tbuckley/cabot-search huggingface dataset:
Abstract A9: The cocaine and amphetamine-regulated transcript (CART) is an independent prognostic factor in lymph node-negative breast cancer and predicts outcome in tamoxifen treated patients
Authors: Darran O'Connor, Donal Brennan, Henriette Laursen, Rene Bernards, John Crown, Karin Jirstrom, William Gallagher
Journal: Clinical Cancer Research (2012)

Abstract The successful identification and translation of informative biomarkers to aid clinical decision making is central to the effective implementation of personalized cancer therapeutic regimens. Antibody-based proteomics occupies a pivotal space in the cancer biomarker discovery and validation pipeline, facilitating the high-throughput evaluation of candidate markers. We have applied this approach to identify the cocaine- and amphetamine-regulated transcript (CART) as an independent poor prognostic marker in early stage breast cancer. The management of lymph node-negative breast cancer is the subject of much debate and two large ongoing clinical trials with particular emphasis on the requirement for adjuvant chemotherapy. Here we demonstrate, by tissue microarray and automated image analysis using a consistently applied threshold for definition of CART levels (median intensity +/− 1 standard deviation), that the neuropeptide hormone CART is expressed in primary and metastatic breast cancer and is an independent poor prognostic factor in ER-positive (p=0.0003), lymph node-negative (p=0.0025) tumors in two large breast cancer cohorts (n&amp;gt;1000). Kaplan-Meier analysis and the log rank test were used to illustrate differences between overall survival (OS) and recurrence free survival (RFS) according to CART protein and mRNA expression. Cox regression proportional hazards models were used to estimate the relationship between outcome and CART expression, grade, age, nodal status, ER status, PR status, Her2, Ki-67 and tumor size. We also show that CART mediates an autocrine/paracrine effect leading to an amplification of the CART signal in breast cancer cells. Furthermore, we additionally demonstrate that CART increases the transcriptional activity of ERα in a ligand-independent manner via the mitogen-activated protein kinase (MAPK) pathway and that CART-High tumors express increased levels of ER-target genes. Finally, we show that ectopic expression of CART in two independent ER+ cell lines protects against tamoxifen-mediated cell death (p=0.025) and that high CART expression predicts outcome in 3 independent tamoxifen-treated cohorts (p=0.002). We clearly demonstrate that both pre- and postmenopausal patients with CART-positive tumors have a poor prognosis and are resistant to tamoxifen and therefore should receive aggressive adjuvant chemotherapy. We believe that CART profiling will facilitate stratification of lymph node-negative breast cancer patients into high- and low-risk categories and allow the personalization of therapy.
1075. Cellular Localization and Cell Cycle Dynamics of φC31 Integrase in Mammalian Cells
Authors: Robert T. Hillman, Lauren E. Woodard, Michele P. Calos
Journal: Molecular Therapy (2006)

Top of pageAbstract
Bacteriophage |[phiv]|C31 integrase is able to catalyze a unidirectional, site-specific DNA recombination reaction. Constrained target sequence preference, combined with an ability to function in a eukaryotic environment, have made |[phiv]|C31 integrase an important tool in higher organism genetic manipulation, including gene therapy applications. To better understand the properties of the enzyme in a mammalian cellular context, we constructed a plasmid expressing |[phiv]|C31 integrase with a hemagglutin (HA) epitope tag. Using immunoflurescence, we determined that |[phiv]|C31 integrase localized to the cytoplasm in HeLa cells. Intriguingly, we found that while |[phiv]|C31 integrase localization did not change during cell cycle progression, the absolute abundance of the enzyme declined rapidly after passage through the G1/S checkpoint. We have shown that this effect is due to degradation by the 26S proteasome. In cells treated with a chemical proteasome inhibitor, we found that |[phiv]|C31 integrase appeared to localize to a peri-centriolar inclusion body, as determined by co-staining of the centrosomal marker |[gamma]|-tubulin. Specialized centrosome-associated proteasomal complexes, known as 'aggresomes', have been identified as sites for clearance of misfolded or aggregated protein products. Our results suggest that, when expressed in cycling mammalian cells, |[phiv]|C31 integrase may be actively trafficked to aggresomes and degraded. The implications of these results for gene therapy and avenues to use this information for enhancement of the integration reaction will be presented.
Delayed animal aging through the recovery of stem cell senescence by platelet rich plasma
Authors: Hen-Yu Liu, Chiung-Fang Huang, Tzu-Chieh Lin, Ching-Yu Tsai, Szu-Yu Tina Chen, Alice Liu, Wei-Hong Chen, Hong-Jian Wei, Ming-Fu Wang, David F. Williams, Win-Ping Deng
Journal: Biomaterials (2014)
Student Medical Researchers and Their Contributions
Authors: William Carleton Gibson
Journal: New England Journal of Medicine (1961)

