tbuckley/cabot-search huggingface dataset:
Abstract 3956: BRCA1 chromatin dissociation induced by oncogene activation promotes formation of senescence-associated heterochromatin foci and senescence via chromatin remodeling factor BRG1
Authors: Zhigang Tu, Rugang Zhang
Journal: Cancer Research (2012)

Abstract Background: Cellular senescence is a state of irreversible cell growth arrest that is an important tumor suppression mechanism in vivo. Activation of oncogenes such as Ras in primary mammalian cells typically triggers senescence and formation of senescence-associated heterochromatin foci (SAHF) that contributes to senescence-associated cell cycle exit. We have previously showed that dissociation of BRCA1 from chromatin induced by oncogenic Ras plays a key role in promoting cellular senescence by driving SAHF formation. However, the mechanism by which BRCA1 chromatin dissociation promotes SAHF formation and senescence remains to be determined. BRG1 is an ATP dependent SWI/SNF chromatin-remodeling factor that interacts with BRCA1. Components of SWI/SNF complex including BRG1 are often deregulated in human cancer. Here we examined the role of BRG1 in regulating formation of SAHF trigged by BRCA1 chromatin dissociation induced by oncogenic Ras. Results: We discovered that the interaction between BRG1 and BRCA1 is disrupted during oncogenic RAS induced senescence. Interestingly, BRG1 accumulates in chromatin fraction while BRCA1 becomes dissociated from chromatin. Notably, BRG1 knockdown suppresses formation of SAHF and senescence, while has no effects on BRCA1 chromatin dissociation in Ras-infected cells, suggesting that BRG1 functions downstream of BRCA1 chromatin dissociation in promoting SAHF formation and senescence. Indeed, BRG1 knockdown is sufficient to inhibit SAHF formation and senescence induced by BRCA1 knockdown. Conversely, BRG1 overexpression drives SAHF formation and senescence. Notably, senescence induced by BRG1 overexpression is independent of DNA damage response, further supporting the idea that BRG1 functions downstream of BRCA1 chromatin dissociation during Ras induced senescence. Mechanistically, chromatin immunoprecipitation analysis revealed that, in Ras-expressing or BRCA1 knockdown cells, there is an increased association of BRG1 with the promoters of p16INK4a and p21CIP, both of which are key regulators of SAHF formation and senescence. Significance: These studies revealed the molecular underpinning by which BRCA1 chromatin dissociation promotes SAHF formation and senescence. They also imply that BRG1 inactivation contributes to cancer development by suppressing cellular senescence. (R.Z. is an Ovarian Cancer Research Fund (OCRF) Liz Tilberis Scholar. This work was supported in part by a NCI FCCC-UPenn ovarian cancer SPORE (P50 CA083638) pilot project and SPORE career development award, a DOD ovarian cancer academy award (OC093420), and an OCRF program project.) 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 3956. doi:1538-7445.AM2012-3956
Why this love for antibiotics in India?
Authors: P. Vohra
Journal: BMJ (2012)

Patient’s mother: “Doctor, can you please prescribe an antibiotic. My 4 year old child has been suffering from diarrhoea for the past three days.”

Doctor: “Madam, there’s no need for an antibiotic. This is a viral infection, which is self limiting. Antibiotics may, in fact, make the child worse.”

Mother: “But doctor, I have only come to you to get antibiotics. I am already doing the rest of the treatment. What is the point in my spending two hours getting the child here, taking half a day’s leave from the office, and paying your fee, without getting an antibiotic? I could have ordered norfloxacin from the chemist and spent less money and less time.”

Doctor: “Madam, your time and money have been well spent. You are paying to protect your child from antibiotics—and for the reassurance that the illness will pass in a week.”

Mother: “A week? No, doctor, that’s too much. The child has important examinations at school. I should not have listened to you in the first place and started norfloxacin on day one. Please refund my money, and I will get the drug from the chemist. I thought you were a good doctor but I won’t come to you again.”

