tbuckley/cabot-search huggingface dataset:
The Combination of Sorafenib and Everolimus Abrogates mTORC1 and mTORC2 Upregulation in Osteosarcoma Preclinical Models
Authors: Ymera Pignochino, Carmine Dell'Aglio, Marco Basiricò, Federica Capozzi, Marco Soster, Serena Marchiò, Stefania Bruno, Loretta Gammaitoni, Dario Sangiolo, Erica Torchiaro, Lorenzo D'Ambrosio, Franca Fagioli, Stefano Ferrari, Marco Alberghini, Piero Picci, Massimo Aglietta, Giovanni Grignani
Journal: Clinical Cancer Research (2013)

The multikinase inhibitor sorafenib displays antitumor activity in preclinical models of osteosarcoma. However, in sorafenib-treated patients with metastatic-relapsed osteosarcoma, disease stabilization and tumor shrinkage were short-lived and drug resistance occurred. We explored the sorafenib treatment escape mechanisms to overcome their drawbacks.Immunoprecipitation, Western blotting, and immunohistochemistry were used to analyze the mTOR pathway [mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2)]. Cell viability, colony growth, and cell migration were evaluated in different osteosarcoma cell lines (MNNG-HOS, HOS, KHOS/NP, MG63, U-2OS, SJSA-1, and SAOS-2) after scalar dose treatment with sorafenib (10-0.625 μmol/L), rapamycin-analog everolimus (100-6.25 nmol/L), and combinations of the two. Cell cycle, reactive oxygen species (ROS) production, and apoptosis were assessed by flow cytometry. Nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice injected with MNNG-HOS cells were used to determine antitumor and antimetastatic effects. Angiogenesis and vascularization were evaluated in vitro by exploiting endothelial branching morphogenesis assays and in vivo in xenografted mice and chorioallantoic membranes.After sorafenib treatment, mTORC1 signaling was reduced (downstream target P-S6), whereas mTORC2 was increased (phospho-mTOR Ser2481) in MNNG-HOS xenografts compared with vehicle-treated mice. Combining sorafenib with everolimus resulted in complete abrogation of both mTORC1 [through ROS-mediated AMP-activated kinase (AMPK) activation] and mTORC2 (through complex disassembly). The sorafenib/everolimus combination yielded: (i) enhanced antiproliferative and proapoptotic effects, (ii) impaired tumor growth, (iii) potentiated antiangiogenesis, and (iv) reduced migratory and metastatic potential.mTORC2 activation is an escape mechanism from sorafenib treatment. When sorafenib is combined with everolimus, its antitumor activity is increased by complete inhibition of the mTOR pathway in the preclinical setting.
Polychlorinated Biphenyls in Microscope Immersion Oil
Authors: David J. Nashel
Journal: JAMA (1983)

To the Editor.—  Examination of the nail-fold capillaries may provide useful diagnostic information in a variety of rheumatic disorders. The capillaries are best seen when a clear viscous liquid is applied to the skin surface, and microscope immersion oil is commonly used for this purpose. 1   In 1973, Bennett and Albro 2 reported that immersion oils used at that time contained 30% to 40% polychlorinated biphenyls (PCBs). In response to increasing concerns about environmental pollution with PCBs and adverse health effects of these compounds, manufacturers began to produce PCG-free immersion oil. Yet, it was not until 1976 that one major supplier of microscope immersion oil finally removed PCBs from its product.  A large body of medical literature suggests that PCBs or associated contaminants are potentially injurious to humans, even at low concentrations. 3 In the rat, microscope immersion oil containing PCBs, when applied to the skin in small quantities daily
Hypercapnia Can Induce Arousal from Sleep in the Absence of Altered Respiratory Mechanoreception
Authors: NAJIB T. AYAS, ROBERT BROWN, STEVEN A. SHEA
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Possible mechanisms of arousal from respiratory stimuli include changes in Po 2, Pco 2, central respiratory drive, or respiratory mechanoreceptor activity. We sought to determine whether hypercapnia alone could induce arousal from sleep in four subjects with high ( ⩾ C3) neurologically complete spinal cord injuries while on constant positive pressure mechanical ventilation (hence, respiratory mechanoreceptor activity remained constant). Subjects were chronically hypocapnic (mean baseline Pet CO2 = 21 mm Hg; range, 13–30 mm Hg). On the first night, the baseline rate of spontaneous awakenings was determined by polysomnography. On night two, Fi CO2 was increased rapidly in stable NREM sleep. Awakenings occurred in 19 of 19 trials within 5 min, with each subject waking and complaining of shortness of breath (mean time to arousal, 115 s; range, 26–264 s). It is unlikely that these were spontaneous, as the times to awakening during hypercapnia were much higher than during baseline conditions (p < 0.05). During rapidly induced hypercapnia, Pet CO2 overestimates the Pco 2 at the central chemoreceptors. To determine more precisely the Pet CO2 arousal threshold, Pet CO2 was increased slowly (approximately 2 mm Hg/min); arousal occurred at a mean Pet CO2 of 37 mm Hg (range, 23–45 mm Hg; mean change from baseline, 15.8 mm Hg, range, 10–20 mm Hg). Hence, both rapid and slow increases in Pet CO2 can induce arousal in humans in the absence of changes in respiratory mechanoreceptor activity.
Mitral valve closure in atrial flutter.
Authors: M A Greenberg, L S Herman, M V Cohen
Journal: Circulation (1979)

