tbuckley/cabot-search huggingface dataset:
Monitoring Reversal of MET-Mediated Resistance to EGFR Tyrosine Kinase Inhibitors in Non–Small Cell Lung Cancer Using 3′-Deoxy-3′-[18F]-Fluorothymidine Positron Emission Tomography
Authors: Francesca Iommelli, Viviana De Rosa, Sara Gargiulo, Mariarosaria Panico, Marcello Monti, Adelaide Greco, Matteo Gramanzini, Giovanni Ortosecco, Rosa Fonti, Arturo Brunetti, Silvana Del Vecchio
Journal: Clinical Cancer Research (2014)

MET amplification is one of the mechanisms underlying acquired resistance to EGFR tyrosine kinase inhibitors (TKI) in non-small cell lung cancer (NSCLC). Here, we tested whether 3'-deoxy-3'-[(18)F]-fluorothymidine ([(18)F]FLT) positron emission tomography/computerized tomography (PET/CT) can detect MET-mediated resistance to EGFR TKIs and monitor the effects of MET inhibitors in NSCLC.H1993 and H820 NSCLC cells with high and low levels of MET amplification, respectively, and HCC827-expressing MET, but without gene amplification, were tested for the effects of MET inhibitors on the EGFR pathway and proliferation both in vitro and in vivo. Nude mice bearing NSCLCs with and without MET amplification were subjected to [(18)F]FLT PET/CT before and after treatment with crizotinib or erlotinib (50 mg/kg and 100 mg/kg p.o. for 3 days).H1993 cells showed high responsiveness to MET inhibitors and were resistant to erlotinib. Conversely, HCC827 cells showed high sensitivity to erlotinib and were resistant to MET inhibitors. Accordingly, H1993 tumors bearing MET amplification showed a mean reduction in [(18)F]FLT uptake of 28% and 41% after low- and high-dose treatment with crizotinib for 3 days, whereas no posttherapy changes of [(18)F]FLT uptake were observed in HCC827 tumors lacking MET amplification. Furthermore, a persistently high [(18)F]FLT uptake was observed in H1993 tumors after treatment with erlotinib, whereas HCC827 tumors showed up to 39% reduction of [(18)F]FLT uptake following erlotinib treatment. Imaging findings were confirmed by Ki67 immunostaining of tumor sections.[(18)F]FLT PET/CT can detect MET-mediated resistance to EGFR TKIs and its reversal by MET inhibitors in NSCLC.
Equilibrative nucleoside transporter-2 (hENT2) protein expression correlates with ex vivo sensitivity to fludarabine in chronic lymphocytic leukemia (CLL) cells
Authors: M Molina-Arcas, S Marcé, N Villamor, I Huber-Ruano, F J Casado, B Bellosillo, E Montserrat, J Gil, D Colomer, M Pastor-Anglada
Journal: Leukemia (2004)
Abstract 5506: Novel toxin library for the discovery of oncology therapeutics
Authors: Valerie Zacny, John S. Higley, Casey Cunningham, Eric E. Poma
Journal: Cancer Research (2010)

Abstract The A subunit of Shiga-like Toxin 1 (SLT1) is a ribosome-inactivating protein that works by catalyzing the depurination of the 28 S rRNA. The A subunit lacks the ability to bind and internalize into cells, and is normally dependent on the B subunit of SLT1 for this function. A toxin variant library has been created by inserting random amino acid stretches into an exposed loop structure of the A subunit. The inserts can confer binding and internalization properties to the SLT1 A variants but do not inhibit the A subunit's ability to intoxicate. This toxin library has been expressed in a phage display system that can be rapidly screened for variants with specific cell kill activity and predictable PK/PD properties. The library is being used to develop novel therapeutics for oncology. 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 5506.
Common missense mutation G1528C in long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency. Characterization and expression of the mutant protein, mutation analysis on genomic DNA and chromosomal localization of the mitochondrial trifunctional protein alpha subunit gene.
Authors: L IJlst, J P Ruiter, J M Hoovers, M E Jakobs, R J Wanders
Journal: Journal of Clinical Investigation (1996)

