tbuckley/cabot-search huggingface dataset:
Mutation of<i>FOXL2</i>in Granulosa-Cell Tumors of the Ovary
Authors: Sohrab P. Shah, Martin Köbel, Janine Senz, Ryan D. Morin, Blaise A. Clarke, Kimberly C. Wiegand, Gillian Leung, Abdalnasser Zayed, Erika Mehl, Steve E. Kalloger, Mark Sun, Ryan Giuliany, Erika Yorida, Steven Jones, Richard Varhol, Kenneth D. Swenerton, Dianne Miller, Philip B. Clement, Colleen Crane, Jason Madore, Diane Provencher, Peter Leung, Anna DeFazio, Jaswinder Khattra, Gulisa Turashvili, Yongjun Zhao, Thomas Zeng, J.N. Mark Glover, Barbara Vanderhyden, Chengquan Zhao, Christine A. Parkinson, Mercedes Jimenez-Linan, David D.L. Bowtell, Anne-Marie Mes-Masson, James D. Brenton, Samuel A. Aparicio, Niki Boyd, Martin Hirst, C. Blake Gilks, Marco Marra, David G. Huntsman
Journal: New England Journal of Medicine (2009)

Granulosa-cell tumors (GCTs) are the most common type of malignant ovarian sex cord-stromal tumor (SCST). The pathogenesis of these tumors is unknown. Moreover, their histopathological diagnosis can be challenging, and there is no curative treatment beyond surgery.We analyzed four adult-type GCTs using whole-transcriptome paired-end RNA sequencing. We identified putative GCT-specific mutations that were present in at least three of these samples but were absent from the transcriptomes of 11 epithelial ovarian tumors, published human genomes, and databases of single-nucleotide polymorphisms. We confirmed these variants by direct sequencing of complementary DNA and genomic DNA. We then analyzed additional tumors and matched normal genomic DNA, using a combination of direct sequencing, analyses of restriction-fragment-length polymorphisms, and TaqMan assays.All four index GCTs had a missense point mutation, 402C-->G (C134W), in FOXL2, a gene encoding a transcription factor known to be critical for granulosa-cell development. The FOXL2 mutation was present in 86 of 89 additional adult-type GCTs (97%), in 3 of 14 thecomas (21%), and in 1 of 10 juvenile-type GCTs (10%). The mutation was absent in 49 SCSTs of other types and in 329 unrelated ovarian or breast tumors.Whole-transcriptome sequencing of four GCTs identified a single, recurrent somatic mutation (402C-->G) in FOXL2 that was present in almost all morphologically identified adult-type GCTs. Mutant FOXL2 is a potential driver in the pathogenesis of adult-type GCTs.
Abstract 3397: The role of <i>Pdef</i> in mammary development, tumorigenesis and metastasis
Authors: Victoria J. Findlay, Patricia M. Watson, Ron J. Feldman, Stacey A. Sigmon, Yong Z. Gong, Omar Moussa, Demetri D. Sypropoulos, David P. Turner, Dennis K. Watson
Journal: Cancer Research (2010)