12 patients who had atrial flutter without clinical, echocardiographic or angiographic evidence of aortic insufficiency were studied with simultaneous echo- and phonocardiograms. In patients with high-grade atrioventricular (AV) block, the mitral valve opened and closed with each flutter wave. Of seven patients, two had persistent and five had intermittent early mitral valve closure before QRS inscription. In five patients (three with 2:1 AV block) the mitral valve closed on time. In one patient with a mitral valve prosthesis, echocardiography and cinefluorography demonstrated closure during mid-diastole, with reopening in late diastole after a flutter wave. Final valve closure occurred before the onset of the QRS, and each closure was associated with a click. Simultaneous phonocardiographic analysis in these patients demonstrated that the first heart sound intensity was inversely related to the degree of mitral valve preclosure. This relationship was independent of the length of the RR interval. Thus, atrial flutter independent of any other cause of abnormal hemodynamics may produce early mitral valve closure. The echocardiographic finding of premature mitral arrhythmias, may not have the same diagnostic or prognostic significance previously described in patients with sinus rhythm and normal AV conduction.
Villanelle for a Dying Smoker
Authors: Ronald Pies
Journal: JAMA (2008)

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
CD34+ Hematopoietic Progenitors From Human Cord Blood Differentiate Along Two Independent Dendritic Cell Pathways in Response to Granulocyte-Macrophage Colony-Stimulating Factor Plus Tumor Necrosis Factor α: II. Functional Analysis
Authors: Christophe Caux, Catherine Massacrier, Béatrice Vanbervliet, Bertrand Dubois, Isabelle Durand, Marina Cella, Antonio Lanzavecchia, Jacques Banchereau
Journal: Blood (1997)
THE COMPARATIVE VALUE OF NOVARSENO-BILLON BY THE INTRAVENOUS AND INTRAMUSCULAR METHODS: With some Notes on the Treatment and Prevention of Syphilis
Authors: L. G. Leonard
Journal: BMJ (1919)

CASE II.P. A., air mechanic R.A.F., aged 28, was admitted to hospital on April 19th, 1918, complaining of pain in the left side of his chest and in his back.XIe stated that he had felt quite well up to two days before admission.
Managing severe pneumonia in children in developing countries
Authors: Zulfiqar A Bhutta
Journal: BMJ (2008)

Increasing resistance to first line antibiotics means recommendations need changing

Despite advances in our understanding of the epidemiology and distribution of deaths from pneumonia,1 more than 150 million cases of pneumonia still occur annually, with almost 2.4 million deaths worldwide. Pneumonia is perhaps the most frequent cause of death in children under 5, including during the newborn period.2 Deaths from pneumonia in children have increased in the wake of the HIV epidemic in Africa. Most deaths occur early in the course of illness. Because severe pneumonia is usually related to bacterial infection, treatment has largely focused on various antibiotic strategies.

