tbuckley/cabot-search huggingface dataset:
Abstract P6-06-02: Molecular characterization of a patient-derived xenograft (PDX) resource for triple negative breast cancer
Authors: Joel H Graber, James G Keck, Susan D Airhart, Carol J Bult, Edison T Liu
Journal: Cancer Research (2015)

Abstract The Jackson Laboratory (JAX) has developed a resource of human tumors implanted into immune deficient mice (patient derived xenografts; PDX) as a platform for testing standard of care and novel therapeutic options for Triple Negative Breast Cancer. PDX models provide an advantage over cell culture based models for testing therapeutic interventions because they retain properties such as tumor cell heterogeneity that are critical to the biological properties of a patient’s tumor and response to treatment. Tumor material acquired from biopsy or surgical resection was implanted subcutaneously into the flank of immune deficient NOD-scid IL2r gamma-chain null (NSG) mice. The PDX resource currently contains 21 established breast cancer PDX models (12 TNBC) with 24 additional models currently in development. Two of the established TNBC PDX models have BRCA1 mutations. The median age of the patients from whom tumor material was obtained for all breast models is 53 (45-89). Tumors that successfully engrafted were characterized for somatic mutations using the new JAX Clinical Cancer Panel, Copy Number Variants using the Affymetrix human 6.0 SNP array, and gene expression using both Affymetrix U133 plus v2 and RNA-Seq. Normalized gene expression was analyzed for characteristic patterns in a pan-cancer approach across all PDX models and further compared with the previously identified TNBC molecular subtypes (Lehmann et al. 2011. JCI 121:2750-2767). The combination of principal components analysis and classification via expression pattern resulted in putative matches of models to most of the known molecularly defined subtypes of TNBC tumors. Tumor bearing mice for the TNBC PDX models have been treated with docetaxel, cisplatin, cyclophosphamide and doxorubicin. Preliminary studies of tumor response to these treatment regimes revealed systematic differences that can be correlated with features of the genomic analysis, including expression subtype characterization. The JAX collection of TNBC cancer PDX models is a well-annotated, publically available resource of models with deep genomic characterization and standard of care therapy response data for use in the development of advanced therapeutic options. Genomically defined subgroups within the collection suggest strategies to refine patient selection and treatment algorithms. Information about the models along with summarized genomic data is publicly available at the Mouse Tumor Biology database PDX web portal (http://tumor.informatics.jax.org). Citation Format: Joel H Graber, James G Keck, Susan D Airhart, Carol J Bult, Edison T Liu. Molecular characterization of a patient-derived xenograft (PDX) resource for triple negative breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-06-02.
Sulfenic Acid Modification of Endothelin B Receptor is Responsible for the Benefit of a Nonsteroidal Mineralocorticoid Receptor Antagonist in Renal Ischemia
Authors: Jonatan Barrera-Chimal, Sonia Prince, Fouad Fadel, Soumaya El Moghrabi, David G. Warnock, Peter Kolkhof, Frédéric Jaisser
Journal: Journal of the American Society of Nephrology (2015)

AKI is associated with high mortality rates and the development of CKD. Ischemia/reperfusion (IR) is an important cause of AKI. Unfortunately, there is no available pharmacologic approach to prevent or limit renal IR injury in common clinical practice. Renal IR is characterized by diminished nitric oxide bioavailability and reduced renal blood flow; however, the mechanisms leading to these alterations are poorly understood. In a rat model of renal IR, we investigated whether the administration of the novel nonsteroidal mineralocorticoid receptor (MR) antagonist BR-4628 can prevent or treat the renal dysfunction and tubular injury induced by IR. Renal injury induced by ischemia was associated with increased oxidant damage, which led to a cysteine sulfenic acid modification in endothelin B receptor and consequently decreased endothelial nitric oxide synthase activation. These modifications were efficiently prevented by nonsteroidal MR antagonism. Furthermore, we demonstrated that the protective effect of BR-4628 against IR was lost when a selective endothelin B receptor antagonist was coadministered. These data describe a new mechanism for reduced endothelial nitric oxide synthase activation during renal IR that can be blocked by MR antagonism with BR-4628.
Abstract 18331: Microvascular Thrombosis Increases Pro-inflammatory Gr-1(+) Cd11b(+) Myeloid Cells Activation and Promotes Endothelial Barrier Disruption
Authors: Evgeny A Zemskov, Marina A Zemskova, Boris A Gorshkov, Alexander D Verin, Irina Y Sazonova
Journal: Circulation (2011)

