tbuckley/cabot-search huggingface dataset:
Abstract 3099: Radiation-induced angiogenesis is associated with MMP-9-miR-494-Syndecan-1 regulatory loop in medulloblastoma cells.
Authors: Swapna Asuthkar, Kiran Kumar Velpula, Christopher Gondi, Arun Kumar Nalla, Venkateswara Rao Gogineni, Jasti S. Rao
Journal: Cancer Research (2013)

Abstract Matrix metalloproteinase-9 (MMP-9) is one of the most prominent proteins associated with tumorigenesis and is a modulator of the tumor microenvironment during angiogenesis. Recently, it has been speculated that Syndecan-1, a transmembrane heparan sulfate-bearing proteoglycan, has a critical role in contributing to angiogenesis when associated with MMP-9. However, the mechanism behind their synergistic regulation is not fully understood. In the current study, we report that ionizing radiation (IR)-induced MMP-9 enhances Syndecan-1 shedding and tube-inducing ability of medulloblastoma cells. Furthermore, tumor angiogenesis is associated with higher MMP-9-Syndecan-1 interactions on both the cell surface and extracellular medium. Our results also revealed the existence of a novel regulatory mechanism where MMP-9 drives the suppression of miR-494, thereby resulting in enhanced Syndecan-1 shedding and angiogenesis. By employing bioinformatics and functional luciferase experiments, we demonstrated that 3’-UTR of Syndecan-1 mRNA is a direct target of miR-494. Moreover, from the in situ hybridization analysis, we found that MMP-9-specific shRNA (pM) treatment of mouse intracranial tumors resulted in elevated expression of miR-494. This negative correlation between MMP-9 and miR-494 levels was found to be dependent on the methylation status of the miR-494 promoter-associated CpG island region (-186 to -20), which was confirmed by bisulfite-sequencing and methylation-specific-PCR (MSP) analysis. Overall, our results demonstrate a previously unrecognized mechanism of angiogenesis regulation in medulloblastoma through which miR-494 modulates the transcription of radiation-induced angiogenesis promoting molecules and that MMP-9-Syndecan-1 activity creates a negative feedback loop by regulating the expression of miR-494. Citation Format: Swapna Asuthkar, Kiran Kumar Velpula, Christopher Gondi, Arun Kumar Nalla, Venkateswara Rao Gogineni, Jasti S. Rao. Radiation-induced angiogenesis is associated with MMP-9-miR-494-Syndecan-1 regulatory loop in medulloblastoma cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3099. doi:10.1158/1538-7445.AM2013-3099
Pamela Anne Davies
Authors: J. Wigglesworth
Journal: BMJ (2009)

Pamela Anne Davies entered paediatrics at the time of her second job as house surgeon at the Royal Hospital for Sick Children, Glasgow. She later became resident medical officer at Tadworth Court, Surrey (the country branch of Great Ormond Street Hospital) and took further posts in Reading and Oxford before spending two years as instructor in paediatrics at Bellevue Medical Centre, New York. 

She returned to Oxford as a lecturer in paediatrics, where she worked with Dr Victoria Smallpiece on the problems of feeding premature babies. She participated …
Pulmonary Embolism in Patients with Unexplained Exacerbation of Chronic Obstructive Pulmonary Disease: Prevalence and Risk Factors
Authors: Isabelle Tillie-Leblond, Charles-Hugo Marquette, Thierry Perez, Arnaud Scherpereel, Christophe Zanetti, André-Bernard Tonnel, Martine Remy-Jardin
Journal: Annals of Internal Medicine (2006)

