tbuckley/cabot-search huggingface dataset:
Flow-dependent expression of ectonucleotide tri(di)phosphohydrolase-1 and suppression of atherosclerosis
Authors: Yogendra Kanthi, Matthew C. Hyman, Hui Liao, Amy E. Baek, Scott H. Visovatti, Nadia R. Sutton, Sascha N. Goonewardena, Mithun K. Neral, Hanjoong Jo, David J. Pinsky
Journal: Journal of Clinical Investigation (2015)

The ability of cells to detect and respond to nucleotide signals in the local microenvironment is essential for vascular homeostasis. The enzyme ectonucleotide tri(di)phosphohydrolase-1 (ENTPD1, also known as CD39) on the surface of leukocytes and endothelial cells metabolizes locally released, intravascular ATP and ADP, thereby eliminating these prothrombotic and proinflammatory stimuli. Here, we evaluated the contribution of CD39 to atherogenesis in the apolipoprotein E–deficient (ApoE-deficient) mouse model of atherosclerosis. Compared with control ApoE-deficient animals, plaque burden was markedly increased along with circulating markers of platelet activation in Cd39+/–Apoe–/– mice fed a high-fat diet. Plaque analysis revealed stark regionalization of endothelial CD39 expression and function in Apoe–/– mice, with CD39 prominently expressed in atheroprotective, stable flow regions and diminished in atheroprone areas subject to disturbed flow. In mice, disturbed flow as the result of partial carotid artery ligation rapidly suppressed endothelial CD39 expression. Moreover, unidirectional laminar shear stress induced atheroprotective CD39 expression in human endothelial cells. CD39 induction was dependent upon the vascular transcription factor Krüppel-like factor 2 (KLF2) binding near the transcriptional start site of CD39. Together, these data establish CD39 as a regionalized regulator of atherogenesis that is driven by shear stress.
When drugs don't make it to market
Authors: B. Mintzes
Journal: BMJ (2015)

We need to know why, and regulators should tell us

Drug regulation aims to protect public health by ensuring that only medicines that are effective and safe are marketed. The key regulatory innovation after the thalidomide tragedy was the requirement for systematic evidence of efficacy before marketing approval, with the understanding that no drug exposure is worth risking without evidence of benefit.

Over 50 years later, premarket evaluations remain much needed but imperfect, with efficacy standards not always ensuring clinical benefit for patients,1 and inadequate public communication on the available evidence and how it has been assessed. The United States Food and Drug Administration (FDA) is more open than many regulatory agencies, but, when it comes to non-approvals, the linked study by Lurie and colleagues (doi:10.1136/bmj.h2758) shows that commercial confidentiality continues to trump public health.2

If the FDA rejects an application, the letter to the manufacturer stating the reasons is confidential. Lurie and colleagues are FDA staff members who compared the content of FDA non-approval letters (n=61) with the firms’ press releases.2 This is the first published study to compare what regulators say in confidence to pharmaceutical manufacturers and what those manufacturers then say to the public. The differences are damning: 85% of the regulator’s …
FeNO (fractional exhaled nitric oxide) measurements in pregnant asthmatic women. The long-term, intra-subject variability of FeNO in controlled asthma
Authors: Anna Dor-Wojnarowska, Marita Nittner-Marszalska, Robert Pawlowicz, Hanna Marszalska, Anna Kazimerczak, Bernard Panaszek
Journal: European Respiratory Journal (2012)

BACKGROUND: Fractional exhaled nitric oxide (FeNO) is considered a good noninvasive marker to assess airway inflammation in asthma and allergic rhinitis. It has been also proposed that adjusting anti-inflammatory drugs guided by the monitoring of exhaled NO could improve overall asthma control. However standards, the assessment of long-term repeatability of this parameter as well as the rate of change which can be considered significant have not been established yet.  The aim of our study was to assess the long-term, intra-subject variability of FeNO in pregnant asthmatic women with controlled asthma.  METHODS: Pregnant, non-smoking women with asthma were recruited between 8 and 24 weeks of gestation. Exhaled nitric oxide (FeNO), lung function, and the asthma control test (ACT) were performed at monthly visits up to delivery. The data of 50 subjects with well controlled asthma (20-25 ACT, normal spirometric parameters, no change in treatment) during pregnancy were analyzed. The variability of the FeNO parameter was assessed in asthmatics using the variation coefficient (standard deviation x 100% / average).  RESULTS: FeNO showed high coefficient of variation (CV): 35.8% (Me 32;Min 2.45, Max 121,9) in all women with well controlled asthma during pregnancy. There was no significant difference in CV between atopic 36,2% (35,5; 2,45-121,9) and nonatopic 33,9% (25,5; 11-71,9) asthmatic women (p= 0,98).  CONCLUSIONS: Long-term variation of FeNO was found to be not satisfactory because the variation coefficient was 35.8%. It means that changes of FeNO should be interpreted with caution.
Role of Divalent Ion Complex Formation in Pyran—Inhibition of Nucleic Acid Biosynthesis 2
Authors: Robert J. Fiel, David A. Musser, Benjamin R. Munson
Journal: JNCI Journal of the National Cancer Institute (1976)

