tbuckley/cabot-search huggingface dataset:
Abstract 842: DNA opilymerase β participates in the repair of DNA damage from topoisomerase II
Authors: Yilun Sun, Sule Bertram, John L. Nitiss
Journal: Cancer Research (2014)

Abstract DNA topoisomerase II (Top2) is the target of several important anti-cancer agents, including doxorubicin and etoposide. Clinically active Top2 agents, termed Top2 poisons, act by blocking the enzyme reaction at a step where the protein is covalently bound to DNA. This leads to the accumulation of Top2/DNA complexes that act as DNA damaging agents that interfere with DNA metabolism and trigger cell death. The mechanisms leading to tumor specific killing by Top2 poisons remain poorly understood, and have been hypothesized to result in part from DNA repair defects that arise during tumorigenesis. If this hypothesis is correct, then targeting repair pathways important for topoisomerase mediated cell killing could be used to enhance the activity of Top2 poisons. Similar reasoning has led to extensive trials of agents such as PARP inhibitors, and other DNA repair inhibitors. The DNA repair pathways that have been examined for sensitization to Top2 poisons include homologous recombination, non-homologous end-joining, proteasome mediated degradation, and nucleolytic activities that may participate in the removal of protein/DNA adducts (such as Tdp1 and Tdp2). We have been studying the repair of damage from Top2 poisons, and have optimized a quantitative assay for Top2/DNA covalent complexes in cultured mammalian cells. This assay, termed the ICE assay, detects Top2 covalent complexes by DNA purification followed by antibody detection of protein adducts. Using this assay, we have demonstrated a role of the MRN complex in processing Top2/DNA adducts, using both MRN knockdowns and small molecule inhibitors of the Mre11 nuclease activities. We also confirmed the importance of proteolytic pathways in repairing Top2 damage. A surprising candidate protein for participation in repair of damage from Top2 poisons is DNA polymerase β (pol β), an “X” family polymerase critical for base excision repair. Recent results have implicated pol β in processing of protein/DNA adducts (1). We found that the pol β inhibitor pamoic acid (4-[(3-Carboxy-2-hydroxynaphthalen-1-yl)methyl]-3-hydroxynaphthalene-2-carboxylic acid) and etoposide led to a large increase in Top2/DNA covalent complexes compared to etoposide alone. We are currently validating these results using other pol β inhibitors and gene knockdown approaches. We speculate that the dRP lyase activity may play a role in processing DNA damage arising from Top2 poisons. Literature cited: 1. Lawson, M.H., et al. (2011) Two Novel Determinants of Etoposide Resistance in Small Cell Lung Cancer. Cancer Res, 71, 4877-4887. Citation Format: Yilun Sun, Sule Bertram, John L. Nitiss. DNA opilymerase β participates in the repair of DNA damage from topoisomerase II. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 842. doi:10.1158/1538-7445.AM2014-842
Abstract 13027: Periostin Cre-mediated Hypoxia-inducible Transfroming Growth Factor-β Receptor Deletion in Pulmonary Artery Attenuates the Progression of Pulmonary Arterial Hypertension in Mice
Authors: Mitsuru Seki, Norimichi Koitabashi, Hirokazu Arakawa, Masahiko Kurabayashi
Journal: Circulation (2014)

Introduction: Mutations in the bone morphogenetic protein type II receptor, transforming growth factor-β (TGF-β) receptor superfamily member, are responsible for heritable pulmonary arterial hypertension (PAH). Although this mutation is associated with TGF-β signal activation, the precise role of TGF-β signaling still remains uncertain in pathogenesis of PAH. Under hypoxic condition, Periostin(Pn) which usually expresses in fibroblasts protein has been shown to express on vascular smooth muscle cell. Therefore, Pn-Cre-loxP system may work as conditional inhibition in hypoxic pulmonary arterial smooth muscle cells. Methods: We established TGF-β type I receptor knockout mice specifically in periostin expressing cell (PnCre/Alk5flox model mice). A mouse model of hypoxia-induced PAH was used for this study. We evaluated right ventricular systolic pressure, function, hypertrophy, and vascular remodeling of pulmonary artery after 3 weeks of exposure to 10% of oxygen. Results: Those mice were induced proliferation of pulmonary arterial smooth muscle cells and perivascular fibrotic change, causing pulmonary hypertension. Right ventricular pressure measured by pressure catheter was significantly decreased in PnCreAlk5flox model mice compared with wild-type mice (44.8±7.8 vs 55.0±9.7mmHg, p&lt;0.05). Right ventricular function and right ventricular weight showed no significant difference between both mice. Histological analysis revealed inhibition of medial thickening of pulmonary artery and perivascular fibrotic change in PnCreAlk5flox model mice compared with wild-type mice (% muscularization of pulmonary artery ; 52.0±14.3 vs 78.4±11.5%, p&lt;0.05). Conclusions: These results indicate that TGF-β signaling in fibroblasts and smooth muscle cells has a critical role on pathogenesis of PAH, suggesting the usefulness of therapy by targeting TGF-β signaling.
Abstract 2514: Automatic Biventricular Capture Verification Based On Morphological Analysis of the Intracadiac Electrogram Signal
Authors: Jie Lian, Garth Garner, Dirk Muessig
Journal: Circulation (2007)