Background: Diagnosis of pulmonary embolism (PE) is difficult in patients with chronic obstructive pulmonary disease (COPD) and exacerbation. Objective: To evaluate PE in patients with COPD and exacerbation of unknown origin and explore factors associated with PE. Design: Prospective cohort study. Setting: University-affiliated hospital in France. Patients: 211 consecutive patients, all current or former smokers with COPD, who were admitted to the hospital for severe exacerbation of unknown origin and did not require invasive mechanical ventilation. Measurements: Spiral computed tomography angiography (CTA) and ultrasonography within 48 hours of admission and assessment of the Geneva score. Patients were classified as PE positive (positive results on CTA or negative results on CTA and positive results on ultrasonography) or PE negative (negative results on CTA and negative results on ultrasonography or negative results on CTA and no recurrence of PE at follow-up 3 months later). Results: 49 of 197 patients (25% [95% CI, 19% to 32%]) met the diagnostic criteria for PE. Clinical factors associated with PE were previous thromboembolic disease (risk ratio, 2.43 [CI, 1.49 to 3.94]), malignant disease (risk ratio, 1.82 [CI, 1.13 to 2.92]), and decrease in Paco 2 of at least 5 mm Hg (risk ratio, 2.10 [CI, 1.23 to 3.58]). A total of 9.2% (CI, 4.7% to 15.9%) of patients with a low-probability Geneva score received a diagnosis of PE. An exploratory analysis suggested that substituting malignant disease for recent surgery in the Geneva score might improve its performance in excluding PE in this sample who were more likely to have malignant disease than to have had recent surgery. However, this improvement seems insufficient to exclude PE with enough certainty to withhold therapy for low-risk patients on the basis of the modified score. Limitations: This study was done in only 1 center. Patients with COPD requiring invasive mechanical ventilation in the intensive care unit were not included. The upper bound of the 95% CI for the low probability of PE according to the Geneva score is too high to rule out PE. The classification of COPD exacerbation of unknown origin was based on the clinician's assessment, not on a standard evaluation for all patients. Conclusion: This study showed a 25% prevalence of PE in patients with COPD hospitalized for severe exacerbation of unknown origin. Three clinical factors are associated with the increased risk for PE. The Geneva score and the modified Geneva score should be prospectively evaluated in patients with COPD.
Public health programmes: you don't know what you've got till it's gone
Authors: Ulf R Dahle
Journal: BMJ (2004)

EDITOR—In 2005 a new inspection regimen will be launched in the British NHS: public health programmes will have to prove that they are providing good value for taxpayers' money.1 The Swedish Institute for Infectious Disease Control was recently publicly criticised by the National Board of Health and Welfare because nearly 70 African immigrants became infected with Mycobacterium tuberculosis. …
Inequalities in mortality during and after restructuring of the New Zealand economy: repeated cohort studies
Authors: Tony Blakely, Martin Tobias, June Atkinson
Journal: BMJ (2008)

Objectives To determine whether disparities between income and mortality changed during a period of major structural and macroeconomic reform and to estimate the changing contribution of different diseases to these disparities. Design Repeated cohort studies. Data sources 1981, 1986, 1991, 1996, and 2001 censuses linked to mortality data. Population Total New Zealand population, ages 1-74 years. Methods Mortality rates standardised for age and ethnicity were calculated for each census cohort by level of household income. Standardised rate differences and rate ratios, and slope and relative indices of inequality (SII and RII), were calculated to measure disparities on both absolute and relative scales. Results All cause mortality rates declined over the 25 year study period in all groups stratified by sex, age, and income, except for 25-44 year olds of both sexes on low incomes among whom there was little change. In all age groups pooled, relative inequalities increased from 1981-4 to 1996-9 (RIIs increased from 1.85 (95% confidence interval 1.67 to 2.04) to 2.54 (2.29 to 2.82) for males and from 1.54 (1.35 to 1.76) to 2.12 (1.88 to 2.39) for females), then stabilised in 2001-4 (RIIs of 2.60 (2.34 to 2.89) and 2.18 (1.93 to 2.45), respectively). Absolute inequalities were stable over time, with a possible fall from 1996-9 to 2001-4. Cardiovascular disease was the major contributor to the observed disparities between income and mortality but decreased in importance from 45% in 1981-4 to 33% in 2001-4 for males and from 50% to 29% for females. The corresponding contribution of cancer increased from 16% to 22% for males and from 12% to 25% for females. Conclusions During and after restructuring of the economy disparities in mortality between income groups in New Zealand increased in relative terms (but not in absolute terms), but it is difficult to confidently draw a causal link with structural reforms. The contribution of different causes of death to this inequality changed over time, indicating a need to re-prioritise health policy accordingly.
Late escape from an immunodominant cytotoxic T-lymphocyte response associated with progression to AIDS
Authors: Philip J.R. Goulder, Rodney E. Phillips, Robert A. Colbert, Stephen McAdam, Graham Ogg, Martin A. Nowak, Paul Giangrande, Graz Luzzi, Barbara Morgana, Anne Edwards, Andrew J. McMichael, Sarah Rowland-Jones
Journal: Nature Medicine (1997)
Population Genetics Without Intraspecific Data
Authors: J. L. Thorne, S. C. Choi, J. Yu, P. G. Higgs, H. Kishino
Journal: Molecular Biology and Evolution (2007)

