tbuckley/cabot-search huggingface dataset:
Synergistic Antitumor Activity of Cetuximab and Namitecan in Human Squamous Cell Carcinoma Models Relies on Cooperative Inhibition of EGFR Expression and Depends on High <i>EGFR</i> Gene Copy Number
Authors: Michelandrea De Cesare, Calogero Lauricella, Silvio Marco Veronese, Denis Cominetti, Claudio Pisano, Franco Zunino, Nadia Zaffaroni, Valentina Zuco
Journal: Clinical Cancer Research (2013)

Abstract Purpose: Despite the frequent overexpression of epidermal growth factor receptor (EGFR) in squamous cell carcinoma (SCC), the efficacy of cetuximab alone is limited. Given the marked activity of namitecan, a hydrophilic camptothecin, against SCC models, the present study was performed to explore the efficacy of the cetuximab–namitecan combination in a panel of SCC models. Experimental Design: We examined the antiproliferative and antitumor activities of the cetuximab–namitecan combination in four SCC models characterized by a different EGFR gene copy number/EGFR protein level. We also assessed the effects of the combination on EGFR expression at both mRNA and protein levels and investigated the molecular basis of the interaction between the two agents. Results: Cetuximab and namitecan exhibited synergistic effects, resulting in potentiation of cell growth inhibition and, most importantly, enhanced therapeutic efficacy, with high cure rates in three SCC models characterized by high EGFR gene copy number, without increasing toxicity. The synergistic antitumor effect was also observed with the cetuximab–irinotecan combination. At the molecular level, the two agents produced a cooperative effect resulting in complete downregulation of EGFR. Interestingly, when singly administered, the camptothecin was able to strongly decrease EGFR expression mainly by transcriptional inhibition. Conclusions: Our results (i) demonstrate a marked efficacy of the cetuximab–namitecan combination, which reflects a complete abrogation of EGFR expression as a critical determinant of the therapeutic improvement, in SCC preclinical models, and (ii) suggest EGFR gene copy number as a possible marker to be used for patient selection in the clinical setting. Clin Cancer Res; 20(4); 995–1006. ©2013 AACR.
INCREASED INTRAOCULAR TENSION IN YOUNG PERSONS AS A CAUSE OF SEVERE FRONTAL HEADACHE
Authors: R. L. Raymond
Journal: BMJ (1934)

TtIME BRITALsmigrans.In the case recorded below the venous throm- boses preceded by many years the objective signs of arterial involvement.CASE REPORT A man, aged 52, a country mason and married, was admitted to the General Hospital, Birmingham, under the care of Dr. J. M. Smellie, on February 7th, 1933, for the investigation of migratory thrornboses of wide distribution and of many years' duration.The first attack of phlebitis occurred when he was 12 years old, in the left leg.He was admitted to St. Thomas's Hospital, London, eight years later, where portions of the left internal saphenous vein were removed.There were frequent recurrences of phlebitis, an J on the outbreak of war he was certified as unfit owing to the condition of his legs.In 1914 the superficial veins of the abdomen were attacked by painful thromboses, and became dilated and obvious.By 1927 the condition had improved somewhat, but attacks of phlebitis in the legs and on the abdominal wall were frequent.In 1931 severe exacerbations
Risks of Nuclear Power
Authors: LEONARD R. SOLON, VICTOR W. SIDEL
Journal: Annals of Internal Medicine (1980)

Letters and Corrections1 January 1980Risks of Nuclear PowerLEONARD R. SOLON, PH.D., VICTOR W. SIDEL, M.D.LEONARD R. SOLON, PH.D.Search for more papers by this author, VICTOR W. SIDEL, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-92-1-125_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: In our view, the editorial note "Fallout at Three Mile Island" in your September 1979 issue (1) is an example of the systematic bias towards underestimation of the risks of nuclear power production that we criticized in our editorial in your March 1979 issue (2) and in our comment on a letter in your August 1979 issue (3).The editorial note states: "The combined maximal thyroidal dose [to young children from iodine-131 released at Three Mile Island] is 1000 times smaller than the lowest dose ever associated with any increase in human thyroid disease." Surely the editorial...References1. MAXON H. Fallout at Three Mile Island. Ann Intern Med. 1979;91:486-7. Editorial note. LinkGoogle Scholar2. SOLONSIDEL LV. Health implications of nuclear power production. Ann Intern Med. 1979:90:424-6. Editorial. LinkGoogle Scholar3. SOLONSIDEL LV. Nuclear power and health. Ann Intern Med. 1979;91:315. Letter. MedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: LEONARD R. SOLON, PH.D.; VICTOR W. SIDEL, M.D. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 January 1980Volume 92, Issue 1Page: 125-126KeywordsChildrenThyroidThyroid diseases ePublished: 1 December 2008 Issue Published: 1 January 1980 PDF downloadLoading ...
The Wedding Goes On Without Us
Authors: A. Meyers
Journal: JAMA (2004)

