tbuckley/cabot-search huggingface dataset:
Cyclin overexpression inhibits Smad 3 tumor suppression in breast cancer cells.
Authors: S Zelivianski, A Cooley, JS Jeruss
Journal: Cancer Research (2009)

Abstract Abstract #5033 Introduction: The transcription factor Smad 3, a member of the TGFβ signaling cascade, contributes to G1 cell cycle arrest in breast cancer cell lines. Overexpression of the cell cycle regulatory protein cyclin E, and its low molecular weight (LMW) counterparts, has been associated with poor prognosis in breast cancer. Cyclin E has been shown to mediate phosphorylation within or near the linker region of Smad 3 by cyclin dependent kinase 2 (CDK 2), and to inhibit Smad 3 activity in normal mouse fibroblasts and epithelial cells. We hypothesize that overexpression of cyclin E may exert tumorigenic effects in breast cancer cell lines through the functional inhibition of Smad 3 mediated by CDK 2 phosphorylation.&amp;#x2028; Methods: Endogenous levels of Smad 3 and phosphorylated Smad 3 in parental, vector only control, full length (FL), and two LMW forms of cyclin E overexpressing MCF-7 breast cancer cell lines were determined by western blotting. To elucidate the impact of cyclin E overexpression on Smad 3 function, constructs containing an empty vector, WT Smad 3, Smad 3 with a CDK phosphorylation site mutation within the linker region (Thr178), and outside the linker region (Thr8) were co-transfected with a Smad 3 reporter into the panel of MCF-7 cells. CDK2 or scrambled control siRNA was also transfected into the study panel of cells. Smad 3 function was then evaluated by luciferase reporter assays.&amp;#x2028; Results: MCF-7 cells overexpressing FL or LMW cyclin E had a higher level of P- SMAD 3 as compared to the parental and vector only control cells. Total SMAD 3 levels were similar in all cells examined. Transfection of WT Smad 3 elicited an increase in reporter activity in parental and vector control cells, while both FL and LMW forms of cyclin E overexpressing cells were resistant to WT Smad 3 reporter induction. In parental and vector control MCF-7 cells, expression of the Smad 3 Thr178 mutation resulted in a three-fold induction in Smad 3 reporter activity as compared to the WT Smad 3 response. In FL and LMW cyclin E overexpressing cells, induction by the Thr178 mutation was more pronounced, as seen by a 5-fold and 8-fold induction of reporter activity in FL and LMW cyclin E cells, respectively. Transient transfection of the Thr8 mutation failed to evoke a reporter response in any of the panel of MCF-7 cells. MCF-7, FL, and LMW cyclin E cells demonstrated the greatest fold induction of Smad 3 reporter activity when transfected with CDK 2 siRNA.&amp;#x2028; Conclusions: Overexpression of cyclin E may circumvent the growth inhibitory effects of Smad 3 signal transduction through the modulation of Smad 3 function. Specifically, this work indicates that cyclin E mediates Smad 3 inhibition in a CDK 2 dependent fashion in breast cancer cells. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5033.
Pancreatic stone protein as a novel marker for neonatal sepsis
Authors: Luregn J. Schlapbach, Rolf Graf, Andreas Woerner, Matteo Fontana, Urs Zimmermann-Baer, David Glauser, Eric Giannoni, Thierry Roger, Christoph Müller, Mathias Nelle, Martin Stocker
Journal: Intensive Care Medicine (2013)
A Systematic Review and Meta-analysis on the Use of Phosphodiesterase 5 Inhibitors Alone or in Combination with α-Blockers for Lower Urinary Tract Symptoms Due to Benign Prostatic Hyperplasia
Authors: Mauro Gacci, Giovanni Corona, Matteo Salvi, Linda Vignozzi, Kevin T. McVary, Steven A. Kaplan, Claus G. Roehrborn, Sergio Serni, Vincenzo Mirone, Marco Carini, Mario Maggi
Journal: European Urology (2012)
Mobile Phones, Brain Tumors, and the Interphone Study: Where Are We Now?
Authors: Anthony J. Swerdlow, Maria Feychting, Adele C. Green, Leeka Kheifets, David A. Savitz
Journal: Environmental Health Perspectives (2011)

