tbuckley/cabot-search huggingface dataset:
AB0182 Sustained PI3-KINASE activity in myeloid cells enhances osteoclastogenesis and augments local bone destruction
Authors: S. Blüml, A. Puchner, E. Sahin, V. Saferding, B. Niederreiter, J.S. Smolen, G. Schabbauer, K. Redlich
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Local bone destruction in rheumatoid arthritis, proriasisarthritis or ankylosing spondylitis often leads to disability and severely reduced quality of life. This damage to the bony structures is almost exclusively mediated by a special cell type, the osteoclasts. Therefore, it is important to understand factors and pathways regulating the generation of osteoclasts. <h3>Objectives</h3> In this study, we analyzed the impact of the PI3-Kinase/PTEN axis on osteoclast generation and bone biology under basal and inflammatory conditions. <h3>Methods</h3> Analysis of in vitro osteoclastogenesis and in vitro osteoclast function, bone histomorphometry, qPCR, clinical and histological examination of myeloid specific PTEN<sup>-/-</sup> crossed into human TNF transgenic mice <h3>Results</h3> We show that mice with a monocyte/macrophage-specific deletion of PTEN (myeloid specific PTEN<sup>-/-</sup>) display increased osteoclastogenesis <i>in vitro</i> and <i>in vivo</i> compared to wild-type mice. However, under homeostatic conditions, enhanced osteoclastogenesis did not result in systemic bone loss due to a significantly increased bone formation evidenced by an enhanced mineral apposition rate in myeloid specific PTEN<sup>-/-</sup> mice. In contrast, under inflammatory conditions in the hTNFtg mouse model of arthritis, myeloid specific PTEN<sup>-/-</sup> displayed enhanced local bone destruction as well as osteoclast formation in the inflamed joints. The extent of synovial inflammation, however, as well as recruitment of osteoclast precursor cells was not different between wt and myeloid specific PTEN<sup>-/-</sup> mice. <h3>Conclusions</h3> These data demonstrate that enhanced PI3-Kinase activity in myeloid cells the osteoclastogenic potential of myeloid cells, leading to enhanced inflammatory local bone destruction. <h3>Disclosure of Interest</h3> None Declared
How safe should drugs be?
Authors: F. G. McMahon
Journal: JAMA (1983)

ON AUG 18, 1982, a nationally televised morning news program featured a segment discussing the issue, "When the Food and Drug Administration approves a drug, does that mean it is safe?" Some three weeks later, the Commissioner of the FDA, Arthur Hull Hayes, MD, debated Sidney Wolfe, MD, of Ralph Nader's Health Research Group, on another nationally televised morning news program. Their debate concerned Dr Hayes' recent efforts to simplify and expedite some of the FDA's regulations concerning the investigation and approval of new drugs. Dr Wolfe wanted regulations tightened rather than relaxed, particularly in view of the necessity to recall such recently approved "unsafe drugs" such as benoxaprofen (Oraflex) and ticrynafen (Selacryn). Dr Wolfe's attack on the FDA's recent efforts to simplify some of its procedures is also an attack on the recent report of the Congressional Commission on the Federal Drug Approval Process. Twenty-six knowledgeable members representing academia,
Failure to Disclose a Potential Conflict of Interest
Authors: Daniel Spratt, Samir Hanash, Ziding Feng, Ayumu Taguchi
Journal: JAMA Oncology (2019)