Objective: We test a new biventricular capture verification algorithm, which can be used to adjust the pacing output in right ventricle (RV) and left ventricle (LV), to ensure the safety and efficacy of the cardiac resynchronization therapy (CRT). Methods: The algorithm calculates a novel index called ASCI, which measures the morphological similarity between the intracardiac electrogram (IEGM) signal and a template waveform representing captured paces. Ventricular capture (CAP) is verified if ASCI is greater than a predefined threshold, whereas non-capture (NC) is declared otherwise. CRT pacemakers were implanted in 6 dogs. During a mean follow-up of 23 days, 175 biventricular threshold tests were conducted by running a customized program, with various combinations of pace/sense polarities. Wideband RV and LV IEGM were recorded and downloaded for off-line analysis by the algorithm. Template signals for each pace/sense configuration in each chamber were created from the average of 4 captured beats. Each pace was annotated for CAP or NC by visual examination of the IEGM and based on stored data log of the pacing parameters. Results: A total of 9991 CAP paces (5104 RV, 4887 LV) and 4474 NC paces (2136 RV, 2338 LV) were eligible for morphology analysis. In both RV and LV, the calculated ASCIs were well separated for CAP and NC paces (Figure ): 0.83 ± 0.12 (RV CAP), 0.85 ± 0.11 (LV CAP), -0.06 ± 0.13 (RV NC), -0.07 ± 0.14 (LV NC). The classification accuracy of the algorithm remained &gt;= 99% for any ASCI threshold value choosing between 0.18 and 0.52. Conclusion: This study demonstrated the feasibility to perform automatic biventricular capture verification based on morphology analysis of the IEGM.
Gene expression changes after one course of chemotherapy in breast cancer
Authors: Romain Boidot, Frédérique Végran, Muriel Cadouot, Lyse Hahnel, Pierre Fumoleau, Sarab Lizard-Nacol
Journal: Clinical Cancer Research (2006)

A83   Breast cancer is the most widespread female cancer in industrialized countries. Mammary tumors are very heterogeneous and each tumor has a unique profile. This gives rise to a large difficulty in treatment choice. With the aim of finding orienting-treatment profiles, a study on locally advanced breast tumors was performed on macroarray membrane containing 266 genes belonging to apoptosis, cell-cycle and stress families (SuperArray). The population (19 cases) was divided in two groups treated with 5-fluorouracil - epirubicin - cyclophosphamide (FEC) or with docetaxel - epirubicin (Tax-Epi). For FEC group, 10 non-treated tumors (NT) and 8 tumors after one course of chemotherapy (TT) were analyzed. In Tax-Epi group, 9 NT tumors and 9 TT were studied. NT expression profiles were compared to TT expression ones for each treatment using Mann-Whitney U-test. Only tests with  p
Noxious Gases and the Principles of Respiration Influencing Their Action.
Authors: Yandell Henderson, Howard Wilcox Haggard
Journal: JAMA (1928)