Abstract ETS proteins represent one of the largest families of transcription factors with diverse functions that activate or repress the expression of genes that are involved in various biological processes, including cellular proliferation, differentiation, development, transformation and apoptosis. The ETS family gene, PDEF (prostate derived ets factor), is expressed in normal epithelial tissues including prostate, breast, colon and bladder. Significantly, PDEF protein is present in non-invasive cancers but reduced or absent in most invasive cancers. By re-expression and knock-down of PDEF in cancer cell lines, we and others have shown that PDEF target genes control aspects of the metastatic process, including cell growth, migration and invasion. We hypothesize that PDEF is important for normal developmental processes and that loss of PDEF regulatory networks is a key event in the development of invasive cancer. To study the function of Pdef in vivo, we generated mice with constitutive Pdef knockout (Pdef −/−). Specific stages of mammary development were examined, including early-pubescent (5 week), virgin adult (8 week), pregnancy (days 7.5 and 13.5), lactation (days 1 and 7) and involution (day 7). Inhibition of the development of the ductal tree and an increase in ductal side branching and terminal end bud proliferation was observed in 5-8 week old virgin Pdef −/− mice. TGFβ1 and ERα are required for development of the ductal tree during puberty and mRNA levels for both are reduced in the Pdef −/− mice at 5 and 8 weeks of age. Incomplete lobuloalveoli development was observed in Pdef −/− pregnant and lactating mice, although no phenotypic effects were observed in the resultant pups. To explore the role of Pdef in mammary tumor progression and metastasis, we generated mice expressing the MMTV-PyMT or MMTV-Neu oncogene in wild type and Pdef −/− backgrounds. No impact of Pdef dosage upon tumor incidence or growth was observed in the PyMT model; however, initial tumor formation was delayed by 4 weeks (8.9 vs. 4.8) and time from tumor initiation to sacrifice was 3 weeks longer (29.4 vs 26.4) in the Pdef −/− Neu model. Significantly, an increase in lung metastasis was observed in the Pdef −/− mice in both the PyMT and Neu models. Thus, loss of Pdef in vivo is associated with defects in mammary development and increased metastasis in mouse models of breast cancer, suggesting Pdef is a metastasis suppressor. 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 3397.
Studies on Thiomerin—A Subcutaneously Administerable Mercurial Diuretic
Authors: J. GROSSMAN, R. E. WESTON, I. S. EDELMAN, L. LEITER
Journal: Circulation (1950)

Results of clinical and physiologic studies with Thiomerin, a new subcutaneously administered mercurial diuretic, are presented. The data indicate a clinical diuretic efficacy comparable to that of other mercurials and a negligible systemic toxicity. Renal clearance studies demonstrate that it acts by producing a reversible depression in tubular reabsorption of electrolyte and water. The effects of intravenous and subcutaneous administration are compared.
TCT-792 Severe Left Ventricular Dysfunction Predicts Mortality In Patients With Symptomatic Functional Mitral Regurgitation Undergoing Percutaneous Edge-To-Edge Repair
Authors: Lorenzo Azzalini, Xavier Millán, Razi Khan, Anique Ducharme, Arsene Basmadjian, Raoul Bonan, Anita W. Asgar
Journal: Journal of the American College of Cardiology (2014)
Spending on Medical Care
Authors: Gerard F. Anderson, Kalipso Chalkidou
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
Internists: More Specialists or More Generalists?
Authors: DAVID E. ROGERS
Journal: Annals of Internal Medicine (1985)

Editorials1 May 1985Internists: More Specialists or More Generalists?DAVID E. ROGERS, M.D.DAVID E. ROGERS, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-102-5-702 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptAll of us who concern ourselves with the overall design and effectiveness of the American medical care enterprise owe a large debt to Dr. Alvin Tarlov and his colleagues. Starting with the work of the Graduate Medical Education National Advisory Commission (GME-NAC) in 1976, they have given us an evolving picture of the number and kinds of physicians this nation produces, and their educated guesses about how supply will match with needs as we move toward the 21st century. Of particular interest to those of us who have chosen the only truly enlightened physician role—that of being internists—are their regular...References1. SCHLEITERTARLOV MA. National Study of Internal Medicine Manpower: IX. Internal Medicine Residency and Fellowship Training: 1984 update. Ann Intern Med. 1985;102:681-5. LinkGoogle Scholar2. Updated Report on Access to Health Care for the American People: The Robert Wood Johnson Foundation Special Report, Number One. Princeton, New Jersey: The Robert Wood Johnson Foundation; 1983. Google Scholar3. SCHROEDER S. Western European responses to physician oversupply: lessons for the United States. JAMA. 1984;252:373-84. CrossrefMedlineGoogle Scholar4. AIKENLEWISCRAIGMENDENHALLBLENDONROGERS LCJRRD. The contribution of specialists to the delivery of primary care. N Engl J Med. 1979;300:1363-70. CrossrefMedlineGoogle Scholar5. ROGERSBLENDON DR. The academic medical center today. Ann Intern Med. 1984;100:751-4. LinkGoogle Scholar6. ROGERS D. Further musings on medical education. Pharos. 1984;47:31-4. Google Scholar7. ROGERSMOLONEY DT. Medical technology—a different view of the contentious debate over costs. N Engl J Med. 1979;301:1413-9. CrossrefMedlineGoogle Scholar8. CYPRESS B. Patterns of Ambulatory Care in Internal Medicine: The National Ambulatory Medical Care Survey. Hyattsville, Maryland: National Center for Health Statistics; 1984; DHEW publication no. (PHS) 84-1741. (Vital Health Statistics; series 13; no. 80). Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: DAVID E. ROGERS, M.D.Affiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byPregna-D1-pentaranes: Synthesis, modifications, and structure (review)Current successes in medical education beyond the bedsideCareer development among residents completing primary care and traditional residencies in medicine at the Boston City Hospital, 1974–1983POSTGRADUATE TRAINING IN INTERNAL MEDICINE IN HONG KONG 1 May 1985Volume 102, Issue 5Page: 702-703KeywordsGraduate medical education ePublished: 1 December 2008 Issue Published: 1 May 1985 PDF downloadLoading ...
Effect of preservation on the elasticity of human aortic valve homografts.
Authors: Y L Ng, J E Wright
Journal: Thorax (1975)

