tbuckley/cabot-search huggingface dataset:
Abstract LB-311: Whole-exome sequencing of polycythemia vera revealed novel driver genes and somatic mutation shared by T cells and granulocytes
Authors: David A. Wheeler, Linghua Wang, Sabina Swierczek, Kimberly Hickman, Jennifer A. Drummond, Donna Muzny, Richard A. Gibbs, Joseph Prchal
Journal: Cancer Research (2014)

Abstract Polycythemia vera (PV) is a myeloproliferative neoplasm characterized by augmented myelopoiesis leading to increased red cell mass with frequent excessive proliferation of other myeloid lineages. Over 95% of PV patients harbor JAK2V617F mutation, which confers proliferative advantage to affected myeloid progenitors. JAK2V617F, which is thought to be necessary but not sufficient for the disease, is often associated with acquired uniparental disomy on chromosome 9p (9pUPD). To better understand the underlying molecular basis of PV, we performed whole-exome sequencing and DNA copy-number analysis of 31 JAK2V617F-positive patients and further investigated the evolution of somatic mutations using longitudinal samples. In addition to JAK2 V617F and 9pUPD, we identified recurrent somatic mutation in an additional 5 genes including ASXL1, TET2, DNMT3A, and SF3B1 and recurrent DNA copy-number alterations at 1q and 18p. Forty-two percent of patients had at least one somatic mutation in an epigenetic modifier gene, and 23% of patients harbored mutation in RTK/RAS, RNA processing pathways, tumor suppressors and protein kinases. In 4 of 31 cases, variant allele abundance suggested somatic mutations of ASXL1, DNMT3A and SF3B1 may have preceded JAK2V617F. Interestingly, in 7 PV patients mutations also present in COSMIC were shared between the patients’ T-cell controls and granulocytes: 4 NF1, 2 ASXL1, and one each in TET2, IDH2, and DNMT3A, suggesting these genes mutated early in hematopoietic development. Absence of JAK2V617F in these T-cells ruled out cross-contamination of cell lineages. In an additional 4 cases, a minor JAK2V617F subclone acquired new mutations in DNMT3A, SF3B1, SMARCA2, and TET2 during PV progression. In summary, seventy percent of patients had mutation of at least one gene important to development of myeloid neoplasms, other than JAK2V617F. Our data reveal that these mutations, in particular NF1, may have arisen in some cases early in hematopoiesis but also in some patients during progression after diagnosis. These results suggest that the order of mutation is not as important as the total mutational burden in the development of PV. Citation Format: David A. Wheeler, Linghua Wang, Sabina Swierczek, Kimberly Hickman, Jennifer A. Drummond, Donna Muzny, Richard A. Gibbs, Joseph Prchal. Whole-exome sequencing of polycythemia vera revealed novel driver genes and somatic mutation shared by T cells and granulocytes. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-311. doi:10.1158/1538-7445.AM2014-LB-311
Systemic Microvascular Leak in an <i>In Vivo</i> Rat Model of Ventilator-induced Lung Injury
Authors: Won-Il Choi, Deborah A. Quinn, Kwon Moo Park, Ramzi K. Moufarrej, Behrouz Jafari, Olga Syrkina, Joseph V. Bonventre, Charles A. Hales
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Positive pressure mechanical ventilation has significant systemic effects, but the systemic effects associated with ventilator-induced lung injury (VILI) are unexplored. We hypothesized that VILI would cause systemic microvascular leak that is dependent on nitric oxide synthase (NOS) expression. Rats were ventilated with room air at 85 breaths/minute for 2 hours with either VT 7 or 20 ml/kg. Kidney microvascular leak, which was assessed by measuring 24-hour urine protein and Evans blue dye, was used as a marker of systemic microvascular leak. A significant microvascular leak occurred in both lung and kidney with large VT (20 ml/kg) ventilation. Injection of 0.9% NaCl corrected the hypotension and the decreased cardiac output related to large VT, but it did not attenuate microvascular leak of lung and kidney. Serum vascular endothelial growth factor was significantly elevated in large VT groups. Endothelial NOS expression significantly increased in the lung and kidney tissue with large VT ventilation but not inducible NOS. The NOS inhibitor, N-nitro-L-arginine methyl ester, attenuated the microvascular leak of lung and kidney and the proteinuria with large VT ventilation. Endothelial NOS may mediate the systemic microvascular leak of the present model of VILI.
Targeted gene transfer to hepatocellular carcinoma cellsin vitro using a novel monoclonal antibody?based gene delivery system
Authors: Leonhard Mohr, Julia I. Schauer, Raymond H. Boutin, Darius Moradpour, Jack R. Wands
Journal: Hepatology (1999)

