tbuckley/cabot-search huggingface dataset:
ATR Pathway Inhibition Is Synthetically Lethal in Cancer Cells with ERCC1 Deficiency
Authors: Kareem N. Mohni, Gina M. Kavanaugh, David Cortez
Journal: Cancer Research (2014)

Abstract The DNA damage response kinase ATR and its effector kinase CHEK1 are required for cancer cells to survive oncogene-induced replication stress. ATR inhibitors exhibit synthetic lethal interactions, with deficiencies in the DNA damage response enzymes ATM and XRCC1 and with overexpression of the cell cycle kinase cyclin E. Here, we report a systematic screen to identify synthetic lethal interactions with ATR pathway–targeted drugs, rationalized by their predicted therapeutic utility in the oncology clinic. We found that reduced function in the ATR pathway itself provided the strongest synthetic lethal interaction. In addition, we found that loss of the structure-specific endonuclease ERCC1-XPF (ERCC4) is synthetic lethal with ATR pathway inhibitors. ERCC1-deficient cells exhibited elevated levels of DNA damage, which was increased further by ATR inhibition. When treated with ATR or CHEK1 inhibitors, ERCC1-deficient cells were arrested in S-phase and failed to complete cell-cycle transit even after drug removal. Notably, triple-negative breast cancer cells and non–small cell lung cancer cells depleted of ERCC1 exhibited increased sensitivity to ATR pathway–targeted drugs. Overall, we concluded that ATR pathway–targeted drugs may offer particular utility in cancers with reduced ATR pathway function or reduced levels of ERCC4 activity. Cancer Res; 74(10); 2835–45. ©2014 AACR.
HDL-mediated mechanisms of protection in cardiovascular disease
Authors: A. Kontush
Journal: Cardiovascular Research (2014)

Low plasma levels of HDL-cholesterol (HDL-C) represent a strong and independent risk factor for cardiovascular disease. HDL particles display a wide spectrum of atheroprotective activities, which include effluxing cellular cholesterol, diminishing cellular death, decreasing vascular constriction, reducing inflammatory response, protecting from pathological oxidation, combating bacterial infection, lessening platelet activation, regulating gene expression by virtue of microRNAs, and improving glucose metabolism. It remains presently indeterminate as to whether some biological activities of HDL are more relevant for the protection of the endothelium from atherogenesis when compared with others. The multitude of such activities raises the question of a proper assay to assess HDL functionality ex vivo. Together with clear understanding of molecular mechanisms underlying atheroprotective properties of HDL, such assay will provide a basis to resolve the ultimate question of the HDL field to allow the development of efficient HDL-targeting therapies.
Coronary thrombolysis with recombinant human tissue-type plasminogen activator.
Authors: H K Gold, J T Fallon, T Yasuda, R C Leinbach, B A Khaw, J B Newell, J L Guerrero, F M Vislosky, C F Hoyng, E Grossbard
Journal: Circulation (1984)

The thrombolytic potency and myocardial infarct--sparing potential of recombinant tissue-type plasminogen activator (rt-PA) were studied in electrocardiographically monitored, open-chest, anesthetized dogs. Localized coronary thrombosis was produced in the left anterior descending artery by endothelial injury and instillation of thrombin and fresh blood. After 2 hr of stable thrombotic occlusion, rt-PA was infused intravenously. At a dose of 4.3 micrograms/kg/min, time to reperfusion was greater than 40 min (n = 3). However, at higher infusion rates a linear, dose-dependent time to coronary reperfusion was obtained (r = .88): at 10 micrograms/kg/min reperfusion occurred after 31 +/- 2 min (n = 3), at 15 micrograms/kg/min it was at 26 +/- 7 min (n = 4), and at 25 micrograms/kg/min, lysis was accomplished within 13 +/- 3 min (n = 3). Thrombolysis was not associated with alterations in either plasma hemostatic factors (fibrinogen, plasminogen, and alpha 2-antiplasmin) or in systemic blood pressures. Epicardial electrographic measurements revealed a significant reduction in ST elevation in all reperfused hearts. A randomized, blinded study was also carried out with 15 micrograms/kg/min of rt-PA saline in 18 dogs with 30 min of coronary thrombosis. Reperfusion in the treated group occurred after 28 +/- 3 min. No evidence of thrombolysis was noted in the saline-treated group within 240 min. Size of myocardial infarction was determined by triphenyl tetrazolium chloride staining and planimetry. Infarction involved 2.5 +/- 0.5% of the left ventricular wall in the group receiving rt-PA, but 16 +/- 3% of the left ventricle in the saline-treated group (p = .001). It is concluded that intravenous infusion of rt-PA results in rapid, dose-dependent coronary thrombolysis without systemic fibrinolytic activation and that early lysis of coronary thrombi is associated with substantial salvage of myocardial tissue.
Adenosine Monophosphate for the Treatment of Varicella Zoster Infections: A Large Dose of Caution
Authors: Christopher H. Sherlock
Journal: JAMA (1985)

