tbuckley/cabot-search huggingface dataset:
Abstract 2477: Design, synthesis and biological evaluation of substituted monocyclic pyrimidines as potent microtubule targeting antitumor agents that circumvent Pgp and βIII-tubulin-mediated resistance.
Authors: Aleem Gangjee, Rishabh Mohan, Ernest Hamel, Ruoli Bai
Journal: Cancer Research (2013)

Abstract Tubulin binding agents are the most effective drugs in p53 resistant cancer cell lines. Although microtubule disrupting agents like paclitaxel are highly successful, they have major limitations against multidrug resistance (MDR) tumors. Overexpression of P-glycoprotein (Pgp) and/or βIII-tubulin can severely limit their clinical utility as cancer chemotherapeutic agents. Antitubulin agents like paclitaxel and other taxoids also have poor water solubility, and this hampers their administration to patients since these compounds must be formulated with polyethoxylated castor oil. This medium can cause hypersensitivity reactions and requires prolonged administration times. Recently, we reported analogs with the pyrrolo[3,2-d]pyrimidine scaffold that circumvent these drawbacks. To explore the structure-activity relationships of these compounds, including simplification of the pyrrolo[3,2-d]pyrimidine scaffold, we designed conformationally flexible substituted monocyclic N-methyl-4-methoxyanilino pyrimidines 1-6 from the corresponding 4-chloro analogs by treatment with N-methyl-4-methoxyaniline followed by N6-alkylation for 2-6 . Compounds 1-6 inhibited tubulin assembly (4, IC50 = 1.5 ± 0.2 μM) and binding of colchicine to tubulin (4, 75% inhibition at 1 μM, 95% at 5 μM with 5 μM [3H]colchicine). Four of these compounds inhibited the growth of human cancer cells in culture with nanomolar IC50’s from 15 to 62 nM. These compounds are also active in paclitaxel resistant tumor cells overexpressing either βIII-tubulin or Pgp, thus apparently overcoming two important mechanisms associated with clinical resistance to paclitaxel. Thus, we have identified simplified substituted monocyclic pyrimidines containing a novel structural scaffold for inhibition of tubulin assembly and colchicine binding and which have potent cytotoxic activity against human cancer cells in culture. Citation Format: Aleem Gangjee, Rishabh Mohan, Ernest Hamel, Ruoli Bai. Design, synthesis and biological evaluation of substituted monocyclic pyrimidines as potent microtubule targeting antitumor agents that circumvent Pgp and βIII-tubulin-mediated resistance. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2477. doi:10.1158/1538-7445.AM2013-2477
Association Between Obesity And Asthma In Mexican Preschool Children
Authors: None Vazquez-Nava, C.F. Vázquez-Rodríguez, A.H. Saldívar-González, E.M. Vázquez-Rodríguez, G.M. Martínez-Perales, M.d. Barrientos-Gómez, D. Lin-Ochoa, V.M. Joffre-Velázquez, J.A. Cordova-Fernández
Journal: Journal of Allergy and Clinical Immunology (2010)
Current use of levothyroxine was associated with increased risk for fractures in patients ≥ 70 years of age
Authors: Douglas C. Bauer
Journal: Annals of Internal Medicine (2011)

