used in the original development of only one of the compared models, and in 25 of these comparisons (78%) the outcome-congruent model had a better area under the receiver operating characteristic curve. Moreover, authors always reported better area under the receiver operating characteristic curves for models that they themselves developed (in five articles on newly introduced models and in three articles on subsequent evaluations). <b>Conclusions</b> Several risk prediction models for cardiovascular disease are available and their head to head comparisons would benefit from standardised reporting and formal, consistent statistical comparisons. Outcome selection and optimism biases apparently affect this literature.
Generation of a Kupffer Cell-evading Adenovirus for Systemic and Liver-directed Gene Transfer
Authors: Reeti Khare, Shannon M May, Francesco Vetrini, Eric A Weaver, Donna Palmer, Amanda Rosewell, Nathan Grove, Philip Ng, Michael A Barry
Journal: Molecular Therapy (2011)

As much as 90% of an intravenously (i.v.) injected dose of adenovirus serotype 5 (Ad5) is absorbed and destroyed by liver Kupffer cells. Viruses that escape these cells can then transduce hepatocytes after binding factor X (FX). Given that interactions with FX and Kupffer cells are thought to occur on the Ad5 hexon protein, we replaced its exposed hypervariable regions (HVR) with those from Ad6. When tested in vivo in BALB/c mice and in hamsters, the Ad5/6 chimera mediated >10 times higher transduction in the liver. This effect was not due to changes in FX binding. Rather, Ad5/6 appeared to escape Kupffer cell uptake as evidenced by producing no Kupffer cell death in vivo, not requiring predosing in vivo, and being phagocytosed less efficiently by macrophages in vitro compared to Ad5. When tested as a helper-dependent adenovirus (Ad) vector, Ad5/6 mediated higher luciferase and factor IX transgene expression than either helper-dependent adenoviral 5 (HD-Ad5) or HD-Ad6 vectors. These data suggest that the Ad5/6 hexon-chimera evades Kupffer cells and may have utility for systemic and liver-directed therapies.
Inherited thrombophilia in children with venous thromboembolism and the familial risk of thromboembolism: an observational study
Authors: Susanne Holzhauer, Neil A. Goldenberg, Ralf Junker, Christine Heller, Monika Stoll, Daniela Manner, Rolf Mesters, Anne Krümpel, Michael Stach, Ulrike Nowak-Göttl
Journal: Blood (2012)
604. Comparative Analysis of Different Methods for Quantitative Evaluation of Neutralizing Antibody to Ebola Virus in a Biosafety Level 2 or 4 Environment
Authors: Hideki Ebihara, Xiangguo Qiu, Steven Theriault, Matthew Klassen, Ute Stroeher, Jim Strong, Steven Jones, James M. Wilson, Heinz Feldmann, Gary Kobinger
Journal: Molecular Therapy (2006)

Ebola hemorrhagic fever virus can be modeled in different animal species such as mice, Guinea pigs and nonhuman primates. Several vaccine strategies were evaluated using DNA-, protein-based and/or viral vectors and found to protect mice against challenge with a lethal dose of mouse-adapted Ebola virus. However, only a few strategies involving DNA, Adenovirus or Vesicular Stomatitis virus (VSV), alone or in combination, succeeded at protecting nonhuman primates from Ebola virus aggressive replication. Ebola virus offers thus a unique disease model for the evaluation and testing of different vaccine platforms and/or strategies that can be screened in vivo in conditions of low to high stringency. One major limitation of using Ebola virus as a disease model is the requirement to manipulate the virus in a biosafety level 4 environment (BSL-4) which makes in vitro and in vivo testing less accessible and more time consuming. We compared four different methodologies to evaluate the levels of neutralizing antibody (NAB) from sera of nonhuman primates vaccinated with VSV- or Adenovirus-based vaccine expressing the Ebola envelope glycoprotein (EboGP). The first strategy evaluates neutralization of wild-type Ebola virus by immunoplaques; the second evaluates neutralization of Ebola expressing EGFP inserted as an additional gene in the viral genome; the third evaluates inhibition of plaque formation by an EboGP-pseudotyped VSV virus and the fourth evaluates neutralization of an EboGP-pseudotyped HIV vector. The first two strategies are using a replication competent Ebola virus and were thus performed in a BSL4 laboratory while the other two, using a replication competent VSV or replication defective HIV vector, were done in an enhanced BSL2 environment. Results indicate that the two methodologies using replication competent Ebola virus are slightly more sensitive than with pseudotyped VSV or HIV vector. Ebola expressing EGFP was found the method of choice in the BSL4 laboratory since it can be performed in 48 hours (instead of 6 days for immunoplaque assay) and does not depend on the sensitivity of an antibody/antigen reaction. Overall, each protocol offers advantages and inconveniences that will be discussed. James Wilson had equity in Targeted Genetics at the moment of the study.
Therapeutic impact and diagnostic performance of multiplex PCR in patients with malignancies and suspected sepsis
Authors: Danièle Maubon, Rebecca Hamidfar-Roy, Stéphane Courby, Aurélien Vesin, Max Maurin, Patricia Pavese, Nadia Ravanel, Claude-Eric Bulabois, Jean-Paul Brion, Hervé Pelloux, Jean-François Timsit
Journal: Journal of Infection (2010)
GATA-3 Links Tumor Differentiation and Dissemination in a Luminal Breast Cancer Model
Authors: Hosein Kouros-Mehr, Seth K. Bechis, Euan M. Slorach, Laurie E. Littlepage, Mikala Egeblad, Andrew J. Ewald, Sung-Yun Pai, I-Cheng Ho, Zena Werb
Journal: Cancer Cell (2008)
Emergency Surgery: Trauma, Shock, Sepsis, Burns
Authors: Robert H. Demling
Journal: JAMA (1982)