These are exciting days for virologists, especially those interested in antiviral chemotherapy. The development of clinically effective antivirals, particularly for the herpes group viruses, is finally being realized. Vidarabine has been shown to be effective in decreasing the mortality from herpes simplex virus (HSV) encephalitis, neonatal herpes, and varicella zoster infections in some immunosuppressed populations.<sup>1,2</sup>Similarly, acyclovir has been shown to be effective in shortening the course of first and recurrent episodes of mucocutaneous HSV and varicella zoster infections in both normal and immunosuppressed patients.<sup>3</sup>Interferon preparations are under study in a wide variety of settings, and reports about the clinical use of antivirals appear nearly monthly. The number of compounds being reported with in vitro activity against the herpes group viruses is increasing exponentially, some the result of planned sequential development and some discovered serendipitously.<sup>2</sup>Adenosine monophosphate (AMP), a purine nucleotide that is an intermediate in
Assessment of Coagulation and Fibrinolysis in Pre-eclampsia
Authors: S. M. Wood, D. Burnett, A. M. Picken, G. W. Farrell, P. Wolf
Journal: BMJ (1974)

A method is described for distinguishing coagulation from fibrinolysis by three estimates of fibrinogen. This "fibrinogen series" together with plasma antithrombin and urinary urokinase have been compared in pregnant patients with venous thrombosis and pre-eclampsia. Evidence is presented for active coagulation during deterioration of the pre-eclampsia state and for enhanced fibrinolysis during improvement.
Transplantation for children with acute myeloid leukemia: a comparison of outcomes with reduced intensity and myeloablative regimens
Authors: Menachem Bitan, Wensheng He, Mei-Jie Zhang, Hisham Abdel-Azim, Mouhab Fakhreddine Ayas, Bella Bielorai, Paul A. Carpenter, Mitchell S. Cairo, Miguel Angel Diaz, John T. Horan, Sonata Jodele, Carrie L. Kitko, Kirk R. Schultz, Morris Kletzel, Kimberly A. Kasow, Leslie E. Lehmann, Parinda A. Mehta, Nirali Shah, Michael A. Pulsipher, Tim Prestidge, Adriana Seber, Shalini Shenoy, Ann E. Woolfrey, Lolie C. Yu, Stella M. Davies
Journal: Blood (2014)
Enteric-Coated Methenamine
Authors: Martin I. Blake
Journal: JAMA (1974)

<h3>To the Editor.—</h3> In a letter by Jansen (226:1361, 1973) commenting on the article titled, "Lipoid Pneumonia Caused by Methenamine Mandelate Suspension," by Timmerman and Schroer (225:1524, 1973), it was implied that methenamine mandelate tablets are available only as entericcoated tablets. At least one pharmaceutical firm (Reid-Provident Laboratories, Atlanta) markets this product as a tablet which is not entericcoated (Prov-U-Sep). There are a number of other tablet-dosage forms on the market containing methenamine or a form of methenamine as the only active ingredient or combined with other drugs, which are not enteric-coated. While the current edition of<i>Drug Evaluations, Pharmacopeia of the United States (USP)</i>does indicate that "methenamine mandelate tablets are enteric-coated," previous editions did not refer to the tablets in this way; and the 19th edition of<i>USP</i>, to become official at the end of this year, will have a permissive statement, "methenamine mandelate tablets may be enteric-coated".
Cromolyn in Combined Gastrointestinal Allergy
Authors: D. J. Salberg
Journal: JAMA (1980)