ACP Journal Club20 September 2011Current use of levothyroxine was associated with increased risk for fractures in patients ≥ 70 years of ageDouglas C. Bauer, MDDouglas C. Bauer, MDUniversity of California, San Francisco, San Francisco, California, USA (D.C.B.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-155-6-201109200-02005 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationTurner MR, Camacho X, Fischer HD, et al. Levothyroxine dose and risk of fractures in older adults: nested case–control study. BMJ. 2011;342:d2238. https://pubmed.ncbi.nlm.nih.gov/21527461Clinical Impact RatingsGIM/FP/GP: Endocrinology: Geriatrics: References1 Cummings SR, Nevitt MC, Browner WS, et al. Risk factors for hip fracture in white women. Study of Osteoporotic Fractures Research Group. N Engl J Med. 1995;332:767-73. [PMID: 7862179] Google Scholar2 Bauer DC, Ettinger B, Nevitt MC, Stone KL; Study of Osteoporotic Fractures Research Group. Risk for fracture in women with low serum levels of thyroid-stimulating hormone. Ann Intern Med. 2001;134:561-8. [PMID: 12803168] Google Scholar3 Flynn RW, Bonellie SR, Jung RT, et al. Serum thyroid-stimulating hormone concentration and morbidity from cardiovascular disease and fractures in patients on long-term thyroxine therapy. J Clin Endocrinol Metab. 2010;95:186-93. [PMID: 19906785] Google Scholar Author, Article, and Disclosure InformationAffiliations: University of California, San Francisco, San Francisco, California, USA (D.C.B.)This article was published at Annals.org on 6 September 2011. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 20 September 2011Volume 155, Issue 6Page: JC3-5KeywordsDatabasesDrugsElderlyHipHyperthyroidismSpineThyroid carcinomaThyroid hormonesThyroid-stimulating hormoneThyroxine ePublished: 20 September 2011 Issue Published: 20 September 2011 CopyrightCopyright © 2011 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Staphylococcus aureus extracellular adherence protein serves as anti-inflammatory factor by inhibiting the recruitment of host leukocytes
Authors: Triantafyllos Chavakis, Muzaffar Hussain, Sandip M. Kanse, Georg Peters, Reinhard G. Bretzel, Jan-Ingmar Flock, Mathias Herrmann, Klaus T. Preissner
Journal: Nature Medicine (2002)
Acupuncture and Knee Osteoarthritis
Authors: Shin-ichi Muramatsu
Journal: Annals of Internal Medicine (2007)

Letters16 January 2007Acupuncture and Knee OsteoarthritisShin-ichi Muramatsu, MD, PhDShin-ichi Muramatsu, MD, PhDFrom Jichi Medical University, Tochigi, Japan.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-146-2-200701160-00013 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR: The impressive finding in the recent study by Scharf and colleagues (1) is that treatment outcomes do not statistically significantly differ between patients treated with sham acupuncture and those treated with real acupuncture. A similar result was reported in a previous study for prophylaxis of migraine (2). Inherent difficulties in the use of sham acupuncture procedures make interpreting the results difficult. What is verum or real acupuncture? How does it differ from sham acupuncture? Although the study protocol carefully avoided deep insertion and manual stimulation of needles in sham acupunctures, these technical modifications alone do not exclude ...References1. Scharf HP, Mansmann U, Streitberger K, Witte S, Krämer J, Maier C, et al. Acupuncture and knee osteoarthritis: a three-armed randomized trial. Ann Intern Med. 2006;145:12-20. [PMID: 16818924] LinkGoogle Scholar2. Diener HC, Kronfeld K, Boewing G, Lungenhausen M, Maier C, Molsberger A, et al. Efficacy of acupuncture for the prophylaxis of migraine: a multicentre randomised controlled clinical trial. Lancet Neurol. 2006;5:310-6. [PMID: 16545747] CrossrefMedlineGoogle Scholar3. Birch SJ, Felt RL. Understanding Acupuncture. Edinburgh, Scotland: Churchill Livingston; 1999:256-9. Google Scholar Author, Article, and Disclosure InformationAuthors: Shin-ichi Muramatsu, MD, PhDAffiliations: From Jichi Medical University, Tochigi, Japan.Disclosures: None disclosed. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoAcupuncture and Knee Osteoarthritis Hanns-Peter Scharf , Ulrich Mansmann , Konrad Streitberger , Steffen Witte , Jürgen Krämer , Christoph Maier , Hans-Joachim Trampisch , and Norbert Victor Acupuncture and Knee Osteoarthritis Dieter Wettig Acupuncture and Knee Osteoarthritis Norbert Victor , Steffen Witte , and Konrad Streitberger Acupuncture and Knee Osteoarthritis Michal R. Pijak Metrics Cited byAcupuncture for musculoskeletal pain: A meta-analysis and meta-regression of sham-controlled randomized clinical trials 16 January 2007Volume 146, Issue 2Page: 147KeywordsAcupunctureConflicts of interestHematologic testsKneesMigraineOsteoarthritisProphylaxisSigns and symptomsTraditional Chinese medicine ePublished: 16 January 2007 Issue Published: 16 January 2007 Copyright & PermissionsCopyright © 2007 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Unraveling the Physician Supply Dilemma
Authors: Richard A. Cooper
Journal: JAMA (2013)