Background: In the past 15 years, mobile telephone use has evolved from an uncommon activity to one with > 4.6 billion subscriptions worldwide. However, there is public concern about the possibility that mobile phones might cause cancer, especially brain tumors.Objectives: We reviewed the evidence on whether mobile phone use raises the risk of the main types of brain tumor—glioma and meningioma—with a particular focus on the recent publication of the largest epidemiologic study yet: the 13-country Interphone Study.Discussion: Methodological deficits limit the conclusions that can be drawn from the Interphone study, but its results, along with those from other epidemiologic, biological, and animal studies and brain tumor incidence trends, suggest that within about 10–15 years after first use of mobile phones there is unlikely to be a material increase in the risk of brain tumors in adults. Data for childhood tumors and for periods beyond 15 years are currently lacking.Conclusions: Although there remains some uncertainty, the trend in the accumulating evidence is increasingly against the hypothesis that mobile phone use can cause brain tumors in adults.
Silicone-Induced Splenomegaly
Authors: Jürgen Bommer, Eberhard Ritz, Rüdiger Waldherr
Journal: New England Journal of Medicine (1981)

SPLENIC sequestration of blood cells has been identified by several investigators as one cause of pancytopenia in dialyzed patients.1 , 2 In the case described below, a foreign-body reaction to silicone in the spleen was identified as a cause of pancytopenia, which responded to splenectomy.Case ReportThe patient was a woman born in 1920, who had polycystic kidneys. In February 1971, her serum creatinine was 9.1 mg per deciliter, her hemoglobin was 12.8 g per deciliter, her leukocyte count was 6500 per microliter, and her platelet count was 204,000 per microliter. Since November 1971, she has been receiving maintenance hemodialysis — . . .
Sudden onset of headache and recent breathlessness
Authors: R. Ramaraj
Journal: BMJ (2008)

A 70 year old man presented with a 30 minute history of throbbing left sided headache that woke him from sleep. He had no history of headache or recent head injury. He also described a four day history of breathlessness when climbing one flight of stairs. He was taking tablets for type 2 diabetes mellitus, hypertension, and congestive cardiac failure. He did not smoke and drank seven units of alcohol a week. The patient was alert and oriented, with a heart rate of 100 beats/minute and a blood pressure of 150/90 mm Hg. Respiratory rate was 16 breaths per minute, oxygen saturation was 98% on air, and his lungs were clear to auscultation. An early diastolic murmur was heard at the base of the heart. He had no temporal artery tenderness or neck stiffness. Haemoglobin was 13.2 g/l; white blood cell count was 7×109 cells/l; urea and electrolytes, liver function, and renal function were normal; and the erythrocyte sedimentation rate was 30 mm/hour (normal <20 mm/hour in men over 50). Electrocardiography showed sinus tachycardia. The results of chest radiography and computed tomography of the brain were normal. He reported increasing headache with radiation down the cervical spine. At this time, blood pressure was 173/88 mm Hg in the right arm and 140/62 mm Hg in the left arm. ### Short answers
My 27 year wait for an NHS diagnosis
Authors: C. Mansley
Journal: BMJ (1996)

The Giilles De La Tourette Syndrome makes a customary appearance in the Christmas issue of the BMJ where it has usually been given a somewhat frivolous treatment. But sufferers have deeper insights into the condition.

When I was a few months old I exhibited hyperactive behaviour and Tourette's Syndrome first manifested itself at the age of 2. The compulsive destruction of objects and people started at 3 and resulted in beatings from my parents. When I started school the compulsive behaviour increased in severity, resulting in a social worker being called in. She observed the compulsive behaviour which manifested itself in motor tics, grunting, sniffing, touching, counting, checking, twirling round in circles, nipping people, throwing things, making obscene gestures (copropraxia), repeating other people's word (echolalia), repeating my own words (palilalia), repeating other people's body movements (echopraxia), and throat clearing. Thirty …
Effect of hormone replacement therapy on the pathological stage of breast cancer: population based, cross sectional study
Authors: S. Stallard
Journal: BMJ (2000)

Hormone replacement therapy is being used increasingly. Although it is known that the risk of developing breast cancer is slightly increased with long term use,1 hormone replacement does not seem to adversely affect mortality from breast cancer.2

Studies have suggested that users of hormone replacement who get breast cancer develop tumours with “favourable” pathological features compared with non-users. One study included women who had been detected at screening and women who had presented with symptoms, with more screen detected women in the study group (users) than in the controls (non-users).2 Another study compared type of tumour in users and non-users in a screen detected population alone3 and showed that grade 1, node negative tumours were more common in the users.