Mitochondrial trifunctional protein (MTP) is a recently identified enzyme involved in mitochondrial beta-oxidation, harboring long-chain enoyl-CoA hydratase, long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) and long-chain 3-ketothiolase activity. A deficiency of this protein is associated with impaired oxidation of long-chain fatty acids which can lead to sudden infant death. Furthermore, it is clear that this inborn error of fatty acid oxidation is very frequent, second to medium chain acyl-CoA dehydrogenase deficiency. In most patients only the LCHAD activity of MTP is deficient with near normal activity of the two other enzyme activities of the complex. We recently described the occurrence of a frequent G1528C mutation in the cDNA coding for the a subunit of MTP. Using S. cerevisiae for expression of wild type and mutant protein we show that the G1528C mutation is directly responsible for the loss of LCHAD activity. Furthermore, we describe a newly developed method allowing identification of the G1528C mutation in genomic DNA. The finding of an 87% allele frequency of the G1528C mutation in 34 LCHAD deficient patients makes this a valuable test for prenatal diagnosis. Finally, we show that the gene encoding the alpha subunit of MTP is located on chromosome 2p24.1-23.3.
Edward Gilbert Abbott: Enigmatic Figure of the Ether Demonstration
Authors: Leroy D. Vandam, John Adams Abbott
Journal: New England Journal of Medicine (1984)

One of the memorable advances in the relief of suffering took place in Boston on October 16, 1846. It was justly celebrated as the first public demonstration of the use of ether for anesthetization during the course of a surgical operation. As a result, the innovator and anesthetist, William Thomas Greene Morton, a dentist, achieved lasting renown. Likewise, a surgeon at the Massachusetts General Hospital, John Collins Warren, professor of surgery at the Harvard Medical Institution and its quondam dean, reaped the rewards for the surgery. Despite the controversy engendered by those who sought credit for this epoch-making occasion, the . . .
IgA and IgG reticulin antibodies in coeliac and non-coeliac patients.
Authors: O E Eade, R S Lloyd, C Lang, R Wright
Journal: Gut (1977)

Using indirect immunofluorescence, comparisons were made of patterns of staining of five tissue substrates with 28 RI reticulin antibody-positive coeliac sera, and 23 RI reticulin antibody-positive non-coeliac sera. IgA and IgG fluorescein conjugates were used separately. IgA antibodies were seen in 22 coeliac patients (78%) compared with three non-coeliacs (13%). Concomitant sinusoidal fluorescence (RS pattern) was seen more frequently with the non-coeliac (60.9%) than with the coeliac sera (10.7%). Such differences may help to distinguish those patients who should have a jejunal biopsy when using the reticulin antibody as a screening test for coeliac disease.
Frey's Syndrome
Authors: Francesco Prattico, Paola Perfetti
Journal: New England Journal of Medicine (2006)

A 30-year-old man had a pleomorphic adenoma removed from his left parotid gland. His postoperative course was uncomplicated. Two months later, he noted that his left cheek became wet while he was eating. Believing that saliva was being discharged from the parotidectomy scar, he went to the emergency department. An examination revealed that the wound had healed well: there were no signs of a fistula (arrow, Panel A). Frey's syndrome was suspected, and the lemon test was performed. As soon as the patient ate a lemon wedge, his left auricular and parotic regions became flushed and sweaty (arrow, Panel B), . . .
Qualifications for Administrative Medicine: Is an MD Enough?
Authors: Deborah M. Shlian
Journal: JAMA (1993)

<h3>To the Editor.</h3> —The discussion by Ott<sup>1</sup>of the future of administrative medicine could not have been more timely. There is indeed growing recognition that physician leaders are needed who are equipped to deal with the changes in American health care. However, contrary to the article by Kindig et al,<sup>2</sup>which stated that typical physician managers entered their "new careers" after 20 years in practice, my experience as a health care consultant and physician-executive recruiter is that today's physician-executive is younger (early 40s), is board certified in one of the three primary care specialties (internal medicine, family practice, or pediatrics), and has an MBA. He or (unfortunately, less typically) she has practiced clinical medicine about 5 years and has actively selected medical management as a positive career choice. The fact that most have obtained formal management degrees reflects the growing realization that as the traditional separation of administrative
In the Kingdom of War
Authors: Fredric L. Coe
Journal: Annals of Internal Medicine (1997)