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
Prognostic Value of QT Interval Parameters for Mortality Risk Stratification in Chagas’ Disease
Authors: Gil Salles, Sergio Xavier, Andrea Sousa, Alejandro Hasslocher-Moreno, Claudia Cardoso
Journal: Circulation (2003)

QT interval parameters are potential prognostic markers of arrhythmogenicity risk and cardiovascular mortality and have never been evaluated in Chagas' disease.Outpatients (738) in the chronic phase of Chagas' disease were enrolled in a long-term follow-up study. Maximal heart rate-corrected QT (QTc) and T-wave peak-to-end (TpTe) intervals and QRS, QT, JT, QTapex, and TpTe dispersions and variation coefficients were measured manually and calculated from 12-lead ECGs obtained on admission. Clinical, radiological, and 2-dimensional echocardiographic data were also recorded. Primary end points were all-cause, Chagas' disease-related, and sudden cardiac mortalities. During a follow-up of 58+/-39 months, 62 patients died, 54 of Chagas' disease-related causes and 40 suddenly. Multivariate Cox survival analysis revealed that the QT-interval dispersion (QTd) (hazard ratio, 1.45; 95% confidence interval, 1.29 to 1.63; P<0.001, for 10-ms increments) and left ventricular (LV) end-systolic dimension (hazard ratio, 1.36; 95% confidence interval, 1.21 to 1.53; P<0.001, for 5-mm increments) were the strongest independent predictors for all end points. The maximum QTc interval (QTcmax) could substitute for QTd with a worse predictive performance. Other predictors were heart rate, presence of pathological Q waves, frequent premature ventricular contractions (PVCs), and isolated left anterior fascicular block (LAFB) on the ECGs. Kaplan-Meier survival curves demonstrated that a QTd > or =65 ms or a QTcmax > or =465 ms1/2 discriminated the 2 groups with significantly different prognoses.Electrocardiographic QTd and echocardiographic LV end-systolic dimension were the most important mortality predictors in patients with Chagas' disease. Heart rate, the presence on ECG of pathological Q waves, frequent PVCs, and isolated LAFB refined the mortality risk stratification.
Abstract 1358: Discovery and optimization of potent and selective benzonaphthyridinone analogs as dual mTOR/ATR small molecular inhibitors for treatment of cancer
Authors: Qingsong Liu, Danny Zhou, Bunsho Shiotani, Nathanael S. Gray, Stephen J. Elledge, Lee Zou
Journal: Cancer Research (2011)

Abstract The Mammalian Target of Rapamycin is a highly conserved Serine/Threonine protein kinase that plays a key role in several fundamental cellular processes such as growth, proliferation and metabolism. As a key node in the PI3K/AKT/mTOR signal pathway, mTOR is currently being actively investigated as a therapeutic target for the treatment of a variety of human cancers. Structurally, mTOR shares high sequence identity in the catalytic domain with other PIKK family kinases including PI3Ks, ATR, ATM, DNA-PK and SMG-1. ATR is an apical kinase in a cell cycle checkpoint pathway that monitors DNA integrity. Upon DNA damage, ATR activation results in cell cycle arrest and the initiation of DNA repair processes. Numerous studies have demonstrated that impairment of ATR function sensitizes cells to death in the presence of chemotherapeutic drugs or ionizing radiation. We hypothesized that a dual mTOR/ATR dual inhibitor might produce a profound apoptotic response in cells with impaired DNA-repair pathways. Starting from the recently developed small molecular ATP competitive mTOR selective inhibitor Torin1, a focused medicinal chemistry exploration of the benzonaphthyridinone structure furnished a library of compounds which was screened in a functional cellular assay for ATR inhibition. Biochemical characterization of select compounds using an immunoprecipitation assays for ATR and mTORC1 kinase activity confirmed that the compounds are dual mTOR/ATR inhibitors. Select compounds were characterized in proliferation assays using p53-deficient HCT-116 cell lines alone and in combination with ionizing radiation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1358. doi:10.1158/1538-7445.AM2011-1358
<i>Plasmodium falciparum</i>Malaria and Perinatally Acquired Human Immunodeficiency Virus Type 1 Infection in Kinshasa, Zaire
Authors: Alan E. Greenberg, Wato Nsa, Robert W. Ryder, Mvula Medi, Matadi Nzeza, Nsimba Kitadi, Matela Baangi, Nsuami Malanda, Farzin Davachi, Susan E. Hassig
Journal: New England Journal of Medicine (1991)