An estimated half of prescriptions for antibiotics …
Swine-Influenza Vaccine
Authors: BURTON A. WAISBREN
Journal: Annals of Internal Medicine (1982)

Letters and Corrections1 July 1982Swine-Influenza VaccineBURTON A. WAISBREN, M.D.BURTON A. WAISBREN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-97-1-149_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Five patients seen over the past 24 months prompted this letter suggesting that swine-influenza injections given in the fall of 1976 have led to cases of bizarre long-standing neurologic diseases that can mimic multiple sclerosis. Our index patient was a 37-year-old man who received a swine-influenza injection on 8 October 1976. He noted on 12 November 1976 the onset of numbness and tingling that progressed over the next 7 months to hyper-reflexia, staggering gait, and partial paralysis of his lower extremities. He has been diagnosed as having multiple sclerosis but has insisted that his disease came after...References1. MORRISYOUNG JB. Guillian-Barre syndrome. Lancet. 1978;2:636. CrossrefMedlineGoogle Scholar2. FORRESTERLASCELLES CR. Association between polyneuritis and multiple sclerosis. Neurol Neurosurg Psychiatry. 1979;42:864-6. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byRelapse risk in patients with multiple sclerosis after H1N1 vaccination, with or without seasonal influenza vaccinationAcquired autoimmunity after viral vaccination is caused by molecular mimicry and antigen complimentarity in the presence of an immunologic adjuvant and specific HLA patternsReferencesEpidemiology of Autoimmune Reactions Induced by VaccinationVaccinations and the Risk of Relapse in Multiple SclerosisVaccination of patients with Encephalomyelitis disseminataPathogenesis of multiple sclerosis 1 July 1982Volume 97, Issue 1Page: 149-149KeywordsFallsMultiple sclerosisParalysisVaccines Issue Published: 1 July 1982 PDF downloadLoading ...
New Tender Nodules After Arthroscopy
Authors: Kathleen Ann Long, Kara Braudis, Brandon Brown
Journal: JAMA Dermatology (2015)

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 Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Dermatology journal
Passionate Medicine: Making the Transition from Conventional Medicine to Homeopathy
Authors: Anita Houghton
Journal: BMJ (2005)

P assionate Medicine 's contributors are five doctors and two vets who struggled with the practice of conventional medicine and found a more natural home in homoeopathy. Together they form the Homeopathic Professionals Teaching Group and teach homoeopathy to professionals in Britain and abroad. Their teaching methods are unusual in having a strong emphasis on self awareness and development of the health professional, and they “walk their talk” in having a regular supervision group themselves, which is run by Robin Shohet, the book's editor.

Ed …
Somatic KRAS mutations associated with a human nonmalignant syndrome of autoimmunity and abnormal leukocyte homeostasis
Authors: Julie E. Niemela, Lianghao Lu, Thomas A. Fleisher, Joie Davis, Iusta Caminha, Marc Natter, Laurel A. Beer, Kennichi C. Dowdell, Stefania Pittaluga, Mark Raffeld, V. Koneti Rao, João B. Oliveira
Journal: Blood (2010)
Altered expression of the receptor-ligand pair CXCR5/CXCL13 in B cells during chronic HIV-1 infection
Authors: Alberto Cagigi, Frida Mowafi, Linh V. Phuong Dang, Klara Tenner-Racz, Ann Atlas, Sven Grutzmeier, Paul Racz, Francesca Chiodi, Anna Nilsson
Journal: Blood (2008)
Composition of gall bladder stones associated with octreotide: response to oral ursodeoxycholic acid.
Authors: S H Hussaini, S P Pereira, G M Murphy, C Kennedy, J A Wass, G M Besser, R H Dowling
Journal: Gut (1995)