The purpose of this book is to "summarize the present state of the art in the care of the traumatized and acutely ill patient" as presented at a University of Minnesota Department of Surgery course in emergency surgery. The content is extremely broad in scope, covering metabolic and physiologic alterations seen after a number of acute disorders as well as how-to approaches to treatment, both operative and nonoperative. Interspersed among a series of chapters are panel discussions where a number of topics are discussed by presenters or chapter authors. Although viewed as a major advantage by the editors, the immense scope of topics is actually a disadvantage. Most chapters are extremely brief, leading to a very general discussion of the topic, although a number of chapters dealing with less technical information such as the treatment of bites and tetanus are complete and informative. The description of operative approaches as presented
Do Diuretics Cause Heart Disease?
Authors: Kalyanam Shivkumar
Journal: Annals of Internal Medicine (1995)

Letters1 December 1995Do Diuretics Cause Heart Disease?Kalyanam Shivkumar, MD and Robert G. Narins, MDKalyanam Shivkumar, MDHenry Ford Hospital; Detroit, MI 48202-2689Search for more papers by this author and Robert G. Narins, MDHenry Ford Hospital; Detroit, MI 48202-2689Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-123-11-199512010-00017 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Treatment of essential hypertension with thiazides can normalize blood pressure but also has various electrolyte and metabolic side effects. Control of these untoward effects should maximize the therapeutic benefits derived from these drugs. In his zeal to promote the use of these antihypertensive agents, Dr. Freis [1] conveys a mixed and somewhat confusing message regarding the side effects of thiazides.Diuretic-induced hypokalemia is perhaps the best studied and most obviously pernicious of these metabolic perturbations. In the first half of his review, Dr. Freis strives to dismiss the importance of this electrolyte abnormality. In the second half ...References1. Freis ED. The efficacy and safety of diuretics in treating hypertension. Ann Intern Med. 1995; 127:223-6. Google Scholar2. Rubini ME. Water excretion in potassium deficient man. J Clin Invest. 1961; 39:2215. Google Scholar3. Gettes L, Surawicz B. Effects of low and high concentrations of potassium on the simultaneously recorded Purkinje and ventricular action potential of the perfused pig moderator band. Circ Res. 1968; 23:717-29. Google Scholar4. Surawicz B. Dispersion of refractoriness in ventricular arrhythmias. In: Zipes DP, Jalife J, eds. Cardiac Electrophysiology: From Cell to Bedside. Philadelphia: WB Saunders; 1990:377-85. Google Scholar5. Holland OB, Nixon JV, Kubnert L. Diuretic-induced ventricular ectopic activity. Am J Med. 1981; 770:762-8. Google Scholar Author, Article, and Disclosure InformationAffiliations: Henry Ford Hospital; Detroit, MI 48202-2689 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byDiuretic Complications 1 December 1995Volume 123, Issue 11Page: 891KeywordsAttentionCationsDiureticsHeartHypertensionParalysisPotassiumSaltsSkeletal musclesTachycardia Issue Published: 1 December 1995 Copyright & PermissionsCopyright © 1995 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Heightened Tissue Factor Associated With Tissue Factor Pathway Inhibitor and Prognosis in Patients With Unstable Angina
Authors: Hirofumi Soejima, Hisao Ogawa, Hirofumi Yasue, Koichi Kaikita, Koichi Nishiyama, Kenji Misumi, Keiji Takazoe, Yuji Miyao, Michihiro Yoshimura, Kiyotaka Kugiyama, Shin Nakamura, Ichiro Tsuji, Kousuke Kumeda
Journal: Circulation (1999)

