tbuckley/cabot-search huggingface dataset:
Abstract 493: NRF2 modulates sensitivity to thymidylate synthase inhibitors in colon cancer cells
Authors: Sarah A. Clinton, Karen W. Barbour, Ufuk Ozer, Franklin G. Berger
Journal: Cancer Research (2014)

Abstract Thymidylate synthase (TYMS) catalyzes the reductive methylation of dUMP, and is the sole de novo source of thymidine for DNA replication and repair. As such, it is an important target of chemotherapeutic drugs, particularly the fluoropyrimidines 5-fluorouracil (FUra) and 5-fluoro-2’-deoxyuridine (FdUrd), as well as the folate analog raltitrexed (RTX). In cells, these drugs are metabolized to derivatives that bind to and inhibit TYMS, leading to depletion of thymidine levels, dysregulation of redox metabolism, generation of oxidative stress, and, eventually, apoptotic cell death. Gene expression profiles of FUra-treated HCT116 cells (a human colon cancer cell line) showed that a number of genes involved in redox metabolism are up-regulated following drug exposure. Several of these were recognized as known targets of nuclear factor-erythroid-2-related factor 2 (NRF2), a member of the cap ‘n’ collar family of bZIP transcription factors that confers protection against oxidative and electrophilic stress. Quantitative PCR assays verified that FUra, FdUrd, and RTX do indeed induce several NRF2-regulated genes, including AKR1B10, ALDH3A1, NQO1, and SERPINE1, among others. Overproduction of NRF2 via DNA transfection increased expression of some, but not all, of these genes, a phenomenon that was reversed by Kelch-like ECH-associated protein-1 (KEAP1), a known negative regulator of NRF2. The impact of TYMS inhibitors on expression of NRF2 target genes was maintained in the presence of exogenous thymidine and the antioxidant N-acetylcysteine, even though these agents completely ameliorated drug-induced apoptosis. This suggests that the response of NRF2 target genes to TYMS-directed drugs occurs independently of TYMS inhibition and subsequent oxidative stress. Utilizing siRNA technology, we examined the impact of NRF2 knockdown on drug-induced apoptosis, and found that increases in the apoptotic index following exposure to TYMS inhibitors were greater in NRF2-knockdown cells as compared to control cells. This was also observed in TYMS-overproducing cells that are profoundly drug resistant, and indicates that reduced NRF2 expression sensitizes cells to these TYMS inhibitors. Overall, we conclude that the induction of NRF2 target genes is a constraining factor in the cytotoxic response to TYMS inhibitors, and that inhibition of the transcription factor may be an effective strategy to enhance sensitivity to these agents. Citation Format: Sarah A. Clinton, Karen W. Barbour, Ufuk Ozer, Franklin G. Berger. NRF2 modulates sensitivity to thymidylate synthase inhibitors in colon cancer cells. [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 493. doi:10.1158/1538-7445.AM2014-493
Biochemistry of Collagen in Diseases
Authors: JOUNI UITTO
Journal: Annals of Internal Medicine (1986)

Collagen, the major extracellular matrix component, comprises a family of closely related, yet genetically distinct proteins that provide physiologic tensile properties to the tissues. The recent progress made in understanding the normal biochemistry and biology of collagens has permitted us to identify different levels at which errors might be introduced into the structure and metabolism of this protein. Several acquired and heritable diseases are now known to involve distinct abnormalities in collagen. This conference reviews some of the latest discoveries in the biochemistry of collagen and highlights some disease entities in which definitive information on molecular alterations in collagen is available.
Size of FLT3 internal tandem duplication has prognostic significance in patients with acute myeloid leukemia
Authors: Derek L. Stirewalt, Kenneth J. Kopecky, Soheil Meshinchi, Julia H. Engel, Era L. Pogosova-Agadjanyan, Jeremy Linsley, Marilyn L. Slovak, Cheryl L. Willman, Jerald P. Radich
Journal: Blood (2005)
Outpatient Care Costs
Authors: ROBERT E. WHITE
Journal: Annals of Internal Medicine (1981)