Gene therapy approaches for the treatment of malignant tumors will require high–level expression of therapeutic genes in tumors compared with normal tissues. This may be achieved either by targeted gene delivery to tumor cells or by the use of tumor–specific promoters. Here, we describe the use of a novel conjugate consisting of a tumor–reactive monoclonal antibody (mAb), designated AF–20, coupled to a DNA–binding cationic amphiphile, cholesteryl–spermine, for gene delivery to hepatocellular carcinoma (HCC) cells. The high–affinity mAb, AF–20, recognizes a rapidly internalized 180–kd cell–surface glycoprotein that is abundantly expressed on HCC and other human tumors. The AF–20 mAb and an isotype–matched control antibody (C7–57) were covalently coupled to cholesteryl–spermine. Binding and internalization of AF–20-cholesteryl–spermine was confirmed by fluorescence microscopy using fluorescein isothiocyanate (FITC)–labeled anti–mouse IgG antibody. Following transfection of FITC–labeled oligonucleotides and ethidium monoazide-labeled plasmid DNA, cellular uptake and intracellular localization of nucleic acids were examined by laser scanning confocal microscopy. Transfection of luciferase or β–galactosidase reporter genes complexed to AF–20-cholesteryl–spermine resulted in high levels of gene expression in AF–20 antigen–positive tumor cells. Very low levels of gene expression were observed using the control compound (C7–57–cholesteryl–spermine), which does not recognize the AF–20 tumor antigen or when AF–20 antigen–negative NIH 3T3 cells were transfected with AF–20-cholesteryl–spermine. Thus, covalent coupling of the AF–20 mAb to cholesteryl–spermine generated a highly specific and efficient nonviral vector system for targeted gene delivery to AF–20 antigen–positive HCC cells.
CD4+CD25high Foxp3+ regulatory T cells in myelodysplastic syndrome (MDS)
Authors: Shahram Y. Kordasti, Wendy Ingram, Janet Hayden, David Darling, Linda Barber, Behdad Afzali, Giovanna Lombardi, Marcin W. Wlodarski, Jaroslaw P. Maciejewski, Farzin Farzaneh, Ghulam J. Mufti
Journal: Blood (2007)
Thrombocytopenia and Decreased Megakaryocytes
Authors: V. P. SUBRAMANIAN
Journal: Annals of Internal Medicine (1981)