Integrative Analysis of Lung Cancer Etiology and Risk (INTEGRAL) Consortium for Early Detection of Lung Cancer; Florence Guida, PhD; Nan Sun, PhD; Leonidas E. Bantis, PhD; David C. Muller, PhD; Peng Li, PhD; Ayumu Taguchi, MD, PhD; Dilsher Dhillon, MS; Deepali L. Kundnani, MS; Nikul J. Patel, MS; Qingxiang Yan, PhD; Graham Byrnes, PhD; Karel G. M. Moons, PhD; Anne Tjønneland, MD, PhD; Salvatore Panico, MD, MS; Claudia Agnoli, PhD; Paolo Vineis, MD, MPH, FFPH; Domenico Palli, MD; Bas Bueno-de-Mesquita, MD, MPH, PhD; Petra H. Peeters, MD, PhD; Antonio Agudo, MD, PhD; Jose M. Huerta, PhD; Miren Dorronsoro, MD; Miguel Rodriguez Barranco, PhD; Eva Ardanaz, MD, PhD; Ruth C. Travis, DPhil; Karl Smith Byrne, DPhil; Heiner Boeing, PhD; Annika Steffen, PhD; Rudolf Kaaks, PhD; Anika Hüsing, MS; Antonia Trichopoulou, PhD; Pagona Lagiou, MD; Carlo La Vecchia, MD; Gianluca Severi, PhD; Marie-Christine Boutron-Ruault, PhD; Torkjel M. Sandanger, PhD; Elisabete Weiderpass, MD, PhD; Therese H. Nøst, PhD; Kostas Tsilidis, PhD; Elio Riboli, MD, MPH, MSc; Kjell Grankvist, MD, PhD; Mikael Johansson, PhD; Gary E. Goodman, MD, MS; Ziding Feng, PhD; Paul Brennan, PhD; Mattias Johansson, PhD; Samir M. Hanash, MD, PhD
Valproic acid therapy in childhood epilepsy
Authors: D. L. Coulter
Journal: JAMA (1980)

Valproic acid, used alone or in combination with other anticonvulsants in 100 children with epilepsy, improved seizure control in all age groups. Mean improvement in seizure control was 82%. Petit mal seizures responded best, but other types of seizures, even with associated mental and physical handicaps, also responded well. A substantial improvement in alertness and behavior often occurred. Leukopenia (27%) and an elevated SGOT value (44%) were frequent but transient. Other side effects included alopecia (1), gastrointestinal distress with vomiting (7), pancreatitis (1), thrombocytopenia (1), edema (2), and coma (2). Three severely retarded children with frequent seizures died while receiving valproic acid, but it is not clear that death was caused by valproic acid. Children must be monitored carefully for potential toxic effects, and drug interactions with other anticonvulsants may cause problems in treatment. (<i>JAMA</i>244:785-788, 1980)
Use of Plastics in Otolaryngology
Journal: JAMA (1963)

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
Protein Interactions of Sulfonylurea Compounds
Journal: JAMA (1963)

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
Transactions of the Indiana State Medical Society.
Authors: None C. E. W.
Journal: JAMA (1884)

In his able address the President, Dr. S. E. Munford, after a review of the present relations of the profession to society and a consideration of its philanthropic position, particularly as shown in the department of sanitary affairs, proceeds to the consideration of the gross wrongs unwittingly perpetrated upon the learned and honorable in the profession by society, which, through its nebulous belief in any loud-mouthed rascal (the phraseology is our own, and is lacking in that scholarly refinement so noticeable in the address), robs the faithful and modest student both of pecuniary success and honorable distinction. The remedy proposed by the doctor is the one so universally advocated, namely: the better education of the profession. There is much of interest and importance in the proceedings, but the general tone of the President's address directs attention to the class of subjects that appeared to awaken exceptional interest. This is due
Key Characteristics of Cardiovascular Toxicants
Authors: Lars Lind, Jesus A. Araujo, Aaron Barchowsky, Scott Belcher, Brian R. Berridge, Nipavan Chiamvimonvat, Weihsueh A. Chiu, Vincent J. Cogliano, Sarah Elmore, Aimen K. Farraj, Aldrin V. Gomes, Cliona M. McHale, Kathleen B. Meyer-Tamaki, Nikki Gillum Posnack, Hugo M. Vargas, Xi Yang, Lauren Zeise, Changcheng Zhou, Martyn T. Smith
Journal: Environmental Health Perspectives (2021)