Background —This study was designed to evaluate the plasma levels of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in patients with unstable angina and investigate whether there is a relationship between these levels and unfavorable outcome. Methods and Results —The plasma TF and free TFPI antigen levels were determined in plasma samples taken from 51 patients with unstable angina, 56 with stable exertional angina, and 55 with chest pain syndrome. The plasma TF and free TFPI antigen levels were higher in the unstable angina group than in the stable exertional angina and chest pain syndrome group. There was a good correlation between TF and TFPI. We established borderline as maximum level in the patients with chest pain syndrome. Seven patients (of the 22 in the high TF group) required revascularization to control their unstable angina during in-hospital stay. On the other hand, only 1 of the 29 patients in the low TF group required myocardial revascularization. Four patients of the 14 patients in the high free TFPI group required myocardial revascularization during in-hospital stay, and 4 of the 37 patients in the low free TFPI group required myocardial revascularization. We compared the TF and free TFPI levels between the cardiac event (+) group and cardiac event (−) group. TF levels were significantly higher in the cardiac event (+) group than in the cardiac event (−) group. Conclusions —We have demonstrated that not only the plasma TF levels but also the plasma-free TFPI levels are elevated in patients with unstable angina. Patients with unstable angina and heightened TF and free TFPI are at increased risk for unfavorable outcomes. The heightened TF level was a more important predictor in patients with unstable angina.
Private companies challenge policy that NHS organisations are "preferred providers"
Authors: N. Timmins
Journal: BMJ (2010)

The policy declared by England’s health secretary, Andy Burnham, that NHS organisations are now the “preferred provider” of NHS care is being challenged in what could prove a key test case.

In what amounts to a class action, representatives of private and voluntary sector organisations have joined forces to take a case to the Co-operation and Competition Panel for NHS-Funded Services. It is likely to prove an important test of a body that has a purely advisory role to the health secretary, with no statutory independence. The panel has confirmed that it will investigate the case.

The NHS …
Autophagy influences glomerular disease susceptibility and maintains podocyte homeostasis in aging mice
Authors: Björn Hartleben, Markus Gödel, Catherine Meyer-Schwesinger, Shuya Liu, Theresa Ulrich, Sven Köbler, Thorsten Wiech, Florian Grahammer, Sebastian J. Arnold, Maja T. Lindenmeyer, Clemens D. Cohen, Hermann Pavenstädt, Dontscho Kerjaschki, Noboru Mizushima, Andrey S. Shaw, Gerd Walz, Tobias B. Huber
Journal: Journal of Clinical Investigation (2010)

Injury and loss of podocytes are leading factors of glomerular disease and renal failure. The postmitotic podocyte is the primary glomerular target for toxic, immune, metabolic, and oxidant stress, but little is known about how this cell type copes with stress. Recently, autophagy has been identified as a major pathway that delivers damaged proteins and organelles to lysosomes in order to maintain cellular homeostasis. Here we report that podocytes exhibit an unusually high level of constitutive autophagy. Podocyte-specific deletion of autophagy-related 5 (Atg5) led to a glomerulopathy in aging mice that was accompanied by an accumulation of oxidized and ubiquitinated proteins, ER stress, and proteinuria. These changes resulted ultimately in podocyte loss and late-onset glomerulosclerosis. Analysis of pathophysiological conditions indicated that autophagy was substantially increased in glomeruli from mice with induced proteinuria and in glomeruli from patients with acquired proteinuric diseases. Further, mice lacking Atg5 in podocytes exhibited strongly increased susceptibility to models of glomerular disease. These findings highlight the importance of induced autophagy as a key homeostatic mechanism to maintain podocyte integrity. We postulate that constitutive and induced autophagy is a major protective mechanism against podocyte aging and glomerular injury, representing a putative target to ameliorate human glomerular disease and aging-related loss of renal function.
Factors Affecting the Outcome of Psychiatric Interagency Referral
Authors: ALEXANDER S. ROGAWSKI, BETTY EDMUNDSON
Journal: American Journal of Psychiatry (1971)