Women with breast cancer who have used hormone replacement, however, may be more likely to have a cancer that was missed at screening; we have shown that women who develop such cancers (interval cancers) within …
AgRP neurons regulate development of dopamine neuronal plasticity and nonfood-associated behaviors
Authors: Marcelo O Dietrich, Jeremy Bober, Jozélia G Ferreira, Luis A Tellez, Yann S Mineur, Diogo O Souza, Xiao-Bing Gao, Marina R Picciotto, Ivan Araújo, Zhong-Wu Liu, Tamas L Horvath
Journal: Nature Neuroscience (2012)
Relationships of Human Papillomavirus Type, Qualitative Viral Load, and Age with Cytologic Abnormality
Authors: Melinda Butsch Kovacic, Philip E. Castle, Rolando Herrero, Mark Schiffman, Mark E. Sherman, Sholom Wacholder, Ana C. Rodriguez, Martha L. Hutchinson, M. Concepción Bratti, Allan Hildesheim, Jorge Morales, Mario Alfaro, Robert D. Burk
Journal: Cancer Research (2006)

Abstract Persistent cervical infections with carcinogenic human papillomaviruses (HPV) cause virtually all cervical cancer. Cytologic abnormalities are the manifestations of HPV infections used to identify women at risk. To compare the potential of the full range of anogenital HPV genotypes to induce cytopathic effects, we examined the influences of HPV type, viral load, and age on cytopathology among 1,222 women having a single HPV type at enrollment into a 10,000-woman population-based study in Costa Rica. Cervical specimens were tested for ∼40 HPV types by MY09/MY11 L1 primer PCR and type-specific dot blot hybridization. Types were organized by phylogenetic species and cancer risk. PCR signal strength served as a qualitative surrogate for viral load. Overall, 24.8% [95% confidence interval (95% CI), 22.4-27.3] of single prevalent HPV infections had concurrent abnormalities (atypical squamous cells or worse) ranging from 0.0% to 80.0% based on HPV type. Noncarcinogenic α3/α15 types, although highly prevalent, uncommonly caused cytologic abnormalities (13.1%; 95% CI, 9.8-17.0). In contrast, one quarter to nearly one half of infections with a single major carcinogenic species type (α9/α11/α7/α5/α6) produced abnormalities. Greater abnormalities were observed with increasing qualitative viral load of carcinogenic types; fewer abnormalities were observed among older women (&amp;gt;54 years). A high percentage (46.2%) of detected abnormalities in women infected with HPV16 or related α9 types were high grade or worse, consistent with strong carcinogenicity, compared with 10.7% in women infected with α7 types, including HPV18, a major cause of adenocarcinoma. The lack of evident severe abnormalities associated with HPV18 and related HPV types might have implications for screening for poorly detected glandular and α7-related lesions. (Cancer Res 2006; 66(20): 10112-9)
Law for Doctors
Authors: Marshall B. Kapp
Journal: Annals of Internal Medicine (2001)

Medical Writings: Book Notes21 August 2001Law for DoctorsMarshall B. Kapp, JD, MPHMarshall B. Kapp, JD, MPHWright State University School of Medicine, Dayton, Ohio. (Kapp)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-135-4-200108210-00034 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Leung WC. 190 pages. Malden, MA: Blackwell Science; 2000. $49.95. ISBN 0632052430. Order phone 800-759-6102.Field of medicine: Legal medicine.Format: Softcover book.Audience: Physicians in all fields, especially those practicing in the United Kingdom.Purpose: To provide concise, practical legal information and guidance for physicians.Content: The first part of the book deals with legal questions that arise in the physician–patient relationship, such as consent to treatment, confidentiality, and relief of symptoms in terminally ill patients. The next part concentrates on the various contexts in which physicians' actions may be challenged legally: for example, vicarious liability, product liability, and ... Author, Article, and Disclosure InformationAffiliations: Wright State University School of Medicine, Dayton, Ohio. (Kapp) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 21 August 2001Volume 135, Issue 4Page: 308KeywordsMedical lawSoftware tools ePublished: 21 August 2001 Issue Published: 21 August 2001 Copyright & PermissionsCopyright © 2001 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Developmental changes in the cardiac effects of amrinone in the dog.
Authors: O Binah, M J Legato, P Danilo, M R Rosen
Journal: Circulation Research (1983)