Vascular thrombosis triggered by accumulation of fibrin results in regional ischemia and blood vessel pathology. Growing evidence demonstrates a strong correlation between thrombogenesis, cardiovascular thrombotic diseases and inflammation. However, the mechanisms that could explain this link are still warranted. Addressing this question, we studied the association between microvascular thrombosis, vascular integrity and pro-inflammatory CD11b+ cells response using plasminogen-deficient mice (Pg -/- ; B6.129P2-Plg tm1Jld /J) whose fibrinolytic system is impaired in the microcirculation. Methods: Pg -/- mice (25±5 weeks old) were compared to heterozygote (Pg +/- ) and wild type (Pg +/+ ) littermates. The total blood cell count, flow-cytometry analysis of leukocytes, and cytokine mRNA levels in lung tissue were assessed. The endothelial barrier permeability of lung microvasculature was also analyzed. Results: Adult Pg -/- mice developed systemic microvascular thrombosis affecting lung tissue as well. Pathological fibrin deposition in microcirculation induced significant increase in platelets (1.4-fold, p&lt;0.001), monocytes (1.7-fold, p&lt;0.01) and granulocytes (3.5-fold, p&lt;0.001) levels in the blood compared to Pg +/- and Pg +/+ controls. Moreover, pro-thrombotic Pg -/- mice had microcytic anemia due to low red blood cell volume (36.7 fl versus 41.6 fl, p&lt;0.001) and reduced level of hemoglobin (12.4 g/dl versus 14.6 g/dl, p&lt;0.001). Analysis of leukocytes obtained from the blood and lungs of Pg -/- mice showed the significant expansion of activated CD11b+ cell type. Further characterization of these CD11b+ cells by flow cytometry revealed a population with a phenotype of CD11b(+)Gr-1(+). The CD11b+ associated level of VCAM-1 was also significantly elevated (2.0-fold, p&lt;0.05). Moreover, lung micro-thrombosis in Pg -/- mice was associated with increased endothelial permeability (1.3-fold, p&lt;0.05) and up-regulation of TNF-α mRNA expression. Conclusion: In a mouse model, microvascular thrombosis promotes the increase of pro-inflammatory GR-1(+)CD11b(+) myeloid cells and endothelial barrier disruption. Our data suggest that Pg -/- mice may be an adequate model for further study of therapeutic approaches against vascular leakage.
Escherichia coli and Staphylococcus aureus: bad news and good news from the European Antimicrobial Resistance Surveillance Network (EARS-Net, formerly EARSS), 2002 to 2009
Authors: C Gagliotti, A Balode, F Baquero, J Degener, H Grundmann, D Gür, V Jarlier, G Kahlmeter, J Monen, D L Monnet, G M Rossolini, C Suetens, K Weist, O Heuer, Collective the EARS-Net Participants (Disease
Journal: Eurosurveillance (2011)

Based on data collected by the European Antimicrobial Resistance Surveillance Network (EARS-Net) and the former EARSS, the present study describes the trends in antimicrobial susceptibility patterns and occurrence of invasive infections caused by Escherichia coli and Staphylococcus aureus in the period from 2002 to 2009. Antimicrobial susceptibility results from 198 laboratories in 22 European countries reporting continuously on these two microorganisms during the entire study period were included in the analysis. The number of bloodstream infections caused by E. coli increased remarkably by 71% during the study period, while bloodstream infections caused by S. aureus increased by 34%. At the same time, an alarming increase of antimicrobial resistance in E. coli was observed, whereas for S. aureus the proportion of meticillin resistant isolates decreased. The observed trend suggests an increasing burden of disease caused by E. coli. The reduction in the proportion of meticillin-resistant S. aureus and the lesser increase in S. aureus infections, compared with E. coli, may reflect the success of infection control measures at hospital level in several European countries.
PRIMARY PULMONARY ARTERIOSCLEROSIS WITH RUPTURE OF THE PULMONARY ARTERY
Authors: R J CONDRY, L H NEFFLIN
Journal: Annals of Internal Medicine (1958)