A central goal of computational biology is the prediction of phenotype from DNA and protein sequence data. Recent models of sequence change use in silico prediction systems to incorporate the effects of phenotype on evolutionary rates. These models have been designed for analyzing sequence data from different species and have been accompanied by statistical techniques for estimating model parameters when the incorporation of phenotype induces dependent change among sequence positions. A difficulty with these efforts to link phenotype and interspecific evolution is that evolution occurs within populations, and parameters of interspecific models should have population genetic interpretations. We show, with two examples, how population genetic interpretations can be assigned to evolutionary models. The first example considers the impact of RNA secondary structure on sequence change, and the second reflects the tendency for protein tertiary structure to influence nonsynonymous substitution rates. We argue that statistical fit to data should not be the sole criterion for assessing models of sequence change. A good interspecific model should also yield a clear and biologically plausible population genetic interpretation.
Once More: The Inaccuracy of Non-EEG Estimations of Sleep
Authors: BRIAN L. WEISS, RICHARD J. MCPARTLAND, DAVID J. KUPFER
Journal: American Journal of Psychiatry (1973)

To test the validity of nurses' estimates and patients' self-reports of the duration and quality of the patients' sleep, the authors compared these estimates with measures of sleep taken with the electroencephalogram. The authors found that nurses correctly estimated the amount of sleep of only two of the 14 subjects and tended to consistently overestimate. Patients showed no tendency to consistently overestimate or underestimate, but only four of the 14 patients correctly estimated the duration of their sleep. The authors argue that conclusions about sleep patterns that are based on observational methods will have to be reexamined.
Drug companies and publishers set out 10 steps to enhance credibility of industry sponsored trials
Authors: B. Roehr
Journal: BMJ (2012)

A coalition of drug companies and major medical journal publishers has recommended 10 steps to help refurbish the tarnished credibility and enhance the quality and transparency of the reporting of industry sponsored clinical trials. The 10 steps were published in the May issue of the Mayo Clinic Proceedings .1

The Medical Publishing Insights and Practices Initiative (MPIP) was established in 2008 by leading drug companies and medical publishers as an ongoing collaboration (www.mpip-initiative.org). The recommendations grew out of a meeting held in New York in November 2010.

The initiative’s first recommendation is that research should be grounded in the asking and answering of questions …
Textbook of Pediatric Nutrition
Authors: Marvin Ament
Journal: JAMA (1981)

This book, to my knowledge, represents the first modern pediatric textbook entirely devoted to normal nutrition, nutritional deficiency states, and clinical nutrition. Such a book is long overdue, and Dr Suskind has to be commended for successfully undertaking the task of putting one together.  The book is divided into four sections (infant nutrition, nutritional deficiency states, nutritional support of the hospitalized child, and clinical nutrition) with 45 chapters. Expertise from every subspecialty is presented, and data on nutrition and growth failure in various disease states that heretofore were not easily found are made easily accessible.  The chapters on nutritional assessment and application to pediatric patients provide useful tables to aid in the assessment. The pictures of how to measure midarm circumference and skin fold thickness are particularly useful.  The role of nutritional assessment in the nutritional management of the patients is shown clearly in the chapters on parenteral support of
61 INCIDENCE AND RISK FACTORS FOR HEPATOCELLULAR CARCINOMA IN PRIMARY BILIARY CIRRHOSIS. COMPARATIVE ANALYSIS FROM TWO EUROPEAN REFERRAL CENTERS
Authors: A. Cavazza, A. Floreani, L. Caballería, F. Farinati, M. Bruguera, D. Caroli, A. Pares
Journal: Journal of Hepatology (2009)
A Reproducible Model of Cardiogenic Shock in the Dog
Authors: S. LLUCH, H. C. MOGUILEVSKY, G. PIETRA, A. B. SHAFFER, L. J. HIRSCH, A. P. FISHMAN
Journal: Circulation (1969)

