tbuckley/cabot-search huggingface dataset:
P2-12-13: Topoisomerase 2 alpha (TOP2A) RNA Expression Provides Prognostic Information in Hormone Receptor Positive Breast Cancer That Is Complementary to a Simulated Algorithm for Recurrence Score.
Authors: JA Sparano, LJ Goldstein, NE Davidson, Jr GW Sledge,, R Gray
Journal: Cancer Research (2011)

Abstract Background We have previously reported that TOP2A RNA expression was prognostic in patients with operable estrogen receptor (ER) positive breast cancer treated with anthracycline containing adjuvant chemotherapy plus endocrine therapy in trial E2197, and provided complementary prognostic information in those who had a mid-range Recurrence Score (RS) (Sparano et al. Clin Cancer Res 2009; 15; 7693). The purpose of this analysis was to provide additional evidence regarding this observation. Methods: We evaluated TOP2A RNA expression in 4 independent data sets individually and in a pooled analysis including all data. We also used an algorithm to simulate the Oncotype DX Recurrence Score (SimRS). The analysis included 752 patients with early stage breast cancer that was ER-positive, HER2−negative defined by gene expression. Results are expressed as the hazard ratio (HR) for estimates of the effect of a one standard deviation increase in the value of the log gene expression (x + 1SD vs. x) as a continuous function. Five-year relapse free survival (RFS) rates were also evaluated for patients with a mid-range SimRS for high vs. low TOP2A expression (above vs. below the median, which was prognostic in E2197). The distribution of SimRS was categorized to be concordant with the distribution of actual RS in E2197 (47%, 34%, 19%, respectively for RS &amp;lt;18 - low, 18–30 - intermediate, &amp;gt;31 - high). Results: The HR for models including TOP2A alone and joint models including TOP2A and SimRS are shown in the table. TOP2A expression was significantly associated with recurrence in all 4 datasets when evaluated individually (HR 1.56, p&amp;lt;0.0001 in pooled analysis), and 2 of 4 datasets individually when adjusted for SimRS (HR 1.26, p=0.003 in pooled analysis). SimRS was significantly prognostic when adjusted for TOP2A individually in 3 of 4 datasets (HR 1.44, p&amp;lt;0.0001 in pooled analysis). For those with an intermediate SimRS, five year RFS rates were significantly higher in 2 datasets individually for high vs. low TOP2A expression (HR 1.82, p=0.007 in pooled analysis). Conclusions: This analysis provides additional evidence that TOP2A expression provides prognostic information in patients with ER-positive, HER2−negative disease, a population known to have low incidence of TOP2A gene alterations. These findings also suggest that TOP2A expression provides information that is complementary to RS, and may be useful for identifying high risk subjects who have a mid-range RS. These findings require prospective validation in other prospective or prospective-retrospective trials using the actual rather than simulated RS. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-12-13.
Hypoxia and the hypoxia-inducible-factor pathway in glioma growth and angiogenesis
Authors: Balveen Kaur, Fatima W. Khwaja, Eric A. Severson, Shannon L. Matheny, Daniel J. Brat, Erwin G. Van Meir
Journal: Neuro-Oncology (2005)

Glioblastomas, like other solid tumors, have extensive areas of hypoxia and necrosis. The importance of hypoxia in driving tumor growth is receiving increased attention. Hypoxia-inducible factor 1 (HIF-1) is one of the master regulators that orchestrate the cellular responses to hypoxia. It is a heterodimeric transcription factor composed of alpha and beta subunits. The alpha subunit is stable in hypoxic conditions but is rapidly degraded in normoxia. The function of HIF-1 is also modulated by several molecular mechanisms that regulate its synthesis, degradation, and transcriptional activity. Upon stabilization or activation, HIF-1 translocates to the nucleus and induces transcription of its downstream target genes. Most important to gliomagenesis, HIF-1 is a potent activator of angiogenesis and invasion through its upregulation of target genes critical for these functions. Activation of the HIF-1 pathway is a common feature of gliomas and may explain the intense vascular hyperplasia often seen in glioblastoma multiforme. Activation of HIF results in the activation of vascular endothelial growth factors, vascular endothelial growth factor receptors, matrix metalloproteinases, plasminogen activator inhibitor, transforming growth factors alpha and beta, angiopoietin and Tie receptors, endothelin-1, inducible nitric oxide synthase, adrenomedullin, and erythropoietin, which all affect glioma angiogenesis. In conclusion, HIF is a critical regulatory factor in the tumor microenvironment because of its central role in promoting proangiogenic and invasive properties. While HIF activation strongly promotes angiogenesis, the emerging vasculature is often abnormal, leading to a vicious cycle that causes further hypoxia and HIF upregulation.
Benjamin Rush on Politics and Human Nature
Authors: Eric T. Carlson
Journal: JAMA (1976)