Case Reports1 November 1958PRIMARY PULMONARY ARTERIOSCLEROSIS WITH RUPTURE OF THE PULMONARY ARTERYR. J. CONDRY, M.D., F.A.C.P., L. H. NEFFLIN, M.D.R. J. CONDRY, M.D., F.A.C.P.Search for more papers by this author, L. H. NEFFLIN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-49-5-1252 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptPulmonary arteriosclerosis may be primary or secondary as defined by Ulrich.1 In a recent textbook of medicine,2 under the title of "Pulmonary Arteriosclerosis," it is noted that "pulmonary arteriosclerosis and hypertension are dependent upon each other but there is a controversy as to which is cause and which is effect" Rupture of the pulmonary artery without obvious pulmonary disease or heart disease of the type imposing resistance to the pulmonary circulation is rather rare, and for this reason the following case is presented.A 61 year old white married businessman was admitted to the Davis Memorial Hospital on October 27,...Bibliography1. Ulrich HL: The clinical diagnosis of pulmonary arteriosclerosis, Ann. Int. Med. 6: 632-644, 1932. LinkGoogle Scholar2. CecilLoeb RLRF: Textbook of medicine, 8th Ed., 1951, W. B. Saunders Co., Philadelphia, pp. 866-867. Google Scholar3. Sodi-PallaresCalder DRM: New basis of electrocardiography, 1956, The C. V. Mosby Co., St. Louis, p. 210. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Elkins, West Virginia*Received for publication September 17, 1957.From the Davis Memorial Hospital, Elkins, West Virginia.Requests for reprints should be addressed to R. J. Condry, M.D., Taylor Avenue, Elkins, West Virginia. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byPulmonary Artery DissectionDissecting Hematomas of the Pulmonary ArteryPartial rupture of pulmonary artery with lesions of medionecrosis in a case of mitral stenosisSpontaneous rupture of the pulmonary artery in pulmonary hypertension 1 November 1958Volume 49, Issue 5Page: 1252-1257KeywordsDyspneaElectrocardiographyGratitudeHypertensionNecrosisPulmonary arteriesPulmonary diseasesPulmonary hypertensionThoraxUpper respiratory tract infections ePublished: 1 December 2008 Issue Published: 1 November 1958 PDF downloadLoading ...
Abstract 2624: An Analysis of CT Angiographic Patterns in Patients With vs. Without Acute Coronary Syndromes Presenting to the Emergency Department With Acute Chest Pain
Authors: Maros Ferencik, Antonio J Pena, Fabian Moselewski, John H Nichols, Javed Butler, Ik-Kyung Jang, Thomas J Brady, John T Nagurney, Udo Hoffmann
Journal: Circulation (2006)

Background: Cardiac multidetector computed tomography (MDCT) permits detection and quantification of coronary plaque. The aim of this study was to compare the presence and extent of coronary artery disease (CAD) as determined by MDCT in patients with and without acute coronary syndromes (ACS). Methods: 103 patients with acute chest pain presenting to the Emergency Department (ED), with negative cardiac biomarkers and no ECG changes indicative for acute myocardial ischemia, underwent cardiac MDCT (Siemens Sensation 64, 64x0.6mm collimation, 330ms gantry rotation). The presence of coronary plaque was treated as a dichotomous outcome, and the extent of CAD was defined as number of coronary segments with plaque, or major coronary arteries with plaque detected by MDCT as assessed by two independent observers. The clinical outcome (ACS) was defined by an adjudicating committee using ACC criteria. Univariate associations between the presence and extent of CAD and the discharge diagnosis of ACS were examined usin...
Exchange protein directly activated by cyclic AMP (EPAC) activation reverses neutrophil dysfunction induced by β2-agonists, corticosteroids, and critical illness
Authors: Jonathan Scott, Graham J. Harris, Emma M. Pinder, James G. Macfarlane, Thomas P. Hellyer, Anthony J. Rostron, Andrew Conway Morris, David R. Thickett, Gavin D. Perkins, Daniel F. McAuley, John D. Widdrington, Sarah Wiscombe, Simon V. Baudouin, Alistair I. Roy, Vanessa C. Linnett, Stephen E. Wright, Marie-Hélène Ruchaud-Sparagano, A. John Simpson
Journal: Journal of Allergy and Clinical Immunology (2015)
Negotiating the Tensions in Patient-Centered Care
Authors: Christina A. Minami, Anthony D. Yang, Eytan Szmuilowicz
Journal: JAMA (2015)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
The neuronal-specific RNA binding protein HuD regulates N-myc pre-mRNA stability and gene copy number in human neuroblastoma cells
Authors: Kathryn B. Grandinetti, Barbara A. Spengler, June L. Biedler, Robert A. Ross
Journal: Cancer Research (2005)

