tbuckley/cabot-search huggingface dataset:
Long-term marrow culture of cells from patients with acute myelogenous leukemia. Selection in favor of normal phenotypes in some but not all cases.
Authors: L Coulombel, C Eaves, D Kalousek, C Gupta, A Eaves
Journal: Journal of Clinical Investigation (1985)

Long-term cultures were initiated with leukemic marrow aspirate cells from each of 13 newly diagnosed acute myelogenous leukemia (AML) patients. Initial assessment of the clonogenic potential of the marrow suggested that normal hemopoietic progenitors were reduced in most cases and progenitors of abnormal colonies and clusters were present in 10 cases. Subsequent assays of both nonadherent and adherent fractions of long-term cultures revealed two patterns of progenitor cell behavior. The most common pattern (nine cases) featured the detection after 1-4 wk of near normal numbers of typical erythroid, granulopoietic, and mixed colony-forming progenitor cells. Progenitors of abnormal (blast) colonies and clusters initially demonstrable in eight of these nine cases were, in these cases, not sustained in long-term culture and could not be found after 4 wk. Conversion to cytogenetic normalcy in long-term culture was confirmed in two experiments in this group. The second pattern (four cases) was characterized by the failure of progenitors capable of normal differentiation to become detectable in long-term cultures, and the concomitant maintenance of blast progenitors in the two cases in this group where such cells were initially demonstrable. Although progenitors capable of producing abnormal (blast) colonies or clusters in methylcellulose were not detected in either of the other two experiments, the maintenance for 6 wk of a hypercellular nonadherent blast population in one of these suggested the persisting activity of an "adherent layer-dependent" leukemic progenitor cell. Taken together, these findings indicate a strong correlation between the presence of leukemic blasts and their progenitors and a decreased level of normal hemopoiesis. In addition, the failure of leukemic cells to be maintained in long-term marrow cultures from some (but not all) AML patients suggests new applications of this methodology for studies of early stages of leukemic cell development.
Injury Prevention by Medication Among Children With Attention-Deficit/Hyperactivity Disorder
Authors: Rafael Mikolajczyk, Johannes Horn, Niklas Schmedt, Ingo Langner, Christina Lindemann, Edeltraut Garbe
Journal: JAMA Pediatrics (2015)

Children and adolescents with attention-deficit/hyperactivity disorder (ADHD) have an increased risk of injuries. Attention-deficit/hyperactivity disorder is often treated with medication, but the evidence regarding prevention of injuries is inconclusive.To determine via a case-only design whether the use of methylphenidate hydrochloride or atomoxetine hydrochloride reduces the risk of injuries among children and adolescents with ADHD.We used the German Pharmacoepidemiological Research Database, which includes records from about 17 million insurees (approximately 20% of the population) from 4 statutory health insurance providers in Germany to identify children aged 3 to 17 years with new diagnoses of ADHD in 2005 and 2006. We identified 37,650 children with ADHD based on inpatient and outpatientdiagnostic codes (F90.0, F90.1, and F90.9) from the German modification of the International Statistical Classification of Diseases and Related Health Problems, 10th Revision. Among them, we identified those with an inpatient injury diagnosis during follow-up until 2009. A total of 2128 children with any injury diagnosis at hospitalization, 821 of whom had a brain injury diagnosis, were included in the analysis. We applied the self-controlled case series design to control for time-invariant characteristics of the patients and time trends in the exposure.Treatment with methylphenidate or atomoxetine based on prescription data.Hospitalization because of any injury or brain injury according to the injury mortality diagnosis matrix.Incidence rate ratios for the periods with medication compared with nonmedicated periods were 0.87 (95% CI, 0.74-1.02) for hospitalization with any injuries and 0.66 (95% CI, 0.48-0.91) for brain injuries only in the full sample. These estimates remained stable in sensitivity analyses restricting the sample to a narrower age range or to patients with a single hospitalization. There was no indication that medication prescriptions are increased after hospitalizations.No significant risk reduction for hospitalizations with injury diagnoses was observed during periods of ADHD medication, but there was a preventive effect on the risk of brain injuries (34% risk reduction). The effects were controlled for time-invariant characteristics of the patients by the study design.
Demonstration of Persistent Left Superior Vena Cava by First Pass Radionuclide Angiography
Authors: CHENG-YI CHENG, DAN-JIANG WANG, WEI-LIAN CHEN, YI-FANG CHANG, FU-KEN CHANG, SHIH-PING YANG, SHYH-MING SHIEH
Journal: Clinical Nuclear Medicine (1987)