Letters and Corrections1 May 1981Thrombocytopenia and Decreased MegakaryocytesV. P. SUBRAMANIAN, M.D.V. P. SUBRAMANIAN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-94-5-711_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: I read with interest the paper by Stoll and colleagues (1) on seven patients with thrombocytopenia and decreased megakaryocytes because I am treating a patient with similar problems but with different clinical evolution.A 62-year-old white man with long history of rheumatoid arthritis developed petechiae and easy bruising in Ocotober 1979 while he was on indomethacin. All the medications were discontinued, and the patient was referred to us. Findings on physical examination were negative except for numerous petechiae. Leukocyte count was 7100/cmm3with a normal differential count; hemoglobin, 13.2 g/dL; and platelet count, 17 000/cmm3. A bone...References1. STOLL D, BLUM S, PASQUALE D, and MURPHY S. Thrombocytopenia with decreased megakaryocytes: evaluation and prognosis. Ann Intern Med. 1981;94:170-5. LinkGoogle Scholar2. AHN Y, BYRNES J, and HARRINGTON W. The treatment of idiopathic thrombocytopenia with vinblastine-loaded platelets. N Engl J Med. 1978;298:1101-7. CrossrefMedlineGoogle Scholar3. BLOCK M, JACOBSON L, and BETHARD W. Preleukemic acute human leukemia. JAMA. 1953;152:1018-28. CrossrefMedlineGoogle Scholar4. DEGOS L, EL YAFI G, and BERNARD J. Les thrombopenies preleucemiques: a propos de trois observations. Nouv Rev Fr Hematol. 1971;11:928-33. MedlineGoogle Scholar5. BERNARD J. Les aplasies pré-leucémiques. Nouv Rev Fr Hematol. 1969;9:41-8. MedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: V. P. SUBRAMANIAN, M.D.Affiliations: West Virginia University Medical Center Morgantown, WV 26506 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1981Volume 94, Issue 5Page: 711-711KeywordsBoneHemoglobinMegakaryocytesPlateletsRheumatoid arthritis ePublished: 1 December 2008 Issue Published: 1 May 1981 PDF downloadLoading ...
Do school exams predict doctors' success?: Is it not a retrospective study?
Authors: R. Chaturvedi
Journal: BMJ (2003)

EDITOR—The title of the paper by McManus et al is rather misleading in saying that it is a 20 year prospective study.1 By definition this would mean that the study was planned 20 years ago and the recruitment of subjects was over the same time. But the subjects were selected retrospectively over seven years only, and at the …
The sight test fee 1988 data may be misleading
Authors: J Pooley, E G Woodward, R Cooling
Journal: BMJ (1994)

and colleagues describe the effect of the introduction of the sight test fee on the number of referrals to Bristol Eye Hospital.'They use the numbers of referrals for 1984-8 to predict the expected numbers of referrals in 1989- 92.This use of their data would have been appropriate if the introduction of the fee on 1 April 1989 had been made without prior warning.The government's proposal for the sight test fee had, however, been made public on 25 November 1987.2This announcement (and subsequent con- firmations) would be expected to have had two effects.Firstly, the high figure for referrals in 1988 may partly simply be due to the increased general publicity about sight tests.Secondly, some people who would have had an eye test after 1 April 1989 may have decided to have one beforehand instead.These "early" sight tests would have increased the figure for referrals in 1988 and reduced that in 1989.The authors consider whether early referrals received in 1988 could account for a reduction in referrals from 1989 onwards.They reject this idea on the grounds that the number of referrals in 1988 was a mere 343 (5 6%) above that expected.Ifthese 343 are regarded as early referrals and are taken from the total for 1988 and added to the total for 1989, however, then the fall in referrals from 1988 to 1989 is not by 15-1% but by only 4-8%.Whether this transfer of numbers of referrals is valid is clearly arguable, but this manoeuvre illustrates that a more cautious analysis might have been appropriate in the study.In particular, it would have been preferable not to have used data for 1988 (the year before introduction of the fee) to predict the numbers of referrals afterwards.If the figure for 1988 is omitted from the analysis the actual numbers of referrals for 1989-92 all fall within the recalculated 95% confidence intervals for the predicted numbers.
Predictors of Improvement of Unrepaired Moderate Ischemic Mitral Regurgitation in Patients Undergoing Elective Isolated Coronary Artery Bypass Graft Surgery
Authors: Martin Penicka, Hana Linkova, Otto Lang, Richard Fojt, Viktor Kocka, Marc Vanderheyden, Jozef Bartunek
Journal: Circulation (2009)