In the accompanying randomised controlled trial, Asghar and colleagues compare the effectiveness of injectable ampicillin plus gentamicin or chloramphenicol in children aged 2-59 months with severe pneumonia (defined by World Health Organization criteria).3 The trial took place in inpatient wards in tertiary care hospitals in Bangladesh, Ecuador, India, Mexico, Pakistan, Yemen, and Zambia. Significantly more children failed treatment with chloramphenicol at five days (16% v 11%, relative risk 1.43, …
Failure of Oral Contraceptives
Authors: G. Maizels
Journal: BMJ (1965)

maximum suppression of plasma cortisol.We have found this dosage of methopyrapone satisfactory in the evaluation of pituitary- corticotrophin reserve.Finally, the diagnosis of isolated corticotrophin deficiency in our patient does not rest solely on the lack of response to metho- pyrapone.We feel sure that Dr. Sprunt will agree that both the correction of insulin- induced hypoglycaemia-unresponsiveness with exogenous corticotrophin and the low-normal plasma cortisol during fever further support the presence of a hypothalamic-pituitary defect affecting the secretion of corticotrophin.-We are, etc.,
Successful Use of Hydroxyurea in β-Thalassemia Major
Authors: Valder R. Arruda, Carmem S.P. Lima, Sara T.O. Saad, Fernando F. Costa
Journal: New England Journal of Medicine (1997)

To the Editor: Hydroxyurea has been used in the treatment of sickle cell anemia to elevate hemoglobin levels and reduce clinical complications.1 The potential usefulness of hydroxyurea in the thala...
An Address on the Study of Physiology in Relation to Medicine
Authors: J. M. Purser
Journal: BMJ (1880)

THE. BRIT-s$ kfA2EDICAL OWU?rAL - 769,In connection with his psycho.physicallaw, Hering developsg his theory in a mathematical form, which may be omitted here.The theory of Hering has not the same wide bearing, as that 'of Young and Helmholtz.It relates exclusively to the central processes.'
The lighter side of myeloma: an easily overlooked diagnosis
Authors: J J Feld
Journal: Gut (2005)

Aim: A subset of functional dyspepsia patients respond to acid suppressive therapy, but the prevalence of non-erosive reflux disease in functional dyspepsia and its relevance to symptoms have never been established.The aim of the present study was to study 24 hour pH monitoring in consecutive functional dyspepsia patients.Methods: A total of 247 patients with dyspeptic symptoms (166 women, mean age 44 (SEM 1) year), with a negative upper gastrointestinal endoscopy and without dominant symptoms of heartburn participated in the study.In all patients, the severity of dyspeptic symptoms and the presence of heartburn was assessed by a questionnaire and a 24 hour oesophageal pH monitoring study was performed.All patients underwent a gastric emptying breath test and in 113 a gastric barostat study was performed.Results: Abnormal pH monitoring (acid exposure .5% of time) was found in 58 patients (23%).Of 21 patients with a positive heartburn questionnaire, 76% had pathological pH monitoring, while this was the case in only 18.5% of patients with a negative heartburn questionnaire.Demographic characteristics and the prevalence of other pathophysiological mechanisms did not differ between heartburn negative patients with normal or abnormal acid exposure.Pathological acid exposure in heartburn negative patients was associated with the presence of epigastric pain (65 v 84%, p,0.005) and of moderate or severe pain (48 v 69%, p = 0.005).Conclusion: Pathological oesophageal acid exposure is only present in a subset of heartburn negative functional dyspepsia patients, which are characterised by a higher prevalence of epigastric pain.
TCT-849 Predictive reliability of logistic EuroSCORE II in patients undergoing transcatheter aortic valve implantation: assessment and comparison to classic systems of preoperative risk stratification
Authors: Lenard Conradi, Miriam Silaschi, Renate Schnabel, Moritz Seiffert, Gerhard Schön, Patrick Diemert, Johannes Schirmer, Stefan Blankenberg, Hermann Reichenspurner, Hendrik Treede, Stephan Baldus
Journal: Journal of the American College of Cardiology (2012)
Science Writers Conference: Late Word From Many Areas of Medical Research
Authors: Timothy F. Kirn
Journal: JAMA (1986)

MEDICINE CONTINUES to be news, and this was especially true at last week's fifth annual Science Writers Conference, cosponsored in Baltimore by the American Medical Association and Johns Hopkins University School of Medicine. For example, the International Agranulocytosis and Aplastic Anemia Study's report on analgesics and their relation to agranulocytosis and aplastic anemia was presented at the conference. Samuel Shapiro, MD, director of the Drug Epidemiology Unit, Boston University School of Medicine, announced that the group's multinational epidemiologic study concluded that the risks of persons developing agranulocytosis and aplastic anemia in relation to analgesic drug use are very low (<i>JAMA</i>1986;256:1749-1757). There were 15 other presentations at this year's conference for science writers. Seven papers from the October issues of AMA specialty journals were among those presentations. The following is a roundup of presentations about which<i>JAMA</i>had information by the deadline for this issue. <h3>PET Developments</h3> Patients with schizophrenia
P98S100/calgranulin-mediated inflammation induces fibroblast growth factor 23 and promotes cardiac remodeling in chronic kidney disease
Authors: MA Hofmann-Bowman, LY Yan, B Chellan, B Gardner, T Puri
Journal: Cardiovascular Research (2014)