It is uncertain whether Plasmodium falciparum malaria is more frequent or more severe in children with perinatally acquired human immunodeficiency virus type 1 (HIV-1) infection and whether P. falciparum infection accelerates the progression of HIV-related disease.We conducted a prospective, longitudinal cohort study in Kinshasa, Zaire. Two hundred sixty children 5 to 9 months of age who had been born to HIV-1-seropositive mothers and 327 children of the same age who had been born to seronegative mothers were monitored intensively for malaria over a 13-month period. All episodes of fever were evaluated with blood smears for malaria, and children found to be infected with P. falciparum were treated with a standard regimen of oral quinine.A total of 2899 fevers were evaluated, with 271 cases of malaria identified. No statistically significant differences were found in the incidence, severity, or response to therapy of malaria among four well-defined groups of children: those with the acquired immunodeficiency syndrome (AIDS), those who were HIV-1-seropositive throughout the study, those who were born to HIV-1-seropositive mothers but reverted to seronegative, and those who were seronegative throughout the study. During the 13-month period the incidence of malaria in the 36 children with HIV infection in whom AIDS developed was lower, although not significantly so, than in the 37 in whom AIDS did not.In this study malaria was not more frequent or more severe in children with progressive HIV-1 infection and malaria did not appear to accelerate the rate of progression of HIV-1 disease.
METHOD OF CLEANSING BLOOD PIPETTES.
Authors: ALBERT ROBIN
Journal: JAMA (1907)

I have used for years the following simple method for cleaning blood pipettes. The suction end of an ordinary air-pump (Chapman's), with a coupling for a smooth faucet is connected with a filter flask. Through the rubber stopper of the latter is inserted a bent glass tube, which is connected with the rubber tube of the blood pipette. The end of the pipette is immersed in a bearer containing distilled water and the pump started. When the pipette is thoroughly washed, alcohol, ether and air are allowed, in turn, to pass through the pipette. The entire operation requires but slight attention and no effort whatever.
Deaths of cyclists in London 1985-92: the hazards of road traffic
Authors: K Gilbert, M McCarthy
Journal: BMJ (1994)

To determine the characteristics of cyclists and vehicles involved in fatal cycling accidents.Analysis of data routinely collected by police for each accident from January 1985 to December 1992 and held in a national master file (Stats 19) by the Department of Transport.Greater London, which comprises inner London (12 boroughs and the City of London) and outer London (20 boroughs).178 cyclists who died (78 in inner London and 100 in outer London; age range 3-88).Associations between characteristics of cyclists, type of vehicle involved, and place of accident.Motor vehicles were involved in 173 deaths. Heavy goods vehicles were involved in 75 deaths (30/100 (30%) in outer London and 45/78 (58%) in inner London); cars in 74 (54/100) (54%) in outer London and 20/78 (26%) in inner London); light goods vehicles in 12/178 (7%); and buses in 6/178 (3%). Thirty five of the people who died were children aged < or = 16. Female cyclists were especially at risk from heavy goods vehicles in inner London (22 deaths), while male cyclists were especially at risk from cars in outer London (50 deaths).Cyclists who died in urban areas are more likely to be adults than children. In inner London, in relation to their traffic volume, heavy goods vehicles are estimated to cause 30 times as many cyclists' deaths as cars and five times as many as buses. Until the factors leading to this excess risk are understood, a ban on heavy goods vehicles in urban areas should be considered.
METHOD FOR THERAPEUTIC EVALUATION OF DIURETIC AGENTS ADMINISTERED ORALLY
Authors: Theodore Greiner
Journal: JAMA (1953)