Ad Libitum15 December 1997In the Kingdom of WarFredric L. Coe, MDFredric L. Coe, MDThe University of Chicago; Chicago, IL 60637Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-127-12-199712150-00013 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail I am out of tune, my dear,my head all turned by heraldicfigures and drums of war;all we did was walkfrom room to room, touch,talk, apply what wepossessed, of cure or remedy;we were tame as air, humbleas any trade, and paidfor our time and troubleas any tradesman is paid;but I remember a gleam of gold braid,medals, ourselves all soldierly,at war with life's pain, life's brevity.to sit, or lie down ... Author, Article, and Disclosure InformationAuthors: Fredric L. Coe, MDAffiliations: The University of Chicago; Chicago, IL 60637Corresponding Author: Fredric L. Coe, MD, Nephrology Section, Department of Medicine, The University of Chicago, 5841 South Maryland Avenue, Box 28, Chicago, IL 60637. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 December 1997Volume 127, Issue 12 Page: 1126-1127 Keywords Brain Interleukins Touch ePublished: 15 August 2000 Issue Published: 15 December 1997 Copyright & PermissionsCopyright © 1997 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Acute intermittent porphyria presenting as epilepsy.
Authors: A C Scane, J P Wight, R B Godwin-Austen
Journal: BMJ (1986)

Une observation: malade de 27 ans presentant des crises convulsives de type grand mal, une tachycardie, une confusion mentale dans le temps, une hypertension et de vagues douleurs abdominales. L'electroencephalogramme est normal. Traitement d'abord par phenytoine, puis par valproate. Au bout de 10 j une grande faiblesse musculaire se manifeste et les reflexes sont absents au niveau des membres superieurs. C'est tardivement que le diagnostic de porphyrie intermittente est fait. Les anticonvulsivants sont supprimes mais le malade presente des sequelles neurologiques graves
Characterization of a Novel, Water-Soluble Hydrogen Sulfide–Releasing Molecule (GYY4137)
Authors: Ling Li, Matthew Whiteman, Yan Yi Guan, Kay Li Neo, Yvonne Cheng, Shiau Wei Lee, Yujun Zhao, Rajamanian Baskar, Choon-Hong Tan, Philip K. Moore
Journal: Circulation (2008)

Background— The potential biological significance of hydrogen sulfide (H 2 S) has attracted growing interest in recent years. The aim of this study was to characterize a novel, water-soluble, slow-releasing H 2 S compound [morpholin-4-ium 4 methoxyphenyl(morpholino) phosphinodithioate (GYY4137)] and evaluate its use as a tool to investigate the cardiovascular biology of this gas. Methods and Results— The acute vasorelaxant effect of drugs was assessed in rat aortic rings and perfused rat kidney in vitro and in the anesthetized rat in vivo. The chronic effect of GYY4137 on blood pressure in normotensive and spontaneously hypertensive rats was determined by tail-cuff plethysmography. GYY4137 released H 2 S slowly both in aqueous solution in vitro and after intravenous or intraperitoneal administration in anesthetized rats in vivo. GYY4137 caused a slow relaxation of rat aortic rings and dilated the perfused rat renal vasculature by opening vascular smooth muscle K ATP channels. GYY4137 did not affect rat heart rate or force of contraction in vitro. GYY4137 exhibited antihypertensive activity as evidenced by ability to reduce N G -nitro- l -arginine methyl ester–evoked hypertension in the anesthetized rat and after chronic (14-day) administration in spontaneously hypertensive rats. Conclusions— These results identify GYY4137 as a slow-releasing H 2 S compound with vasodilator and antihypertensive activity. GYY4137 is likely to prove useful in the study of the many and varied biological effects of H 2 S. GYY4137 may also prove of therapeutic value in cardiovascular disease.
Distinct Subcellular Localization of Different Sodium Channel α and β Subunits in Single Ventricular Myocytes From Mouse Heart
Authors: Sebastian K.G. Maier, Ruth E. Westenbroek, Kimberly A. McCormick, Rory Curtis, Todd Scheuer, William A. Catterall
Journal: Circulation (2004)

Background— Voltage-gated sodium channels composed of pore-forming α and auxiliary β subunits are responsible for the rising phase of the action potential in cardiac muscle, but their localizations have not yet been clearly defined. Methods and Results— Immunocytochemical studies show that the principal cardiac α subunit isoform Na v 1.5 and the β2 subunit are preferentially localized in intercalated disks, identified by immunostaining of connexin 43, the major protein of cardiac gap junctions. The brain α subunit isoforms Na v 1.1, Na v 1.3, and Na v 1.6 are preferentially localized with β1 and β3 subunits in the transverse tubules, identified by immunostaining of α-actinin, a cardiac z-line protein. The β1 subunit is also present in a small fraction of intercalated disks. The recently cloned β4 subunit, which closely resembles β2 in amino acid sequence, is also expressed in ventricular myocytes and is localized in intercalated disks as are β2 and Na v 1.5. Conclusions— Our results suggest that the primary sodium channels present in ventricular myocytes are composed of Na v 1.5 plus β2 and/or β4 subunits in intercalated disks and Na v 1.1, Na v 1.3, and Na v 1.6 plus β1 and/or β3 subunits in the transverse tubules.
Catheter ablation for atrial fibrillation
Authors: Steven A Lubitz, Avi Fischer, Valentin Fuster
Journal: BMJ (2008)