Purpose: S100A12 and fibroblast growth factor (FGF) 23 are biomarkers for cardiovascular mortality in patients with chronic kidney disease (CKD). The present study was designed to test the hypothesis that elevated serum levels of S100/calgranulin in mice with CKD would accelerate pathological cardiac remodeling, and to discover a potential link between S100A12 and FGF23.
Soft drug design: General principles and recent applications
Authors: Nicholas Bodor, Peter Buchwald
Journal: Medicinal Research Reviews (2000)

Soft drug design represents a new approach aimed to design safer drugs with an increased therapeutic index by integrating metabolism considerations into the drug design process. Soft drugs are new therapeutic agents that undergo predictable metabolism to inactive metabolites after exerting their therapeutic effect. Hence, they are obtained by building into the molecule, in addition to the activity, the most desired way in which the molecule is to be deactivated and detoxified. In an attempt to systematize and summarize the related work done in a number of laboratories, including ours, the present review presents an overview of the general soft drug design principles and provides a variety of specific examples to illustrate the concepts. A number of already marketed drugs, such as esmolol, remifentanil, or loteprednol etabonate, resulted from the successful application of such design principles. Many other promising drug candidates are currently under investigation in a variety of fields including possible soft antimicrobials, anticholinergics, corticosteroids, β-blockers, analgetics, ACE inhibitors, antiarrhythmics, and others. Whenever possible, pharmacokinetic and pharmacodynamic properties are briefly summarized and compared to those of other compounds used in the same field. © 2000 John Wiley & Sons, Inc. Med Res Rev, 20, No. 1, 58–101, 2000.
History Of Asthma Maintenance Medication Use And Asthma Exacerbation Risk Factors Before Initiation Of Inhaled Corticosteroid/long-acting β-agonist (ICS/LABA) Combination Therapy For Asthma: Comparison Of Budesonide/formoterol (BFC) And Fluticasone/salmeterol (FCS) In A US Commercially Insured Population
Authors: O. Tunceli, D. Kern, S. Ramachandran, N. Pethick
Journal: Journal of Allergy and Clinical Immunology (2012)
Subgluteal Abscess and Endocervical Canal Infection
Authors: W. W. Kridelbaugh
Journal: JAMA (1977)

<h3>To the Editor.—</h3> I read with interest the article on retropsoas and subgluteal abscesses (237:892, 1977). Spreading infection from the endocervical canal can also be a source of subgluteal abscess, as evidenced in a patient of ours two years ago. This young woman had an intrauterine device (IUD) in place, and a<i>Bacteroides</i>infection in the endocervical canal developed; it spread into the adjacent paracervical tissue and caused a severe pain in her left hip when walking. She saw an orthopaedic surgeon who noted a swelling in the left buttock, and in due course he admitted her to the hospital and drained a subgluteal abscess. The cultures recovered the same organism as those taken from the endocervical canal in and about the area of the IUD. We ultimately had to redrain the abscess in the subgluteal area on two different occasions. It was only with long-term intravenous antibiotics therapy and
Apoptosis inhibition in P. aeruginosa-induced lung injury influences lung fluid balance
Authors: Rozenn Le Berre, Karine Faure, Harold Fauvel, Nathalie B. Viget, Florence Ader, Thierry Prangère, Anne Marie Thomas, Xavier Leroy, Jean-François Pittet, Philippe Marchetti, Benoit P. Guery
Journal: Intensive Care Medicine (2004)
Rapid Progress of Acute Suppurative Cholangitis to Secondary Sclerosing Cholangitis Sequentially Followed-up by Endoscopic Retrograde Cholangiography
Authors: Y. Tanaka, H. Koshiyama, K. Nakao, Y. Makita, Y. Kobayashi, Y. Yoshida, M. Kimura, Y. Adachi
Journal: Endoscopy (2001)