In the treatment of the patient with congestive failure, the experience of recent years has firmly established the fact that it is the major if not the first order of business to put to work an effective system of diuretic medication. The recognition of this fact has altered the therapeutic approach and results in the management of these patients. In a study published from our clinics a few years ago,<sup>1</sup>it was shown that with the daily mercurial as the nucleus of the regimen for the routine treatment of congestive failure, approximately 90%, instead of the usual 50 to 60%, of hospital patients may be discharged free of congestive failure in an average of about a week, in place of about three or four weeks. One of the points of emphasis in the current planning for this group is that of adequate maintenance with the continued use of potent
Pharmacokinetics of the Cardioprotector ADR-529 (ICRF-187) in Escalating Doses Combined With Fixed-Dose Doxorubicin
Authors: H. Hochster, L. Liebes, S. Wadler, R. Oratz, J. C. Wernz, M. Meyers, M. Green, R. H. Blum, J. L. Speyer
Journal: JNCI Journal of the National Cancer Institute (1992)

Although doxorubicin is an anticancer agent with a wide spectrum of activity, therapy with this anthracycline must often be discontinued at a time of benefit to the patient because of the drug's cumulative cardiotoxicity. ICRF-187 (ADR-529, dexrazoxane) is a bisdioxopiperazine compound that protects against cardiac toxicity induced by doxorubicin.Our objectives in this study were to determine the maximum tolerated dose of ADR-529 (which uses a different vehicle than ICRF-187) when given with a fixed doxorubicin dose and to determine whether ADR-529 alters doxorubicin pharmacokinetics.Twenty-five patients were treated with doxorubicin (60 mg/m2) preceded by administration of ADR-529 in escalating dosages (i.e., 60, 300, 600, 750, and 900 mg/m2) to groups of three to nine patients. ADR-529 was administered over a 15-minute period beginning 30 minutes before doxorubicin treatment; the protocol was repeated every 3 weeks. Blood was sampled frequently for drug levels, which were determined by high-pressure liquid chromatography with fluorescence (doxorubicin) and electrochemical detection (ADR-529).Dose-limiting neutropenia occurred in four of six previously treated patients at an ADR-529 dose of 600 mg/m2; the dose ratio of ADR-529 to doxorubicin was 10:1. For three additional patients with better Eastern Cooperative Oncology Group performance status and a maximum of one prior chemotherapy regimen, 600 mg/m2 was tolerated, but grade 3 or 4 neutropenia occurred in four of six patients who received an ADR-529 dose of 900 mg/m2 and in three of four patients at a dose of 750 mg/m2. Doxorubicin's estimated terminal half-life was 39.5 +/- 18.3 (mean +/- SD) hours; the area under the curve for plasma concentration of drug x time (AUC) was 1.74 +/- 0.40 (micrograms/microL) x hour. Total-body clearance was 598 +/- 142 microL/m2 per minute (N = 20), and it did not vary with ADR-529 dose. Estimated distribution and elimination phase half-lives for plasma ADR-529 were 0.46 +/- 0.30 hours and 4.16 +/- 2.94 hours, respectively. Total-body clearance was 111 +/- 87 microL/m2 per minute (N = 18); AUC was linear (r2 = .92), and the clearance rate was constant (r2 = .18) from 60 to 900 mg/m2.Myelotoxicity was dose limiting for ADR-529 at 600-750 mg/m2 when given with a fixed dose of doxorubicin at 60 mg/m2 (dose ratios of ADR-529 to doxorubicin ranged from 10:1 to 12.5:1). When used in combination, ADR-529 did not perturb doxorubicin's distribution, metabolism, or excretion; therefore, other mechanisms of cardioprotection must be involved.We recommend that an ADR-529 dose of 600 mg/m2 be given with single-agent doxorubicin at a dose of 60 mg/m2 in future studies.