BACKGROUND:The concept of chemical agents having properties that confer potential hazard called key characteristics (KCs) was first developed to identify carcinogenic hazards.Identification of KCs of cardiovascular (CV) toxicants could facilitate the systematic assessment of CV hazards and understanding of assay and data gaps associated with current approaches.OBJECTIVES: We sought to develop a consensus-based synthesis of scientific evidence on the KCs of chemical and nonchemical agents known to cause CV toxicity along with methods to measure them.METHODS: An expert working group was convened to discuss mechanisms associated with CV toxicity.RESULTS: The group identified 12 KCs of CV toxicants, defined as exogenous agents that adversely interfere with function of the CV system.The KCs were organized into those primarily affecting cardiac tissue (numbers 1-4 below), the vascular system (5-7), or both (8-12), as follows: 1) impairs regulation of cardiac excitability, 2) impairs cardiac contractility and relaxation, 3) induces cardiomyocyte injury and death, 4) induces proliferation of valve stroma, 5) impacts endothelial and vascular function, 6) alters hemostasis, 7) causes dyslipidemia, 8) impairs mitochondrial function, 9) modifies autonomic nervous system activity, 10) induces oxidative stress, 11) causes inflammation, and 12) alters hormone signaling.DISCUSSION: These 12 KCs can be used to help identify pharmaceuticals and environmental pollutants as CV toxicants, as well as to better understand the mechanistic underpinnings of their toxicity.For example, evidence exists that fine particulate matter [PM ≤2:5 lm in aerodynamic diameter (PM 2:5 )] air pollution, arsenic, anthracycline drugs, and other exogenous chemicals possess one or more of the described KCs.In conclusion, the KCs could be used to identify potential CV toxicants and to define a set of test methods to evaluate CV toxicity in a more comprehensive and standardized manner than current approaches.
Proteogenomic analysis of the autoreactive B cell repertoire in blood and tissues of patients with Sjögren’s syndrome
Authors: Mathijs G A Broeren, Jing J Wang, Giulia Balzaretti, Patricia J T A Groenen, Barbera D C van Schaik, Tim Chataway, Charlotte Kaffa, Sander Bervoets, Konnie M Hebeda, Gergana Bounova, Ger J M Pruijn, Thomas P Gordon, Niek De Vries, Rogier M Thurlings
Journal: Annals of the Rheumatic Diseases (2022)

To comparatively analyse the aberrant affinity maturation of the antinuclear and rheumatoid factor (RF) B cell repertoires in blood and tissues of patients with Sjögren's syndrome (SjS) using an integrated omics workflow.Peptide sequencing of anti-Ro60, anti-Ro52, anti-La and RF was combined with B cell repertoire analysis at the DNA, RNA and single cell level in blood B cell subsets, affected salivary gland and extranodal marginal zone lymphomas of mucosa-associated lymphoid tissue (MALT) of patients with SjS.Affected tissues contained anti-Ro60, anti-Ro52, anti-La and RF clones as a small part of a polyclonal infiltrate. Anti-Ro60, anti-La and anti-Ro52 clones outnumbered RF clones. MALT lymphoma tissues contained monoclonal RF expansions. Autoreactive clones were not selected from a restricted repertoire in a circulating B cell subset. The antinuclear antibody (ANA) repertoires displayed similar antigen-dependent and immunoglobulin (Ig) G1-directed affinity maturation. RF clones displayed antigen-dependent, IgM-directed and more B cell receptor integrity-dependent affinity maturation. This coincided with extensive intra-clonal diversification in RF-derived lymphomas. Regeneration of clinical disease manifestations after rituximab coincided with large RF clones, which not necessarily belonged to the lymphoma clone, that displayed continuous affinity maturation and intra-clonal diversification.The ANA and RF repertoires in patients with SjS display tissue-restricted, antigen-dependent and divergent affinity maturation. Affinity maturation of RF clones deviates further during RF clone derived lymphomagenesis and during regeneration of the autoreactive repertoire after temporary disruption by rituximab. These data give insight into the molecular mechanisms of autoreactive inflammation in SjS, assist MALT lymphoma diagnosis and allow tracking its response to rituximab.
Sex and social class.
Journal: BMJ (1973)