Letters1 January 1981Outpatient Care CostsROBERT E. WHITE, M.D., M.P.H.ROBERT E. WHITE, M.D., M.P.H.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-94-1-136 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The Reilly and Reilly (1) calculation of Veterans Administration (VA) outpatient care cost was an important contribution to the analysis of public care, but their work requires debate as well as replication. Two sources of bias could be operating to increase per-visit salary costs. First, physician salaries are allocated to outpatient costs based on the 4-hour clinic sessions they are to attend. In the various institutions with which I have been familiar, physicians are rarely present in clinics over 3 hours. Second, although the outpatient area may account for one third of the radiologic examinations, the radiology...References1. REILLY P and REILLY M. The cost of outpatient physicians' services at a Veterans Administration hospital. Ann Intern Med. 1980;93 (Part 1):128-32. LinkGoogle Scholar2. . Trends Affecting the U.S. Health Care System. Germantown, Maryland: Aspens Systems Corporation; 1976: 7-25. (DHEW Publication No. HRA 76-14503). Google Scholar3. . Study of Health Care for American Veterans. Washington, D.C.: U. S. Government Printing Office; 1977:28-9. (Senate Committee Print No. 4, 95th Congress, 1st session). Google Scholar4. NATIONAL CENTER FOR HEALTH STATISTICS. Personal Out-of-Pocket Health Expenses, United States, 1975. Hyattsville, Maryland: National Center for Health Statistics; 1978. (Vital and health statistics. Series 10: Data from the National Health Survey, No. 122) (DHEW publication No. [PHS] 79-1550). Google Scholar5. BLUMBERG M. Provider price changes for improved health care use. In: CHACKO G, ed. Health Handbook. New York: North-Holland Publishing Co.;1979:1090. Google Scholar1. REILLY P and REILLY M. Costs in Veterans Administration hospitals. Ann Intern Med. 1980;93:783-4. Letter. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: ROBERT E. WHITE, M.D., M.P.H.Affiliations: Albuquerque Veterans Administration Medical Center Albuquerque, NM 87108 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byMore or Less? 1 January 1981Volume 94, Issue 1Page: 136-137KeywordsDiagnostic radiologyOutpatient clinicsOutpatients ePublished: 1 December 2008 Issue Published: 1 January 1981 PDF downloadLoading ...
SAFETY AND EFFICACY OF VARIOUS ANTITHROMBOTIC REGIMENS IN PATIENTS WITH INDICATIONS FOR ANTICOAGULATION WHO UNDERGO PERCUTANEOUS CORONARY INTERVENTIONS
Authors: Anand Deshmukh, Nathan Almeida, Suman Pasupuleti, Daniel E. Hilleman, Michael DelCore, Chandra K. Nair
Journal: Journal of the American College of Cardiology (2011)
THE IMPACT OF PULMONARY VEIN ISOLATION ON ATRIAL FUNCTION IN PATIENTS WITH ATRIAL FIBRILLATION COMPARED TO AGE-PREDICTED DOPPLER PARAMETERS
Authors: Srisakul Chirakarnjanakorn, Allan L. Klein, Mohamed H. Kanj, Brian P. Griffin, Zoran B. Popovi
Journal: Journal of the American College of Cardiology (2014)
Generalised epileptic fits in renal transplant recipients given cyclosporin A.
Authors: D Shah, P B Rylance, M E Rogerson, M Bewick, V Parsons
Journal: BMJ (1984)

3 observations. Les crises epileptiques semblent bien dues a la cyclosporine, les autres causes etant eliminees. Ce type d'accident avait ete signale apres greffe de moelle, jamais encore apres transplantation renale
Patients with rheumatoid arthritis and those with diabetes mellitus had a similar increased risk for myocardial infarction
Authors: Roland Staud
Journal: Annals of Internal Medicine (2011)

Source Citation Lindhardsen J, Ahlehoff O, Gislason GH, et al. The risk of myocardial infarction in rheumatoid arthritis and diabetes mellitus: a Danish nationwide cohort study. Ann Rheum Dis. 2011;70:929-34. 21389043
Counseling the HIV Infected Patient/Asesoria del Paciente HIV Positivo
Authors: Jerry D. Smilack
Journal: JAMA (1992)

This videotape provides the viewer with a simulated encounter between a newly diagnosed patient infected with the human immunodeficiency virus and his physician. Through example, one sees how to discuss such delicate issues as bisexuality and homosexuality, patient confidentiality, and HIV transmission through "unsafe" practices. Doing this in the compassionate, empathetic, and nonjudgmental manner needed for a positive doctor-patient relationship can be challenging. In 18 minutes, this reasonably priced program guides the viewer almost effortlessly. Available in English and Spanish versions,<i>Counseling the HIV-Infected Patient</i>is intended for physicians. The producers might want to consider a similar program for patients.
Spontaneous erythroid colony formation in Brazilian patients with sickle cell disease
Authors: R.C.R. Perlingeiro, F.F. Costa, S.T.O. Saad, V.R. Arruda, M.L.S. Queiroz
Journal: American Journal of Hematology (1999)