The elastic properties of preserved human aortic homografts after different storage times in antibiotic-nutrient medium solution have been measured. There was a definite loss of elasticity within nine months leading to a rapid decrease after a year of preservation. It is likely that satisfactory valve function depends on its elasticity, and these studies indicate that aortic valves which have been exposed to antibiotic media for more than nine months should not be used in valve replacement surgery.
THE BENEFICENCE OF DISEASE.Read in the Section of State Medicine, at the Forty-second Annual Meeting of the American Medical Association, Washington, D. C., May 5, 1891.
Authors: A. N. BELL
Journal: JAMA (1891)

The first thought which this title suggests to the unreflective mind is, that it is in conflict with the almost universally popular belief that disease is an independent, active principle or entity, the result of sin—a penalty for the transgression of some physiological or sanitary law—which is identified with the punishment of our first parents for partaking of the forbidden fruit; a belief which, logically considered, without any conception of organic structure, would imply that man, as originally constituted, was intended to occupy this world forever. That disease was unknown in the world before the fall of Adam, is only equally true with the statement that so was all knowledge of the concerns of mankind unknown. It is not my purpose to analyze the sacred record with regard to such special manifestations and miracles as appear to have been adapted by the Creator to the comprehension of man in his
Mortality among under 5s falls below 10 million for first time
Authors: John Zarocostas
Journal: BMJ (2007)

The annual number of deaths of children aged 5 years or younger reached a record low last year, says Unicef, falling for the first time to less than 10 million—to 9.7 million, down from 12.7 million in 1990.

“More children are surviving today than ever before. Now we must build on this public health success to push for the achievement of the millennium development goals,” said Unicef's chief, Ann Veneman. But she also said that there is no room for complacency.

“The loss of 9.7 million young lives each year is unacceptable. Most of these deaths are preventable—and, as recent progress shows, the solutions are tried and tested,” she added.

Of the 9.7 million children who died in 2006, 4.8 million were from …
Extended prescribing by UK nurses and pharmacists
Authors: Stephen C Earwicker
Journal: BMJ (2005)

Editor—In terms of the issue of nurse and pharmacist prescribing Avery and Pringle are right to raise the issue of patient safety, which must be at the heart of all we do.1

We have been in the forefront of nurse prescribing in our general practice and have found both good practice and some frustrations. Intrinsically we have found our extended and supplementary nurse prescribing to be safe. Nurses by their training are driven by the concept of competency, and we have found it central to the way of working to assess and prescribe only within the bounds of clear competency. The introduction of safe nurse prescribing has undoubtedly been helped by the presence of a strong and open clinical team supporting the nurses throughout their initial training and on an ongoing basis. Our frustration has been the lack of integration of nurse prescribing with our clinical computer system.