IT is always an honor to be asked to give the first annual lecture memorializing a member of the medical profession. I feel doubly honored, however, in being asked to memorialize John B. Rhoads, a third-year medical student at Boston University who died last year of leukemia, for his personal and scholarly qualities so endeared him to his student colleagues that they established this lectureship in his name. A young man of great promise, he would undoubtedly have been happy to hear the amazing story of discoveries made by medical undergraduates, and I trust that his relatives and friends assembled . . .
Isolation and biochemical characterization of tyrosinase-rich GERL and coated vesicle in melanin synthesizing cells
Authors: GENJI IMOKAWA, YUTAKA MISHIMA
Journal: British Journal of Dermatology (1981)

The site of condensation and activation of tyrosinase prior to melanosome melanogenesis has been investigated using subcellular fractionation and enzymic analysis of so‐called Golgi apparatus of melanoma cells. Two different functional units have been found in the so‐called Golgi fraction, the tyrosinase‐rich GERL‐coated vesicle unit and the TPPase‐rich Golgi unit. The tyrosinase‐rich unit consists of a tubular structure with a cisternal portion corresponding to the three‐dimensional structural characteristics of GERL, and spheroid vesicles, corresponding to the currently accepted criteria for coated vesicles. This fact suggests, in agreement with electron microscopic observations, that the GERL‐coated vesicle unit is a specialized portion of smooth endoplasmic reticulum having the function of activating and condensing the tyrosinase synthesized by ribosomes.
Hypofractionated Image-Guided Radiation Therapy for Patients with Limited Volume Metastatic Non-small Cell Lung Cancer
Authors: Michael D. Hasselle, Daniel J. Haraf, Kyle E. Rusthoven, Daniel W. Golden, Ravi Salgia, Victoria M. Villaflor, Niket Shah, Philip C. Hoffman, Steven J. Chmura, Philip P. Connell, Everett E. Vokes, Ralph R. Weichselbaum, Joseph K. Salama
Journal: Journal of Thoracic Oncology (2011)
Eptifibatide provides additional platelet inhibition in non-ST elevation myocardial infarction patients already treated with aspirin and clopidogrel: Results of the PEACE study
Authors: Miles C. Dalby, Gilles Montalescot, Claire Bal-dit-Sollier, Eric Vicaut, Jean-Phillipe Collet, Remi Choussat, banessa Gallois, Gerard Drobinski, Ludovic Drouet, Daniel Thomas
Journal: Journal of the American College of Cardiology (2003)
Transesophageal Echocardiography-Guided Cardioversion: Going for Broke?
Authors: Eric N. Prystowsky
Journal: Annals of Internal Medicine (1997)

Letters15 October 1997Transesophageal Echocardiography-Guided Cardioversion: Going for Broke?Eric N. Prystowsky, MDEric N. Prystowsky, MDNorthside Cardiology, P.C.; Indianapolis, IN 46260Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-127-8_Part_1-199710150-00018 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:The TEE-guided approach to cardioversion used by experts is safe, as shown by Manning and colleagues [1]. The ACUTE Pilot Study [2] compared the TEE-guided approach with the conventional approach to cardioversion. In my editorial, I suggested that a larger-scale clinical trial should provide valuable data about the risk for thromboembolism. However, I also questioned the “supposed” major limitations of the conventional approach, as outlined by Klein and coworkers [2]. The use of anticoagulation before cardioversion carries a risk for embolism of 1% or less. Thus, the data to date do not suggest a major risk for emboli ...References1. Manning WJ, Silverman DI, Keighley CS, Oettgen P, Douglas PS. Transesophageal echocardiography facilitated early cardioversion from atrial fibrillation using short-term anticoagulation: final results of a prospective 4.5-year study. J Am Coll Cardiol. 1995; 25:1354-61. Google Scholar2. Klein AL, Grimm RA, Black IW, Leung DY, Chung MK, Vaughn SE, et al. Cardioversion guided by transesophageal echocardiography: the ACUTE Pilot Study. A randomized, controlled trial. Ann Intern Med. 1997; 126:200-9. Google Scholar3. Prystowsky EN, Benson DW Jr, Fuster V, Hart RG, Kay GN, Myerburg RJ, et al. Management of patients with atrial fibrillation. A statement for healthcare professionals. From the Subcommittee on Electrocardiography and Electrophysiology, American Heart Association. Circulation. 1996; 93:1262-77. Google Scholar Author, Article, and Disclosure InformationAffiliations: Northside Cardiology, P.C.; Indianapolis, IN 46260 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 October 1997Volume 127, Issue 8_Part_1Page: 652-653 Issue Published: 15 October 1997 Copyright & PermissionsCopyright © 1997 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Needs assessment of humanitarian crises
Authors: Anthony D Redmond
Journal: BMJ (2005)

