tbuckley/cabot-search huggingface dataset:
Abstract 1910: Infiltration of ovarian carcinoma by altered plasmacytoid dendritic cells could contribute to local immune tolerance
Authors: Sana Intidhar Labidi-Galy, Isabelle Ray-Coquard, Vanja Sisirak, Isabelle Treilleux, Pierre Meeus, François Mithieux, Alexandre Cassignol, François Bouchard, Philippe Gabelle, Jean-Paul Guastalla, Christine Ménetrier-Caux, Christophe Caux, Nathalie Bendriss-Vermare
Journal: Cancer Research (2010)

Abstract Ovarian carcinomas are usually considered as immunogenic tumors, as they are capable of inducing tumor-associated antigen immunity. However, immune system fails to eradicate established tumors partly due to alteration of immunosurveillance and induction of an active process of « tolerization » by the tumor microenvironment. We prospectively collected blood, tumors, and ascites samples from 38 patients with ovarian carcinomas (localized and advanced stages) and 35 healthy donors that gave written informed consent. Lin−CD4+CD11c−CD123+BDCA2+ pDC are the most abundant DC subset within ovarian carcinomas and neoplasic ascitis while they are profoundly depleted in peripheral blood of ovarian carcinoma patients compared to healthy donors. The depletion of pDC in patient's blood is partially restored when they are in complete remission (after chemotherapy and surgery). These observations suggest preferential pDC recruitment into tumor tissues that may involve CCR7 and CD62L which are downregulated in Tumor-associated (TA)-pDC compared to ascitis or blood pDC. Furthermore, TApDC express a partially mature phenotype compared to patient's blood and ascitis pDC that may reflect an in situ activation. Importantly, ex vivo TApDC produce lower amounts of IFN-α, TNF-α, IL-6 and RANTES in response to TLR ligands than ascitis or healthy donor pDC, suggesting a specific inhibition by ovarian tumor environment. In vitro, tumor or ascitis-derived surnageants (SNTUM) induce inhibition of the production of IFN-α and TNF-α by healthy pDC in response to TLR activation, suggesting the implication of soluble factors in this functional inhibition. In addition, TApDC but not ascitis pDC or healthy donors pDC direct allogeneic naive CD4+ T lymphocytes to produce high amounts of IL-10. Thus, TApDC may contribute to the tumor environmental immunosuppressive network. Elucidation of the mechanisms of dysfunctions of TApDC could have clinically relevant implications for future therapeutic strategies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1910.
Ubiquitin-Proteasome Pathway as a New Target for the Prevention of Restenosis
Authors: Silke Meiners, Michael Laule, Wim Rother, Christoph Guenther, Ines Prauka, Peter Muschick, Gert Baumann, Peter-Michael Kloetzel, Karl Stangl
Journal: Circulation (2002)

Background — The ubiquitin-proteasome system is the major intracellular protein degradation pathway in eucaryotic cells. It regulates central mediators of proliferation, inflammation, and apoptosis that are fundamental pathomechanisms in the development of vascular restenosis. Methods and Results — Effects of proteasome inhibition on neointima formation were studied in a balloon injury model in the rat carotid artery. Local application of the proteasome inhibitor MG132 (1 mmol/L) resulted in significant inhibition of intimal hyperplasia, that is, by 74% ( P =0.008). This effect was accompanied by decreased proliferation, reduced infiltration of macrophages, and prolonged apoptosis, as determined by immunohistochemical and TUNEL analyses. Functional effects of proteasome inhibition on proliferation, activation of nuclear factor kappa B, and apoptosis were further characterized in rat primary vascular smooth muscle cells. MG132 dose-dependently inhibited vascular smooth muscle cell proliferation with 50% inhibition at 10 μmol/L. TNFα-induced degradation of IκBα and β was blocked, and activation of nuclear factor kappa B was suppressed in a concentration-dependent manner in bandshift assays. Moreover, proteasome inhibition (1 to 50 μmol/L MG132) induced apoptotic cell death up to 80%, as confirmed by DNA/Histone-ELISA and TUNEL-FACS analysis. Specificity of proteasome inhibition was shown by accumulation of multiubiquitinylated proteins and accumulation of specific proteasomal substrates. Conclusions — These proof-of-principle experiments demonstrate that inhibition of the ubiquitin-proteasome system effectively reduces neointima formation in vivo, which corresponds to strong antiproliferative, anti-inflammatory, and proapoptotic effects in vitro and in vivo. Our data suggest the ubiquitin-proteasome system as a new target in the prevention of vascular restenosis.
Abstract 2939: Discovery and synthesis of highly potent and selective small molecule inhibitors of the histone methyltransferase EZH2
Authors: Sharad K. Verma, Louis V. LaFrance, Xinrong Tian, Ken Newlander, Céline Duquenne, Dominic Suarez, Steven D. Knight, Joelle Burgess, James Brackley, Neil W. Johnson, Alan P. Graves, Mark Mellinger, Stuart Romeril, Seth W. Grant, Daryl Scherzer, Art Shu, Caretha L. Creasy, Ryan Kruger, Elsie Diaz, Baochau Le, Christine Thompson, Heidi Morgan-Ott, Michael T. McCabe, Charles F. McHugh, William H. Miller, Peter Tummino, Dash Dhanak
Journal: Cancer Research (2012)