This has, as the editorial points out, removed a potential safety feature open to doctors when they prescribe. There are ways around this, but it would have been far better to encourage computer prescribing by nurses from the outset. We need a rapid roll-out of nurse prescribing software on general practitioners' and community clinical computing systems before April 2006.
Studies of DNA Methylation in Cancer Beginning to Yield Clinical Applications
Authors: Tracy Hampton
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
Interleukin 1 stimulates granulocyte macrophage colony-stimulating activity release by vascular endothelial cells.
Authors: G C Bagby, C A Dinarello, P Wallace, C Wagner, S Hefeneider, E McCall
Journal: Journal of Clinical Investigation (1986)

Studies designed to characterize monocyte-derived recruiting activity (MRA) a monokine that stimulates endothelial cells to produce granulocyte macrophage-colony-stimulating activity (CSA) by endothelial cells, show that it is a thermolabile protein of from 12,000 to 24,000 D which, on chromatofocusing, shows three separate peaks of eluted activity from pH 7.5 to 5.0. Because these and many other properties of MRA are identical to those of interleukin 1 (IL-1), we tested the hypothesis that MRA and IL-1 are identical. We cultured vascular endothelial cells with various concentrations of purified native and recombinant IL-1 (pI 7 form), then tested the endothelial cell supernatants for GM-CSA. Purified native IL-1 and recombinant IL-1 stimulated endothelial cells to release CSA. The MRA of native IL-1, recombinant IL-1, and unfractionated monocyte conditioned medium was neutralized by a highly specific rabbit anti-human IL-1 antiserum. Chromatofocusing fractions that contained MRA contained immunoreactive IL-1 on immunoblotting and the bioactivity was neutralized completely by treatment with the antiserum. We conclude that IL-1 induces the release of CSA by vascular endothelial cells, that IL-1 is constitutively produced by monocytes in vitro, and that MRA and IL-1 are biologically, biophysically and, immunologically identical.
Clonal drift demonstrates unexpected dynamics of the T-cell repertoire in T-large granular lymphocyte leukemia
Authors: Michael J. Clemente, Marcin W. Wlodarski, Hideki Makishima, Aaron D. Viny, Isabell Bretschneider, Mohammad Shaik, Nelli Bejanyan, Alan E. Lichtin, Eric D. Hsi, Ronald L. Paquette, Thomas P. Loughran, Jaroslaw P. Maciejewski
Journal: Blood (2011)
One Thousand Vasectomies
Authors: M. N. Barnes, J. P. Blandy, H. R. England, G. Gunn, G. Howard, B. Law, B. Mason, J. Medawar, C. Reynolds, R. J. Shearer, M. Singh, D. G. Stanley-Roose
Journal: BMJ (1973)

In a prospective study of 1,000 people treated by vasectomy at the Margaret Pyke Centre under local anaesthesia as outpatients minor sepsis occurred in 12 cases, an abscess in one, and haematoma needing drainage in seven. Spontaneous recanalization of the vasa occurred in six patients and an unsuspected third vas was found in one.Except in patients with recanalization or a third vas the semen was always free from motile spermatozoa within three months, but non-motile spermatozoa have so far persisted for up to 17 months in a few cases.
The pathophysiology of allergic rhinitis: Impact of therapeutic intervention
Authors: Robert M. Naclerio
Journal: Journal of Allergy and Clinical Immunology (1988)