Atrial fibrillation is the most common arrhythmia in clinical practice and is associated with significant morbidity and mortality. 1Catheter ablation is increasingly being used to treat atrial fibrillation, although it is not suitable for all patients. 2Referring doctors must confront challenges such as the appropriate selection of patients for ablation and proper management of patients after the procedure, and must be familiar with the expected outcomes.Many unanswered questions exist surrounding the appropriate application of this technique.This review summarises current ablative techniques and emphasises the appropriate application and limitations of catheter ablation on the basis of recent clinical trials and guidelines.
Breast lumps in adolescent girls
Authors: D McCracken
Journal: BMJ (1978)

his health would have suffered and he might well have lost his job.It must be understood that the best form of life insurance that this man could have taken was to obtain medical advice and help rather than spend more money on insurance premiums.I would therefore like to suggest that, in order to protect our patients, doctors should not be expected to disclose any information about alcohol consumption.
Inhibitors of Tyrosine Kinase Signaling Cascade Attenuated Antigen Challenge of Guinea-Pig Airways <i>In Vitro</i>
Authors: FAI TSANG, W. S. FRED WONG
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Activation of nontransmembrane protein tyrosine kinases (PTKs), phosphatidylinositol 3-kinase (PI3K), and mitogen-activated protein kinase (MAPK) has been shown to be responsible for high-affinity Fc receptor (Fc ɛ RI)-mediated mast cell degranulation. Effects of inhibitors of the PTK signaling cascade on ovalbumin (OA)-induced anaphylactic contraction of isolated guinea-pig bronchi and release of histamine and peptidoleukotrienes from chopped lung preparations were studied. Genistein (30 μ M) and tyrphostin 47 (50 μ M), two PTK inhibitors, as well as LY294002 (10 μ M), a selective PI3K inhibitor, significantly reduced (p < 0.05) peak anaphylactic bronchial contraction and facilitated relaxation of the contracted bronchi. PD 098059 (30 μ M), a selective MAPK kinase inhibitor, failed to suppress OA-induced peak bronchial contraction, but facilitated the relaxation of the contracted bronchi (p < 0.05). At the same concentrations, none of these inhibitors showed any inhibitory effects on histamine-, leukotriene D4 (LTD4)- or KCl-induced bronchial contraction. On the other hand, these inhibitors significantly prevented (p < 0.05) OA-induced release of both histamine and peptidoleukotrienes from chopped lung preparations. In addition, combined PD 098059 and LY294002 treatment markedly (p < 0.05) suppressed the peak anaphylactic bronchial contraction and facilitated relaxation of the contracted bronchi. The combination of these two inhibitors further inhibited the release of peptidoleukotrienes from chopped lung preparations. Taken together, our data show that inhibition of tyrosine kinase signaling cascade can markedly attenuate anaphylactic contraction of airways, probably via inhibition of mast cell degranulation, and that inhibitors of this signaling cascade may have therapeutic potential for the treatment of asthma.
Atos Healthcare replies to Greg Wood
Authors: A. Graham
Journal: BMJ (2013)

I wish to respond on behalf of Atos Healthcare to certain points raised by Wood in his recent article.1

Firstly, Wood talks about “five . . . rules of thumb” when referring to functions such as manual dexterity and the ability to mobilise and alleges that these take precedence over the work capability assessment (WCA) regulations.

I wish to make it clear that Atos requires all its healthcare professionals to take full account of all evidence gathered during each assessment.