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
Grieving the death of a child: Supporting health professionals who care for grieving patients may benefit all
Authors: Svetlin V Vrabtchev
Journal: BMJ (2006)

EDITOR—Davies outlined two cases of palliative care in the community for children where mothers committed suicide after the death of their children by using the remaining opioid drugs.1 Supporting healthcare professionals who work in palliative care, and particularly in such circumstances, could be as helpful for them as it may be for their patients. Published work has recognised that patients' …
PERSISTENT THYMUS AND SUDDEN DEATH
Authors: S. H. Daukes
Journal: BMJ (1909)

suppressed; by therefore adjusting the tube this portion of the retina was exercised.December 24th.On this date the vision in the right eye had improved to f, and the ability to take up and maintain fixation was,greatly improved.He was seen once a week, and at each visit exercises were carried out with the pictures anid the letters, and by degrees the ability to maintain fusion was cultivated, until he could read type equal to J. 8 and J. 4. For nearly two months very little progress beyond this stage was obtained, and during the time atropine had been used in the fixing eye-the left; this was supplemented by a total-exclusion pad, whilst at the same time he did all his school work with the right eye.March 20th.Vision in the right eye equal a without glasses, and Apartly with the glasses, but by the end of April he got four letters of 5 vision.During the last six weeks of this period
Abnormally elevated frequency of Epstein-Barr virus-infected B cells in the blood of patients with rheumatoid arthritis.
Authors: G Tosato, A D Steinberg, R Yarchoan, C A Heilman, S E Pike, V De Seau, R M Blaese
Journal: Journal of Clinical Investigation (1984)

Patients with rheumatoid arthritis (RA) are known to have in vitro regulatory T cell abnormalities relating to Epstein-Barr virus (EBV). In this report, we asked whether patients with RA have more circulating EBV-infected B cells than normals. To address this question, we determined the frequency of spontaneously transforming B cells in the peripheral blood of 18 normals, 15 patients with RA, and 8 patients with systemic lupus erythematosus (SLE). The mean frequency of spontaneously transforming B cells in RA patients was 10.1/10(6) B cells, which was significantly greater than that of the normal controls, 2.8/10(6) B cells (P less than 0.005). The group of patients with SLE did not differ from the normals (P greater than 0.4). In further studies undertaken to investigate as to whether RA B cells are more easily transformed by EBV than normal B cells, we determined that the frequencies of transforming B cells in the presence of exogenous EBV were similar in RA patients and normals. Lymphocytes obtained from patients with RA demonstrate a profound T cell defect in their EBV-specific suppression, as measured in vitro; there was no direct correlation, however, between this in vitro T cell abnormality and the number of circulating EBV-infected B cells. Thus, patients with RA, as a group, have abnormally elevated numbers of circulating EBV-infected B cells, and this abnormality most likely derives from a complex dysregulation of the defense mechanisms for infection with EBV.
By the Sweat of Thy Brow
Authors: Samuel Vaisrub
Journal: JAMA (1975)

Bold, aggressive, self-assertive—how else can one describe a nutrient that inspires its votaries to ecstatic poetry ("Ode on Cheese," by James McIntyre) and equates its name with power ("the big cheese")—cheese must often assume a defensive posture when medicine, not gourmandise, is the judge. For instance, cheese has to be on the defensive when charged with causing indigestion ("an elf that digests everything but itself"). But then, it is so easy to shift the blame onto the "indiscretions" of a consumer who is either too gluttonous or too bibulous. The apple pie that often accompanies the cheese and the wine that washes it down, serve as useful scapegoats. It is also easy to pass on the blame for the occasional outbreak of brucellosis<sup>1</sup>or gastroenteritis of which cheese has been accused. After all, it is not cheese that caused the infection, but the<i>Brucella melitensis, the Escherichia coli</i>,<sup>2</sup>
The Divided Self
Authors: Paul Crichton
Journal: BMJ (2007)