In individuals with allergic rhinitis, exposure to antigens, such as pollens, can activate the nasal mast cells to initiate the allergic process. During this process, the patient develops symptoms and mediators are released (including histamine, prostaglandin D2, thromboxane B2, and leukotriene C4) to produce the inflammation characteristic of allergic rhinitis. The allergic process can be divided into three phases: early, occurring within minutes of allergen challenge; late, occurring in about half those challenged about 3 to 10 hours later; and rechallenge, occurring 12 to 24 hours after the first exposure. Mediators are released in each phase; in the late and rechallenge phases, cells, including basophils, eosinophils, neutrophils, and mononuclear cells, enter the nose in large numbers. The basophils can release mediators, increasing the allergic response. Pretreatment of patients with allergic rhinitis with systemic steroids, such as prednisone, prevents the late and rechallenge phases of the allergic process. However, with the exception of kinin generation, such pretreatment has no effect on the early phase. In contrast, pretreatment with the topical steroid flunisolide prevents many more aspects of the allergic process: the production of symptoms and the release of mediators in the early phase and the further development of symptoms and mediator release in the late and rechallenge phases. Flunisolide pretreatment also prevents the influx into the nose of mediator-releasing cells, including basophils. Therefore, physicians should consider pretreating their patients with allergic rhinitis with flunisolide several days before the pollen season begins. Early response to the antigen will be reduced, and the inflammation associated with chronic allergic rhinitis will be suppressed.
Major Racial Differences in Coronary Constrictor Response Between Japanese and Caucasians With Recent Myocardial Infarction
Authors: Christian Pristipino, John F. Beltrame, Maria L. Finocchiaro, Ryuichi Hattori, Masatoshi Fujita, Rocco Mongiardo, Domenico Cianflone, Tommaso Sanna, Shigetake Sasayama, Attilio Maseri
Journal: Circulation (2000)

Enhanced coronary vasomotion may contribute to acute coronary occlusion during the acute phase of myocardial infarction (AMI). Japanese have a higher incidence of variant angina than Caucasian patients, but racial differences in vasomotor reactivity early after AMI are controversial.The same team studied 15 Japanese and 19 Caucasian patients within 14 days of AMI by acetylcholine injection into non-infarct-related (NIRA) and infarct-related (IRA) coronary arteries followed by nitroglycerin. Incidence of vasodilation, vasoconstriction, spasm, and basal tone were assessed in proximal, middle, and distal segments after each drug bolus by quantitative angiography. Japanese patients had much lower cholesterol levels than Caucasians (183+/-59 versus 247+/-53 mg/dL, P<0.006) but showed a lower incidence of vasodilation (2% versus 9% of coronary segments) and a greater incidence of spasm after acetylcholine (47% versus 15% of arteries, P<0.00001). Incidence of spasm was higher in IRAs than in NIRAs in both populations (67% versus 39% and 23% versus 11%, respectively). Multivessel spasm was more common (64% versus 17%, P<0.02) and vasoconstriction of nonspastic segments was greater in Japanese patients (-23.4+/-14.9% versus -20.1+/-15.7%, P<0.02) in the presence of similar average basal coronary tone with respect to post-nitroglycerin dilation and of nonsignificant differences of coronary atherosclerotic score.Soon after AMI, Japanese patients exhibited a 3-fold-greater incidence of spasm and greater vasoconstriction of nonspastic segments after acetylcholine than Caucasians. The causes of such differences warrant further investigation because they may have relevant pathophysiological and therapeutic implications.
Alternative glucocorticoids for use in cases of adverse reaction to systemic glucocorticoids: a study on 10 patients
Authors: M.T. Ventura, G.F. Calogiuri, M.G. Matino, M. Dagnello, R. Buquicchio, C. Foti, R. Di Corato
Journal: British Journal of Dermatology (2003)

Reactions to systemically administered corticosteroids are rare, despite their widespread use.To identify alternative glucocorticoids for emergency use in patients with adverse reactions to systemic glucocorticoids.Ten patients were identified as having adverse reactions after the use of systemic corticosteroids. Skin prick tests and intradermal tests to hydrocortisone (HC) and methylprednisolone (MP), and intradermal tests to betamethasone and dexamethasone, were performed in all patients, and oral challenge tests to betamethasone (n=10) and deflazacort (n=6).Skin prick tests were negative in all patients, whereas intradermal tests to HC and MP were positive in eight; two patients showed only an isolated cutaneous sensitivity to MP. Intradermal tests to betamethasone and dexamethasone were negative, and oral challenge tests were negative in all patients.Our results suggest the possibility of an IgE-mediated mechanism for allergic reactions to HC and MP, probably due, at least in part, to a steroid-glyoxal. We suggest that betamethasone and deflazacort could be reserved for emergency use in patients with adverse reactions to other corticosteroids.