Octreotide, an effective treatment for acromegaly, induces gall bladder stones in 13-60% of patients. Because knowledge of stone composition is essential for studies of their pathogenesis, treatment, and prevention, this was investigated by direct and indirect methods in 14 octreotide treated acromegalic patients with gall stones. Chemical analysis of gall stones retrieved at cholecystectomy from two patients, showed that they contained 71% and 87% cholesterol by weight. In the remaining 12 patients, localised computed tomography of the gall bladder showed that eight had stones with maximum attenuation scores of < 100 Hounsfield units (values of < 100 HU predict cholesterol rich, dissolvable stones). Gall bladder bile was obtained by ultrasound guided, fine needle puncture from six patients. All six patients had supersaturated bile (mean (SEM) cholesterol saturation index of 1.19 (0.08) (range 1.01-1.53)) and all had abnormally rapid cholesterol microcrystal nucleation times (< 4 days (range 1-4)), whilst in four, the bile contained cholesterol microcrystals immediately after sampling. Of the 12 patients considered for oral ursodeoxycholic acid (UDCA) treatment, two had a blocked cystic duct and were not started on UDCA while one was lost to follow up. After one year of treatment, five of the remaining nine patients showed either partial (n = 3) or complete (n = 2) gall stone dissolution, suggesting that their stones were cholesterol rich. This corresponds, by actuarial (life table) analysis, to a combined gall stone dissolution rate of 58.3 (15.9%). In conclusion, octreotide induced gall stones are generally small, multiple, and cholesterol rich although, in common with spontaneous gall stone disease, at presentation some patients will have a blocked cystic duct and some gall stones containing calcium.
Therapy for Bronchiolitis: When Some Become None
Authors: Caroline Breese Hall
Journal: New England Journal of Medicine (2007)

In past centuries, infant mortality in the first year of life was described as the greatest plague.1 Infants in the 21st century continue to be plagued by high rates of hospitalization, and bronchiolitis is the number one cause.2,3 Despite therapeutic advancements, hospitalizations for bronchiolitis have continued to increase. The annual rate of emergency department visits for bronchiolitis during the season of respiratory syncytial virus, the major cause of this condition, has been estimated as 22.8 per 1000 for children 12 months of age or younger.2 Yearly costs for bronchiolitis hospitalizations exceed $700 million. Yet even these striking figures underestimate . . .
Effect of endosulfan on male reproductive development.
Authors: Habibullah Saiyed, Aruna Dewan, Vijay Bhatnagar, Udyavar Shenoy, Rathika Shenoy, Hirehall Rajmohan, Kumud Patel, Rekha Kashyap, Pradip Kulkarni, Bagalur Rajan, Bhadabhai Lakkad
Journal: Environmental Health Perspectives (2003)

There is experimental evidence of adverse effects of endosulfan on the male reproductive system, but there are no human data. Therefore, we undertook a study to examine the relationship between environmental endosulfan exposure and reproductive development in male children and adolescents. The study population was composed of 117 male schoolchildren (10-19 years of age) of a village situated at the foothills of cashew plantations, where endosulfan had been aerially sprayed for more than 20 years, and 90 comparable controls with no such exposure history. The study parameters included recording of clinical history, physical examination, sexual maturity rating (SMR) according to Tanner stages, and estimation of serum levels of testosterone, luteinizing hormone (LH), follicle-stimulating hormone, and endosulfan residues (70 study and 47 control subjects). Mean +/- SE serum endosulfan levels in the study group (7.47 +/- 1.19 ppb) were significantly higher (p < 0.001) than in controls (1.37 +/- 0.40 ppb). Multiple regression analysis showed that SMR scoring for development of pubic hair, testes, penis, and serum testosterone level was positively related to age and negatively related to aerial exposure to endosulfan (AEE; p < 0.01). Serum LH levels were significantly positively related to AEE after controlling for age (p < 0.01). The prevalence of congenital abnormalities related to testicular descent (congenital hydrocele, undescended testis, and congenital inguinal hernia) among study and controls subjects was 5.1% and 1.1%, respectively, but the differences were statistically nonsignificant. Our study results suggest that endosulfan exposure in male children may delay sexual maturity and interfere with sex hormone synthesis. Our study is limited by small sample size and nonparticipation.
Normal-Pressure Hydrocephalus-Reply
Authors: Robert P. Friedland
Journal: JAMA (1990)