Abstract The histone methyltransferases are a group of enzymes which catalyze the transfer of a methyl group from the co-factor S-Adenosylmethionine (SAM) to the lysine and arginine residues of histone tails. This post-translational modification is a key event in maintaining gene expression patterns. In recent years, the relationships between aberrant histone methylation patterns and cancer progression have been recognized. These developments, along with an improved understanding of the underlying structural biology, have made histone methyltransferases highly attractive targets for therapeutic intervention. The histone lysine methyltransferase EZH2 (Enhancer of Zeste Homolog 2) is frequently over-expressed in a wide variety of cancerous tissues. There is a strong correlation between overexpression of EZH2 and aberrant transcriptional signaling in cells, ultimately resulting in poor clinical prognosis. Inhibition of EZH2 is expected to alter transcriptional expression and ultimately lead to an improved clinical outcome. This presentation will describe medicinal chemistry efforts in the development of highly potent and selective small molecule inhibitors of EZH2. The synthesis, SAR, and identification of a clinical candidate will be discussed. 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 2939. doi:1538-7445.AM2012-2939
PASSAGE OF NATIVE PROTEINS THROUGH THE NORMAL GASTRO-INTESTINAL WALL 1
Authors: Bret Ratner, H. L. Gruehl
Journal: Journal of Clinical Investigation (1934)

The view most generally held to-day by the physiologist, chemist and clinician is that undigested antigens are not absorbed through the normal gastro-intestinal wall; and that when such absorption does occur, it is be- cause abnormal or pathological conditions exist, such as stasis, the excessive flooding of the intestines with protein foods, lessened activity of the di- gestive enzymes, altered conditions of the intestinal mucosa, and greater permeability of the intestinal wall characteristic of new-borns and suck- lings.There is some evidence for the absorption of unsplit proteins under normal conditions but this is regarded as a fortuitous occurrence.In the light of the conflicting opinions present in the literature and the important role this subject plays in allergy and other conditions as yet not clearly de- fined, we determined to reopen the problem.
Equity in the selection of recipients for cardiac transplants.
Authors: A L Caplan
Journal: Circulation (1987)

The problem of perceived inequities in the distribution of hearts and other solid organs for the purposes of transplantation.In recent years there has been a great deal of discussion of problems in the allocation of hearts and other organs for the purposes of transplantation."2Charges of bias and discrimination have haunted those involved in the procurement and distribution of or- gans.Many observers of the transplantation field have worried about making organs procured in the United States available to recipients who are not American citizens,3 while others have bemoaned the practice of shipping kidneys procured in the United States over- seas to those institutions willing to pay for them.4'Likewise, there have been many criticisms leveled at the everyday practice of most transplant centers of requiring those needing transplants to prove their abili- ty to pay for such surgery in advance of any determina- tion of their eligibility.6Not all of the criticism has concerned the selection of adult recipients.An enormous controversy surrounded the initial decision at Loma Linda University Medical Center in California to reject a newborn in- fant, identified in the popular media as Baby Jesse, as a candidate for a heart transplant.The medical center cited "psychosocial" factors as the grounds for the decision not to accept the infant into the experimental infant heart transplant program at the medical school.7Upon hearing of the decision, the child's family apparently enlisted the help of a local "Right-to-Life" organization to create a media campaign with the goal of pressuring the medical center to reverse its decision.Charges were made that the infant had been rejected as a candidate simply because his parents were not mar- ried.The media gave a great deal of play to the story that Baby Jesse had been rejected as a cardiac trans- plant candidate solely for the reason of illegitimacy.8In fact, the hospital had followed what is standard practice in every cardiac transplant center in considering psychosocial variables as a part of determining From the Hastings Center, Hastings-on-Hudson, NY
<i>MTOR</i> Mutations in the Crosshairs of Targeted Therapy
Authors: Paul A. Rejto, Robert T. Abraham
Journal: Cancer Discovery (2014)