The persistence of moderate ischemic mitral regurgitation (IMR) after isolated coronary artery bypass graft surgery is an important independent predictor of long-term mortality. The aim of the present study was to identify predictors of postoperative improvement in moderate IMR in patients with ischemic heart disease undergoing elective isolated coronary artery bypass graft surgery.The study population consisted of 135 patients with ischemic heart disease (age, 65+/-9 years; 81% male) and moderate IMR undergoing isolated coronary artery bypass graft surgery. Fourteen patients died before the 12-month follow-up echocardiography and were excluded. At the 12-month follow-up, 57 patients showed no or mild IMR (improvement group), whereas 64 patients failed to improve (failure group). Before coronary artery bypass graft surgery, the improvement group had significantly more viable myocardium and less dyssynchrony between papillary muscles than the failure group (P<0.001). All other preoperative parameters were similar in both groups. Large extent (> or =5 segments) of viable myocardium (odds ratio, 1.45; 95% confidence interval, 1.22 to 1.89; P<0.001) and absence (<60 ms) of dyssynchrony (odds ratio, 1.49; 95% confidence interval, 1.29 to 1.72; P<0.001) were independently associated with improvement in IMR. The majority (93%) of patients with viable myocardium and an absence of dyssynchrony showed an improvement in IMR. In contrast, only 34% and 18% of patients with dyssynchrony and nonviable myocardium, respectively, showed an improvement in IMR, whereas 32% and 49%, respectively, of these patients showed worsening of IMR (P<0.001).Reliable improvement in moderate IMR by isolated coronary artery bypass graft surgery was observed only in patients with concomitant presence of viable myocardium and absence of dyssynchrony between papillary muscles.
Intestinal pseudo-obstruction: a new complication of oesophageal sclerotherapy.
Authors: S Rasbridge, C Sheldon, S M Hardman, F R Vicary
Journal: BMJ (1986)

immunity in neonates was impaired.Our experience strongly suggested that the technique of vaccination was the important factor, which was why experienced tuberculosis health visitors performed all the vaccinations.The Dermo-jet overcomes the difficulty of giving intradermal injections in neonates but should be used by experienced operators who can immediately detect whether it is functioning incorrectly.The variable results, if not related to technique, could be due to a racial factor or to other factors in early childhood; our results, however, showed that cell mediated immunity in neonates is sufficient to allow them to become sensitive to tuberculin after BCG vaccination.This is supported by retrospective data from Manchester showing 75% protection from neonatal BCG,5 a figure similar to that found in adolescents. 1
Financial Support of Continuing Medical Education
Authors: Robert Steinbrook
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
Come Follow Me
Authors: Louis M. Profeta
Journal: JAMA (1988)

Come—follow me. Today I am going to walk you through the third floor of the Children's Pavilion. Before we go upstairs, let's sit down and imagine we are young again. Think about the neighborhood playground; see yourself playing kickball, climbing the jungle gym, jumping rope. If you listen, you can hear the laughing, the playful screams of childhood. Close your eyes and think about how strong and indestructible you are as a child, how carefree. There are no such things as cancer, pneumonia, muscular dystrophy, spinal meningitis. There are only youth, happiness, and health. Let's go upstairs. This is the spinal recovery ward of the pavilion. Nowhere in the world are you as close to the outdoors and yet as far away. There are patients on this ward who have not been outside of the hospital for a year. The third floor is a sea of lifeless limbs and painted
Is Aspirin Resistance a Real Problem in People With Type 2 Diabetes?
Authors: Jozef Drzewoski, Cezary Watala
Journal: Diabetes Care (2004)

We read with great interest the article by Sacco et al. (1) on the problem of aspirin efficacy in primary prevention of cardiovascular events in type 2 diabetic patients. In our opinion, this is an important yet somewhat understudied area in the field of diabetes care. The Diabetes Prevention Project (DPP) trial has shown lower effects of primary prevention of cardiovascular disease with low-dose aspirin in diabetic subjects compared with nondiabetic subjects. The …
FDA accepts weakened antidepressant warning
Authors: Jeanne Lenzer
Journal: BMJ (2005)

New “black box” warnings will appear this month in the United States on antidepressant labels about the risk of increased suicidality among children using the drugs. The warnings initially advised by the US Food and Drug Administration, however, have been weakened by industry, say critics.