<h3>In Reply.—</h3> I agree that radionuclide cisternography is often of benefit in cases of dementia being evaluated for possible shunt surgery. This technique provides information on the status of the cerebrospinal circulation that is of value in many patients suspected of having normalpressure hydrocephalus, particularly when there are atypical clinical or radiological features. Radionuclide cisternography should not be relied on, however, to make the diagnosis without regard to the other findings.<sup>1,22</sup>Neither should it be used to exclude the diagnosis in patients who are clinically and radiologically characteristic of normal-pressure hydrocephalus. In the case under discussion, both the clinical and magnetic resonance imaging examinations supported the diagnosis of normal-pressure hydrocephalus at the time the decision to place the shunt was made. The additional information provided by radionuclide cisternography would not have been of value. Overall, data from studies of the value of radionuclide cisternography in patients suspected of having
762-2 Correlation Between the Stress-Velocity Index and the Mean dP/dt During Isovolumetric Contraction, a New Index of Contractility Well Suited for Patients with Congenital Heart Disease
Authors: Jonathan Rhodes, Gerald R. Marx, Frances Andruskiewicz, Barbara A. Romero, Yvette B. Dambach, Susan Aylain, Nicholas S. Apostolos
Journal: Journal of the American College of Cardiology (1995)
Lung toxicity associated with cyclophosphamide use. Two distinct patterns.
Authors: S W Malik, J L Myers, R A DeRemee, U Specks
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Cyclophosphamide-induced lung toxicity may be difficult to recognize because of the presence of confounding variables such as concomitant use of other cytotoxic drugs, opportunistic infections, diffuse pulmonary malignancy, radiation pneumonitis, and oxygen toxicity. The purpose of this retrospective analysis was to identify the clinical spectrum of pulmonary toxicity of cyclophosphamide. In our review of case records, we sought to identify patients in whom cyclophosphamide was the only identifiable etiologic factor for lung toxicity. In a 20-yr period six patients were identified with cyclophosphamide-induced lung disease, including five men and one woman ranging in age from 42 to 78 yr. Clinical features of toxicity include dyspnea, fever, cough, new parenchymal infiltrates, gas exchange abnormalities on pulmonary function tests, and pleural thickening on chest roentgenogram. Two patterns of cyclophosphamide-induced lung toxicity were identified. A single patient presented with early-onset pneumonitis and responded to discontinuation of the drug. Five patients with late-onset pneumonitis developed progressive pulmonary fibrosis associated with bilateral pleural thickening. Patients with late-onset pneumonitis showed no response to cessation of cyclophosphamide and institution of corticosteroid therapy. Three of these patients died of respiratory failure. Careful review of the individual cases reported in the literature as cyclophosphamide lung toxicity revealed only 12 cases in whom none of the additional confounding factors could be identified. These could easily be divided in the same two categories. Early-onset pneumonitis is reversible and may respond to corticosteroid therapy. Late-onset pneumonitis, frequently associated with pleural thickening, is clinically distinct from idiopathic pulmonary fibrosis but has a chronically progressive course. It appears unresponsive to corticosteroid therapy.
A Randomized, Phase 2 Trial of Docetaxel with or without PX-866, an Irreversible Oral Phosphatidylinositol 3-Kinase Inhibitor, in Patients with Relapsed or Metastatic Non–Small-Cell Lung Cancer
Authors: Benjamin Levy, Alexander Spira, Daniel Becker, Tracey Evans, Ian Schnadig, D. Ross Camidge, Julie E. Bauman, Diana Hausman, Luke Walker, John Nemunaitis, Charles M. Rudin, Balazs Halmos, Daniel W. Bowles
Journal: Journal of Thoracic Oncology (2014)