Abstract Summary: The identification of genetic lesions that affect tumor sensitivity to targeted therapies is a major objective of precision medicine. Two reports in this issue combine tumor genome analyses with functional characterization to uncover activating mutations in MTOR that confer sensitivity to a clinically used mTOR inhibitor. Cancer Discov; 4(5); 513–5. ©2014 AACR. See related article by Wagle et al., p. 546 See related article by Grabiner et al., p. 554
Discovery of somatic STAT5b mutations in large granular lymphocytic leukemia
Authors: Hanna L. M. Rajala, Samuli Eldfors, Heikki Kuusanmäki, Arjan J. van Adrichem, Thomas Olson, Sonja Lagström, Emma I. Andersson, Andres Jerez, Michael J. Clemente, Yiyi Yan, Dan Zhang, Andy Awwad, Pekka Ellonen, Olli Kallioniemi, Krister Wennerberg, Kimmo Porkka, Jaroslaw P. Maciejewski, Thomas P. Loughran, Caroline Heckman, Satu Mustjoki
Journal: Blood (2013)
Procoagulant Membrane Microparticles Correlate with the Severity of Pulmonary Arterial Hypertension
Authors: Babe Bakouboula, Olivier Morel, Antoine Faure, Fatiha Zobairi, Laurence Jesel, Annie Trinh, Michel Zupan, Matthieu Canuet, Lelia Grunebaum, Agnès Brunette, Dominique Desprez, François Chabot, Emmanuel Weitzenblum, Jean-Marie Freyssinet, Ari Chaouat, Florence Toti
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Procoagulant microparticles constitute valuable hallmarks of cell damage. Microparticles also behave as cellular effectors.We hypothesized that the extent of the vascular cell damage measured by circulating microparticles could be related to the severity of pulmonary arterial hypertension (PAH).Circulating biomarkers of vascular damage and cell activation were measured in blood samples from 20 patients with PAH. Samples were withdrawn from occluded pulmonary artery and jugular vein. Peripheral venous blood samples were obtained in 23 control subjects. The microparticle procoagulant abilities were quantified by functional prothrombinase and tissue factor assays and their cellular origin was determined.Soluble vascular cellular adhesion molecule-1 and proinflammatory markers, such as monocyte chemoattractant protein-1 and highly specific C-reactive protein, were elevated in patients with PAH compared with control subjects. Microparticles bearing active tissue factor and CD105 (endoglin) were also elevated in patients with PAH compared with control subjects (29 +/- 13 vs. 16 +/- 6 fmol/L, P < 0.001, and 1.10 +/- 0.46 vs. 0.49 +/- 0.33 nmol/L phosphatidylserine equivalent, P < 0.001, respectively). A further increase in endothelium-derived CD105 microparticles was observed in pulmonary arterial blood compared with venous blood in patients with PAH (1.73 +/- 0.77, P = 0.038). Microparticles bearing active tissue factor were at a higher level in patients in functional class III and IV and who were walking fewer than 380 m with the six-minute-walk test.Circulating markers of endothelium damage, proinflammatory markers, and cell stimulation estimated with circulating microparticles appear to be valuable tools in determining the severity of PAH.
Complete Heart Block with Gonococcal Septicemia
Authors: DIETMAR GANN
Journal: Annals of Internal Medicine (1977)