The degree of inhibition of mammalian DNA-dependent RNA polymerases I and II and Moloney leukemia virus RNA-dependent DNA polymerase by pyran copolymer was dependent on the concentration of the divalent cation cofactor in the reaction mixture. Inhibition was completely blocked by an excess of divalent cations. It was concluded that pyran inhibited these enzymes by com pie xing with the essential divalent cation cofactor.
A Ki-1 (CD30)-positive human cell line (Karpas 299) established from a high-grade non-Hodgkin's lymphoma, showing a 2;5 translocation and rearrangement of the T-cell receptor beta-chain gene
Authors: P Fischer, E Nacheva, DY Mason, PD Sherrington, C Hoyle, FG Hayhoe, A Karpas
Journal: Blood (1988)
Monoclonal Antibody (G10) to a Common Antigen of Human Squamous Cell Carcinoma: Binding of the Antibody to the H Type 2 Blood Group Determinant&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Kimmel Ka, Carey Te, Judd Wj, McClatchey Kd
Journal: JNCI Journal of the National Cancer Institute (1986)

The IgM monoclonal antibody G10 was raised against the human squamous cell carcinoma (SCC) cell line UM-SCC-1. In initial screening against cultured cells, G10 bound to 2 SCC lines (UM-SCC-1 and UM-SCC-13) and 1 pancreatic carcinoma line (UM-PAd-1) but not to cultured fibroblasts (WI-38), ovarian carcinoma cells (SK-OV-3), or malignant melanoma cells (SK-MEL-28 and MeWo). In subsequent tests against cultured cell lines, G10 gave positive reactions with 30 of 33 SCC lines but only 4 of 29 non-SCC lines. The non-SCC lines that bound G10 were UM-PAd-1, 2 transitional cell carcinoma lines (T24 and RT4), and 1 melanoma line (SK-MEL-22). When tested against cultures derived from normal skin or mucosa, G10 was reactive with the epithelioid squamous cells but not with the fibroblasts in each culture. The antigen defined by antibody G10 was stable to fixation with Formalin, and its distribution in tissue sections was examined with the use of immunoperoxidase assays. All SCC biopsy specimens examined in this way were reactive with antibody G10. In similar tests against sections of fixed normal tissues, G10 stained the superficial squamous cells of the epidermis and the basal and suprabasal layers of mucosal squamous epithelial cells from the esophagus. All layers of the laryngeal epithelium were positive. Endothelial cells and certain glandular cells were also positive for G10 binding. G10 agglutinated human red blood cells of all blood groups except those from individuals of the Bombay group (Oh) who lack the H blood group determinant. Against defined oligosaccharides, G10 bound strongly only to the monofucosyl H type 2 structure and was slightly cross-reactive with the synthetic difucosyl H type 2 or Y structure. These results are consistent with previous reports of blood group antigen tissue distribution and indicate that the H type 2 determinant is expressed by all or nearly all mucosal squamous cancers. Less frequent expression by cells of other tumor types may correlate with tissue-specific activation of the H gene-specified fucosyltransferase.
Democrats block vote on bill to deny federal funds to Planned Parenthood
Authors: Michael McCarthy
Journal: BMJ (2015)

Senate Democrats successfully blocked a Republican sponsored bill on 3 August that would have denied all federal funding of Planned Parenthood, the largest provider of family planning services in the United States. In a 53-46 largely party line vote, Republicans failed to reach the 60 votes needed to advance the bill to the Senate floor for debate.