An animal model of cardiogenic shock has been developed in the intact unanesthetized dog. Selective embolization of the circumflex coronary artery with 0.2 ml of mercury produces infarction of the posterolateral wall of the left ventricle and a shocklike state in the dog which results in death of the animal in 5 to 48 hr. The syndrome of cardiogenic shock in the animal model simulates closely that observed in man. Systemic blood pressure falls sharply (25 to 30% of control) immediately after embolization, remains low for several hours, then slowly increases toward normal, but never reaches preinfarct levels. The left ventricular end-diastolic pressure (LVEDP) remains within normal limits (5 to 10 mm Hg) during the initial hypotensive state, but increases to values above 10 mm Hg during the period of rising systemic pressures. As left ventricular failure begins to develop as evidenced by the rise in LVEDP, the mean pulmonary artery pressure also rises above control values. The cardiac output falls to 40% of control levels following embolization and never recovers. Peripheral resistance rises to compensate for the reduction of cardiac output and remains above control levels. Electrocardiograms indicate an essentially normal sinus rhythm with short runs (5 to 15 beats) of ventricular tachycardia with A-V dissociation. The hypotensive state does not seem to be related to this arrhythmia. Death of the animal appears to be due to progressive failure of the left ventricular pump to maintain cardiac output and systemic pressures.
Serum BLyS levels increase after rituximab as initial therapy in patients with follicular grade 1 non‐Hodgkin lymphoma
Authors: Stephen M. Ansell, Anne J. Novak, Steven Ziesmer, Tammy Price‐Troska, Betsy LaPlant, Stacey R. Dillon, Thomas E. Witzig
Journal: American Journal of Hematology (2008)

Serum B-lymphocyte stimulator (BLyS) levels are elevated in a subset of non-Hodgkin lymphoma (NHL) patients, particularly those with a family history of B-cell malignancies or a polymorphism in the BLyS gene. BLyS promotes growth of malignant B-cells and increased serum BLyS levels are associated with a poor clinical outcome. In this study, BLyS levels were measured before and after 4 weekly doses of rituximab in 30 patients with previously untreated follicular Grade 1 NHL. A significant increase was seen in the serum levels of BLyS (P = 0.0001) after rituximab therapy. The increase was independent of genetic variability in the BLyS gene.
LOCATION AND SEVERITY OF AORTIC VALVE CALCIFICATIONS: IMPLICATIONS FOR AORTIC REGURGITATION POST TRANSCATHETER AORTIC VALVE IMPLANTATION
Authors: See Hooi Ewe, Arnold C.T. Ng, Victoria Delgado, Joanne D. Schuijf, Frank van der Kley, Andrea Colli, Arend de Weger, Nina Marsan, Eduard R. Holman, Albert de Roos, Martin J. Schalij, Jeroen J. Bax
Journal: Journal of the American College of Cardiology (2011)
Microtumor growth initiates angiogenic sprouting with simultaneous expression of VEGF, VEGF receptor-2, and angiopoietin-2
Authors: Peter Vajkoczy, Mohammad Farhadi, Andreas Gaumann, Regina Heidenreich, Ralf Erber, Andreas Wunder, Jörg C. Tonn, Michael D. Menger, Georg Breier
Journal: Journal of Clinical Investigation (2002)

Tumors have been thought to initiate as avascular aggregates of malignant cells that only later induce vascularization. Recently, this classic concept of tumor angiogenesis has been challenged by the suggestion that tumor cells grow by co-opting preexisting host vessels and thus initiate as well-vascularized tumors without triggering angiogenesis. To discriminate between these two mechanisms, we have used intravital epifluorescence microscopy and multi-photon laser scanning confocal microscopy to visualize C6 microglioma vascularization and tumor cell behavior. To address the mechanisms underlying tumor initiation, we assessed the expression of VEGF, VEGF receptor-2 (VEGFR-2), and angiopoietin-2 (Ang-2), as well as endothelial cell proliferation. We show that multicellular aggregates (<< 1 mm3) initiate vascular growth by angiogenic sprouting via the simultaneous expression of VEGFR-2 and Ang-2 by host and tumor endothelium. Host blood vessels are not co-opted by tumor cells but rather are used as trails for tumor cell invasion of the host tissue. Our data further suggest that the established microvasculature of growing tumors is characterized by a continuous vascular remodeling, putatively mediated by the expression of VEGF and Ang-2. The results of this study suggest a new concept of vascular tumor initiation that may have important implications for the clinical application of antiangiogenic strategies.
THE WARBURG EFFECT AND BEYOND
Authors: Z. Lu
Journal: Neuro-Oncology (2014)

BACKGROUND: Pyruvate kinase M2 (PKM2) is highly expressed in multiple cancer types and contributes to the Warburg effect. METHODS: We have used various approaches including animal studies, human GBM specimen analyses, and biochemical studies, to understand the cellular functions of PKM2. RESULTS: We have uncovered the mechanisms underlying the upregulation of PKM2, nuclear translocation of PKM2, and metabolic and non-metabolic functions of PKM2 in promoting cancer cell metabolism, proliferation, and cell cycle progression. CONCLUSIONS: We have concluded that the nuclear function of PKM2 is essential for the Warburg effect and brain tumor development. SECONDARY CATEGORY: n/a.
Luminal Foam Cell Accumulation Is Associated With Smooth Muscle Cell Death in the Intimal Thickening of Human Saphenous Vein Grafts
Authors: Mark M. Kockx, Guido R.Y. De Meyer, Hilde Bortier, Nathan de Meyere, Johannes Muhring, Annette Bakker, Willem Jacob, Luc Van Vaeck, Arnold Herman
Journal: Circulation (1996)