Letters1 June 1977Complete Heart Block with Gonococcal SepticemiaDIETMAR GANN, M.D., ONKAR S. NARULA, M.D., SHERMAN KAPLAN, M.D., PHILIP SAMET, M.D.DIETMAR GANN, M.D.Search for more papers by this author, ONKAR S. NARULA, M.D.Search for more papers by this author, SHERMAN KAPLAN, M.D.Search for more papers by this author, PHILIP SAMET, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-86-6-749 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptAn 18-year-old white girl presented to the emergency room with a chief complaint of lightheadedness and syncope. An electrocardiogram showed complete heart block, atrial rate of 120/min, ventricular rate of 32/min with a pattern of complete right bundle branch block, and +95° axis. One week before admission she noticed macules on her left hand that developed into papules and hemorrhagic vesicles. She then noticed a mild pharyngitis. Fever, chills, arthralgias, and arthritis were all absent.At physical examination her blood pressure was 120/80 mm Hg, pulse 32 and regular, and temperature 36.6°C. The pharynx appeared normal, and lungs were clear...References1. NARULA O: Current concepts of atrioventricular block, in His Bundle Electrocardiography and Clinical Electrophysiology, edited by NARULA OS. Philadelphia, F. A. Davis Co., 1975, pp. 139-175 (p. 163) Google Scholar2. EL-SHERIFSHERLAGLAZARRA NBR: Pathophysiology of tachycardia- and bradycardia-dependent block in the canine proximal His-Purkinje system after acute myocardial ischemia. Am J Cardiol 33:529-540, 1974 CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Mount Sinai Medical Center 4300 Alton Road Miami Beach, FL 33140 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByRole of electrophysiologic testing in the diagnosis and treatment of patients with known and suspected bradycardias and tachycardiasDisseminated gonococcal infection (DGI) and gonococcal arthritis (GCA): II. Clinical manifestations, diagnosis, complications, treatment, and preventionAdult Respiratory Distress Syndrome and Gonococcemia 1 June 1977Volume 86, Issue 6Page: 749-750KeywordsHeartHeart rateLungsPharyngitisPharynxRight bundle branch blockSepsisSyncopeTemperatureVesicles Issue Published: 1 June 1977 PDF DownloadLoading ...
Relative resistance to HIV–1 infection of CD4 lymphocytes from persons who remain uninfected despite multiple high–risk sexual exposures
Authors: William A. Paxton, Scott R. Martin, Doris Tse, Thomas R. O'Brien, Joan Skurnick, Nancy L. VanDevanter, Nancy Padian, James F. Braun, Donald P. Kotler, Steven M. Wolinsky, Richard A. Koup
Journal: Nature Medicine (1996)
Understanding self and other
Authors: John Barresi, Chris Moore
Journal: Behavioral and Brain Sciences (1996)

Abstract We consider the various criticisms and requests for clarification made by the commentators of our framework for understanding intentional relations. Our response is organized according to the main themes in the target article: general theory, phylogeny, development, and autism. We also add some discussion of further issues, such as simulation and moral theory, that were not addressed in the target article.
Zen Diets vs Buddhism
Authors: Philip Kapleau
Journal: JAMA (1971)

<h3>To the Editor.—</h3> Several members of our Center have called to my attention the article, "Zen Macrobiotic Diets," inThe Journal, and to pickup of it in a number of newspapers. I have not only written about the dangers and errors of this diet, but have spoken out against it on colleges and university campuses where I have conducted seminar-workshops on Zen Buddhism. Naturally, I have taken great pains to point out that the Zen macrobiotic diet has no connection with Zen Buddhism. Perhaps you are unaware of this distinction and for that reason do not mention it, but you can appreciate the harm done to Zen Buddhism by such captions as "Zen Diet Called Health Threat" which appeared in many newspapers. Inevitably the "Zen" of the marcobiotic diet is assumed to be the "Zen" of Buddhism. You would win the gratitude of our own Zen community (which numbers over
Scientific Foundations of Orthopaedics and Traumatology
Authors: Irwin M. Siegel
Journal: JAMA (1982)

It has been said that specialists come of two minds: those interested in their specialty, and those interested in medical science and fascinated by their specialty. This book, an Anglo-American enterprise that has put together an essential review of basic science as it applies to the theory and practice of orthopedics and traumatology, should appeal to the latter. Its three editors (two English, one American) have called on 64 contributing authors to assist them in providing a "foundation of knowledge upon which to build" by writing a text "not intended to be an encyclopedic reference book but rather a guide through the complexities of modern science." All this is accomplished in 58 succinct chapters divided into six sections: "Morphology, Biochemistry and Material Properties of Skeletal Tissues"; "Design of the Locomotor System"; "Development and Growth of the Locomotor System"; "Maintenance, Breakdown and Repair"; "The Scientific Basis of Some Diagnostic Techniques"; and
Right Ventricular Myxoma Simulating Pulmonic Stenosis
Authors: G. GOTTSEGEN, J. WESSELY, A. ÁRVAY, A. TEMESVÁRI
Journal: Circulation (1963)