In a speech before the vote the Senate minority leader, Harry Reid, a Democrat from Nevada, said that if passed the bill would have limited women’s access to critical health services such as contraception, breast and cervical cancer screenings, and well woman visits. “This legislation is just another Republican attack on the healthcare …
MicroRNA-103/107 Regulate Programmed Necrosis and Myocardial Ischemia/Reperfusion Injury Through Targeting FADD
Authors: Jian-Xun Wang, Xiao-Jie Zhang, Qian Li, Kun Wang, Yin Wang, Jian-Qin Jiao, Chang Feng, Sun Teng, Lu-Yu Zhou, Ying Gong, Zhi-Xia Zhou, Jia Liu, Jian-Ling Wang, Pei-feng Li
Journal: Circulation Research (2015)

Necrosis is one of the main forms of cardiomyocyte death in heart disease. Recent studies have demonstrated that certain types of necrosis are regulated and programmed dependent on the activation of receptor-interacting serine/threonine-protein kinase (RIPK) 1 and 3 which may be negatively regulated by Fas-associated protein with death domain (FADD). In addition, microRNAs and long noncoding RNAs have been shown to play important roles in various biological processes recently.The purpose of this study was to test the hypothesis that microRNA-103/107 and H19 can participate in the regulation of RIPK1- and RIPK3-dependent necrosis in fetal cardiomyocyte-derived H9c2 cells and myocardial infarction through targeting FADD.Our results show that FADD participates in H2O2-induced necrosis by influencing the formation of RIPK1 and RIPK3 complexes in H9c2 cells. We further demonstrate that miR-103/107 target FADD directly. Knockdown of miR-103/107 antagonizes necrosis in the cellular model and also myocardial infarction in a mouse ischemia/reperfusion model. The miR-103/107-FADD pathway does not participate in tumor necrosis factor-α-induced necrosis. In exploring the molecular mechanism by which miR-103/107 are regulated, we show that long noncoding RNA H19 directly binds to miR-103/107 and regulates FADD expression and necrosis.Our results reveal a novel myocardial necrosis regulation model, which is composed of H19, miR-103/107, and FADD. Modulation of their levels may provide a new approach for preventing myocardial necrosis.
Congenital diaphragmatic hernia: The effect on growth and neurodevelopment in young children
Authors: Lisette Leeuwen, Karen Walker, Robert Halliday, Dominic Fitzgerald
Journal: European Respiratory Journal (2013)

Background:  Congenital Diaphragmatic Hernia (CDH) survivors are at risk of poor growth and neurodevelopmental outcomes.   Aims:  To describe the effect of CDH on growth and neurodevelopmental outcome during the first 3 years in a prospective cohort of CDH infants and controls.   Methods:  Infants with CDH admitted to our centre between 2005 and 2011 were included. Anthropometric measurements were collected and neurodevelopmental outcomes were compared with locally born controls.   Results:  55 infants with CDH were admitted with a survival rate of 82%. Weight was most affected in early infancy: mean(±SD)  z -score of -1.65±1.30 at 3 months, -1.35±1.18 at 6 months with improvement to -0.41±0.97 at 3 years. Days of mechanical ventilation, duration of hospital stay, patch repair, prenatal diagnosis and oxygen requirement at discharge were found as predictors of failure to thrive. There were no differences in neurodevelopmental outcome scores between CDH patients and controls.   Conclusion:  Poor growth is a common early finding in CDH patients, which improves dramatically after six months. Importantly, neurodevelopmental outcome was normal compared to healthy matched controls.
Predicting survival in interstitial lung disease (ILD): Multidisciplinary team (MDT) diagnosis versus technetium-99m diethylene triamine pentacetic acid (DTPA) clearance scans
Authors: Akshay Dwarakanath, Su Su Win, Mark Elliiott, Michael Darby, Paul Beirne
Journal: European Respiratory Journal (2013)

Introduction Between 2003 - 2007 in St James’ DTPA scans were used to predict prognosis in ILD (Wells et al. ERJ 1993; 6:797).Now MDT diagnosis predicts prognosis.We investigated whether DTPA scans might augment MDT diagnosis in predicting prognosis.

Method 47 cases underwent retrospective MDT discussion of clinical data and radiology contemporaneous with the DTPA.The MDT was blinded to the DTPA result and the subsequent clinical course.

Results 31/47 DTPAs were abnormal and associated with reduced survival (p=0.04).The MDT diagnosed 20/47 as Idiopathic Pulmonary Fibrosis (IPF) and 27/47 as non-IPF.18/20 IPF had an abnormal DTPA (2 with a normal DTPA both died).0/13 non-IPF with a normal DTPA died; 6/14 with an abnormal DTPA died. An abnormal DTPA scan was more likely in IPF (P=0.0028).In non-IPF, an abnormal scan predicted mortality in 2/8 with non-specific interstitial pneumonia, 2/7 with connective tissue disease, 2/3 with unclassified fibrosis.