Background Occlusion of saphenous vein grafts is a major problem after coronary artery bypass graft surgery. Diffuse intimal thickening develops in all implanted aortocoronary saphenous vein grafts within 6 months to 1 year. In some regions of the thickened intima, foam cells accumulate along the luminal margin. This particular morphology resembles the morphology of unstable atherosclerotic plaques as they occur in coronary arteries. In the present study, we focused on the possible topographic relation between luminal foam cell accumulation and cell death of smooth muscle cells (SMCs) within the adjacent thickened intima. Methods and Results Segments of occluded and suboccluded implanted human aortocoronary saphenous vein grafts were obtained during reintervention coronary artery bypass graft surgery in 30 patients. In the regions of the vein grafts with luminal foam cell accumulation, the percentage of SMC α-actin immunoreactive area of the superficial intimal thickening was 6±1.4%, which was different from the 17.6±2.3% of the deep intimal thickening. A strong negative correlation between the number of foam cell nuclei and the percentage of SMC α-actin immunoreactive area in the adjacent superficial intimal thickening was present ( r =−.77, P &lt;.001). Within the superficial intimal thickening, cytoplasmic and DNA fragmentation could be detected, which points to apoptotic cell death. A fraction of the cytoplasmic fragments fitted the ultrastructural characteristics of matrix vesicles and showed pronounced calcium and phosphorus accumulation as demonstrated with the use of x-ray microanalysis. Conclusions The close spatial relation among foam cell accumulation, pronounced intimal SMC loss, and cell death suggests the presence of a foam cell–derived factor that can induce cell death in the SMC population of the intimal thickening. The depletion of the intimal SMC population could promote plaque rupture and thrombotic complications in the grafts.
An Economic Analysis of Captopril in the Treatment of Diabetic Nephropathy
Authors: Roger A Rodby, Louise M Firth, Edmund J Lewis
Journal: Diabetes Care (1996)

OBJECTIVE The results of a recent clinical trial. The Effect of ACE inhibition on Diabetic Nephropathy, demonstrated that captopril reduced the rate of renal failure, end-stage renal disease (ESRD), and death in patients with IDDM and nephropathy. The purpose of this study was to determine the cost-benefitand cost-effectiveness of captopril as a therapy in patients with IDDM as well as the potential savings for all patients with diabetes and nephropathy. RESEARCH DESIGN AND METHODS We used the results from a randomized, placebo-controlled trial comparing captopril (207 patients) with placebo (202 patients), whose purpose was to determine whether captopril has kidney-protecting properties independent of its effect on blood pressure in diabetic nephropathy to develop a model of medical treatment for patients before progression to ESRD. To model the course of illness after progression to ESRD and to extend the model to patients with NIDDM, we used data from the U.S. Renal Data System and published literature. Medical resource cost data were based predominantly upon Medicare reimbursement levels, published wholesale drug prices, and surveying health care providers. The economic model uses a payer perspective to estimate direct cost. The cost to society (indirect cost) associated with lost patient productivity due to ESRD was also estimated. Using this information, we predicted the costs incurred annually and over a lifetime if patients with IDDM and NIDDM and overt nephropathy were treated with either placebo or captopril. We also constructed a model of the overall prevalence of diabetic nephropathy to estimate the aggregate savings in total U.S. health care expenditures. RESULTS Treatment with captopril resulted in an absolute direct cost savings or benefit of $32,550 per patient with IDDM over the course of a lifetime compared to treatment with placebo. For patients with NIDDM, the direct cost savings totaled $9,900 per patient. Absolute savings were found for indirect costs as well: $84,390 per patient with IDDM and $45,730 per patient with NIDDM. If captopril therapy were initiated in 1995 for patients with either IDDM or NIDDM and nephropathy, the aggregate health care cost savings (i.e. direct cost savings alone) would be $189 million a year for the year 1999 and $475 million a year in 2004, the present value of cumulative health care cost savings for these 10 years would be $2.4 billion. CONCLUSIONS The use of captopril in diabetic nephropathy will provide significant savings in health care costs; in addition, it will result in savings in indirect cost, which reflects the broader societal benefit.