An attempt to trace the development of all geniuses from the generally abnormal elements of mankind, rather than from the well-bred, speaking from the eugenic point of view.When one has waded through these half- baked conclusions a mental refreshment may be recom- mended in the shape of Galton 's "Hereditary Genius".La Tuberculose M6dicale de l'Enfance.Maurice P6hu et Andre Dufourt. 740pages, avec figures dans le texte, 75 fr.Gaston Doin & Cie., Paris, 1927.The authors of this carefully written treatise assign but little weight to the persistently recurring theory of hereditary tuberculosis.The place of this they think will eventually be settled by deciding whether or not there are filterable forms of the tubercle bacillus.In the meanwhile what we have to deal with in the vast pro- portion of eases is infection during life.This is so simple a proposition that many overlook it.One fact which brings the study of tuberculosis in infancy within bounds is the absence of any other chronic condition at that age excepting syphilis.The distinguishing features between the two, however, as well as other limiting factors, are well marked.One of these features is that tuberculosis may exist in such complete latency from infancy till adult life.Some maintain that all adult tuberculosis begins in infancy: that it represents in the pieturestle words of the authors "a song which-the candid'ate for tuberculosis
Hepcidin levels in humans are correlated with hepatic iron stores, hemoglobin levels, and hepatic function
Authors: Lénaïck Détivaud, Elizabeta Nemeth, Karim Boudjema, Bruno Turlin, Marie-Bérengère Troadec, Patricia Leroyer, Martine Ropert, Sylvie Jacquelinet, Brice Courselaud, Tomas Ganz, Pierre Brissot, Olivier Loréal
Journal: Blood (2005)
My elective: The silent sentinels
Authors: D. Cummins
Journal: BMJ (1999)

The air outside was warm and sultry, with no wind. Dark clouds covered the mountains, and mist lay over the forest and nearby hills. The scattered wooden houses seemed empty and derelict; the dusty roads were deserted. “Take a look around,” he had said, “but be back by five.”

The doctor visited the reservation once a fortnight. His patients were Gitksin Indians. Traditionally the Gitksin were hunters and skilled wood carvers, but those we had seen in the clinic were sad and smelt of whisky. The doctor said that when it all gets too much the Gitksin walk out on to the highway to join the Great Spirit.

I strolled to the settlement's northern edge, where the road to Alaska …
THE IMMEDIATE PROGNOSIS OF CONGESTIVE HEART FAILURE
Authors: Norman H. Boyer, C. Edward Leach, Paul D. White
Journal: Annals of Internal Medicine (1941)

Article1 June 1941THE IMMEDIATE PROGNOSIS OF CONGESTIVE HEART FAILURENORMAN H. BOYER, M.D., C. EDWARD LEACH, M.D., PAUL D. WHITE, M.D., F.A.C.P.NORMAN H. BOYER, M.D.Search for more papers by this author, C. EDWARD LEACH, M.D.Search for more papers by this author, PAUL D. WHITE, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-14-12-2210 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIn a previous study1the underlying causes and precipitating factors in 1000 patients with congestive heart failure were analyzed, and in 748 patients followed for three months or longer the immediate prognosis was appraised. Patients who died or who remained in failure at rest during the minimal three months' follow-up period were considered together as a single group and designated as having a poor outcome. The results of this study indicated that the immediate prognosis was, in general, independent of the underlying type of heart disease. The precipitating cause of failure, however, played an important röle in prognosticating the outcome,...Bibliography1. BOYERLEACHWHITE NHCEPD: Underlying causes and precipitating factors of congestive heart failure. Symposium on the blood, heart and circulation, Am. Assoc. Adv. Sci., Publication No. 13, The Science Press, 1940, p. 203. Google Scholar2. NATHANSON MH: Disease of the coronary arteries, Am. Jr. Med. Sci., 1925, clxx, 240. CrossrefGoogle Scholar3. CLAWSONBELL BJET: The heart in syphilitic aortitis, Arch. Path., 1927, iv, 922. Google Scholar4. BELLCLAWSON ETBJ: Primary (essential) hypertension, Arch. Path., 1929, v, 939. Google Scholar5. GROSSSPARK HC: Coronary and extra-coronary factors in hypertensive heart failure, Am. Heart Jr., 1937, xiv, 160. CrossrefGoogle Scholar6. DAVISBLUMGART DHL: Cardiac hypertrophy—its relation to coronary arteriosclerosis and congestive heart failure, ANN. INT. MED., 1937, xi, 1024. LinkGoogle Scholar7. LEVINE SA: Coronary thrombosis—its various clinical features, 1931, Williams and Wilkins Co., Baltimore. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Boston, Massachusetts*Received for publication June 18, 1940.From the Cardiac Laboratory, Massachusetts General Hospital. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byFactors influencing the return to work of men with congestive heart failureThe epidemiology of cardiac failureUseful Life After Development of Congestive Heart FailureThe treatment of hypertensive heart failure and of hypertensive cardiac overload by blood pressure reductionTherapie 1 June 1941Volume 14, Issue 12Page: 2210-2219KeywordsCardiovascular therapyHeart failureLongitudinal studiesResearch laboratories ePublished: 1 December 2008 Issue Published: 1 June 1941 PDF downloadLoading ...
Staphylococcus aureus small colony variants: rate of selection and MIC values compared to wild-type strains, using ciprofloxacin, ofloxacin, levofloxacin, sparfloxacin and moxifloxacin
Authors: Franz-Josef Schmitz, Christof von Eiff, Mechthild Gondolf, Ad C. Fluit, Jan Verhoef, Georg Peters, Ulrich Hadding, Hans-Peter Heinz, Mark E. Jones
Journal: Clinical Microbiology and Infection (1999)
Targeting the Pim kinases in multiple myeloma
Authors: N A Keane, M Reidy, A Natoni, M S Raab, M O'Dwyer
Journal: Blood Cancer Journal (2015)