Of the dedicated band of 57 men who put their signatures to the Declaration of Independence on July 4, 1776, five were physicians—Josiah Bartlett and Matthew Thornton of New Hampshire, Lyman Hall and Oliver Wolcott of Connecticut, and Benjamin Rush of Pennsylvania. Rush, in particular, would soon exert a great influence on the new nation, both in medicine and politics, and he took special pride in participating in the independence effort<i>as a physician</i>, for he believed physicians were naturally inclined to patriotism, and that they had a great opportunity to exercise it.<sup>1</sup> Rush had begun agitating for political reform two years earlier. Angered like so many others by the June 1773 Act of Parliament that placed an import tax on tea, he published a series of articles in a Philadelphia newspaper under the pseudonym "Hamden," after John Hampden, hero of the Cromwellian rebellion, who had died fighting for
THE RELATION OF THE PHYSICIAN TO PROPRIETARY REMEDIES.HOW MAY SUBSTITUTION BE AVOIDED AND THE DESIRED PREPARATION OBTAINED WITHOUT UNDULY ADVERTISING THE MANUFACTURER?
Authors: WILLIAM J. ROBINSON
Journal: JAMA (1904)

In their relation to proprietary preparations, physicians may be divided into three classes: A, B and C. To class A, unfortunately a very numerous class, belong those physicians who prescribe everything and anything that is brought to their notice. The composition of the products they prescribe is a matter of utter indifference to them. The prescribed product may consist of two or three well-known substances; it may be as common a substance as sodium bicarbonate under a disguised name, or it may contain morphin, strychnin, pilocarpin or other dangerous alkaloids in a strong alcoholic menstruum—they care not. It answers, or they think it answers, the intended purpose and they are satisfied. They are supported and encouraged in this attitude by such journals as the<i>Medical Brief</i>, of which many physicians of class A are readers, if not subscribers. What our opinion is of such physician it is
Sensitivity testing for Helicobacter pylori should be more widely available
Authors: G Cammarota, A Tursi, A Papa, G Fedeli, G Gasbarrini
Journal: BMJ (1996)

EDITOR,—Greg Rubin and Richard Stevens are right to ask for the wider availability of non-invasive diagnostic tests for managing Helicobacter pylori infection in primary care.1 We believe that the implementation of management guidelines for peptic ulcer disease also requires the wider availability of tests to determine the sensitivity of H pylori, because increased prescribing of antimicrobial drugs to treat the infection may be associated with increased drug resistance. Furthermore, our data indicate that if the global eradication …
Limitations of Solid-Phase Radioimmunoassay for HB Ag in Reducing Frequency of Post-Transfusion Hepatitis
Authors: F. Blaine Hollinger, Richard D. Aach, Gary L. Gitnick, James K. Roche, Joseph L. Melnick
Journal: New England Journal of Medicine (1973)

Abstract To determine if a recently licensed radioimmunoassay (Ausria-125) would further reduce the incidence of type B hepatitis, 139 presumably susceptible recipients were prospectively studied after they had received blood negative for hepatitis B antigen by counterelectrophoresis. Fifteen cases of icteric or anicteric hepatitis occurred, but only four could be attributed to hepatitis B. No hepatitis B occurred in nine subjects who received radioimmunoassay-positive blood alone, and only one in 10 who had received radioimmunoassay-positive and hepatitis-B-antigen-positive blood. Type B hepatitis developed in three of 120 patients who received radioimmunoassay-negative blood, If serologic responses only are compared, exposure to hepatitis B or hepatitis B antigen occurred in six of 19 recipients (31.6 per cent) of radioimmunoassay-positive blood. Only eight of 120 (6.7 per cent) responded among the recipients of radioimmunoassay-negative blood. These findings do not support proposals for universal compu...
Parkinson's disease: a journey
Authors: Kamran Abbasi
Journal: BMJ (2004)