A case of the left superior vena cava draining to the coronary sinus without associated intracardiac shunt was initially demonstrated by first pass radionuclide angiography. The patient had atypical chest pain for 8 years, and had sick sinus syndrome with a long cardiac pause. Cardiac catheterization confirmed this diagnosis, and a transvenous pacemaker was successfully implanted through the left superior vena cava.
Assessing siRNA Pharmacodynamics in a Luciferase-expressing Mouse
Authors: Robert U Svensson, Michael R Shey, Zuhair K Ballas, J Robert Dorkin, Michael Goldberg, Akin Akinc, Robert Langer, Daniel G Anderson, David Bumcrot, Michael D Henry
Journal: Molecular Therapy (2008)

A significant barrier to the successful general development of small-interfering RNA (siRNA) therapeutics is the ability to deliver them systemically to target organs and cell types. In this study, we have developed a mouse strain that will facilitate the evaluation of the efficacy of siRNA delivery strategies. This strain contains robust ubiquitous expression of firefly luciferase from germ line Cre-mediated recombination of the ROSA26-LSL-Luc allele. We show that luciferase is highly and uniformly expressed in all tissues examined. Using this mouse model, we describe a facile assay that enables the assessment of the pharmacodynamics of a systemically delivered siRNA formulation. These mice can also be used as universal donors, enabling the efficient and sensitive monitoring of cell trafficking or tissue transplantation. The primary advantage of this approach is that siRNA efficacy against a nonessential target can be easily evaluated in any tissue. This strain should generally enhance the ability to rapidly screen, compare and optimize various siRNA formulations for tissue-targeted or -enhanced systemic delivery in a preclinical development setting. A significant barrier to the successful general development of small-interfering RNA (siRNA) therapeutics is the ability to deliver them systemically to target organs and cell types. In this study, we have developed a mouse strain that will facilitate the evaluation of the efficacy of siRNA delivery strategies. This strain contains robust ubiquitous expression of firefly luciferase from germ line Cre-mediated recombination of the ROSA26-LSL-Luc allele. We show that luciferase is highly and uniformly expressed in all tissues examined. Using this mouse model, we describe a facile assay that enables the assessment of the pharmacodynamics of a systemically delivered siRNA formulation. These mice can also be used as universal donors, enabling the efficient and sensitive monitoring of cell trafficking or tissue transplantation. The primary advantage of this approach is that siRNA efficacy against a nonessential target can be easily evaluated in any tissue. This strain should generally enhance the ability to rapidly screen, compare and optimize various siRNA formulations for tissue-targeted or -enhanced systemic delivery in a preclinical development setting.
Nitrate Resistance In Platelets From Patients With Stable Angina Pectoris
Authors: Yuliy Y. Chirkov, Andrew S. Holmes, Larissa P. Chirkova, John D. Horowitz
Journal: Circulation (1999)

Background —Hemodynamic resistance to nitrates has been previously documented in congestive heart failure. In patients with stable angina pectoris (SAP), we have observed a similar phenomenon: decreased platelet response to disaggregating effects of nitroglycerin (NTG) and sodium nitroprusside (SNP). Methods and Results —In blood samples from normal subjects (n=32) and patients with SAP (n=56), we studied effects of NO donors (NTG and SNP) on ADP-induced platelet aggregation and on intraplatelet cGMP. NTG and SNP inhibited platelet aggregation in patients to lesser extents than in normal subjects ( P &lt;0.01). The cGMP-elevating efficacy of NTG and SNP was diminished in platelets from patients in comparison with those from normals ( P &lt;0.001). Inhibition of the anti-aggregatory effects of NTG and SNP by ODQ, a selective inhibitor of NO-stimulated guanylate cyclase, was significantly less pronounced in patients than in normal subjects. Content of O 2 − was higher in blood samples from patients than in those from normal subjects ( P &lt;0.01). In blood samples from patients with SAP, but not in normal subjects, the O 2 − scavenger superoxide dismutase (combined with catalase) suppressed platelet aggregation ( P &lt;0.01) and increased the extent of anti-aggregatory effect of SNP ( P &lt;0.01). Conclusions —In patients with SAP, platelets are less responsive to the anti-aggregating and cGMP-stimulating effects of NO donors; this may reflect both reduction in guanylate cyclase sensitivity to NO and inactivation of the released NO by O 2 − . The implied impairment of anti-platelet efficacy of endogenous NO (in the form of EDRF) may contribute to platelet hyperaggregability associated with angina pectoris.
Critical Pathway for Chest Pain
Authors: Thomas H. Lee
Journal: Annals of Internal Medicine (1998)