BRITISH mEDICAL JouRNAL 21 JuLy 1973 1 adrenal haemorrhage is diagnosed it is important to ensure it is not part of a more general disease, the most important part of which is thrombosis of a renal vein, the inferior vea cava, or mesenteric veins.All these lesions have much more serious sequelae and are the commonest causes of death when children succumb with gross adrenal haemorrhages.Massive adrenal haemorrhage in newborn babies needs to be recognized for what it is, but the treatment of the child's general state is of paramount importance, and the mass can be left to look after itself.
Effect of prophylactic endoscopic clipping for prevention of delayed bleeding after endoscopic papillectomy for ampullary neoplasm: a multicenter randomized trial
Authors: Se Woo Park, Tae Jun Song, Jin Seok Park, Jae Hyuk Jun, Tae Young Park, Dong Wook Oh, Sang Soo Lee, Myung-Hwan Kim
Journal: Endoscopy (2022)

Background Endoscopic clip placement is technically challenging using a duodenoscope, limiting their application for treatment of bleeding after endoscopic papillectomy. This study evaluated the efficacy of newly designed clips to prevent bleeding after endoscopic papillectomy. Methods Patients (n = 80) with suspected benign adenomas on the major papilla who were scheduled for endoscopic papillectomy with or without clipping were randomized. A new duodenoscope-compatible clip capable of being rotated, reopened, and repeatedly repositioned was used. The primary end point was incidence of delayed bleeding. Results The clipping procedure was successful in all patients. The incidence of delayed bleeding was nonsignificantly higher in the no-clipping group than in the clipping group (31.6 % [95 % confidence interval (CI) 19.1–47.5] vs. 15.0 % [95 %CI 7.1–29.1]). The incidence of post-endoscopic retrograde cholangiopancreatography pancreatitis did not differ significantly between the groups (clipping vs. no-clipping: 17.5 % [95 %CI 8.7–31.9] vs. 5.3 % [95 %CI 1.5–17.3]), and all cases were mild. Conclusions Placement of the newly designed rotatable clip was technically feasible and tended to have a protective effect by preventing delayed bleeding after endoscopic papillectomy, although statistical significance was not reached.
Antithrombotic treatment.
Authors: P Buckler, A S Douglas
Journal: BMJ (1983)

Recent advances in the management of thrombotic disease have mainly been in prevention-for instance, prophylaxis of deep venous thrombosis.This article is confined to the use of drugs as possible prophylactic agents-namely, the antiplatelet drugs, low dose heparin, dextran, and ancrod.All of these drugs are still being examined in different clinical settings, and the intention is to discuss the current state of evaluation of their clinical efficacy. Antiplatelet drugsThe part that platelets play in initiation and propagation of thrombus remains controversial.Despite the theoretical benefits expected from the use of prophylactic antiplatelet treatment, the results of several large studies have so far shown only small unimportant trends in favour of treatment.There are many possible explanations why this should be, and with the expanding knowledge of platelet biochemistry it may be possible to develop more selectively potent drugs effective in small dosage.At the present time many drugs are known to modify platelet function (including the beta-blockers and calcium antagonists) but only three drugs are currently used specifically for their antiplatelet effects-namely, aspirin, sulphinpyrazone, and dipyridamole.ASPIRIN Platelet aggregation is a complex phenomenon and a vital part is played by prostaglandins, both in the platelet and in the vascular endothelial cells.The platelet contains enzymes that enable it to synthesise a prostaglandin called thromboxane, which is a potent stimulator of platelet aggregation.The endothelial cells, on the other hand, synthesise another prosta- glandin called prostacyclin and this inhibits platelet aggregation.Both pathways use an enzyme called cyclo-oxygenase, although slightly different forms of this enzyme are found in the two types of cell.Aspirin irreversibly acetylates cyclo-oxygenase, and since the platelet is unable to resynthesise this enzyme, this effect of aspirin lasts for the lifespan of the platelet.Since thromboxane promotes platelet aggregation, it would be reasonable to expect that blocking thromboxane synthesis
PERITYPHLITIS.
Authors: J. W. COWDEN
Journal: JAMA (1883)