An FDA advisory panel that met last September ( BMJ 2004;329: 702) urged the FDA to demand the new black box warnings. The FDA issued a labelling recommendation in October that read “Antidepressants increase the risk of suicidal thinking and behaviour (suicidality) in children and adolescents with major depressive …
Textbook of Diabetic Neuropathy
Authors: Mark J. Brown
Journal: Annals of Internal Medicine (2004)

Medical Writings: Book Notes3 August 2004Textbook of Diabetic NeuropathyMark J. Brown, MDMark J. Brown, MDFrom Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-141-3-200408030-00030 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Gries FA, Cameron NE, Low PA, Ziegler D, eds. 394 pages. New York: Thieme; 2003. $89.00. ISBN 1588900053. Order phone 800-782-3488.Field of medicine: Diabetes, general medicine, and neuromuscular diseases.Format: Hardcover book.Audience: Clinicians who want an in-depth understanding of diabetic complications; clinical and basic investigators who study diabetic neuropathy. The book belongs in endocrinology and neurology libraries and in units that develop treatment trials for diabetes.Purpose: To present a “systematic review that covers both the physiology of the nervous system and the pathology and pathophysiology of the various forms of [diabetic neuropathy].” The book also emphasizes the ... Author, Article, and Disclosure InformationAffiliations: From Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 3 August 2004Volume 141, Issue 3Page: 248KeywordsLibrariesNervous systemNeurologyNeuromuscular diseasesNeuropathyNeurophysiologyPathogensPeripheral nervous systemSoftware toolsSystematic reviews ePublished: 3 August 2004 Issue Published: 3 August 2004 Copyright & PermissionsCopyright © 2004 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Serum Enzymes and Electrocardiograms after Coronary Arteriography
Authors: Harvey J. Matlof, Jan Buhl, Lewis Wexler, Donald C. Harrison
Journal: New England Journal of Medicine (1973)

CONFLICTING results regarding the effect of cardiac catheterization and angiocardiography on serum enzyme values have previously been reported.1 2 3 4 Although myocardial infarction is a complication of coronary arteriography,5 some patients may experience chest pain during coronary arteriography without development of criteria for acute infarction. It is essential to establish an early diagnosis of infarction, if it occurs, by changes in serum enzymes and electrocardiograms. Since other noncardiac factors, such as intramuscular injections,6 , 7 may contribute to changes in serum creatine phosphokinase values, their effects must also be recognized. Thus, when patients receive intramuscular premedication for angiographic procedures, it is necessary to know . . .
Modifying disability in progressive multiple sclerosis
Authors: Jacqueline Palace, Neil Robertson
Journal: The Lancet (2014)

Multiple sclerosis is the most common cause of chronic neurological disability in young adults in developed countries and seems to be increasing in frequency.1,2 Disease presentation in 80–90% of patients follows an initial phase characterised by bouts of relapsing-remitting neurological dysfunction.3 These relapses are thought to represent focal areas of inflammation in the CNS, and arise with unpredictable frequency and variable recovery.4 However, after an inconsistent interval, most patients then develop a progressive disease course, with a gradual development of disability in the absence of relapses.
Cushing's Syndrome Associated with a Basophilic Carcinoma of the Pituitary
Authors: BENJAMIN SIMKIN
Journal: Annals of Internal Medicine (1962)

Excerpt Only nine cases of Cushing's syndrome associated with a carcinoma of the pituitary gland are known to us to have been reported in the literature up to the present (1-8). One of these has not been reported in detail (7). Two other cases have been alluded to, but no details were given (9). The following case report is presented as another rare occurrence of Cushing's syndrome associated with a carcinoma of the pituitary gland. It may also fall within the realm of a newly described clinical entity consisting of an adrenocorticotrophin-producing pituitary tumor, following adrenalectomy for Cushing's syndrome (10-13). CASE
TCT-803 3D Transesophageal Echocardiography provides optimal real-time guidance for off-pump, transapical implantation of artificial chordae tendineae. An imaging study
Authors: Kestutis Rucinskas, Diana Zakarkaite, Rita Kramena, Robertas S. Samalavicius, Vilius Vilius Janusauskas, Giovani Speziali, Audrius Aidietis
Journal: Journal of the American College of Cardiology (2014)