Conclusion In MDT-diagnosed IPF a DTPA provides no additional prognostic data. In non-IPF, a normal DTPA predicts survival but an abnormal predicts mortality in some patients. DTPA scans may augment MDT discussion in non-IPF ILD.

Median survival (Kaplan-Meier): Non-IPF normal DTPA x months, non-IPF abnormal DTPA 108 months, IPF normal DTPA 27 months, IPF abnormal DTPA 30 months (Mantel-Cox p<0.0001).

![Figure][1]  [1]: pending:yes
Lung Cancer and Lung Stem Cells
Authors: Adam Giangreco, Karen R. Groot, Sam M. Janes
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Lung cancer is a significant disease with survival rates remaining poor despite numerous therapeutic advances during the last 30 years. Understanding lung cancer pathogenesis through murine modeling may improve future human therapies, and new data indicate that mutations within different endogenous stem cells situated throughout airways can drive cancer formation. Airway stem cells maintain prototumorigenic characteristics, including high proliferative capacity, multipotent differentiation, and a long lifespan relative to other cells. These cells localize to proximal airway submucosal glands/intercartilagenous rings, neuroepithelial bodies, and terminal bronchioles/bronchoalveolar duct junctions. Recent studies suggest that endogenous stem cell signaling and differentiation pathways are maintained within distinct cancer types, and that destabilization of this signaling machinery may initiate region-specific lung cancers. A better understanding of this relationship among stem cell regulation, cellular mutation, and lung cancer oncogenesis is critical for developing the next wave of lung cancer therapies.
Prognostic factors in small-cell carcinoma of the lung: an analysis of 1,521 patients.
Authors: D Spiegelman, L H Maurer, J H Ware, M C Perry, A P Chahinian, R Comis, W Eaton, B Zimmer, M Green
Journal: Journal of Clinical Oncology (1989)

Cancer and Leukemia Group B (CALGB) accrued 1,745 patients with limited (LD) or extensive (ED) small-cell lung cancer (SCCL) to five separate trials between 1972 and 1986. We reviewed these data to evaluate the impact of pretreatment prognostic factors on outcome. In multivariate analysis, female gender was predictive of improved response (LD, P = .01; ED, P = .04) and survival (LD, P = .01; ED, P = .02). A performance status of 0 or 1 was associated with improved response rates in both subsets, but was statistically significant (P = .04) only for overall objective response in LD patients. Performance status was a highly significant predictor of survival in both LD and ED groups (P less than .001). Supraclavicular lymph node involvement, while still LD, had a borderline unfavorable impact on survival (P = .06) compared with a lesser extent of LD involvement. In ED patients, a decrease in survival rates was associated with an increased number of metastatic sites (P = .01). Changes in the patient population were noted with time: the percentage of women increased from 21% to greater than 35%; an increased number of metastatic sites was identified among ED patients; mean performance status improved for both LD and ED subsets. These trends reflect the changing demographics of lung cancer, improved lung cancer staging, and probably lead-time bias. Response rates, overall survival, and long-term (greater than 2-year) survival varied significantly among the five protocols, both before and after multivariate correction for identified prognostic variables. However, the changing character of the study population limits the ability to determine retrospectively how much improvements in therapy contributed to the positive changes in failure-free survival, overall survival, and long-term survival observed in our sequentially studied population.
Polymorphisms in Genes Related to Oxidative Stress Are Associated With Inferior Cognitive Function After Therapy for Childhood Acute Lymphoblastic Leukemia
Authors: Peter D. Cole, Yaron Finkelstein, Kristen E. Stevenson, Traci M. Blonquist, Veena Vijayanathan, Lewis B. Silverman, Donna S. Neuberg, Stephen E. Sallan, Philippe Robaey, Deborah P. Waber
Journal: Journal of Clinical Oncology (2015)