As many as two billion people are at risk of or exposed to crisis conditions, and some 20 million people live in such conditions.Communities are exposed to crisis conditions when local and national systems are overwhelmed and are unable to meet their basic needs.This may be because of a sudden increase in demand (when food and water are in short supply) or because the institutions that support communities are weak (when government and local services collapse because of staff shortages or lack of funds).Crises can be triggered by: x Sudden, catastrophic events-such as earthquakes, hurricanes, flooding, or industrial incidents x Complex, continuing emergencies-including the 100 or so conflicts currently under way, and the many millions of people displaced as a result x Slow onset disasters-such as widespread arsenic poisoning in the Ganges delta, the increasing prevalence of HIV infection and AIDS, or economic collapse.
Reducing the Risk of AIDS in High School Students: Lifelong Monogamy Is the Moral Solution
Authors: Glenn P. Dewberry
Journal: JAMA (1994)

<h3>To the Editor.</h3> —The recent contribution by Dr Walter and Mr Vaughan<sup>1</sup>demonstrates statistical significance in changes in attitudes and specific behaviors between students who had attended a special six-lesson acquired immunodeficiency syndrome (AIDS)—prevention curriculum and students who received no formal AIDS-prevention curriculum. Walter and Vaughan pointed out that "the relatively brief postintervention follow-up interval limits inference regarding maintenance of the treatment effects over time." This caution has failed to deter the media from drawing incorrect conclusions.<sup>2</sup> An important factor that was neglected is that the only "type" of monogamy that is truly associated with reducing risk of contracting AIDS is "extended or lifelong mutually monogamous relationships," and "a period of monogamy on the order of a year does not necessarily provide much protection."<sup>3</sup>It is difficult, therefore, to see the relevance of an adolescent's self-reporting monogamy for 3 months. Hearst and Hulley<sup>3</sup>also point out
How to manage the first episode of schizophrenia
Authors: S. Frangou, P. Byrne
Journal: BMJ (2000)

The lifetime prevalence of schizophrenia is about 1%, but the associated social disability and cost are disproportionately large. According to the World Health Organization, schizophrenia is among the leading causes of disability worldwide. Representative measures have estimated the annual cost of schizophrenia in England to be £2.6bn and in Canada to be $C2.35bn (£1.06bn).1–3 A growing body of evidence suggests that the early stages of schizophrenia are critical in forming and predicting the course and outcome of the disorder.4 Accordingly, clinical and research interest is now focused on the early stages of the illness because early detection and treatment may result in a better prognosis and functional outcome.

The first episode of schizophrenia typically occurs in the late teenage years or the early 20s.5 However, the illness can remain undetected for about 2–3 years …
Effects of cocaine on epicardial coronary artery reactivity in miniature swine after endothelial injury and high cholesterol feeding. In vivo and in vitro analysis.
Authors: K Egashira, F S Pipers, J P Morgan
Journal: Journal of Clinical Investigation (1991)

The purpose of this study was to determine the effects of cocaine on vasoreactivity in the swine model. Eight miniature pigs underwent regional endothelial denudation of the left anterior descending coronary artery and were then fed a high cholesterol diet. Cross-sectional area (CSA) of coronary arteries was measured by quantitative angiography. Before denudation, intravenous cocaine (1, 3, and 10 mg/kg) decreased CSA of epicardial vessels by 19-44%. At 3 mo after the denudation, the percent reduction in CSA of the denuded vessels induced by the 10 mg/kg dose was significantly augmented compared to nondenuded vessels (59 +/- 5% vs. 48 +/- 4%, P less than 0.05). Under in vitro conditions where isometric force of isolated ring segments was measured, methoxamine (an alpha 1 agonist) or BHT-920 (an alpha 2 agonist) produced similar degrees of contraction of denuded and control vessels; however, cocaine in concentrations up to 3 x 10(-3) M did not produce contraction. These responses were unaffected by removal of the endothelium. Histologically, myointimal thickening was noted at the denuded site. The present study demonstrates an enhanced vasoreactivity of atherosclerotic coronary arteries to cocaine in vivo, the mechanism of which appears to be mediated by endogenous vasoactive substances rather than by a direct action of cocaine on vascular smooth muscle.
Medical Student Financial Assistance, 1996-1997
Authors: Robert L. Beran
Journal: JAMA (1998)