In his short life the Scottish psychiatrist Ronald (“Ronnie”) Laing progressed from iconoclast to guru and mystic. The Divided Self was written at the beginning of this journey, when he was only 30. He went on to write other books in which he expressed some of the main tenets of the anti-psychiatry movement, including the belief that madness can be a useful interpersonal strategy or even a healing process rather than an illness—but this first book, published in 1960, is probably his best. 

In it he describes with empathy some of his patients and concludes that those who developed schizophrenia did so because of disturbed family relationships. Although he followed Freud in regarding schizophrenia as a disorder of ego identity, his book made schizophrenic symptoms—often regarded as …
Renal Handling of Diamino Acids in Lysinuric Protein Intolerance
Authors: Olli Simell, Jaakko Perheentupa
Journal: Journal of Clinical Investigation (1974)

Lysinuric protein intolerance (LPI) is a rare recessively inherited disease in which one of the fundamental physiological defects is in the mechanism by which diamino acids are transported by the kidney. The purpose of the present studies was to examine that mechanism in four controls and seven patients with LPI. Two types of studies were conducted. In the first set, the renal handling of l-arginine and l-ornithine was evaluated by gradually increasing the plasma concentration of each of these amino acids by constant infusion techniques. In the second set of studies, the possible existence of competitive inhibition between l-arginine, l-ornithine, and l-lysine was examined.
Activated innate lymphoid cells are associated with a reduced susceptibility to graft-versus-host disease
Authors: J. Marius Munneke, Andreas T. Björklund, Jenny M. Mjösberg, Karin Garming-Legert, Jochem H. Bernink, Bianca Blom, Cynthia Huisman, Marinus H. J. van Oers, Hergen Spits, Karl-Johan Malmberg, Mette D. Hazenberg
Journal: Blood (2014)
Indications for Lumbar Puncture
Authors: Philip B. Gorelick
Journal: JAMA (1980)

To the Editor.—  I read the answers of Herbert N. Hultgren, MD (241:2549, 1979), to the questions concerning anticoagulation therapy for stroke in evolution. Concerning the CSF examination to exclude hemorrhage or hemorrhagic infarction, the following recommendations serve as guidelines for those considering spinal puncture.  In the presence of an intracerebral hematoma, lumbar puncture entails a risk of tentorial or cerebellar herniation. If computerized axial tomographic examination shows no evidence of a mass lesion, uniformly blood-stained CSF may be sought. 1   The accurate diagnosis of meningitis, meningeal carcinomatosis, 2 and diseases requiring CSF globulin quantitation 3 requires completion of spinal puncture.  With evidence of intracranial mass lesions, lumbar puncture rarely generates information sufficient to justify complications. 4
Does intensive medical treatment improve outcomes in aortic dissection?
Authors: F. A. Lederle, J. T. Powell, C. A. Nienaber
Journal: BMJ (2014)

Each year, aortic dissection affects one in 20 000 people,1 2 resulting in 3000 deaths in the United States. Men are affected twice as often as women, and most people affected are over the age of 65 years.1 2 Two thirds of dissections involve the ascending aorta (type A), and many of these patients die before reaching hospital.1 The survivors, who are usually treated with immediate surgery (open or endovascular) unless contraindicated, have a 30 day mortality of 20-50%.1 2 3 Dissections confined to the descending aorta (type B) are usually managed without repair unless complications develop,2 4 and with this approach they have a 30 day mortality of about 12%.1 3

For nearly half a century, the recommended initial medical management of acute aortic dissection of both types has been “aggressive” lowering of systolic blood pressure to below 100 or 120 mm Hg and heart rate to below 60 beats per minute, with first line use of intravenous β blockers.4 5