[Read before the Iowa and Illinois Central District Medical Association, October 9, 1883] Mrs McF., a resident of Rock Island, Ill., born in Wales; 35 years of age; the mother of three children; weight 135 pounds; began complaining of pain in the right iliac fossa in the fall of 1882. Her family physician, Dr. Thomas Galt, diagnosed the case as neuralgia, and gave her prescriptions which he said would remove the trouble. The pain continued throughout the winter, the patient herself during that time being conscious of a swelling or induration on the right side. About the 10th of March, 1883, she was compelled to take to her bed. The doctor, then visiting her from day to day, told her “there might be danger of an abscess,” and immediately set in operation vigorous and active measures for “scattering” the tumor. These measures consisted in kneading and rubbing, at the
Primary and consultant care. Can they be distinguished?
Authors: D. M. Barr
Journal: JAMA (1980)

Four of five national data sets were adequate to distinguish primary and consultant care by specialty. The one data set that could not be used in this way includes most acute hospital care provided in the United States. Using a functional classification that was independent of specialty, one of five national data sets is purported by its sponsors to distinguish primary from consultant care, and that effort is not ongoing. Greater effort is needed to collect ongoing data distinguishing primary and consultant care specialties by function. (<i>JAMA</i>243:2510-2512, 1980)
British Medical Journal, London
Journal: JAMA (1967)

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
Autoimmune Hypophysitis
Authors: Patrizio Caturegli, Craig Newschaffer, Alessandro Olivi, Martin G. Pomper, Peter C. Burger, Noel R. Rose
Journal: Endocrine Reviews (2005)

Autoimmune (lymphocytic) hypophysitis is a rare disease that should be considered in the differential diagnosis of any nonsecreting pituitary mass, especially when occurring during pregnancy or postpartum. We have analyzed 370 articles published from January 1962 to October 2004 and identified a total of 379 patients with primary lymphocytic hypophysitis. The present review synthesizes the clinical and research data reported in this body of scientific literature.
Intrinsic IL-2 production by effector CD8 T cells affects IL-2 signaling and promotes fate decisions, stemness, and protection
Authors: Shannon M. Kahan, Rakesh K. Bakshi, Jennifer T. Ingram, R. Curtis Hendrickson, Elliot J. Lefkowitz, David K. Crossman, Laurie E. Harrington, Casey T. Weaver, Allan J. Zajac
Journal: Science Immunology (2022)

Here, we show that the capacity to manufacture IL-2 identifies constituents of the expanded CD8 T cell effector pool that display stem-like features, preferentially survive, rapidly attain memory traits, resist exhaustion, and control chronic viral challenges. The cell-intrinsic synthesis of IL-2 by CD8 T cells attenuates the ability to receive IL-2-dependent STAT5 signals, thereby limiting terminal effector formation, endowing the IL-2-producing effector subset with superior protective powers. In contrast, the non-IL-2-producing effector cells respond to IL-2 signals and gain effector traits at the expense of memory formation. Despite having distinct properties during the effector phase, IL-2-producing and nonproducing CD8 T cells appear to converge transcriptionally as memory matures to form populations with equal recall abilities. Therefore, the potential to produce IL-2 during the effector, but not memory stage, is a consequential feature that dictates the protective capabilities of the response.
Diabetic Cholecystomegaly
Authors: Alan A. Bloom
Journal: JAMA (1969)

In three patients with diabetes, gallbladders were enlarged three to nine times normal size. In a series of patients with diabetes, four (16%) of the 25 studied had enlarged gallbladders, while no examples of this could be demonstrated in the 50 control patients. No correlation was demonstrated between cholecystomegaly and other manifestations of diabetes, severity of diabetes, or mode of therapy. The condition resembles cholecystomegaly induced by vagotomy, but other mechanisms remain to be excluded. At the present time, neither medical nor surgical therapy for this condition appears warranted.