<h3>To the Editor.—</h3> The article by Kocoshis and Gryboski entitled "Use of Cromolyn in Combined Gastrointestinal [GI] Allergy" (242:1169, 1979) is of interest, but I must take issue with several of their observations and conclusions. Food allergy was not established as the cause of GI disease in the subjects studied. Recently, investigators have recommended use of a double-blind food challenge to document food allergy.<sup>1,2</sup>Positive responses occurred within two hours of ingestion of the challenge substance. By contrast the authors did not use a double-blind oral challenge protocol. In addition, they accepted as positive any responses occurring up to 48 hours following ingestion of a test substance. Second, positive immediate-type skin test responses are frequently associated with positive double-blind oral challenges when the prick method is used.<sup>1,2</sup>However, the authors used intradermal skin test technique that will not distinguish as well between asymptomatic and symptomatic hypersensitivity.<sup>2</sup>The preparation
Advantages of Pinhole Collimator Double-Phase Scintigraphy With 99mTc-MIBI in Secondary Hyperparathyroidism
Authors: David Fuster, Marina Depetris, José-Vicente Torregrosa, Mattia Squarcia, Raphael P. Paschoalin, Maria Mayoral, Ulises Granados, Patrick M. Colletti, Domenico Rubello, Francesca Pons
Journal: Clinical Nuclear Medicine (2013)

Purpose The aim of the study was to determine if pinhole collimator-acquired images can improve the detection of hyperfunctioning parathyroid glands in patients with secondary hyperparathyroidism. Methods Forty-two patients being treated with cinacalcet for secondary hyperparathyroidism were studied prospectively. Patients were divided into 2 groups according to their levels of parathyroid hormone (PTH), the hormone that defines response to treatment: “responders” (PTH <300 pg/mL) and “nonresponders” (PTH ≥300 pg/mL). Double-phase scintigraphy using 888 MBq of 99mTc-MIBI was used to acquire early and late parallel-hole and pinhole collimator images. Neck ultrasonography was performed on all patients to identify intrathyroid nodules. All focal uptake in any of the acquired scintigraphic images was considered positive. Results The responder group included 24 patients, whereas 18 patients were considered as nonresponders. At least 1 parathyroid gland with 99mTc-MIBI uptake was detected in 33 of 42 patients, with a total of 50 parathyroid glands located. We found significant differences between the detection rates of late pinhole collimator and the late parallel-hole images (74% vs 48%, P = 0.0036). This detection rate was highest with late parallel-hole images in the nonresponder group (89%). Conclusions The late pinhole collimator acquisition showed the highest detection rate of hyperfunctioning parathyroid glands using 99mTc-MIBI scintigraphy in secondary hyperparathyroidism patients treated with cinacalcet.
Electrical Remodeling of the Atria in Congestive Heart Failure
Authors: Prashanthan Sanders, Joseph B. Morton, Neil C. Davidson, Steven J. Spence, Jitendra K. Vohra, Paul B. Sparks, Jonathan M. Kalman
Journal: Circulation (2003)

Background— Atrial fibrillation (AF) frequently complicates congestive heart failure (CHF). However, the electrophysiological substrate for AF in humans with CHF remains unknown. We evaluated the electrophysiological and electroanatomic characteristics of the atria in patients with CHF. Methods and Results— Twenty-one patients (aged 53.7±13.6 years) with symptomatic CHF (left ventricular ejection fraction 25.5±6.0%) and 21 age-matched controls were studied. The following were evaluated: effective refractory periods (ERPs) from the high and low lateral right atrium (LRA), high septal right atrium, and distal coronary sinus (CS); conduction time along the CS and LRA; corrected sinus node recovery times; P-wave duration; and conduction at the crista terminalis. In a subset, electroanatomic mapping was performed to determine atrial activation, regional conduction velocity, double potentials, fractionated electrograms, regional voltage, and areas of electrical silence. Patients with CHF demonstrated an increase in atrial ERP with no change in the heterogeneity of refractoriness, an increase of atrial conduction time along the LRA and the CS, prolongation of the P-wave duration and corrected sinus node recovery times, and greater number and duration of double potentials along the crista terminalis. Electroanatomic mapping demonstrated regional conduction slowing with a greater number of electrograms with fractionation or double potentials, associated with areas of low voltage and electrical silence (scar). Patients with CHF demonstrated an increased propensity for AF with single extrastimuli, and induced AF was more often sustained. Conclusions— Atrial remodeling due to CHF is characterized by structural changes, abnormalities of conduction, sinus node dysfunction, and increased refractoriness. These abnormalities may be responsible in part for the increased propensity for AF in CHF.
The Physician Payment Sunshine Act
Authors: Sachin Santhakumar, Eli Y. Adashi
Journal: JAMA (2014)