The ability of circulating progenitor cells to develop erythroid colonies was studied in vitro in the presence or absence of growth factors (5637-CM and erythropoietin) in 63 patients with sickle cell disease (SCD) (36 homozygotes for hemoglobin [Hb] S, 13 double heterozygotes for Hb S and beta thalassemia, and 14 SC patients) in Southeast Brazil. In the presence of growth factors, SCD patients (all genotypes) presented significantly higher numbers of circulating burst-forming unit-erythroid (BFU-E/5 x 10(5) MNC), when compared with control subjects. However, when the progenitor cells were cultured in the absence of added stimulus, high numbers of BFU-E were observed only in the genotypes SS and S/beta thalassemia. SC patients presented a similar response to the control subjects. Moreover, there was an inverse correlation between spontaneous (without stimulus) BFU-E and Hb levels in SCD patients. These results suggest that the formation of spontaneous BFU-E observed in SCD may be due to an expanded erythropoiesis secondary to hemolysis.
Evolution of SINE S1 retroposons in Cruciferae plant species
Authors: A. Lenoir, B. Cournoyer, S. Warwick, G. Picard, J. M. Deragon
Journal: Molecular Biology and Evolution (1997)

The S1 element is a plant short interspersed element (SINE) that was first described and studied in Brassica napus. In this work, we investigated the distribution and the molecular phylogeny of the S1 element within the Cruciferae (= Brassicaceae). S1 elements were found to be widely distributed within the Cruciferae, especially in species of the tribe Brassiceae. The molecular phylogeny of S1 elements in eight Cruciferae species (Brassica oleracea, Brassica rapa, Brassica napus, Brassica nigra, Sinapis, arvensis, Sinapis pubescens, Coincya monensis, and Vella spinosa) was inferred using 14-36 elements per species. Significant neighbor-joining and maximum-parsimony phylogenetic clusters, supported by high bootstrap P values and/or represented in 100% of the most-parsimonious trees, were observed for each species. Most of these clusters probably correspond to recent species-specific bursts of S1 amplification. Since these species diverged recently, S1 amplification in Cruciferae plants is proposed to be a highly dynamic process that could contribute to genome rearrangements and eventually lead to reproductive isolation. S1 sequence analysis also revealed putative gene conversion events that occurred between different S1 elements of a given species. These events suggest that gene conversion is a minor but significant component of the molecular drive governing S1 concerted evolution.
The recognition of adsorbed and denatured proteins of different topographies by β2 integrins and effects on leukocyte adhesion and activation
Authors: Thomas Brevig, Bjørn Holst, Zahida Ademovic, Noemi Rozlosnik, Jette H. Røhrmann, Niels B. Larsen, Ole C. Hansen, Peter Kingshott
Journal: Biomaterials (2004)
GENETIC AND PHARMACOLOGICAL INACTIVATION OF PI3Kα PREVENTS VASCULAR REMODELING AND HYPOXIA-INDUCED PH IN MICE
Authors: Eva Maria Berghausen, Wiebke Janssen, Marius Vantler, Henrik ten Freyhaus, Jean J. Zhao, Ralph T. Schermuly, Stephan Rosenkranz
Journal: Journal of the American College of Cardiology (2013)
Latent variables and the network perspective
Authors: Catherine Belzung, Etienne Billette de Villemeur, Mael Lemoine, Vincent Camus
Journal: Behavioral and Brain Sciences (2010)

Abstract We discuss the latent variables construct, particularly in regard to the following: that latent variables are considered as the sole explanatory factor of a disorder; that pragmatic concerns are ignored; and that the relationship of these variables to biological markers is not addressed. Further, we comment on the relationship between bridge symptoms and causality, and discuss the proposal in relationship to other constructs (endophenotypes, connectionist-inspired networks).
Manuale di Antropologica E Psicologia Criminale. Applicata alla Pedagogia Emendativa, alla Polizia ea al Dritto Penale E Penitenziario. (Manual of Criminal Psychology and Anthropology.) By B. Di. Tullio (Rome: Anonima Romana Editoriale, 1931.)
Authors: E. A. Manginelli
Journal: American Journal of Psychiatry (1933)
Recruitment of host progenitor cells in rat liver transplants
Authors: Zhaoli Sun, Xiuying Zhang, Jayme E. Locke, Qizhi Zheng, Shingo Tachibana, Anna Mae Diehl, George Melville Williams
Journal: Hepatology (2008)

