tbuckley/cabot-search huggingface dataset:
Abstract LB-295: Identification of the first class of proteasome inhibitors that impair 26S proteasome assembly <i>in vitro.</i>
Authors: Chantal Etievant, William Riquet, Nicolas Roullet, Martine Knibiehler, Isabelle Vandenberghe, Isabelle Carletti, Jean Edouard Gairin
Journal: Cancer Research (2010)

Abstract The Ubiquitin-Proteasome System (UPS) is the main non-lysosomial proteolytic machinery in the eukaryotic cells. Prior to their degradation proteins are adressed to the catalytic 26S proteasome complex composed of a 20S “core” that contains proteolytic activities, assembled with one or two 19S regulatory particles that bind proteins to be degraded. Due to its central role of in regulating cell cycle progression and signal transduction the UPS has been proposed as a suitable target for antineoplastic strategies. To date only catalytic inhibitors of proteasome, targeting proteolytic activities of the 20S core particle, have been characterized and/or have emerged as potent anticancer drugs (1). However, the capacity of the UPS to degrade proteins not only depends of the catalytic activities of the 20S core, but also of the 26S proteasome assembly, a dynamic and tightly controlled cellular process. Thus, compounds impairing 26S proteasome assembly could represent a novel class of proteasome inhibitors. With the aim of identifying such molecules we first set up a robust biochemical screening assay allowing us to follow 26S proteasome assembly in vitro. First, 26S proteasome was purified from Hela cells using affinity chromatography followed by gel filtration. Then, experimental conditions were determined for in vitro 26S disassembly into its constitutive sub-complexes (19S+20S) ands its re-assembly as an active and functional 26S entity. The differential CTL-activity between 26S and 20S proteasomes (2) was then used as the readout to follow the reassembly of 26S in vitro, prior to be confirmed using in gel overlay experiments and western-blotting. Using this biochemical assay: 1) we screened naturals compounds endowed with antiproliferative properties and described as inhibitors of the ubiquitine-proteasome pathway (3). 2) we identified structurally-related natural molecules, epidithiodioxopiperazine and diketodithiopiperazine derivatives, as the first class of molecules inhibiting proteasome assembly without significantly affecting neither 26S nor 20S catalytic activity in vitro. Our research efforts now concentrate in showing that: 1) these molecules inhibit proteasome assembly in cells, and that 2) this inhibition can be correlated with their antiproliferative effects. References Sterz J. et al. Extert Opin. Invest. Drugs, 2008, 17 Rivett AJ et al., Experimental Gerontology, 2002, 37 Vandenberghe I. et al., Biochem. Pharmacol., 2008, 76 Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-295.
Thomas William Francis Gann — Mayan Explorer
Authors: Francis H. McGovern
Journal: New England Journal of Medicine (1969)

THE extraordinary and colorful career of Thomas William Francis Gann as an explorer and authority on the ancient Mayan civilization is a striking example of a physician who achieved fame in a field other than that of his chosen profession.Although not generally appreciated, Gann's contributions to our information of pre-Columbian Middle America are impressive. His discoveries of Mayan ruins of great importance, his bibliography of 40 books and articles on his jungle travels and archeologic findings and the unparalleled Gann collection of Mayan jade and other material in the British Museum testify to the extent of his achievements.Gann . . .
A Multicenter Phase 1 Study of EMD 525797 (DI17E6), a Novel Humanized Monoclonal Antibody Targeting αv Integrins, in Progressive Castration-resistant Prostate Cancer with Bone Metastases After Chemotherapy
Authors: Manfred Wirth, Axel Heidenreich, Jürgen E. Gschwend, Thierry Gil, Stefan Zastrow, Michael Laniado, Joachim Gerloff, Michael Zühlsdorf, Giacomo Mordenti, Wolfgang Uhl, Heinrich Lannert
Journal: European Urology (2013)
A Self-Controlled, Naturalistic Study of Selective Serotonin Reuptake Inhibitors versus Tricyclic Antidepressants
Authors: C. Faravelli, F. Cosci, M. Ciampelli, M.A. Scarpato, R. Spiti, V. Ricca
Journal: Psychotherapy and Psychosomatics (2003)