The phosphotidylinositol-3 kinase/serine-threonine kinase (AKT)/mammalian target of rapamycin signaling pathway is frequently altered in non-small-cell lung cancer (NSCLC). PX-866 is an oral, irreversible, pan-isoform inhibitor of phosphotidylinositol-3 kinase. Preclinical models revealed synergy with docetaxel and a phase 1 trial demonstrated tolerability of this combination. This randomized phase 2 study evaluated PX-866 combined with docetaxel in patients with advanced, refractory NSCLC.Patients with locally advanced, recurrent, or metastatic NSCLC who had received at least one and no more than two prior systemic treatment regimens were randomized (1:1) to a combination of docetaxel (75 mg/m intravenous every 21 days) with or without PX-866 (8 mg orally daily; arms A and B, respectively). The primary end point was progression-free survival (PFS). Secondary end points included objective response rate, overall survival (OS), toxicity, and correlation of biomarker analyses with efficacy outcomes.A total of 95 patients were enrolled. Median PFS was 2 months in arm A and 2.9 months in arm B (p = 0.65). Objective response rates were 6% and 0% in arms A and B, respectively (p = 0.4). There was no difference in OS between the two arms (7.0 versus 9.2 months; p = 0.9). Grade 3 or higher adverse events were infrequent, but more common in the combination arm with respect to diarrhea (7% versus 2%), nausea (4% versus 0%), and vomiting (7% versus 0%). PIK3CA mutations or PTEN loss were infrequently observed.The addition of PX-866 to docetaxel did not improve PFS, response rate, or OS in patients with advanced, refractory NSCLC without molecular preselection.
Osteopontin is a prognostic factor for survival of acute myeloid leukemia patients
Authors: Ruediger Liersch, Joachim Gerss, Christoph Schliemann, Michael Bayer, Christian Schwöppe, Christoph Biermann, Iris Appelmann, Torsten Kessler, Bob Löwenberg, Thomas Büchner, Wolfgang Hiddemann, Carsten Müller-Tidow, Wolfgang E. Berdel, Rolf Mesters
Journal: Blood (2012)
Unstable Angina and Non–ST Elevation Myocardial Infarction
Authors: Eugene Braunwald
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Non-ST elevation acute coronary syndromes are responsible for approximately 1 million admissions to U.S. hospitals and twice as many to European hospitals each year. Thus, they are among the most common serious illnesses in adults, and are associated with an in-hospital mortality of approximately 5%. The most common cause is rupture of an atherosclerotic coronary plaque, resulting in subtotal coronary occlusion. Diagnosis is based on the clinical picture of retrosternal chest pain, aided by electrocardiographic findings of ST segment deviations and biomarker abnormalities (elevation of troponin and natriuretic peptides) and cardiac imaging (myocardial scans showing perfusion defects). Treatment involves antiischemic agents (nitrates and β blockers), antiplatelet drugs (aspirin, P2Y(12), and glycoprotein IIb/IIIa receptor blockers), and anticoagulants (unfractionated and low-molecular-weight heparins). Patients should undergo risk stratification, and those with high-risk factors should undergo coronary arteriography promptly with the intent to carry out coronary revascularization. Those at low risk should continue to receive intensive antiischemic and antithrombotic therapy. At discharge, patients should receive intensive lipid-lowering therapy with high doses of a statin, as tolerated.
PRIMARY TULAREMIA OF THE EYE
Authors: Malcolm C. Pfunder
Journal: JAMA (1925)

The paucity of reported cases of tularemia with the primary infection in the eye makes it seem desirable to add one more to the four that have been reported by Vail, Sattler and Lamb of Cincinnati, and Martin<sup>1</sup>of Phoenix, Ariz. <h3>REPORT OF CASE</h3> W. C. F., aged 63, a farmer, who consulted me, April 11, 1925, noticed several wood ticks on the horses while harnessing his team, April 6. He removed these with his fingers, and while so doing a foreign body was blown into his left eye; he removed this with his finger. April 8, what he described as a "pimple" appeared on the conjunctiva of the lower lid of the left eye, and a marked swelling appeared just in front of the left ear. April 11, when he appeared for treatment, there was tremendous swelling extending from the superciliary region to the upper lip, and backward