Only 42 percent of patients referred to various community resources by a metropolitan evaluation unit completed the referral. Data about the patients, referring professionals, referral technique, and receiving agency were correlated with the rate of completed referrals. The most significant success factor was the interest and involvement of the referring professional; surprisingly, patient characteristics and distance of patient residence from the community resource did not have a significant effect.
Does setting good practice standards for research ethics committees increase their legal liability?
Authors: J. Savulescu, I. Chalmers, J. Blunt
Journal: BMJ (1997)

Editor—As a result of our paper1 Neville W Goodman and Alaisdair MacGowan “feel most beleaguered” and fear that research ethics committees must brace themselves to be sued when they fail to meet the standards of good practice that we have set them.2 We stated that research ethics committees should be held accountable if they failed to meet these standards, but our article was concerned with moral, not legal, accountability.

Could research …
An intrinsic adrenergic system in mammalian heart.
Authors: M H Huang, D S Friend, M E Sunday, K Singh, K Haley, K F Austen, R A Kelly, T W Smith
Journal: Journal of Clinical Investigation (1996)

We have identified a previously undescribed intrinsic cardiac adrenergic (ICA) cell type in rodent and human heart. Northern and Western blot analyses demonstrated that ICA cell isolates contain mRNA and protein of enzymes involved in catecholamine biosynthesis. Radioenzymatic catecholamine assays also revealed that the catecholamine profile of adult rat ICA cell isolates differed from that of sympathetic neurons. Unlike sympathetic neuronal cells, isolated ICA cells have abundant clear vesicles on electron microscopy. Endogenous norepinephrine and epinephrine constitutively released by ICA cells in vitro affect the spontaneous beating rate of neonatal rat cardiac myocytes in culture. Finally, ICA cells could be identified in human fetal hearts at a developmental stage before sympathetic innervation of the heart has been documented to occur. These findings support the concept that these cells constitute an ICA signaling system capable of participating in cardiac regulation that appears to be independent of sympathetic innervation.
THERAPEUTICS OF PNEUMONIA.
Authors: FRANK G. WHEATLEY
Journal: JAMA (1899)

score like it.In permanence and pleasantness of effect, I have seen nothing to compare with it, and in these small doses 1 have seen no irritation of the stomach.As to its effect in cases where other remedies have failed, I will briefly state the essential points in two cases, each of which I had seen four or five years before, and in which I had made the diagnosis respectively of aortic insufficiency and of mitral insufficiency.A gen¬ tleman of large frame, 52 years of age, presented him¬
Analysis of errors in measurement of cardiac output by simultaneous dye and thermal dilution in cardiothoracic surgical patients
Authors: A. P. FISCHER, A. M. BENIS, R. A. JURADO, E. SEELY, P. TEIRSTEIN, R. S. LITWAK
Journal: Cardiovascular Research (1978)

The purpose of this study was a detailed analysis of the random and systematic errors encountered in the measurement of cardiac output by dye and thermal dilution under actual clinical conditions in cardiothoracic surgical patients. Two hundred simultaneous dye and thermal cardiac output measurements were performed in 20 patients by injection of a 10 cm3 bolus of cold indocyanine green dye with on-line analysis employing two portable analogue computers. Agreement between the dye and thermal methods was significantly better in the intensive care unit (r values of 0.88 to 0.94) when compared with the operating room (0.68 to 0.84), a difference thought to reflect the better haemodynamic stability of patients in the intensive care unit. A statistical method was devised allowing separation of random and calibration errors for both the dye and thermal methods. The random error (reproducibility) of a single measurement of cardiac output by either the dye or thermal method, expressed as a standard deviation, approximated ± 7%. The calibration error of a single measurement was estimated to have a standard deviation approximating ± 15% for the dye method, but of less than 5% for the thermal method. A significant difference between simultaneous dye and thermal cardiac outputs was found only for measurements done in the operating room following the induction of anaesthesia. With this exception, it is concluded that both the dye and thermal methods are clinically reliable despite the changing postoperative state of cardiothoracic patients. The ease of performance of thermal dilution measurement recommends its preferential use with no loss of accuracy.