&lt;i&gt;Objective:&lt;/i&gt; To compare the effectiveness of serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) for anxiety and mood disorders in a naturalistic setting. &lt;i&gt;Methods:&lt;/i&gt; 114 of 2,000 outpatients drawn from a private facility with a diagnosis of mood or anxiety disorder had two separate episodes during which they were treated once with a SSRI and once with a TCA. The drugs had to be in monotherapy and appropriate according to the recent guidelines. Key outcome measures included several rating scales, the results of which were combined into three measures of outcome: full response (no symptom), partial response (residual symptoms), poor response. &lt;i&gt;Results:&lt;/i&gt; TCAs produced a better response in 63 cases and SSRIs in 18 cases (p &lt; 0.00001). When the outcome was dichotomized, TCAs were still superior (stricter criterion of full response: p = 0.0002; lower threshold: p &lt; 0.0001). Considering depressive and anxiety disorders separately, TCAs remained superior in terms of efficacy (for depression: p &lt; 0.0001; for anxiety: p = 0.026). Moreover, the second episode of illness showed a better outcome than the first (p = 0.0008). &lt;i&gt;Conclusions:&lt;/i&gt; In those cases where two different antidepressants were prescribed over two different episodes of illness, TCAs were significantly more effective than SSRIs, regardless of the type of disorder and order of prescription.
Increased basal contractility of cardiomyocytes overexpressing protein kinase Cε and blunted positive inotropic response to endothelin-1
Authors: S Baudet
Journal: Cardiovascular Research (2001)

Objective: Protein kinase C (PKC) is thought to be involved in the regulation of the mammalian cardiac excitation–contraction coupling process by vasoactive peptides like endothelin-1 (ET-1). However, the demonstration of a causal link between activation of specific PKC isoforms and the increase in contractility mediated by ET-1 is still inferential. Methods: By means of adenovirus-mediated gene transfer, we specifically overexpressed PKCϵ in cultured adult rabbit ventricular myocytes (Ad-PKCϵ). Myocyte shortening and [Ca2+]i transients under basal and ET-1-stimulated conditions were measured in Ad-PKCϵ and Ad-LacZ control transfected cells. Results: Infection with Ad-PKCϵ resulted in a strong, virus dose-dependent increase in PKCϵ protein levels, whereas protein expression of other PKC isoforms remained unchanged. Using a multiplicity of infection of 100 plaque-forming units/myocyte, basal and cofactor-dependent PKCϵ kinase activity was increased 28- and 90-fold, respectively, when compared to control. Myocyte basal fractional shortening and [Ca2+]i transient amplitude were both increased by 21% (P<0.05 each) in Ad-PKCϵ transfected myocytes when compared to Ad-LacZ transfected control myocytes. The positive inotropic effect of ET-1 in control myocytes was markedly blunted in PKCϵ-overexpressing myocytes. Conclusion: Specific overexpression of PKCϵ in rabbit ventricular myocytes increases basal myocyte contractility and [Ca2+]i transients, and modifies their responsiveness to ET-1.
Novel Role of the CXC Chemokine Receptor 3 in Inflammatory Response to Arterial Injury
Authors: Johannes B.K. Schwarz, Nicolas Langwieser, Nicole N. Langwieser, Martin J. Bek, Stefan Seidl, Hans-Henning Eckstein, Bao Lu, Albert Schömig, Hermann Pavenstädt, Dietlind Zohlnhöfer
Journal: Circulation Research (2008)