Some drugs are like weapons of mass destruction: often heard about but seldom seen. Selegiline, a monoamine oxidase type B inhibitor, was hailed in the 1980s as a drug that might alter the clinical course of idiopathic Parkinson's disease—and not just relieve symptoms (p 581). A research paper published in the BMJ in 1995 (bmj.com/cgi/content/full/311/7020/1602) curbed that optimism by indicating that people taking selegiline and levodopa had a higher risk of death than those taking levodopa alone. Now this week's issue carries a meta-analysis of 17 trials comparing monoamine oxidase type B inhibitors with placebo and finds …
Nutrition and Bone Disease
Authors: J. C. Gallagher, B. Lawrence Riggs
Journal: New England Journal of Medicine (1978)

THE most important nutrients affecting bone are vitamin D, calcium, and phosphorus.Vitamin DVitamin D is obtained either from the diet or from endogenous production in the skin after exposure to ultraviolet light. Wavelengths capable of photoactivation of precursors to vitamin D in the skin occur in northern parts of America from March through October. Dermal production of vitamin D after extensive ultraviolet radiation may be as much as 10,000 units per day. Vitamin D undergoes hydroxylation at the 25-position in the liver and at the 1-position in the kidney to produce 1,25-dihydroxyvitamin D, the physiologically important, active form . . .
The Treatment of Hemophilia
Authors: Harold R. Roberts
Journal: New England Journal of Medicine (1989)

Concentrated preparations of factor VIII became commercially available in 1965 and were soon widely used in the United States and throughout the world to treat hemophilia. The development of these concentrates represented a tremendous therapeutic advance. The enthusiasm that greeted them was only mildly dampened by the early realization that all factor VIII products were contaminated with hepatitis viruses and by the resulting epidemic of hepatitis B and non-A, non-B hepatitis among people with hemophilia. Although 90 percent of the patients severely affected with hemophilia eventually became seropositive for hepatitis B antibody and although non-A, non-B hepatitis was thought to . . .
Malignant melanoma metastasis to the colon
Authors: S.-L. Yan, C.-C. Yang, Y.-T. Liu
Journal: Endoscopy (2006)

The large intestine is the least common site in the gastrointestinal tract for malignant melanoma metastases, and does not appear to be a site of primary tumor [1]. Endoscopically, metastatic melanoma may present as submucosal nodules, polypoid masses, or colonic intussusception [1] [2], or as a large exophytic mass that mimicks colon cancer [3]. The liver is the site most commonly affected by melanoma metastases, and the most common cause of death is respiratory failure resulting from pulmonary invasion by tumor cells [2]. We report here a case which demonstrates the typical findings of metastatic melanoma involving the colon.
Letter by Magalhaes et al Regarding Article, “Long-Term Survival and Repeat Coronary Revascularization in Dialysis Patients After Surgical and Percutaneous Coronary Revascularization With Drug-Eluting and Bare Metal Stents in the United States”
Authors: Marco A. Magalhaes, Israel M. Barbash, Ron Waksman
Journal: Circulation (2013)
Percutaneous closure of atrial septal defect under intracardiac ultrasound guidance: comparison with procedures guided by transesophageal echocardiography
Authors: Eulogio Garcia, Enrique Maroto, Raul Moreno, Ignacio Zabala, Oscar Diaz-Castro, Carlos Maroto, Jose L. Zunzunegui, Ruben Greco
Journal: Journal of the American College of Cardiology (2002)
Fish zona radiata (eggshell) protein: a sensitive biomarker for environmental estrogens.
Authors: A Arukwe, F R Knudsen, A Goksøyr
Journal: Environmental Health Perspectives (1997)