On September 30, 2014, the Centers for Medicare & Medicaid Services (CMS) released the Open Payment Program (OPP) database, replete with payments made to physicians and teaching hospitals by manufacturers of federally covered drugs, devices, biologics, or medical supplies.1 Physician ownership or investment interest in manufacturers or in group purchasing organizations was also included in the database.1 In so doing, CMS complied with Section 6002 (Transparency Reports and Reporting of Physician Ownership or Investment Interests) of the Affordable Care Act while adding yet another layer to its National Physician Payment Transparency Program.1,2 Indeed, it was only on April 9, 2014, that CMS announced the release of a data set comprising $77 billion in Medicare part B payments to 880 000 participating Medicare providers for 6000 different types of services and procedures.2 Limited to fiscal year 2012, the public-use data file afforded consumers a clear view of the number of services and procedures carried out by individual providers along with payments made.
Cardiovascular Effects of Cimetidine
Authors: GlDEN KOREN
Journal: Annals of Internal Medicine (1983)

Letters and Corrections1 May 1983Cardiovascular Effects of CimetidineGlDEN KOREN, M.D.GlDEN KOREN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-98-5-673_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: In his recent letter (1), Nikolic claimed that "the cardiovascular effects of Cimetidine have never been documented through organized studies addressing this problem." I draw your attention to the report by Kato and associates on various cardiovascular effects of the drug in experimental studies (2).In dogs, Cimetidine induced various electrocardiographic changes, namely T wave augmentation, R depression, and PR prolongation. Decreases in blood pressure, cardiac rate, aortic blood flow, among many other reactions, are also reported. A dose-related vasodilation of coronary arteries was observed....References1. NIKOLIC G. Cardiovascular effects of Cimetidine [Letter]. Ann Intern Med. 1983;98:258-9. LinkGoogle Scholar2. KATOKURIHARAKASUYA HJY. Cardiovascular effects of Cimetidine. Arch Int Pharmacodyn Ther. 1981;249:247-56. MedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1983Volume 98, Issue 5_Part_1Page: 673-673KeywordsBlood flowBlood pressureCoronary arteriesDrugsElectrocardiographyHeart rateVasodilation Issue Published: 1 May 1983 PDF DownloadLoading ...
Comparison of 1α-hydroxycholecalciferol and 25-hydroxycholecalciferol in the treatment of renal osteodystrophy: Greater effect of 25-hydroxycholecalciferol on bone mineralization
Authors: Albert Fournier, Philippe Bordier, Jean Gueris, Jean Luc Sebert, Pierre Marie, Christine Ferrière, Jeanine Bedrossian, Hector F. DeLuca
Journal: Kidney International (1979)
1058 ANALYSIS OF CELLULAR ORIGIN AND DEGRADATION PATHWAYS OF THE ENDOCANNABINOID 2-ARACHIDONOYL GLYCEROL DURING LIVER FIBROGENESIS
Authors: A. Wojtalla, F. Herweck, M.V. Singer, T. Sauerbruch, A. Zimmer, S.V. Siegmund
Journal: Journal of Hepatology (2011)
SATIRE
Authors: Walter Cane
Journal: JAMA (1969)

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
A CASE OF GLOSSODYNIA WITH LINGUAL TONSILLITIS AS ITS ETIOLOGY: CONTROL THROUGH THE NASAL GANGLION
Authors: Greenfield Sluder
Journal: JAMA (1923)

In 1918, I<sup>1</sup>reported an observation to the effect that glossodynia was secondary to lingual tonsillitis. In 1921, Lee Wallace Dean<sup>2</sup>recorded that glossodynia was controllable through the nasal ganglion. I know that glossodynia may be an isolated manifestation of a nasal ganglion lesion. Many times, however, I have seen it secondary to lingual tonsillitis. The report of this case seems to me of interest because it brings out lingual tonsillitis as the cause of glossodynia; but although it was established in this way, it persisted after the lingual tonsillitis, and was controllable through the nasal ganglion. <h3>REPORT OF CASE</h3> Miss L. B., aged 32, consulted me, Oct. 20, 1919, because of a chronic faucial tonsillitis for which I did a tonsillectomy, October 28. The result was satisfactory; her general condition improved, and the throat became comfortable. Feb. 10, 1921, she consulted me because of an acute follicular
SAFETY AND EFFICACY OF ENOXAPARIN AND FONDAPARINUX AS ADJUNCTIVE TREATMENT TO THROMBOLYSIS IN PATIENTS WITH HIGH AND INTERMEDIATE RISK PULMONARY EMBOLISM: AN ADJUSTED PROPENSITY SCORE ANALYSIS
Authors: Nicolas F. Meneveau, Vincent Descotes-Genon, Romain Chopard, Marie-France Seronde, Florent Briand, Alexandre Guignier, Yvette Bernard, Francois Schiele
Journal: Journal of the American College of Cardiology (2011)
Study finds no connection between MMR vaccine and autism
Authors: Scott Gottlieb
Journal: BMJ (2004)

The results of a large new study in the journal Pediatrics show no relation between the combined vaccination against measles, mumps, and rubella (MMR) and the development of autism.