Loans account for the major portion of financial aid available to medical students. In the academic year 1996-1997, 80.1% of all available financial aid came from loans, and medical students borrowed more than $1.11 billion. Of the 1997 medical school graduating class, 83.2% had educational debt, 46% of whom had mean educational debt levels higher than $75000.
THE TONSILS AS PATHOLOGICAL PRODUCTS.Read by Title at the Annual Meeting of the Mississippi Valley Medical Society.
Authors: GREEN V. WOOLEN
Journal: JAMA (1890)

It doubtless has been observed by others engaged in throat work that but few people, old or young, have tonsils. It doubtless has been observed further, that when seen, they have always been associated with present or preëxisting catarrhal disease of the naso-pharynx. It, therefore, soon became a question with the writer, if they were a true anatomical structure and organ, or a pathological product. As is well known, they are described by anatomical writers as the former, but with no fixed idea as to size and character of function. Gray probably gives a more correct description than his predecessors, and says: "The tonsils are two glandular organs situated on each side of the fauces, between the anterior and posterior pillars of the soft palate. They are of a rounded form, and vary considerably in size in different individuals. . . . . Their inner surfaces present from twelve to
THE EFFECT OF PROLONGED TOPICAL APPLICATION OF AN ANTICHOLINERGIC AGENT ON THE SEBACEOUS GLANDS
Authors: M. CARTLIDGE, J. L. BURTON, S. SHUSTER
Journal: British Journal of Dermatology (1972)

Journal Article THE EFFECT OF PROLONGED TOPICAL APPLICATION OF AN ANTICHOLINERGIC AGENT ON THE SEBACEOUS GLANDS Get access M. CARTLIDGE, M. CARTLIDGE University Department of Dermatology and Wellcome Laboratories for Research into Skin Disease, Newcastle upon Tyne Search for other works by this author on: Oxford Academic Google Scholar J. L. BURTON, J. L. BURTON University Department of Dermatology and Wellcome Laboratories for Research into Skin Disease, Newcastle upon Tyne Search for other works by this author on: Oxford Academic Google Scholar S. SHUSTER S. SHUSTER University Department of Dermatology and Wellcome Laboratories for Research into Skin Disease, Newcastle upon Tyne Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 86, Issue 1, 1 January 1972, Pages 61–63, https://doi.org/10.1111/j.1365-2133.1972.tb01892.x Published: 01 January 1972 Article history Accepted: 16 July 1971 Published: 01 January 1972
INCREASE IN CLONOGENIC TUMOUR CELLS IN BONE MARROW OF PATIENTS WITH MULTIPLE MYELOMA TREATED WITH VINCRISTINE, DOXORUBICIN, AND METHYLPREDNISOLONE
Authors: J.B.G Bell, J.A Maitland, M Gore, B.C Millar, A Nandi, T.J Mcelwain
Journal: The Lancet (1988)
Plasma levels of soluble E-selectin in patients with mild to moderate hypertension treated by a calcium antagonist or a I 1 -imidazoline agonist
Authors: E.V. Economou, C.P. Pitsavos, C.I. Stefanadis, M.G. Toutouza, A.G. Trikas, G.P. Vyssoulis, K.I. Kapetanios, E.E. Giannakopoulou, A.A. Livanou, P.K. Toutouzas
Journal: Journal of the American College of Cardiology (1998)
Surfactant in Pulmonary Disease
Authors: John A. Clements
Journal: New England Journal of Medicine (1965)

THOUGH Neergaard pointed out thirty-five years ago1 that the properties of pulmonary alveolar surfaces must influence the function of the lungs and Macklin2 suggested more than ten years ago that certain alveolar epithelial cells may regulate these properties, their proposals received little attention. More recently it was deduced3 from the behavior of microscopic bubbles removed from the lungs that the alveoli are lined with a substance that greatly reduces surface tension, and the presence of such material (surfactant) in saline extracts of normal lungs was directly demonstrated.4 Subsequently, it was shown that extracts prepared from the lungs of infants dying . . .
Significance of Marginal Extension in Excised Basal-Cell Carcinoma
Authors: Charles A. Gooding, George White, Masao Yatsuhashi
Journal: New England Journal of Medicine (1965)