As well as reviewing individuals’ claim forms, in which claimants give their opinion on their level of disability, practitioners record a clinical history of each condition, an account of the individual’s normal daily activities, a physical or mental state examination (as appropriate), and relevant observations made during the assessment. They also take account of any additional medical evidence that is …
Response of the Distal Tubule and Cortical Collecting Duct to Vasopressin in the Rat
Authors: Philip B. Woodhall, C. Craig Tisher
Journal: Journal of Clinical Investigation (1973)

Renal micropuncture observations in the rat suggest that the entire "distal tubule" (defined by the micropuncturist as that portion of the renal tubule extending between the macula densa and its first junction with another (renal tubule) may be responsive to vasopressin. However, this portion of the renal tubule contains two segments that are morphologically dissimilar. The "early" distal tubule is lined by epithelium characteristic of the distal convoluted tubule, while the "late" distal tubule is lined by epithelium characteristic of the cortical collecting duct. Thus, the present study was initiated to identify the most proximal site of action of vasopressin in the distal renal tubule. A water diuresis was established in rats with hereditary hypothalamic diabetes insipidus. In one-half of the animals the diuresis was interupted by an i.v. infusion of exogenous vasopressin. Morphological preservation of the kidneys was initiated after induction of vasopressin-induced antidiuresis or during maximum water diuresis. Cell swelling and dilatation of intercellular spaces, morphological findings indicative of vasopressin responsiveness, were observed in the cortical collecting duct including the late segment of the distal tubule, a segment that has also been described by morphologists as the initial collecting tubule. Morphological evidence of vasopressin-responsiveness was not observed in the early distal tubule (distal convoluted tubule). Additional morphological studies in Wistar, Long-Evans, and Sprague-Dawley rats demonstrated a marked difference in the random availability of distal convoluted tubules versus initial collecting tubules potentially available for micropuncture just beneath the renal capsule. The results suggest that hypotonic tubular fluid entering the early distal tubule (distal convoluted tubule) remains hypotonic to plasma until it enters the late distal tubule (initial collecting tubule) and that vasopressin-induced osmotic equilibration is a function of the latter segment alone. The findings emphasize the importance of morphological characterization of those segments of the renal tubule that are subjected to physiological investigation.
Improved fluorescence staining technique for estimating turnover of the human stratum corneum
Authors: L.H. Jansen, M.T. Hojyo-Tomoko, A.M. Kligman
Journal: British Journal of Dermatology (2006)

The replacement time of the human stratum corneum of fifteen body regions was determined by measuring the days required for a strongly substantive fluorescent marker, Dansyl chloride, to disappear. Tbe horny layer was stained by a 24-h patch exposure to 5% Dansyl chloride (5-dimethylamino- 1-naphthalene-sulphonyl chloride) in petrolatum. In most body regions the renewal time for the horny layer was about 2 weeks, in agreement with the findings of other investigators. The advantage of Dansyl chloride over another compound, tetrachlorosalicylanilide, which has been used for this purpose, is that it is not an irritant.
Frequency, clinical and dermoscopic features of benign papillomatous melanocytic naevi (Unna type)
Authors: A. Niederkorn, V. Ahlgrimm-Siess, R. Fink-Puches, I.H. Wolf, E. Richtig, H.K. Lackner, R. Hofmann-Wellenhof
Journal: British Journal of Dermatology (2009)

Background Most previous studies on melanocytic naevi have not distinguished between the different types of naevi, except for some studies trying to define atypical naevi. No large, population‐based studies on papillomatous or Unna‐type melanocytic naevi have been performed. Objectives To investigate the dermoscopic and clinical features of papillomatous naevi and to study some of the factors which could potentially influence their development. Methods Seven hundred and seven caucasians aged 1–82 years participated in a screening campaign at open‐air recreation facilities in Austria. The volunteers underwent a total body examination by experienced dermatologists and answered a questionnaire. Clinical and dermoscopic images of one representative papillomatous naevus per person were taken. Results Twenty‐nine per cent of the volunteers exhibited papillomatous naevi, the highest frequency being found in young adults. No correlation between the frequency of papillomatous naevi and gender, skin type, sunburns, sunbed use or hormonal factors was found. Most lesions were brown papules (median diameter 5·0 mm), located on the trunk. Dermoscopy showed a predominance of homogeneous and globular pattern, multifocal hypo/hyperpigmentation and comma vessels. Of the papillomatous naevi, 9·8% showed suspicious scores with dermoscopic algorithms. Conclusions The lack of exogenous influencing factors and the predominance of globular dermoscopic pattern strengthen the hypothesis that papillomatous naevi belong to the same spectrum as small congenital melanocytic naevi. As the role of papillomatous naevi as precursors of melanoma remains unclear and they are frequently not recognized by the patients, one should perform dermoscopy of papillomatous naevi during skin cancer screening.