A 66-year-old man was admitted to our hospital because of right hypochondralgia and fever after colonic polypectomy. Endoscopic examination revealed purulent bile excretion from the duodenal papilla orifice; based on this finding, acute suppurative cholangitis was diagnosed. An endoscopic retrograde cholangiography revealed no abnormality in the biliary tree. However, chronic cholestasis persisted, and endoscopic cholangiography performed 4 months later disclosed a beaded appearance of the intrahepatic bile ducts; this sign is a characteristic finding of sclerosing cholangitis. This is the first report of rapid progression of acute suppurative cholangitis to secondary sclerosing cholangitis sequentially followed-up by endoscopic retrograde cholangiography.
The Psychoanalytic Interpretation of History
Authors: Lester S. King
Journal: JAMA (1971)

This book is an extraordinary hybrid, divided into two parts. The first, "Interpretation of History," has four discursive essays that between them deal, in one or another way, with art, literature, literary criticism, sociology, methodology of science, the complexity of man, mythology, scattered historical events, and various disjointed topics. The contribution of Dr. Wolman, the editor, entitled "Sense and Nonsense in History," is particularly disjointed. I can discern no common thread in part 1. Granted that "history" is a most complex term, and very patient of almost any interpretation, I still cannot understand how this group of essays can justify the title. However, the second part, "Biographical Studies," is closely knit. It contains three essays which offer a psychoanalytical approach to Stalin, Theodor Herzl, and the anti-Semitism of Adolph Hitler. The study of Herzl is an outstanding contribution, while the analysis of Hitler's anti-Semitism is a close second. The authors
Calcitonin and exocrine pancreatic secretion in man: inhibition of enzymes stimulated by CCK-pancreozymin, caerulein, or calcium no response to vagal stimulation
Authors: J. Hotz, H. Goebell, R. Ziegler
Journal: Gut (1977)

The effect of calcitonin on human pancreatic secretion was studied under various conditions of stimulation. During administration of both secretin plus cholecystokinin-pancreozymin (CCK-PZ) or secretin plus caerulein, enzyme secretion was promptly reduced by an infusion of calcitonin of more than 50%. In contrast, vagally stimulated enzyme secretion induced by insulin-hypoglycaemia or carbamyl-choline was not altered against a background infusion of calcitonin in comparison with control experiments. Calcium-induced enzyme secretion was abolished by additional calcitonin infusion which also prevented an increase in serum calcium. On the other hand, additional high grade calcium infusion did not modify the inhibitory action of calcitonin on enzyme output stimulated by secretin and CCK-PZ. Secretion of fluids and bicarbonate remained unaffected by calcitonin in all experimental conditions, whereas the outputs of calcium and magnesium paralleled generally the changes in enzymes. It is suggested that calcitonin interferes with hormonemediated stimulation of the acinar cells without influencing cholinergic mechanisms. The inhibitory action of calcitonin on enzyme secretion does not appear to be mediated by a depletion of extracellular calcium in the pancreatic tissue by calcitonin.
Boston heart surgeon shot and killed at Harvard teaching hospital
Authors: M. McCarthy
Journal: BMJ (2015)

A prominent Boston cardiovascular surgeon died late Tuesday night, 20 January, after being shot in an exam room area at Brigham and Women’s Hospital, a teaching hospital in Boston affiliated with Harvard Medical School.

Boston police officials said that Michael J Davidson, director of endovascular cardiac surgery at the hospital, was shot twice shortly after 11 am Tuesday. Police officials said that Davidson was shot by Stephen Pasceri, 55, of Millbury, Massachusetts, a son of Marguerite E Pasceri, a patient of Davidson’s who …
'Beeper Obliterans': Clinical Staging and Natural History
Authors: N. Izenberg, S. A. Dowshen
Journal: JAMA (1992)

<h3>To the Editor.</h3> —In this report, we describe a common but previously uncharacterized clinical entity affecting hospital staff physicians: "beeper obliternas." The essential element of this syndrome is the periodic emission of high-pitched electronic tones secondary to an everincreasing abdominal girth that impinges on the test button located on the superior aspect of the wearer's pager-beeper. Using a modified version of the<i>Disease Staging</i><sup>1</sup>methodology, we (two staff pediatricians with 25 years of combined experience) have described this condition's inexorable march (see Table). Advancement to stage 4 is directly correlated to a body mass index of 35 kg/m<sup>2</sup>or greater, clinical service of 10 or more years, and knowledge of the code for the patient pantry-door lock. Of interest is the notable "silent phase" seen at the level of departmental chairman (when beeper is shed and all calls are taken by the secretary, program director, or safely ignored).