Atherosclerosis, restenosis, and posttransplant graft atherosclerosis are characterized by endothelial damage, infiltration of inflammatory cells, and proliferation of smooth muscle cells. The CXCR3-activating chemokines interferon-γ inducible protein 10 (IP10) and MIG (monokine induced by interferon-γ) have been implicated in vascular repair and remodeling. The underlying molecular mechanisms, however, remain elusive. Here, we show that wire-mediated arterial injury induced local and systemic expression of IP10 and MIG, resulting in enhanced recruitment of CXCR3 + leukocytes and hematopoietic progenitor cells. This was accompanied by profound activation of mammalian target of rapamycin complex (mTORC)1, increased reactive oxygen species production, apoptosis, and intimal hyperplasia. Genetic and pharmacological inactivation of CXCR3 signaling not only suppressed recruitment of inflammatory cells but also abolished mTORC1 activation, reduced reactive oxygen species generation, and blocked apoptosis of vascular cells, resulting in significant reduction of intimal hyperplasia in vivo. In vitro, stimulation of T cells with IP10 directly activated mTORC1 and induced generation of reactive oxygen species and apoptosis in an mTORC1-dependent manner. These results strongly indicate that CXCR3-dependent activation of mTORC1 directly links stimulation of the Th1 immune system with the proliferative response of intimal cells in vascular remodeling.
A NEW SURFACE MARKER ON T LYMPHOCYTES OF HUMAN PERIPHERAL BLOOD
Authors: Sten Hammarström, Ulla Hellström, Peter Perlmann, Marie-Louis Dillner
Journal: The Journal of Experimental Medicine (1973)

Neuraminidase treatment of human peripheral blood lymphocytes uncovers cell surface receptors that bind purified A hemagglutinin from the snail Helix pomatia. No hemagglutinin was bound to untreated lymphocytes. Binding studies with (125)I-labeled hemagglutinin suggested that the number of receptors on neuraminidase-treated lymphocytes was approximately 1.10(6)/cell. The apparent association constant for hemagglutinin binding to lymphocytes, as calculated from Scatchard's plots, was 5-7.10(8) liters/mol. Immunofluorescent staining with FITC-conjugated hemagglutinin gave positive reactions with approximately 60% of the lymphocytes from normal donors. Positive staining was inversely related to the number of lymphocytes with Fc or complement receptors or with surface immunoglobulin, thus suggesting that See PDF for Structure the lymphocytes with receptors for Helix pomatia A hemagglutinin are T cells. Cell fractionation on columns charged with hemagglutinin indicate that these receptors may be used for separating subpopulations of human peripheral lymphocytes.
Outcome of carbon dioxide laser therapy for persistent viral warts
Authors: R.A. Logan, C.B. Zachary
Journal: British Journal of Dermatology (1988)

Journal Article Outcome of carbon dioxide laser therapy for persistent viral warts Get access R.A. Logan, R.A. Logan St. John's Hospital for Diseases of the Skin, London Search for other works by this author on: Oxford Academic Google Scholar C.B. Zachary C.B. Zachary St. John's Hospital for Diseases of the Skin, London Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 119, Issue s33, 1 July 1988, Pages 37–38, https://doi.org/10.1111/j.1365-2133.1988.tb05371.x Published: 01 July 1988
Appraisal of Medical Students' Abilities as Related to Training and Careers after Graduation
Authors: Osler L. Peterson, Fremont J. Lyden, H. Jack Geiger, Theodore Colton
Journal: New England Journal of Medicine (1963)

IN 1869 Sir James Paget1 posed the question, "What becomes of medical students?" He introduced his treatise as follows: "It is said that, on entering the anatomical theatre for one of his Introductory Lectures, Mr. Abernethy looked round at the crowd of pupils and exclaimed, as if with painful doubt, 'God help you all! What will become of you?' "Of the thousand British students who were the subjects of Paget's examination, nearly 13 per cent died during pupilage or in the early years of practice. A further 15 per cent "failed entirely" or left the profession. The present study . . .
Mediastinal Tumor Presenting as a Cardiac Halo on Equilibrium Radionuclide Angiography A Differential Diagnosis to Pericardial Effusion
Authors: NATHAN BETTER, MILOS J. JANICEK, MARILYN L. ANNESE, WILLIAM D. KAPLAN
Journal: Clinical Nuclear Medicine (1996)