Letters1 July 1998Critical Pathway for Chest PainThomas H. Lee, MD and Graham Nichol, MDThomas H. Lee, MDPartners Community Health Care, Inc.; Boston, MA 02199University of Ottawa; Ottawa, Ontario K1Y 4E9, CanadaSearch for more papers by this author and Graham Nichol, MDPartners Community Health Care, Inc.; Boston, MA 02199University of Ottawa; Ottawa, Ontario K1Y 4E9, CanadaSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-129-1-199807010-00019 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:We appreciate that evidence of the potential role of rapid bedside testing in patients with chest pain in the emergency department is rapidly evolving. Dr. Bosch cites a non-experimental study of use of troponin-T and troponin-I. However, negative test results were insufficient to rule out short-term risks in all subgroups.The other studies that he cites are worth considering further. Lindahl and colleagues assessed troponin T in patients with crescendo angina or ischemia on electrocardiography. The sensitivity of troponin T was overestimated because testing was conducted up to 24 hours after symptom onset. Furthermore, another prospective study [1] ...References1. Brogan GX Jr, Hollander JE, McCuskey CF, Thode HC, Snow J, Sama A, et al. Evaluation of a new assay for cardiac troponin I vs creatine kinase-MB for the diagnosis of acute myocardial infarction. The Biochemical Markers for Acute Myocardial Ischemia (BAMI) Study Group. Acad Emerg Med. 1997; 4:6-12. Google Scholar2. Lachs MS, Nachamkin I, Edelstein PH, Goldman J, Feinstein AR, Schwartz JS. Spectrum bias in the evaluation of diagnostic tests: lessons from the rapid dipstick test for urinary tract infection. Ann Intern Med. 1992; 117:135-40. Google Scholar Author, Article, and Disclosure InformationAffiliations: Partners Community Health Care, Inc.; Boston, MA 02199University of Ottawa; Ottawa, Ontario K1Y 4E9, Canada PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 July 1998Volume 129, Issue 1Page: 70-71KeywordsEmergency departmentEvidence based medicineIschemiaMyocardial infarctionPatientsProspective studiesSpecificityTroponinTroponin TUnstable angina Issue Published: 1 July 1998 CopyrightCopyright © 1998 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Abstract 5469: Trastuzumab resistant HER2+ breast cancer cells retain sensitivity to poly (ADP-ribose) polymerase (PARP) inhibition
Authors: Monica E. Wielgos, Tiffiny Cooper, Andres Forero, James A. Bonner, Francisco J. Esteva, C K. Osborne, Rachel Schiff, Albert F. LoBuglio, Eddy S. Yang
Journal: Cancer Research (2014)