The fourth case of right ventricular myxoma is reported, the first one in which the tumor was removed surgically. The clinical picture was that of pulmonic stenosis with some unusual features: effort syncope, changing hemodynamic pattern, and a rapidly progressive clinical course of irreversible congestive heart failure. The importance of early diagnosis, the angiocardiographic findings, and the necessity of operation before development of serious myocardial damage are stressed.
Indian students protest against decision to postpone new national exam for admission to medical school
Authors: M. Chaudhuri
Journal: BMJ (2013)

The hope among aspiring Indian medical students that they might gain admission to medical colleges through a new national entrance test has been quashed, at least temporarily, by the Supreme Court.

The central government’s first nationwide Common Entrance Test, the National Eligibility cum Entrance Test (NEET) for medical school, which was meant to begin in 2013, has been stayed by India’s senior court.

The new test was considered by many to be a breakthrough in medical education in India because students would not have to pay to take the examination and success would be on merit. It would mean that students would be able to get into medical student on aptitude rather than their ability to pay. 

In an interim order, the Supreme Court said that, until a final decision was taken, state medical …
Patricia Ann Nettleton (née Girling)
Authors: Margaret Siriol Colley
Journal: BMJ (2004)

Former general practitioner Bramcote, Nottingham (b 1932; q Sheffield 1957; DCH), d 27 May 2004.​2004.




Figure 1




Pat decided at an early age to become a doctor. Her first house job was in Sheffield, in casualty, and then in medicine at Nottingham General Hospital. She gained her diploma in child health after working at Nottingham Children's Hospital. Before becoming a general practitioner Pat took a part time job with the Nottingham Schools Health Service. Ten years ago she retired and took up bird watching as hobby. She leaves a husband, Don; two sons; and two grandsons.
P2-094: Progostic impact of Epidermal Growth Factor Receptor (EGFR) concentration in plasma in advanced non-small cell lung cancer (NSCLC) patients
Authors: Rafael Sirera, Carlos Camps, Guillermo López-Vivanco, G Alonso, Blanca Cantos, Ana Blasco, Crsitina Caballero, Mireia Muñoz-Navarro, Miquel Tarón, Rafael Rosell
Journal: Journal of Thoracic Oncology (2007)
Phase-plane trajectories of atrial cell action potentials: effects of temperature reduction
Authors: S. E. FREEMAN, R. J. TURNER
Journal: Cardiovascular Research (1974)

A study has been made of atrial transmembrane potentials of rabbit and guinea pig hearts. In addition to the voltage-time record the first time derivative of the action potential was displayed as a function of voltage, yielding a phase-plane trajectory. A number of parameters of the action potential were determined from the trajectory, assuming cable behaviour. The validity of this assumption is discussed, and the effects of temperature reduction determined.
Challenges and opportunities for reinvigorating the physician-scientist pipeline
Authors: Dania Daye, Chirag B. Patel, Jaimo Ahn, Freddy T. Nguyen
Journal: Journal of Clinical Investigation (2015)

Physician-scientists, with in-depth training in both medicine and research, are uniquely poised to address pressing challenges at the forefront of biomedicine. In recent years, a number of organizations have outlined obstacles to maintaining the pipeline of physician-scientists, classifying them as an endangered species. As in-training and early-career physician-scientists across the spectrum of the pipeline, we share here our perspective on the current challenges and available opportunities that might aid our generation in becoming independent physician-scientists. These challenges revolve around the difficulties in recruitment and retention of trainees, the length of training and lack of support at key training transition points, and the rapidly and independently changing worlds of medical and scientific training. In an era of health care reform and an environment of increasingly sparse NIH funding, these challenges are likely to become more pronounced and complex. As stakeholders, we need to coalesce behind core strategic points and regularly assess the impact and progress of our efforts with appropriate metrics. Here, we expand on the challenges that we foresee and offer potential opportunities to ensure a more sustainable physician-scientist workforce.
Evaluating Health and Social Care
Authors: D Allen
Journal: BMJ (1994)

Ceri Phillips, Colin Palfrey, Paul Thomas Macmillan, (pounds sterling )10.95, pp 178 ISBN 0-33-59186-0

The development of the internal market will produce the most radical change in providing care that the NHS has undergone. The introduction of the purchaser-provider split means that all existing methods of provision in the NHS can be re-examined, but health service decision makers need some framework for assessing what should be provided. Ceri Phillips and his …