Environmental estrogens have recently caused great concern because of their ability to mimic natural hormones and influence vital endocrine functions in humans and wildlife. The induction of vitellogenin (Vtg) synthesis by environmental estrogens in viviparous vertebrates has been proposed as an effective and sensitive biomarker of estrogenicity. Immunochemical analysis of plasma from Atlantic salmon (Salmo salar) exposed to 4-nonylphenol (NP) or to effluent from oil refinery treatment plant (ORTP), shows that NP and ORTP effluent induces Vtg and zona radiata proteins (Zrp) in a dose-dependent manner. However, Zrp-beta cross-reactive proteins are more responsive than Zrp-alpha, Zrp-gamma, and Vtg. The sensitivity of Zrp induction points to the zona radiata proteins as alternate biomarkers of estrogenicity.
Physicians' Forecasts of Medical Practice: Why is the Glass Half Empty?
Authors: MALCOLM L. PETERSON
Journal: Annals of Internal Medicine (1982)

Editorials1 November 1982Physicians' Forecasts of Medical Practice: Why is the Glass Half Empty?MALCOLM L. PETERSON, M.D., PH.D.MALCOLM L. PETERSON, M.D., PH.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-97-5-778 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptWhy would nearly half of the physicians in the practice of medicine in this country not recommend their profession to a young person today as highly as they might have 10 years ago? In a poll commissioned by the Kaiser Family Foundation and conducted in 1981 by Louis Harris and Associates (1), 48% of the 1814 physicians surveyed said they were less inclined to recommend a career in medicine; their views hinged on six points: loss of autonomy (as reflected in government regulations and third party controls); loss of personal satisfaction (through erosion of the doctor-patient relationship and the public's...References1. . Medical Practice in the I980's: Physicians Look at their Changing Profession. Menlo Park, California: The Henry J. Kaiser Family Foundation; 1981. Google Scholar2. LESERMAN J. Changes in the professional orientation of medical students: a follow-up study. J Med Educ. 1980;55:415-22. MedlineGoogle Scholar3. Report of the Graduate Medical Education National Advisory Committee: Volume 1. Summary Report. Hyattsville, Maryland: Health Resources Administration; 1980. DHHS publication no. (HRA) 81-651. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: MALCOLM L. PETERSON, M.D., PH.D. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byInfluence of medical and premedical education on important personal qualities of physiciansThe impact of the expanding supply of physicians on continuing medical education 1 November 1982Volume 97, Issue 5Page: 778-779 ePublished: 1 December 2008 Issue Published: 1 November 1982 PDF downloadLoading ...
Transgenic mouse model: a new approach for the investigation of endocrine pancreatic B-cell growth.
Authors: R F Power, R Holm, A E Bishop, I M Varndell, S Alpert, D Hanahan, J M Polak
Journal: Gut (1987)

The transformation and adaptation of pancreatic insulin-producing (B) cells has been studied in a transgenic mouse model using a panel of antisera recognising peptides and general neuroendocrine markers at both light and electron microscopical levels. Stages of tumour genesis in the transgenic mouse model from hyperplasia to neoplasia, have been compared with human B-cell tumours. A normal complement of peptide containing cells was seen in the transgenic mouse pancreas, but cells containing pro-insulin-derived peptides became more numerous as hyperplasia commenced. The transgenic mouse tumours were composed of B cells, although 30-35% of the tumours were also found to contain PP cells--a finding which is directly comparable with that in human insulin-producing tumours. NSE, 7B2 and chromogranin immunoreactivities were found in most cells from all the tumours examined. Antisera to PGP 9.5, a novel marker for elements of the neuroendocrine system, were found to stain hyperplastic and neoplastic B-cells intensely. In contrast, normal mouse B-cells did not show PGP 9.5 immunoreactivity thus it appears that PGP 9.5 is differentially expressed in transformed and/or growing mouse B-cells and hence may be used as an indicator in studies of early tumour growth.
The use and impact of inquiries in the NHS
Authors: K. Walshe
Journal: BMJ (2002)

When things go wrong in the NHS an inquiry is often set up to find how what happened and what can be learnt. Kieran Walshe and Joan Higgins show that since the 1970s inquiries have been resorted to increasingly often to investigate service failures. Such inquiries take various forms, but the pressures seem to be increasing for them to be set up as independent external investigations with full inquisitorial powers 