Amrinone, a bipyridine compound, has been shown to exert a positive inotropic effect on the heart, without producing cardiac arrhythmias. Because of preliminary observations suggesting that the actions of amrinone might change significantly with growth and development, we studied its effects on the contractility and electrophysiology of isolated cardiac muscle of 0- to 96-day-old beagles and Purkinje fibers of 5-year-old beagles. Amrinone's effects on ventricular muscle contractility were age-related. A significant decrease in contractility of right ventricular trabeculae and papillary muscles (not associated with changes in action potential characteristics) was observed in the 0- to 3-day newborn, whereas, by day 4-10, amrinone increased contractility. The magnitude of the increase became greater through day 96 of life. The negative inotropic effect of amrinone is unassociated with changes in the action potential plateau, suggesting that the slow inward current is not involved in this mechanism.
CATHETER BASED, PERCUTANEOUS MITRAL VALVE CLIPPING - THE ADDED VALUE OF REAL TIME TRANSESOPHAGEAL ECHOCARDIOGRAPHY
Authors: Robert J. Siegel, Gila Perk, Takahiro Shiota, Itzhak Kronzon, James Slater, Saibal Kar, Asma Hussani, Simon Biner
Journal: Journal of the American College of Cardiology (2010)
Transmural differences in sympathetic coronary constriction during exercise in the presence of coronary stenosis.
Authors: W M Chilian, P H Ackell
Journal: Circulation Research (1988)

The goal of this study was to determine the effect of sympathetic neural activation on the transmural distribution of myocardial perfusion distal to a flow-limiting coronary artery stenosis. Treadmill exercise in conscious dogs was used as a physiological stimulus to activate the sympathetic nervous system. In the experimental model, the anterior region of the circumflex artery was innervated, but the posterior circumflex region was treated with phenol to produce regional sympathectomy within the stenotic territory. Myocardial perfusion to innervated and sympathectomized left ventricular regions was measured before and after inflation of the occluder to reduce distal coronary pressure to 45 mm Hg. Measurements were obtained during control conditions with the animal standing on the treadmill, during inflation of the occluder with the animal standing, during exercise alone, during exercise with beta-adrenergic blockade, and during exercise with combined alpha- and beta-adrenergic blockade. Exercise (6 km/hr) resulted in a marked increase in heart rate from 128 +/- 9 (standing) to 218 +/- 7 beats/min. beta-Adrenergic blockade blunted the tachycardia during exercise (146 +/- 6 beats/min). Under control conditions (while standing), there were no differences in myocardial perfusion between the innervated and sympathectomized regions, 187 +/- 26 and 181 +/- 24 ml.min-1.100 g-1, respectively. During exercise or in combination with beta-adrenergic blockade, subepicardial perfusion was significantly less (18-25%) in the innervated stenotic region than that in the sympathectomized stenotic region. In contrast, subendocardial perfusion was significantly greater in the innervated stenotic region (17-26%) than that in the sympathectomized stenotic region. The subendocardial-to-subepicardial blood flow ratio during exercise was 0.60 +/- 0.08 in the innervated stenotic region and 0.42 +/- 0.07 in the sympathectomized stenotic region (p less than 0.05). During exercise with beta-adrenergic blockade, the endocardial-to-epicardial blood flow ratios in the innervated and sympathectomized stenotic regions were 0.47 +/- 0.09 and 0.37 +/- 0.07, respectively (p less than 0.05). These differences were abolished during alpha- and beta-adrenergic blockade. These data indicate that alpha-adrenergic coronary constriction distal to a flow-limiting stenosis facilitates redistribution of blood flow toward the subendocardium. This redistribution was produced by alpha-adrenergic constriction in the outer layers of the left ventricle.
INTERLEUKIN-1β NEUTRALIZATION AMELIORATES POST-INFARCTION CARDIAC REMODELING IN THE MOUSE
Authors: Antonio Abbate, Benjamin W. Van Tassell, Ignacio M. Seropian, Stefano Toldo, Fadi N. Salloum, Amit Varma, Charles A. Dinarello
Journal: Journal of the American College of Cardiology (2010)
Recommendations to Guide Revision of the &lt;EMPH TYPE="ITAL"&gt;Guides to the Evaluation of Permanent Impairment&lt;/EMPH&gt;
Authors: Emily A. Spieler
Journal: JAMA (2000)

The American Medical Association's Guides to the Evaluation of Permanent Impairment, Fourth Edition, is the most commonly used tool in the United States for rating permanent impairments for disability systems. The Guides, currently undergoing revision, has been the focus of considerable controversy. Criticisms have focused on 2 areas: internal deficiencies, including the lack of a comprehensive, valid, reliable, unbiased, and evidence-based system for rating impairments; and the way in which workers' compensation systems use the ratings, resulting in inappropriate compensation. We focus on the internal deficiencies and recommend that the Guides remains a tool for evaluation of permanent impairment, not disability. To maintain wide acceptance of the Guides, its authors need to improve the validity, internal consistency, and comprehensiveness of the ratings; document reliability and reproducibility of the results; and make the Guides easily comprehensible and accessible to physicians.
B-Type Natriuretic Peptide Signal Peptide Circulates in Human Blood
Authors: Maithri Siriwardena, Torsten Kleffmann, Peter Ruygrok, Vicky A. Cameron, Tim G. Yandle, M. Gary Nicholls, A. Mark Richards, Chris J. Pemberton
Journal: Circulation (2010)