A 52-year-old man with metastatic liposarcoma underwent equilibrium radionuclide angiography before commencing chemotherapy. Biventricular systolic function was normal, but an enlarged photon deficient area (cardiac halo) was seen surrounding the cardiac blood pool. Correlation with computed tomography was sought to exclude the possibility of a pericardial effusion, but a large mediastinal tumor was seen in the absence of a pericardial effusion. Literature review suggests alternative causes of a cardiac halo as clotted blood, particularly seen after cardiac surgery, ventricular hypertrophy, or subepicardial fat. The authors conclude that the presence of a cardiac halo, particularly within an oncologic population, can represent mediastinal tumor as an alternative to pericardial effusion. This possibility should be strongly considered in the analytical process.
Failure to Report Financial Disclosure Information
Authors: Pascale Barberger-Gateau
Journal: JAMA (2009)

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
Mouse Genetics/Genomics: An Effective Approach for Drug Target Discovery and Validation
Authors: David B. West, Olga Iakougova, Christine Olsson, David Ross, Jeffrey Ohmen, Alu Chatterjee
Journal: Medicinal Research Reviews (2000)

The mouse has become the premier mammalian system for the identification of the genetic basis of both mono- and oligogenic disorders, as well as the understanding of complex diseases with gene–gene and gene–environment interactions. The similarity between human and mouse genetic disease is sometimes striking, while in other cases the phenotypes are less similar. The ability to genetically map and then clone single gene disorders rapidly, and the emerging technologies that will allow the economical identification of the polygenes controlling quantitative traits further demonstrate the utility of the mouse as a model for gene discovery. Additionally, the ability to genetically manipulate the mouse through transgenesis and gene targeting allows for the testing of hypotheses regarding specific gene function and their role in disease. The utility of the mouse extends beyond being just a gene discovery tool to provide prevalidated targets. It can also be used for the development of animal models, and the testing of compounds in specifically constructed transgenic and knockout strains to further define the target and pathway of a therapeutic compound. © 2000 John Wiley & Sons, Inc. Med Res Rev, 20, No. 3, 216–230, 2000
Proton pump inhibitors match surgery in gastroesophageal reflux
Authors: Susan Mayor
Journal: BMJ (2006)

Proton pump inhibitors are as effective as surgery in the management of gastroesophageal reflux disease, a report from the US Agency for Healthcare Research and Quality has found. The agency reviews the effectiveness of medical treatments used by Medicare, Medicaid, and the State Children's Health Insurance Program.

The report reviewed treatments for chronic uncomplicated gastroesophageal reflux disease, which was defined as heartburn or acid regurgitation at least once a week. The report analysed randomised and non-randomised comparative studies, recent meta-analyses and cohort studies of over the counter drugs, proton pump inhibitors, fundoplication surgery (wrapping the top part of the stomach around the bottom of the oesophagus), …
Arrhythmogenic Right Ventricular Cardiomyopathy Causing Sudden Cardiac Death in Boxer Dogs
Authors: Cristina Basso, Philip R. Fox, Kathryn M. Meurs, Jeffrey A. Towbin, Alan W. Spier, Fiorella Calabrese, Barry J. Maron, Gaetano Thiene
Journal: Circulation (2004)

Background— Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a primary familial heart muscle disease associated with substantial cardiovascular morbidity and risk of sudden death. Efforts to discern relevant pathophysiological mechanisms have been impaired by lack of a suitable animal model. Methods and Results— ARVC was diagnosed in 23 boxer dogs (12 male; 9.1±2.3 years old). Clinical events alone or in combination included sudden death (n=9; 39%), ventricular arrhythmias of suspected right ventricular (RV) origin (n=19; 83%), syncope (n=12, 52%), and heart failure (n=3; 13%). Right ventricular enlargement or aneurysms occurred in 10 (43%). Striking histopathological abnormalities were present in each boxer dog but not in controls, including severe RV myocyte loss with replacement by fatty (n=15, 65%) or fibrofatty (n=8, 35%) tissue. Focal fibrofatty lesions were also present in both atria (n=8) and the left ventricle (LV) (n=11). Fatty replacement occupied substantially greater RV wall area in ARVC dogs than controls (40.4±18.8% versus 13.8±3.4%, respectively) ( P &lt;0.001); residual myocardium was correspondingly reduced (56.6±19.2% versus 84.8±3.8% in controls) ( P &lt;0.001). MRI demonstrated bright anterolateral and/or infundibular RV myocardial signals, confirmed as fat by histopathology. Myocarditis appeared in the RV (n=14, 61%) and LV (n=16, 70%) and in each dog with sudden death, but not in controls. Familial transmission was evident in 10 of the 23. Conclusions— We describe a novel, spontaneous, and genetically transmitted animal model of ARVC associated with sudden death in the boxer dog, closely resembling the human disease. This model may aid in understanding the pathogenic mechanisms of ARVC.
Medical Librarianship; Principles and Practice.
Authors: Susan Crawford
Journal: JAMA (1963)