In the past few years the NHS has been subject to several major inquiries. Such inquiries have been established to investigate poor clinical performance, major service failure, or even criminal misconduct, and they seem to have become an increasingly common political and managerial response to any major problem in the NHS. As a result, the costs, methods and effects of inquiries have begun to be questioned.1

This paper explores the use and impact of inquiries in the NHS. It presents an overview of their history and development; describes their purposes and how and why they are set up; discusses the models, methods, and processes that inquiries use; and reviews how their findings and recommendations are used. We conclude with some lessons for policy makers and other stakeholders in the NHS, which might inform the design and conduct of future inquiries.

#### Summary points

We define an inquiry as a retrospective examination of events or circumstances surrounding a …
Abstract 397: Soluble Tumor Necrosis Factor Receptor shed by breast tumor cells modulates macrophage migration
Authors: Stephen Rego, Krista Ricci, Muthulekha Swamydas, Didier Dreau
Journal: Cancer Research (2012)

Abstract Tumor necrosis factor alpha (TNFα) present within the tumor microenvironment, especially in breast tumor with a strong inflammatory component, promotes tumor death. TNFα also stimulates the migration of immune cells including macrophages to the tumor site. Breast cancer cells express both TNFR1 and TNFR2, the cell surface receptors for TNFα. The breast tumor microenvironment also contains soluble forms of TNFR1 and TNFR2. We investigated the origins and effects of soluble TNFR1 and TNFR2 on monocyte/macrophage cell migration. Our results indicate that both sTNFR1 and sTNFR2 were shedded by tumor cells but also by stroma cells including adipocytes. In addition, the amounts of sTNFR2 shedded by adipocytes and 4T1 mammary tumor cells were significantly higher than the amounts of sTNFR2 shedded by normal murine epithelial NMuMG cells (p&amp;lt;0.05). The migration of M2 subtype macrophages but not of M1 subtype macrophages derived from either murine bone derived monocytes, J774 or Raw cells toward 4T1 mammary tumor cells’ conditioned media was significantly increased following treatment of 4T1 cells with the sheddase inhibitor TAPI-0 (p&amp;lt;0.05). Indeed, TAPI-0 treatment decreased sTNFR2 concentrations in 4T1-conditioned media (p&amp;lt;0.05). These observations suggest a role for sTNFR1 and sTNFR2 in the dynamic interplays between immune and tumor cells during breast progression. (This works is supported by grants from the Department of Defense Era of Hope research program (BC044778) and the National Science Foundation EFRI program (CBE0736007) 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 397. doi:1538-7445.AM2012-397
Effects of living with and looking after survivors of a stroke.
Authors: D T Wade, J Legh-Smith, R L Hewer
Journal: BMJ (1986)

Information from a two year, longitudinal study on a community sample of patients with acute stroke was analysed to determine the effects of the stroke on the mood of the chief carer (the person living with the patient). Increased anxiety was the most commonly reported change six months after stroke. Significant depression was seen in 11-13% of carers over the first two years after stroke. The patient9s functional disability was associated with depression in the carer over the first year but not at two years. A perceived poor recovery by the patient, a low level of general activities by the patient, and depression in the patient were also associated with depression in the carer within the first year. At two years after stroke none of the measured factors were related to a carer9s level of depression. Carers of patients who have suffered stroke showed anxiety and emotional distress unrelated to the patient9s physical disability after two years. More help from stroke support groups for carers is perhaps needed.
THE CORTICOTROPIN-RELEASING-HORMONE TEST VERSUS THE HIGH-DOSE DEXAMETHASONE TEST IN THE DIFFERENTIAL DIAGNOSIS OF CUSHING'S SYNDROME
Authors: AdR. Hermus, GerardJ. Pesman, TheoJ. Benraad, GerlachF. Pieters, AnthonyG. Smals, PeterW. Kloppenborg
Journal: The Lancet (1986)
Knockout Science: Massive Mouse Project to Provide Window Into Human Diseases
Authors: Tracy Hampton
Journal: JAMA (2011)

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