These recommendations for aortic dissection are notable in light of the increasing awareness in other areas of medicine of the risks of intensive treatment in general and regarding blood pressure in particular.6 7 After a series of reports of adverse events following rapid blood pressure lowering in hypertensive emergencies,7 the sixth and seventh reports of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure recommended lowering mean arterial blood pressure by no more than 25% within minutes to one hour, then to 160/100 mm Hg within the next two to six hours, noting that “excessive falls in pressure that may precipitate renal, cerebral, or coronary ischemia should be avoided.”8 However, an exception was made for “patients with aortic dissection who should have their [systolic …
Targeting Transgene Expression for Cystic Fibrosis Gene Therapy
Authors: David R. Koehler, Vicky Hannam, Rosetta Belcastro, Brent Steer, Yanxia Wen, Martin Post, Gregory Downey, A.Keith Tanswell, Jim Hu
Journal: Molecular Therapy (2001)

<h2>Abstract</h2> We have developed an expression cassette for cystic fibrosis (CF) gene therapy using control elements from the human cytokeratin 18 gene (KRT18, also known as K18). KRT18 is naturally expressed in a spatial pattern similar to that of CFTR, the gene mutated in CF. We delivered a KRT18-driven lacZ plasmid complexed with cationic liposomes intravenously to mice and examined expression in various tissues. We found expression in nasal and bronchial epithelium, airway submucosal glands, gall bladder, and kidneys. Expression was low in pancreas and gut, and absent from liver and alveolar lung. This is consistent with the expression pattern reported for a K18lacZ transgenic mouse. Following delivery of a cytomegalovirus (CMV) major immediate-early promoter/enhancer-driven lacZ plasmid, we found expression in bronchi, submucosal glands, alveolar cells, liver, and kidney. We did not detect expression in nose, pancreas, gall bladder, or gut. Using fluorescently labeled plasmid delivered by means of liposomes, we identified the liver, alveolar lung, and kidneys as the major plasmid deposition sites. Our data demonstrate that a KRT18-driven expression vector delivered systemically can target gene expression to CF-affected tissues, despite an uneven distribution of plasmid DNA. A KRT18-based vector may be a useful alternative to viral promoter-based vectors in clinical gene therapy trials to treat CF.
CLINICAL IMPORTANCE OF THE OS TIBIALE EXTERNUM, OR ACCESSORY TARSAL SCAPHOID
Authors: JAMES WARREN SEVER
Journal: JAMA (1927)

The frequency of supernumerary bones about the foot is not generally known, nor their significance well appreciated. In various special journals attention has been called to these anatomic abnormalities, but as a whole the medical profession is uninformed in regard to them, and therefore possibilities of mistakes in diagnosis still exist. The occurrence or presence of these extra bones has been known to anatomists for many years and their discovery was not dependent on the advent of the roentgen ray. They were discovered in the dissecting room. Vesalius in 1555, Bauhin in 1605 and Rosenmuller in 1804 described several of these accessory bones from anatomic dissections. The special abnormality to which I call attention is the so-called os tibiale externum, or accessory scaphoid, first described by Bauhin in 1605. This bone has been confused with what was thought to be a sesamoid fibrocartilage in the tendon of the tibialis posticus
An Experiment on the Disinfection of Enteric Excreta
Authors: J. Dougall
Journal: BMJ (1878)

THE BRITISH MEDICAL _7OURNAL.(March i6, T878.such, for instance, as the medulla oblongata and the contiguous nerve-centres at the base of the brain.Hence epilepsy or apoplexy may be about to supervene; the petit mal of the former disease being the signal note of the labyrinth, betokening the condition of its circula- tion, and suagesting the search for sources of suspended nerve inhibition,In the disturbance of some one or more of the multitudinous sympathies, thus imperfectly sketched, will be found an explanation of the' occurrence of those sintple attacks of labyrinthine vertigo, which come on1 without any p;eviously existing ear-disease, the desire to understand which furnished the key-note of this paper.
A hesitation to be brave
Authors: F. Godlee
Journal: BMJ (2009)