Survivors of childhood acute lymphoblastic leukemia (ALL) exhibit increased rates of neurocognitive deficits. This study was conducted to test whether interpatient variability in neurocognitive outcomes can be explained by polymorphisms in candidate genes conferring susceptibility to neurocognitive decline.Neurocognitive testing was conducted in 350 pediatric leukemia survivors, treated on Dana-Farber Cancer Institute ALL Consortium Protocols 95-01 or 00-01. Genomic DNA was isolated from bone marrow collected at remission. Candidate polymorphisms were selected on the basis of prior literature, targeting genes related to drug metabolism, oxidative damage, altered neurotransmission, neuroinflammation, and folate physiology. Single nucleotide polymorphisms were detected using either a customized multiplexed Sequenom MassARRAY assay or polymerase chain reaction-based allelic discrimination assays. Multivariable logistic regression models were used to estimate the effects of genotype on neurocognitive outcomes, adjusted for the effects of demographic and treatment variables. False-discovery rate correction was made for multiple hypothesis testing, indicated as a Q value.Inferior cognitive or behavioral outcomes were associated with polymorphisms in three genes related to oxidative stress and/or neuroinflammation: NOS3 (IQ, Q = 0.008; Vocabulary Q = 0.011; Matrix Reasoning Q = 0.008), SLCO2A1 (IQ Q = 0.043; Digit Span Q = 0.006; Block Design Q = 0.076), and COMT (Behavioral Assessment System for Children-2 Attention Q = 0.080; and Hyperactivity Q = 0.084). Survivors homozygous for NOS3 894T, with at least one SLCO2A1 variant G allele or with at least one GSTP1 variant allele, had lower mean estimated IQ scores than those without these genotypes.These data are consistent with the hypothesis that oxidative damage contributes to chemotherapy-associated neurocognitive decline among children with leukemia.
HEMORRHAGIC TELANGIECTASIA TREATED WITH STILBESTROL
Authors: J V WALLER
Journal: Annals of Internal Medicine (1956)

Case Reports1 January 1956HEMORRHAGIC TELANGIECTASIA TREATED WITH STILBESTROLJOHN V. WALLER, M.D.JOHN V. WALLER, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-44-1-204 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptDisabling and severe anemia occurs frequently in persons who have epistaxis from congenital hemorrhagic telangiectasia. Repeated epistaxis in this disease defied treatment until Koch et al.,1 in August, 1952, described suppression of recurrent epistaxis following the use of oral estrogens. In addition to the beneficial effect on the bleeding, these investigators noted that the atrophic nasal mucosa became pink, moist and soft. The patient reported in this communication had an initial excellent result, with severe exacerbation after seven months of continuous treatment.CASE REPORTA 57 year old white male was admitted to the Lenox Hill Hospital on January 25,...Bibliography1. KochEscherLewis JHGCJS: Hormonal management of hereditary hemorrhagic telangiectasia, J. A. M. A. 149: 1376-1380, 1952. CrossrefMedlineGoogle Scholar2. Heyde EC: Hereditary hemorrhagic telangiectasia: a report of pulmonary arteriovenous fistulae in mother and son; medical (hormonal) and surgical therapy of this disease, Ann. Int. Med. 41: 1042-1054 (Nov.) 1954. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: New York, N. Y.*Received for publication November 15, 1954.From the Lenox Hill Hospital, New York, N. Y. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byESTROGENIC CONTROL OF CORTICOSTEROID-INDUCED BRUISING, WITH A COMMENTARY ON ESTROGEN-CORTICOSTEROID INTERRELATIONSHIPSTHE CONTROL OF GASTRO-INTESTINAL HEMORRHAGE IN CIRRHOSIS BY COMBINED ADRENOCORTICAL AND ESTROGENIC THERAPYTREATMENT OF DIABETIC RETINOPATHY WITH ESTROGENSORAL AND INTRAVENOUS ESTROGENS IN THE TREATMENT AND PREVENTION OF BLEEDING ASSOCIATED WITH LONG-TERM ANTICOAGULANT THERAPYKrankheiten der Gefäße 1 January 1956Volume 44, Issue 1Page: 204-206KeywordsAnemiaEstrogensFistulasHemoglobinHemorrhageMucous membranesNasal mucosaPneumoniaTuberculosis Issue Published: 1 January 1956 PDF downloadLoading ...
Abstract 17617: Predictors of Exercise in Ambulatory Patients with Heart Failure
Authors: Nancy M Albert, Harshida Patel, Kristen Sethares, Colin O'Rourke, Jennifer Forney, Jacqueline Gannuscio, Rochelle Armola, Diane Philip, Barbara Riegel, Sarah Fontana, Eileen Hsich
Journal: Circulation (2012)