It is the author's intention that this book be an introduction to medical librarianship, surveying medical libraries, their contents and procedures. With this in mind he states that the libraries in the US which he discusses are "selected for mention because of their reputations, or because information regarding them was readily available." This haphazard methodology in approaching the subject matter characterizes the entire volume. The content of the volume is divided into six main categories: medical libraries, hospital libraries, materials, classification and cataloging, bibliography and bibliographers, reference work. Under these categories, subclassifications are listed, with the frequent omission of important principles, aspects, and institutions. For example, the<i>Index to Nursing Literature</i>is mentioned, but not the<i>Index to Hospital Literature</i>. The role of the Joint Commission on Accreditation of Hospitals in elevating standards of hospital libraries is central to the development of these libraries, but reference to it is entirely
Living Beyond Limits: New Hope and Help for Facing Life-Threatening Illness
Authors: Burton C. Einspruch
Journal: JAMA (1994)

At the turn of the century there was little physicians could do to treat chronic tuberculosis, an illness that frequently foretold a lifetime of uncertain medical care and debilitation. During the preantibiotic era, an observant spa physician noted that consumptives who participated in lectures, social activities, and group learning experiences seemed to have a better clinical course. Though this observation was perhaps apocryphal, and certainly unproven, there was something inherent in the group process that extended the quality of life, although none thought of this as curative.
Hyperpyrexia during anaesthesia.
Authors: P. Furniss
Journal: BMJ (1970)

report on aids for the disabled' said, "In theory wheel chairs are prescribed by consul- tants, but in practice few consultants have studied this problem adequately and the re- sponsibility is often passed on to social workers or appliance clerks who have not been trained to do this work.Part of the fault stems from gaps in the doctor's educa- tion, particularly at a postgraduate level, but the situation could be improved by delegating responsibility to physiotherapists or occupational therapists specially trained to assess patients and their wheel-chair needs."The B.M.A. working party estimated that possibly as high as 30% O. of wheel chairs were unsuitable for the patient concerned.This may well be an underestimate.-Weare, etc.,
Live Attenuated Varicella Virus Vaccine
Authors: Robert E. Weibel, Beverly J. Neff, Barbara J. Kuter, Harry A. Guess, Carol A. Rothenberger, Alison J. Fitzgerald, Karen A. Connor, Arlene A. McLean, Maurice R. Hilleman, Eugene B. Buynak, Edward M. Scolnick
Journal: New England Journal of Medicine (1984)

We conducted a double-blind, placebo-controlled efficacy trial of the live attenuated Oka/Merck varicella vaccine among 956 children between the ages of 1 and 14 years, with a negative clinical history of varicella. Of the 914 children who were serologically confirmed to be susceptible to varicella, 468 received vaccine and 446 received placebo. The vaccine produced few clinical reactions and was well tolerated. There was no clinical evidence of viral spread from vaccinated children to sibling controls. Approximately eight weeks after vaccination, 94 per cent of the initially seronegative children who received vaccine had detectable antibody to varicella. During the nine-month surveillance period, 39 clinically diagnosed cases of varicella, 38 of which were confirmed by laboratory tests, occurred among study participants. All 39 cases occurred in placebo recipients; no child who received vaccine contracted varicella. The vaccine was 100 per cent efficacious in preventing varicella in this population of healthy children (P less than 10(-9).