Despite major histocompatibility complex incompatibility, liver transplants from Lewis rats to dark agouti (DA) rats survive indefinitely without immunosuppression, and the studies we report sought the mechanism(s) responsible for this. At 1 year, most of the liver reacted positively to host anti-DA antibody. When small (50%) grafts were transplanted, recruitment was more rapid because most of the organ assumed the host phenotype at 3 months. After transplantation, the Y chromosome was detected in the hepatocytes of XX to XY grafts by both in situ hybridization and polymerase chain reaction. Further, livers from transgenic Lewis rats carrying strong green fluorescent protein (GFP) markers lost the marker with time after transplantation to DA, GFP-negative hosts. Few liver cells contained the Y chromosome in syngeneic XX to XY liver grafts or when the hosts of Lewis XX to DA XY allografts were treated with cyclosporine A at 10 mg/kg/day. This dosage also impeded enlargement of the liver at 10 days. Using GFP-positive XX Lewis donors transplanted to GFP-negative XY DA hosts, we found little Y DNA in GFP-positive cells at 10 days. Host-derived OV-6-positive and c-kit-positive, albumin-positive cells were present at 3-10 days, but cells with the CD34 marker were less common and some clearly still had the donor phenotype at 10 days. Cells positive for chemokine cysteine-X-cysteine receptor-4 increased with time and were abundant 1 month after transplantation. We conclude: (1) extrahepatic cells can differentiate into liver tissues; (2) regenerative stimuli accelerate stem cell recruitment; (3) both regeneration and recruitment are impeded by cyclosporine A immunosuppression, and (4) donor GFP-positive cells contained little host Y chromosome after transplantation, suggesting that cell fusion was uncommon and, therefore, unlikely to be the mechanism leading to the changes in genotype and phenotype we observed.
Effects of long-acting and short-acting beta-agonists on methacholine dose-response curves in asthmatics
Authors: AG Wong, AD O'Shaughnessy, CM Walker, MR Sears
Journal: European Respiratory Journal (1997)

Regular use of short-acting beta-agonists may decrease control of asthma and increase airway responsiveness to bronchoconstrictor stimuli. The aim of this study was to determine the effects of regular treatment with the long-acting beta-agonist, salmeterol, on the methacholine dose-response curve (DRC) in mild-to-moderate asthmatics. Changes in methacholine airway responsiveness were measured in 14 stable adult asthmatics, randomized in a double-blind, three-way cross-over design to receive salmeterol 50 micrograms, salbutamol 200 micrograms or placebo, each twice daily for 4 days. Two baseline methacholine DRC, were performed, one without premedication and one following a single dose of 200 micrograms salbutamol. Following 4 days of regular treatment, methacholine DRC to plateau were carried out commencing 15 min after the final dose of trial medication. There were no significant differences in mean baseline forced expiratory volume in one second (FEV1) between treatments. Four days treatment with salmeterol and salbutamol shifted the DRC to the right, but salmeterol provided less protection than salbutamol. The point of inflection of the curve from baseline moved 1.9 and 3.2 doubling doses, respectively, compared to placebo (p &lt; or = 0.001), and the provocative concentration of methacholine required to produce a 20% fall in FEV1 (PC20) increased 1.6 and 3.1 doubling doses, respectively (p &lt; or = 0.001). The slope of the DRC was increased slightly by both beta-agonists compared to placebo (log slope 3.11, 3.06 and 2.77 for salmeterol, salbutamol and placebo, respectively). This effect of regular salmeterol on slope was more marked in subjects with lower baseline FEV1. Maximal response plateaus did not differ between the three treatments. These results suggest that regular use either of short- or long-acting beta-agonists could increase the risk of a more precipitous asthma episode associated with "breakthrough" bronchoconstrictor responses, particularly in those with more severe initial airflow obstruction, if subjects are exposed to a sufficiently potent stimulus.
Beyond etiquette based medicine
Authors: B. J. Secemsky
Journal: BMJ (2014)

I was introduced to Ms B earlier this year as a new patient in my outpatient continuity panel. Her demographic was not unique to patients seen in the safety net community clinic where I work: undocumented Spanish speaking woman in her early 60s, out of medical care, and with no medical insurance.