In 2001, a panel of experts convened by the US Institute of Medicine, Washington, DC, rejected the contention that vaccination with MMR caused autism, on the basis of overall data at a population level. The panel did, however, encourage additional studies to …
Oxygen-dependent lipid peroxidation during lung ischemia.
Authors: A B Fisher, C Dodia, Z T Tan, I Ayene, R G Eckenhoff
Journal: Journal of Clinical Investigation (1991)

The effect of alveolar oxygen tension on lung lipid peroxidation during lung ischemia was evaluated by using isolated rat lungs perfused with synthetic medium. After a 5-min equilibration period, global ischemia was produced by discontinuing perfusion while ventilation continued with gas mixtures containing 5% CO2 and a fixed oxygen concentration between 0 and 95%. Lipid peroxidation was assessed by measurement of tissue thiobarbituric acid-reactive products and conjugated dienes. Control studies (no ischemia) showed no change in parameters of lipid peroxidation during 1 h of perfusion and ventilation with 20% or 95% O2. With 60 min of ischemia, there was increased lipid peroxidation which varied with oxygen content of the ventilating gas and was markedly inhibited by ventilation with N2. Perfusion with 5-, 8-, 11-, 14-eicosatetraynoic acid indicated that generation of eicosanoids during ischemia accounted for approximately 40-50% of lung lipid peroxide production. Changes of CO2 content of the ventilating gas (to alter tissue pH) or of perfusate glucose concentration had no effect on lipid peroxidation during ischemia, but perfusion at 8% of the normal flow rate prevented lipid peroxidation. Lung dry/wet weight measured after 3 min of reperfusion showed good correlation between lung fluid accumulation and lipid peroxidation. These results indicate that reperfusion is not necessary for lipid peroxidation with ischemic insult of the lung and provide evidence that elevated PO2 during ischemia accelerates the rate of tissue injury.
Organophosphate Pesticide Exposure and Attention in Young Mexican-American Children: The CHAMACOS Study
Authors: Amy R. Marks, Kim Harley, Asa Bradman, Katherine Kogut, Dana Boyd Barr, Caroline Johnson, Norma Calderon, Brenda Eskenazi
Journal: Environmental Health Perspectives (2010)

BackgroundExposure to organophosphate (OP) pesticides, well-known neurotoxicants, has been associated with neurobehavioral deficits in children.ObjectivesWe investigated whether OP exposure, as measured by urinary dialkyl phosphate (DAP) metabolites in pregnant women and their children, was associated with attention-related outcomes among Mexican-American children living in an agricultural region of California.MethodsChildren were assessed at ages 3.5 years (n = 331) and 5 years (n = 323). Mothers completed the Child Behavior Checklist (CBCL). We administered the NEPSY-II visual attention subtest to children at 3.5 years and Conners’ Kiddie Continuous Performance Test (K-CPT) at 5 years. The K-CPT yielded a standardized attention deficit/hyperactivity disorder (ADHD) Confidence Index score. Psychometricians scored behavior of the 5-year-olds during testing using the Hillside Behavior Rating Scale.ResultsPrenatal DAPs (nanomoles per liter) were nonsignificantly associated with maternal report of attention problems and ADHD at age 3.5 years but were significantly related at age 5 years [CBCL attention problems: β = 0.7 points; 95% confidence interval (CI), 0.2–1.2; ADHD: β = 1.3; 95% CI, 0.4–2.1]. Prenatal DAPs were associated with scores on the K-CPT ADHD Confidence Index &gt; 70th percentile [odds ratio (OR) = 5.1; 95% CI, 1.7–15.7] and with a composite ADHD indicator of the various measures (OR = 3.5; 95% CI, 1.1–10.7). Some outcomes exhibited evidence of effect modification by sex, with associations found only among boys. There was also limited evidence of associations between child DAPs and attention.ConclusionsIn utero DAPs and, to a lesser extent, postnatal DAPs were associated adversely with attention as assessed by maternal report, psychometrician observation, and direct assessment. These associations were somewhat stronger at 5 years than at 3.5 years and were stronger in boys.