Abstract Background: Overexpression of HER2 in breast cancer is associated with aggressive tumor features and poor patient survival. Current therapeutic agents targeting this receptor have increased the survival rate of patients with HER2+ breast cancer; however some patients eventually develop resistance to these therapies. We have previously reported that HER2+ breast cancers are susceptible to poly (ADP-Ribose) polymerase inhibitors (PARPi) alone independent of a basal or induced DNA repair deficiency but instead via suppression of NF-κB signaling. In this study, we investigated PARPi sensitivity in HER2+ breast cancer cells that are resistant to the HER2 targeted agent trastuzumab. Materials and Methods: HER2+ breast cancer cell lines BT-474, UACC812, SKBRR3 and their trastuzumab resistant counterparts were used in this study. Cells were treated with vehicle or 10µM ABT-888 or transfected with scrambled or PARP1 siRNA. NF-κB transcriptional activity was measured using a NF-κB-driven luciferase reporter assay. Protein expression was measured by Western blot analysis. Cellular cytotoxicity and viability following PARPi was assessed with colony formation and ATPlite assays, respectively. Results: HER2+ parent and trastuzumab resistant breast cancer cells showed similar susceptibility to the PARPi ABT-888. There was a dose response reduction in survival fraction (greater than 70% at 10μM) and a greater than 40% decrease in cell viability with 10μM ABT-888. This cytotoxicity was associated with more than 50% attenuation of NF-κB transcriptional activity and reduced expression of the NF-κB activator IKKα. Suppression of NF-κB signaling was also observed utilizing PARP1 siRNA. Conclusions: HER2+ breast cancer cells resistant to trastuzumab continue to be sensitive to PARP inhibition through attenuation of the NF-κB signaling pathway. These results support the use of PARPi as part of a therapeutic strategy for patients with HER2+ breast cancer. Citation Format: Monica E. Wielgos, Tiffiny Cooper, Andres Forero, James A. Bonner, Francisco J. Esteva, C K. Osborne, Rachel Schiff, Albert F. LoBuglio, Eddy S. Yang. Trastuzumab resistant HER2+ breast cancer cells retain sensitivity to poly (ADP-ribose) polymerase (PARP) inhibition. [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 5469. doi:10.1158/1538-7445.AM2014-5469
THE INCIDENCE AND EFFECT OF SOME DISEASES ON OTHERS
Authors: J. R. Charles
Journal: BMJ (1905)

IT will be generally agreed, I think, that it is an unusual event to meet with two acute diseases running their course concurrently in the same patient, although, as is well known, such an event may be occasionally encountered.With regard to the co-Pxistence of infectious diseases, Caiger, in his article on this subject in Allbutt's System of Medicine, quotes many cases, inclhding one in which the unfortunate patient was suffering from four such diseases at the same time.He says that " the symptoms of one disease are neither delayed in their appearance, nor mitigated in their severity by the presence of another."I shall, however, return to points in this connexion later on.On the other hand, acute secondary infective disease very frequently arises during the course of chronic diseases.It is, indeed, so often the immediate cause of death in some of these conditions, that the mortality from this cause, combined with the number of deaths due to certain mechaniil causes-for example, aneurysm or cerebral haemorrhage in chronic interstitial nephritis-has led to the
Exogenous peptides compete for the presentation of endogenous antigens to major histocompatibility complex class II-restricted T cells.
Authors: L Adorini, J Moreno, F Momburg, G J Hämmerling, J C Guéry, A Valli, S Fuchs
Journal: The Journal of Experimental Medicine (1991)

Antigen-presenting cells (APC) transfected with a construct encoding the hen egg-white lysozyme (HEL) amino acid sequence 1-80 constitutively present HEL peptides complexed to major histocompatibility complex (MHC) class II molecules to specific T cell hybridomas, indicating that endogenous cellular antigens can be efficiently presented to class II-restricted T cells. Here we show that exogenous peptide competitors added to HEL-transfected APC can inhibit the presentation of endogenous HEL peptides to class II-restricted T cells. The inhibition is specific for the class II molecule binding the competitor peptide, and it affects to the same extent presentation of exogenous or endogenous HEL peptides. These results, demonstrating that an exogenous competitor can inhibit class II-restricted T cell activation induced by endogenous as well as exogenous antigen, suggest lack of strict compartmentalization between endogenous and exogenous pathways of antigen presentation. Since autoreactive T cells may recognize endogenous, as well as exogenous antigens, the results have implications for the treatment of autoimmune diseases by MHC blockade.
PSA Thresholds for Prostate Cancer Detection-Reply
Authors: William J. Catalona
Journal: JAMA (1997)

<h3>To the Editor.</h3> —A PSA test should be viewed as a risk assessment for prostate cancer over a continuum of PSA values. Our article reported that (1) in the PSA range of 2.6 to 4.0 ng/mL, 22% of 317 volunteers with a benign-feeling prostate gland had cancer detected, and (2) measurement of percent-free PSA (%FPSA) could avoid 18% of the unnecessary biopsies while detecting 90% of cancers. These cancers would not be detected using traditional biopsy criteria. We hypothesize that earlier detection will result in improved outcomes. To this end, we are conducting longitudinal outcomes studies. Dr Moul points out the contradiction that Carter et al<sup>1</sup>consider biannual testing sufficient in men with PSA levels less than 2.0 ng/mL and that diagnosing cancer at levels of 4.0 to 5.0 ng/mL is sufficient for detecting curable cancer, while we recommend biopsy in men with PSA levels higher than 2.6 ng/mL. Moul believes that
Thrombopoietin: Platelets on Demand
Authors: Richard L. Golden
Journal: Annals of Internal Medicine (1997)