What caught my attention upon meeting Ms B was the urgency in her demeanor; she made it very clear that she had a specific issue to discuss. By the end of the …
Is the Message Clear?-Reply
Authors: Joseph Greensher
Journal: JAMA (1977)

In Reply. —  Dr Rosen's well-intentioned letter misses our purpose, but we are pleased that the letter caught his attention. There were two points that we wished to bring to the attention of practicing physicians. There has been serious confusion of ipecac syrup with other potentially harmful products (Purepac Oil of Wintergreen and Purepac Tincture of Benzoin). Adopting a slogan identifying ipecac syrup as  Poison Retriever in educating the lay public may avoid confusion.  Pediatric care should include a discussion on safety and the hazards of poisonings. It is at this time that physicians can explain the need for obtaining Syrup of Ipecac—The Poison Retriever for the home that has toddlers. The picture of the dog and the slogan are intended for education and recall purposes, not as a logo for the already overcrowded label on a 30-ml bottle of ipecac syrup.
Recombinant granulocyte/macrophage colony-stimulating factor activates macrophages to inhibit Trypanosoma cruzi and release hydrogen peroxide. Comparison with interferon gamma.
Authors: S G Reed, C F Nathan, D L Pihl, P Rodricks, K Shanebeck, P J Conlon, K H Grabstein
Journal: The Journal of Experimental Medicine (1987)

Recombinant granulocyte/macrophage colony-stimulating factors (rGM-CSF) of mouse and human origins activated macrophages of the homologous species to inhibit the replication of the protozoan parasite T. cruzi. Activation could be induced with 10-100 ng/ml of rMu-GM-CSF, whether it was added before or after uptake of the parasite, in either adherent or suspension cultures. However, the degree of inhibition of parasite replication after exposure to rMu-GM-CSF was not as great as after treatment with rMu-IFN-gamma, and much more rMu-GM-CSF than rMu-IFN-gamma was required to achieve an equivalent antimicrobial effect. These results were mirrored by effects of the cytokines on enhancement of H2O2-releasing capacity in resident mouse peritoneal macrophages. In the latter tests, rMu-IFN-gamma and rHu-TNF-alpha afforded a 44-51-fold enhancement over the untreated control, with a 50% effective concentration (EC50) for rMu-IFN-gamma of approximately 0.05 ng/ml. Using rMu-GM-CSF or rM-CSF, enhancement of H2O2-releasing capacity was 14-15-fold over control, with EC50s of 1 and 14 ng/ml, respectively. However, peak enhancement of macrophage H2O2-releasing capacity was seen at least 24 h earlier with rMu-GM-CSF or rHu-M-CSF than with r-Mu-IFN-gamma or rHu-TNF-alpha. Thus, rMu-GM-CSF and rHu-GM-CSF displayed clear-cut macrophage-activating activity in vitro, but rMu-GM-CSF was less potent and less effective than rMu-IFN-gamma in the tests used.
District cancer physicians
Authors: T J McElwain, J S Malpas
Journal: BMJ (1987)

Convulsions stopped (they had lasted for no more than 10 minutes), and subsequent blood glucose measurements were satisfactory.Shewas nauseated and complained of headache but had no neck stiffness, photophobia, or focal neurological signs.In a blood sample taken at 740 am the same morning the white cell count was 26 2 x 10/1, 91% neutrophils.A medical senior registrar ordered blood cultures and a viral antibody screen to be performed.At 11 00 am her white cell count was 21 4x 109/1.Further investigations ordered in- cluded culture of nose, throat, rectal, and high vaginal swabs and a catheter specimen of urine.The following morning her white cell count was 12-8 x 109/l.At no stage did she have fever or any symptoms not attributable to hypoglycaemia.All bacteriological and viral investigations yielded negative results.The patient remained well and at 38 weeks delivered a normal, healthy infant.Given the combination of circumstances (late pregnancy, hypoglycaemia with concomitant adrenaline release, and a grand mal convulsion), the pronounced leucocytosis and its time course might reasonably have been predicted and the investigations, which were by no means trivial, either to the patient or to the laboratories, avoided.
A METHOD OF SECURING RAPID HEALING OF BONE SINUSES
Authors: A. K. Henry, D. K. M. Henry
Journal: BMJ (1919)

VuNE 21, 19 I freely enlarged and a sequestrum removed.The sinuses over the fibula were curetted, but 11o sequestra were found; the sur- rounding skin was extensively underiined and thick silk sutures were put in so as to close the wound except in the centre.Bipp was applied to the bone cavity, which was packed with bipp iodoform gauze.This was removed after forty-eight lhours, and a cavity the size of a large walnut was filled with bipp.The dressings were changed every fourth or fifth dav.'The cavity gradually filled up and when he left hospital on September 10th, nine weeks after the operation, the wound was complete:y healed.CASE II.A soldier admitted on July 9th, 1918, had been wounded by a shell in the left arm on April 30th, 1918.The left humerus was fractured in the upper third.On September 13th, four and a lhalf months after being wouinded, he presented fistulae of the tipper third of the arm; the x ray showed that the fracture was