2806   Amplification and overexpression of the proto-oncogene N- myc  is an important indicator of aggressiveness in human neuroblastoma tumors. One factor that influences the expression and amplification of N- myc  is HuD, one member of the Hu family of neuronal-specific RNA binding proteins. Studies have shown that this protein regulates processing and thereby expression of several mRNA species, including N- myc . Previous work in this laboratory has shown that (1) HuD binds to the first intron of the N- myc  transcript as well as the 3’ untranslated region, and (2) N-myc mRNA and protein levels are dependent upon HuD expression levels. The studies described here sought to determine how HuD regulates N- myc  expression and how such regulation might affect gene amplification. To test the hypothesis that HuD enhances stability of nascent transcripts, we stably transfected a sense  HuD  construct, or vector alone, into N- myc  amplified, non-neuronal LA1-5s neuroblastoma cells - HuD-negative cells with low-level expression of N-myc. Relative to vector controls, nuclear Hu protein levels increased 7-fold and N-myc mRNA and protein levels increased as much as 8-fold in the  HuD -transfected LA1-5s cells without changing the non-neuronal phenotype. The increase in N-myc levels is not due to an increase in the half-life of the message or to a difference in the rate of transcription as measured by nuclear run-on assays. However, levels of splice intermediates are increased 2-fold in the  HuD  transfectants due to the stabilization of N- myc  pre-mRNA by HuD. A second line of research has implicated reduced levels of HuD as a selective factor in amplification of the N- myc  gene. Previous studies had shown that transfection of HuD into N- myc  amplified cells with only one  HuD  allele decreased N- myc  gene copy number. To directly test the involvement of HuD in N- myc  gene amplification, we stably transfected N- myc  nonamplified SH-SY5Y cells, which have two normal  HuD  alleles, with an antisense  HuD  construct regulated by a β-actin promoter. The transfectants retain their neuroblastic phenotype although Hu protein levels are reduced 4-fold and, consequently, N- myc  mRNA levels are decreased 2-fold. Analysis of N- myc  gene copy number in these cells by semi-quantitative PCR as well as FISH reveals from 2-8 additional gene copies in the antisense- HuD  transfected cells. Our studies support a vital role for HuD in N- myc  expression and provide evidence that the loss of  HuD  can lead to amplification of the N- myc  gene in human neuroblastoma cells.
Loss of vision due to central serous chorioretinopathy following psychological stress
Authors: Gary S. Gelber, Howard Schatz
Journal: American Journal of Psychiatry (1987)

The authors studied 33 patients with central serous chorioretinopathy and found that a very disturbing psychological event had preceded the loss of vision in 91% of the cases. The acute disturbance preceded the first visual symptoms by an average of 7 days. When relapses occurred, the psychological disturbances were often less severe and preceded the visual symptoms by minutes or hours. In some cases vision improved 1 to 2 weeks after the patient learned of the amelioration of the original distressing situation. The majority of the patients were found to be tension ridden, and 48% had cardiovascular abnormalities.
Regional Chemotherapy of Liver Cancer
Authors: Richard W. Opfell, Joseph Bowen
Journal: Liver Cancer (1985)