Letters1 November 1997Thrombopoietin: Platelets on DemandRichard L. Golden, MDRichard L. Golden, MDState University of New York at Stony Brook School of Medicine Stony Brook, NY 11794Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-127-9-199711010-00019 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:In his incisive editorial on the identification and cloning of thrombopoietin [1], Dr. Kaushansky implies that James H. Wright first observed blood plates (platelets) in 1906. This discovery is usually attributed to Alexandre Donne, distinguished French microscopist, who in 1842 described platelets as a third blood particle. Later investigators who more fully described the platelets and their function include Max Schultze (1865), William Osler (1873), Georges Hayem1875, and Giulio Bizzozero (1883). To James H. Wright goes the distinction of the 1906 discovery of the role of the megakaryocyte in the production of platelets.References1. Kaushansky K. Thrombopoietin: platelets on demand? [Editorial] Ann Intern Med. 1997; 126:731-3. Google Scholar2. Donne A. De l'origine des globules du sang, de leur mode de formation et de leur fin. C R Acad Sci (Paris). 1842; 14:366-8. Google Scholar3. Castiglioni A. A History of Medicine. 2d ed. New York: Alfred A Knopf; 1947:773, 777. Google Scholar4. Garrison FH. An Introduction to the History of Medicine. 4th ed. Philadelphia: WB Saunders; 1929:445, 524. Google Scholar Author, Article, and Disclosure InformationAuthors: Richard L. Golden, MDAffiliations: State University of New York at Stony Brook School of Medicine Stony Brook, NY 11794 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 November 1997Volume 127, Issue 9Page: 847KeywordsBloodCloningMegakaryocytesPlatelets ePublished: 15 August 2000 Issue Published: 1 November 1997 Copyright & PermissionsCopyright © 1997 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Hurford's partial vindication of classical empiricism
Authors: Fiona Cowie
Journal: Behavioral and Brain Sciences (2003)

Hurford's discussion also vindicates the classical empiricist program in semantics. The idea that PREDICATE(x) is the logical form of the sensory representations encoded via the dorsal and ventral streams validates empiricists' insistence on the psychological primacy of sense data, which have the same form. In addition to knowing the logical form of our primitive representations, however, we need accounts of (1) their contents and (2) how more complex thoughts are derived from them. Ideally, our semantic vocabulary would both reflect the psychological "primitiveness" of these representations and make clear how more complex representations derive from them.
Lack of endogenous TRIM5α-mediated restriction in rhesus macaque dendritic cells
Authors: Nathalie J. Arhel, Sébastien Nisole, Laetitia Carthagena, Frédéric Coutant, Philippe Souque, Audrey Brussel, Jérôme Estaquier, Pierre Charneau
Journal: Blood (2008)
Re: Christian Walter, Bilal Al-Nawas, Knut A. Grötz, et al. Prevalence and Risk Factors of Bisphosphonate-Associated Osteonecrosis of the Jaw in Prostate Cancer Patients with Advanced Disease Treated with Zoledronate. Eur Urol 2008;54:1066–72
Authors: Athanassios Kyrgidis, Zisis Teleioudis, Konstantinos Vahtsevanos
Journal: European Urology (2008)
Compendium of pastoral medicine.
Authors: Paul B. McCleave
Journal: JAMA (1963)

The purpose of this book is determined, as the author says, "by the need which the spiritual advisor has. And Pastoral Medicine is of no less importance to the doctor since he needs a guide in his practice.... Pastoral Medicine is a very important part of medical science and a very important branch of Pastoral Theology. Its importance for both branches of knowledge becomes more clearly evident as time goes on." This book is for the non-Catholic as well as the Catholic physician, for we must recognize that, in caring for a patient, we must treat within that patient's faith. For the doctor in his relations with the sick, the importance of the ideas expressed in Pastoral Medicine is incalculable. Doctor Niedermeyer has divided his work into three main sections: "Fundamental Principles," "Special Pastoral Medicine," and "Religion and Therapeutics" (Deontology). The section "Special Pastoral Medicine" can be used as a