No one doubts that there’s going to be less money for health in the next few years. But is this a disaster or, as John Appleby believes (doi:10.1136/bmj.b2736), a potential opportunity? Taking his cue from White House chief of staff Rahm Emanuel, Appleby says we can’t let this economic crisis go to waste. It would be too easy to slash budgets, grow waiting lists, cut training, and reduce spending on prevention just to store up problems for the future. Instead we should “get radical with improving quality,” he says. “Doing the right thing for patients the …
Hypoxia-inducible factors in human pulmonary arterial hypertension: a link to the intrinsic myeloid abnormalities
Authors: Samar Farha, Kewal Asosingh, Weiling Xu, Jacqueline Sharp, Deepa George, Suzy Comhair, Margaret Park, W. H. Wilson Tang, James E. Loyd, Karl Theil, Raymond Tubbs, Eric Hsi, Alan Lichtin, Serpil C. Erzurum
Journal: Blood (2011)
Abstract 1439: Loss of expression of SWI/SNF subunits in high risk Wilms tumor is accompanied by global gene expression changes
Authors: Samantha L. Gadd, Daniela S. Gerhard, Malcom A. Smith, Jaime Guidry Auvil, Vicki Huff, James I. Geller, Jeffrey Dome, Chiang-Ching Huang, Elizabeth J. Perlman
Journal: Cancer Research (2012)

Abstract Introduction: The TARGET initiative seeks to identify therapeutic targets through genomic sequencing supported by copy number and gene expression analysis. The High Risk Wilms Tumor TARGET project, currently in progress, includes the analysis of favorable histology (FH) tumors that relapsed and tumors with anaplasia (unfavorable histology). We report the identification of a group of Wilms tumors (WT) identified by a unique gene expression pattern. Methods and Results: 102 high risk WT (43 anaplastic, 59 relapsed FH) were analyzed using Affymetrix U133+2 chips. Unsupervised hierarchical analysis consistently selected 9 tumors (5 anaplastic, 4 FH) that shared a striking gene expression pattern. These patients presented at 15-96 months (median 51); 7 had a triphasic histology and 2 were blastemal predominate; 4 died of their disease. When the top differentially expressed genes (P&amp;lt;0.0001) were analyzed with PANTHER, significant repression (p=5x10−7) of genes responsible for the regulation of chromatin architecture was apparent. Among the most significantly down-regulated were ARID1A (fold change (FC) 0.2, p=5.2x10−8) and SMARCA4 (BRG1, FC 0.16 p=9x10−6), among others. Transcriptomic analysis using hierarchical clustering based on chromosomal position displayed a unique pattern of alternating increased and decreased expression of small genetic regions for all chromosomes in this group. These findings may represent long-range genomic regulation that has been attributed to histone modifications and are in keeping with the role of the SWI/SNF chromatin remodeling complex. Analysis using the Affymetrix 6.0 SNP chip demonstrated LOH for 1p31 (ARID1A) and 19p13 (BRG1) in 2 and 1 of the 9 tumors, respectively. Global methylation analysis is underway. Conclusion: Mutations in several SWI/SNF subunits (including ARID1A, BRG1, SMARCB1, PBRM1) have been implicated in the development of a wide range of neoplasias. In normal cells, SWI/SNF subunit protein levels are tightly controlled in a coordinated fashion in order to maintain constant cellular levels. Little is known about the transcriptional regulation of these subunits. This report suggests that a subset of Wilms tumors show striking repression of many SWI/SNF subunits, resulting in a unique globally abnormal gene expression pattern that has not been previously described in tumors with ARID1A or SMARCB1 loss. Whole genomic or exomic sequencing of our tumor set is in progress. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1439. doi:1538-7445.AM2012-1439
Narrative based medicine: Why study narrative?
Authors: T. Greenhalgh, B. Hurwitz
Journal: BMJ (1999)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following Why study narrative? Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
224 NON-INVASIVE PREDICTION OF UPPER GASTROINTESTINAL BLEEDING BY RUPTURE OF ESOPHAGEAL VARICES (ROV) USING LIVER AND SPLEEN STIFFNESS (AIXPLORER), LIVER STIFFNESS BY FIBROSCAN AND FIBROTEST
Authors: M. Rouyer, L. Royer, H. Perazzo, M. Munteanu, Y. Ngo, E. Luckina, L. Fedchuck, F. Sattonet, P. Lebray, M. Rudler, D. Thabut, V. Ratziu, T. Poynard
Journal: Journal of Hepatology (2013)