The diagnosis of cardiac necrosis such as myocardial infarction can be difficult and relies on the use of circulating protein markers like troponin. However, there is a clear need to identify circulating, specific biomarkers that can detect cardiac ischemia without necrosis.Using specific immunoassay and tandem mass spectrometry, we show that a fragment derived from the signal peptide of B-type natriuretic peptide (BNPsp) not only is detectable in cytosolic extracts of explant human heart tissue but also is secreted from the heart into the circulation of healthy individuals. Furthermore, plasma levels of BNPsp in patients with documented acute ST-elevation myocardial infarction (n=25) rise to peak values ( approximately 3 times higher than the 99th percentile of the normal range) significantly earlier than the currently used biomarkers myoglobin, creatine kinase-MB, and troponin. Preliminary receiver-operating characteristic curve analysis comparing BNPsp concentrations in ST-elevation myocardial infarction patients and other patient groups was positive (area under the curve=0.97; P<0.001), suggesting that further, more rigorous studies in heterogeneous chest pain patient cohorts are warranted.Our results demonstrate for the first time that BNPsp exists as a distinct entity in the human circulation and could serve as a new class of circulating biomarker with the potential to accelerate the clinical diagnosis of cardiac ischemia and myocardial infarction. Clinical Trial Registration- URL: http://www.anzctr.org.au. Unique identifier: ACTRN12609000040268.
Psychosocial Intervention in Cancer
Authors: D. Spiegel
Journal: JNCI Journal of the National Cancer Institute (1993)

The following commentary, the fourth of a five-part series to be published in the Journal, summarizes a presentation from a minisymposium addressing some of the issues of “living with cancer.” The minisymposium was presented to the National Cancer Advisory Board in 1992. It is our hope that these commentaries will stimulate new research initiatives and changes in current health care education and practice, as well as in health policy, to make living with cancer a more humane experience.
Immunisation against influenza among people aged over 65 living at home in Leicestershire during winter 1991-2.
Authors: K G Nicholson
Journal: BMJ (1993)

To assess the size of the elderly population for whom influenza vaccine is indicated and how many are vaccinated.Cohort questionnaire study.Leicestershire general practices.800 elderly subjects selected a random from the Leicestershire family health services authority list who were not living in residential care, 565 of whom returned a questionnaire.Patient profile, vaccine offers, vaccination status, and reasons for not accepting vaccine.170 of 334 (51%) people aged 65-74 years and 106 of 205 (52%) aged > or = 75 years had one or more medical indications for influenza vaccine. 195 people were offered vaccine, 49 of whom had no risk factor. 152 offers were made opportunistically during visits to the practice and only six were made in writing or by telephone. Overall 113 of 266 patients with known medical indications were immunised. Vaccine was accepted by 148 of 189 (78%) offered it, and, as judged by acceptance in sequential years, influenza vaccine was well tolerated. The main reasons for not being vaccinated were misconception about risk status and inadequate advice from doctors.The prevalence of medical indications for vaccine is not large enough to justify a policy of universal immunisation. Most patients offered vaccine accept it and tolerate it well. Improved targeting and education is needed to increase immunisation of people at risk.
OCT-Verified Neointimal Hyperplasia Is Increased at Fracture Site in Drug-Eluting Stents
Authors: Manabu Kashiwagi, Atsushi Tanaka, Hironori Kitabata, Yasushi Ino, Hiroto Tsujioka, Kenichi Komukai, Yuichi Ozaki, Kohei Ishibashi, Takashi Tanimoto, Shigeho Takarada, Takashi Kubo, Kumiko Hirata, Masato Mizukoshi, Toshio Imanishi, Takashi Akasaka
Journal: JACC. Cardiovascular imaging (2012)
Diminished Schwann Cell Repair Responses Underlie Age-Associated Impaired Axonal Regeneration
Authors: Michio W. Painter, Amanda Brosius Lutz, Yung-Chih Cheng, Alban Latremoliere, Kelly Duong, Christine M. Miller, Sean Posada, Enrique J. Cobos, Alice X. Zhang, Amy J. Wagers, Leif A. Havton, Ben Barres, Takao Omura, Clifford J. Woolf
Journal: Neuron (2014)