Primary liver cancer is very rare in the United States, but worldwide is one of the ten most common malignancies with 250,000 new cases yearly [1]. Liver metastases are found at autopsy in 41–75% of patients dying of cancer [2 and table 14–1]. Surgery offers the only possibility of cure [chapter 7]; but resection is possible in only 10–20% of primary and 5% of secondary liver cancers. Systemic chemotherapy has not consistently produced responses in more than 20% of patients [chapter 11] and has had no significant impact upon survival. Radiation therapy has provided significant relief of pain but little else [chapters 18 and 19]. The facts about liver cancer can be summed up by stating that liver cancer is common and usually kills rapidly. This grim prognosis has stimulated the rapid development of many novel approaches to the management of liver cancer. This chapter reviews the progress in intrahepatic arterial (IHA) chemotherapy of liver cancer.
Surgeon performs bypass operation by microsurgery
Authors: David Spurgeon
Journal: BMJ (1999)

A surgeon at the London (Ontario) Health Sciences Centre is believed to have become the first person to perform a cardiac bypass operation without opening the chest wall and stopping the heart.

Dr Douglas Boyd, assistant professor of surgery at the University of Western Ontario, reached 60 year old farmer John Penner's beating heart through three pencil sized incisions and another small incision …
Abstract P097: Low Medication Adherence is Related to Poor Hypertension Control among Patients with Chronic Kidney Disease
Authors: Suma Vupputuri, Paul Muntner, Wolfgang C Winkelmayer, David H Smith, Gregory A Nichols
Journal: Circulation (2012)

Inadequately controlled blood pressure (BP) is an important risk factor for the progression of chronic kidney disease (CKD). Few data are available on the association between adherence to antihypertensive medications and BP control among patients with CKD. We investigated the association of adherence to angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) with BP levels and BP control among CKD patients (n=3077) at Kaiser Permanente Georgia (an insurer and health care provider). Patients were required to have 2 outpatient diagnoses of CKD in 2008-2009, at least 2 fills of ACEi/ARBs, be 18+ years of age, with at least 1 year of continuous membership and prescription benefits prior to 01/01/08 and have no history of end-stage renal disease. We defined uncontrolled BP as systolic/diastolic of ≥140/90 mmHg and also ≥130/80 mmHg. As a measure of adherence we calculated the medication possession ratio (MPR): # of days medication supplied between the first and last prescription fills Duration from first to last prescription date + days supply from last prescription The mean age of our sample was 64.1 ±11.9 years; 53.1% were female, and 57.6% African-American. In this sample, 22.6% and 8.9% had low and very low medication adherence, respectively; while 25.6% and 58.6% had systolic/diastolic BP of ≥140/90 and ≥130/80 mmHg, respectively. The mean BPs and odds ratios (ORs) for uncontrolled BP associated with level of adherence to antihypertensive medications are given in the table . In conclusion, among patients with CKD, poor medication adherence to antihypertensive medications was consistently associated with uncontrolled hypertension. Targeting interventions to improve medication adherence among patients with CKD may be an important strategy to improve BP control and, in turn, slow the progression of CKD. Medication Adherence p-trend High (MPR: ≥0.8) N=2109 Low (MPR: 0.5 to &lt;0.8) N=694 Very low (MPR: &lt;0.5) N=274 Mean systolic BP, mmHg 131.3 (13.0) 134.0 (14.7) 137.5 (15.4) &lt;0.0001 Mean diastolic BP, mmHg 72.5 (8.12) 75.7 (9.21) 78.7 (10.1) &lt;0.0001 OR for SBP/DBP ≥140/90 mmHg Age, race, sex adjusted 1.0 (ref) 1.40 (1.14, 1.73) 2.30 (1.73, 3.06) &lt;0.0001 Multivariate adjusted * 1.0 (ref) 1.24 (0.97, 1.57) 1.96 (1.40, 2.75) &lt;0.0001 OR for SBP/DBP ≥130/80 mmHg Age, race, sex adjusted 1.0 (ref) 1.21 (1.00, 1.46) 1.81 (1.33, 2.45) &lt;0.0001 Multivariate adjusted * 1.0 (ref) 1.11 (0.89, 1.38) 1.43 (1.01, 2.01) 0.04 * Adjusted for age, race, sex, socioeconomic status, co-morbidities, clinical measures, and number of medication classes.