Abstract Multiple myeloma (MM) is a plasma cell malignancy that remains incurable. Novel treatment strategies to improve survival are urgently required. The Pims are a small family of serine/threonine kinases with increased expression across the hematological malignancies. Pim-2 shows highest expression in MM and constitutes a promising therapeutic target. It is upregulated by the bone marrow microenvironment to mediate proliferation and promote MM survival. Pim-2 also has a key role in the bone destruction typically seen in MM. Additional putative roles of the Pim kinases in MM include trafficking of malignant cells, promoting oncogenic signaling in the hypoxic bone marrow microenvironment and mediating resistance to therapy. A number of Pim inhibitors are now under development with lead compounds entering the clinic. The ATP-competitive Pim inhibitor LGH447 has recently been reported to have single agent activity in MM. It is anticipated that Pim inhibition will be of clinical benefit in combination with standard treatments and/or with novel drugs targeting other survival pathways in MM.
Promoting Evidence-Based High-Value Health Care
Authors: Joseph S. Ross
Journal: JAMA Internal Medicine (2015)

recommendations may contribute to these high rates. 3-5No statistical difference in discordance rates existed between EGDs that were referred by primary care physicians vs gastroenterologists.Possible explanations include the relatively recent guideline publication and potential selection bias for greater symptom severity among gastroenterologists. 6Limitations included our short study duration and inability to capture patientdriven referrals, insurance data, and additional endoscopies performed at other institutions.A multidisciplinary approach of specialist prereview of open-access referrals, incorporation of appropriate indications in referral orders, and continued education may result in improved concordance with the evidence-based guidelines.
Smad2 and Smad3 Inversely Regulate TGF-β Autoinduction in Clostridium butyricum-Activated Dendritic Cells
Authors: Ikkou Kashiwagi, Rimpei Morita, Takashi Schichita, Kyoko Komai, Keita Saeki, Makoto Matsumoto, Kiyoshi Takeda, Masatoshi Nomura, Atsushi Hayashi, Takanori Kanai, Akihiko Yoshimura
Journal: Immunity (2015)
Lipoprotein Subclass Profiling Reveals Pleiotropy in the Genetic Variants of Lipid Risk Factors for Coronary Heart Disease
Authors: Peter Würtz, Antti J. Kangas, Pasi Soininen, Terho Lehtimäki, Mika Kähönen, Jorma S. Viikari, Olli T. Raitakari, Marjo-Riitta Järvelin, George Davey Smith, Mika Ala-Korpela
Journal: Journal of the American College of Cardiology (2013)
Management of melanomas in primary care
Authors: A. Skellett, S. Gibbs, S. Handfield-Jones, R. Graham, E. Tan, J. Garioch
Journal: British Journal of Dermatology (2010)

Journal Article Management of melanomas in primary care Get access A. Skellett, A. Skellett Department of Dermatology, Norfolk and Norwich University Hospital NHS Foundation Trust, Norwich, NR4 7UY, U.K. Search for other works by this author on: Oxford Academic Google Scholar S. Gibbs, S. Gibbs Department of Dermatology, Ipswich Hospital NHS Trust, Ipswich, U.K. Search for other works by this author on: Oxford Academic Google Scholar S. Handfield‐Jones, S. Handfield‐Jones Department of Dermatology, West Suffolk Hospital NHS Trust, West Suffolk Hospital, Bury St Edmonds, IP33 2QZ, U.K. Search for other works by this author on: Oxford Academic Google Scholar R. Graham, R. Graham Department of Dermatology, James Paget University Hospital NHS Foundation Trust, Great Yarmouth, U.K. E‐mail: anne.skellett@nnuh.nhs.uk Search for other works by this author on: Oxford Academic Google Scholar E. Tan, E. Tan Department of Dermatology, Norfolk and Norwich University Hospital NHS Foundation Trust, Norwich, NR4 7UY, U.K. Search for other works by this author on: Oxford Academic Google Scholar J. Garioch J. Garioch Department of Dermatology, Norfolk and Norwich University Hospital NHS Foundation Trust, Norwich, NR4 7UY, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 164, Issue 3, 1 March 2011, Pages 680–682, https://doi.org/10.1111/j.1365-2133.2010.10106.x Published: 01 March 2011
Rationale and design of a randomized, double‐blind, event‐driven, multicentre study comparing the efficacy and safety of oral rivaroxaban with placebo for reducing the risk of death, myocardial infarction or stroke in subjects with heart failure and significant coronary artery disease following an exacerbation of heart failure: the <scp>COMMANDER HF</scp> trial
Authors: Faiez Zannad, Barry Greenberg, John G.F. Cleland, Mihai Gheorghiade, Dirk J. van Veldhuisen, Mandeep R. Mehra, Stefan D. Anker, William M. Byra, Min Fu, Roger M. Mills
Journal: European Journal of Heart Failure (2015)