DEFINITIVE surgical excision of basal-cell carcinoma of the skin is generally successful and results in complete removal of the lesion and subsequent cure.1 Occasionally, the histopathological report indicates that the tumor extends to the margin of the specimen and, hence, signals presumably incomplete excision of the cancer.2 Such a report usually prompts consideration of immediate surgery or radiation to eradicate residual disease. However, it has been uncertain whether viable residual tumor with a potential for recurrent growth is really present.To investigate the significance of the marginal extension of excised basal-cell carcinomas, a conservative approach was instituted of deferring additional . . .
Helicobacter pylori reinfection with identical organisms: transmission by the patients' spouses.
Authors: K Schutze, E Hentschel, B Dragosics, A M Hirschl
Journal: Gut (1995)

Reinfection with Helicobacter pylori after eradication is responsible for the recurrence of duodenal ulcer disease. The mode of transmission has not yet been established. In this study, 18 patients with chronic duodenal ulcers in whom H pylori had been eradicated with amoxicillin and metronidazole were entered into a prospective follow up study. Control endoscopies were performed 4, 8, 14, 27, and 43 months after starting treatment and the results of direct tests were compared with the kinetics of H pylori specific IgG titres. After eradication there was a noticeable and consistent fall in anti-H pylori IgG, while reinfections were characterised by a significant increase in specific titres. Reinfection was detected in two patients after 14 and 43 months, respectively. The H pylori strains responsible for these reinfections, the corresponding pretreatment isolates, and the strains isolated from the spouses of these patients were examined by polymerase chain reaction based DNA fingerprinting. Analysis showed that reinfection had been caused by the same H pylori strain and identified the spouses of these patients as carriers of the identical strain. Considering the genomic diversity and the interpatient heterogeneity of H pylori these results suggest a person to person transmission of H pylori reinfection. By the end of the observation period reflux oesophagitis had developed in 10 of the 16 patients who had not been reinfected. This surprising finding may be explained by the changed eating habits of patients after healing of duodenal ulcer disease.
Points: Late consequences of abortion
Authors: W. Savage
Journal: BMJ (1981)

question about the distinction between a Down's syndrome baby aged 1 week and a fetus of 20 weeks' gestation (28 November, p 1464) has, I think, an answer in a recent article by the legal correspondent of the Lancet.'Killing a baby of 1 week is illegal because in English law it is held to be a "living being" in a way that a fetus of 20 weeks is not (despite the fact that a fetus, or zygote, is even more distinctly alive than most living human tissue and has unique potential).The baby is capable of an independent existence, and so, of course, potentially is a fetus of 28 weeks or more (or perhaps 24 weeks, as discussed recently).Its independence exists even though (as Diana Brahams points out') it may be attached to its mother by the umbilical cord, and obviously is almost totally dependant on it for food....
Morphometric abnormalities in brains of great blue heron hatchlings exposed in the wild to PCDDs.
Authors: D S Henshel, J W Martin, R Norstrom, P Whitehead, J D Steeves, K M Cheng
Journal: Environmental Health Perspectives (1995)

Great blue heron hatchlings from colonies in the Strait of Georgia, British Columbia, Canada are being monitored for environmental contaminant exposure and effects by the Canadian Wildlife Service. The contaminants of concern are polychlorinated dibenzodioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs), primarily derived from kraft pulp mill effluent. The levels of PCDDs and PCDFs in eggs from the most contaminated colonies peaked in 1988 and 1989 and dropped dramatically through 1990 to 1992. Brains of heron hatchlings (taken as eggs from the wild and hatched in the laboratory) were analyzed for gross morphological abnormalities. Brains from highly contaminated colonies (Crofton, British Columbia and University of British Columbia Endowment Lands) in 1988 exhibited a high frequency of intercerebral asymmetry. The frequency of this abnormality decreased in subsequent years as the levels of TCDD and TCDD-TEQs (toxic equivalence factors) decreased. The asymmetry was significantly correlated with the level of TCDD and TCDD-TEQs in eggs taken from the same nest. Yolk-free body weight negatively correlated and the brain somatic index positively correlated with the TCDD level in such pair-matched eggs. These results indicate that gross brain morphology, and specifically intercerebral asymmetry, may be useful as a biomarker for the developmental neurotoxic effects of PCDDs and related chemicals.