Aims Thrombin is a critical element of crosstalk between pathways contributing to worsening of established heart failure ( HF ). The aim of this study is to explore the efficacy and safety of rivaroxaban 2.5 mg bid compared with placebo (with standard care) after an exacerbation of HF in patients with reduced ejection fraction ( HF‐rEF ) and documented coronary artery disease. Methods This is an international prospective, multicentre, randomized, double‐blind, placebo‐controlled, event‐driven study of approximately 5000 patients for a targeted 984 events. Patients must have a recent symptomatic exacerbation of HF , increased plasma concentrations of natriuretic peptides (B‐type natriuretic peptide ≥200 pg/mL or N ‐terminal pro–B‐type natriuretic peptide ≥800 pg/ mL ), with left ventricular ejection fraction ≤40% and coronary artery disease. Patients requiring anticoagulation for atrial fibrillation or other conditions will be excluded. After an index event (overnight hospitalization, emergency department or observation unit admission, or unscheduled outpatient parenteral treatment for worsening HF ), patients will be randomized 1:1 to rivaroxaban or placebo (with standard of care). The primary efficacy outcome event is a composite of all‐cause mortality, myocardial infarction or stroke. The principal safety outcome events are the composite of fatal bleeding or bleeding into a critical space with potential permanent disability, bleeding events requiring hospitalization and major bleeding events according to International Society on Thrombosis and Haemostasis bleeding criteria. Conclusion COMMANDER HF is the first prospective study of a target‐specific oral antithrombotic agent in HF . It will provide important information regarding rivaroxaban use following an HF event in an HF‐rEF patient population with coronary artery disease.
87. APOBEC3G and Immunity to Retroviruses
Authors: Reuben S. Harris
Journal: Molecular Therapy (2004)

APOBEC3G is capable of providing a cellular defense against retroviruses by deaminating deoxycytidine to deoxyuridine in the first strand of nascent retroviral cDNA. However, this defense can be counteracted by the HIV virion-infectivity factor (Vif), which targets APOBEC3G for degradation by the proteasome. The delicate balance between the anti-viral effect of APOBEC3G and the pro-viral effect of Vif will be discussed.
Human Protein Reference Database
Authors: Natalie Wilson
Journal: Nature Reviews Genetics (2004)

Browse, query or BLAST?Or why not view one of the available protein-interaction networks?It's up to you.The Human Protein Reference Database (HPRD) is a userfriendly resource that lets you do it all.However you find your protein of choice, information on every possible feature -alternative names, function, sequence, domains, motifs, interactions, expression, localization, post-translational modifications, substrates and any disease association -is just a click away.Couple all of this with links to external resources, such as the OMIM, Swiss-Prot, LocusLink and Unigene web sites, and this really is a unified protein bioinformatics platform.Almost all of the information that is included in the HPRD has been obtained manually by biologists who read hundreds of thousands of publications and interpreted and analysed the data.Every protein is reviewed twice, but should you spot any errors, they can be reported online.The HPRD ontology should soon be fully compliant with that of the Gene Ontology consortium, and the HPRD data will eventually be downloadable.This resource is a joint venture between Akhilesh Pandey's laboratory (http:// pandeylab.bs.jhmi.edu)and the Institute of Bioinformatics (http://www.ibioinformatics.org), but contributions from 'the outside world' are also encouraged -so how about becoming a 'molecule authority' for your favourite protein?And if your protein of interest cannot be found, then let the curators know and they will annotate it for you.With more than 3,000 proteins in the HPRD already, and that number expected to reach 10,000 by the end of 2003, this really is a great resource for anyone who is interested in the human proteome!