tbuckley/cabot-search huggingface dataset:
Abstract 2125: Circadian crosstalk modulation of estrogen receptor alpha promoter activity
Authors: Linda M. Villa, Sarah Cousins, Daniel G.S. Capelluto, Carla V. Finkielstein
Journal: Cancer Research (2011)

Abstract The proper timing of cell division is a major factor contributing to the regulation of normal growth and emerges as a fundamental process in the development of most cancers. The existence in most, if not all, living organisms of many behavioral and physiological events that occur at well-defined and controlled times argues for the presence of time-keeping systems that allow them to adapt to cyclic changes in environmental conditions. Disruption of circadian rhythm has recently emerged as a new potential risk factor in the development of cancer, pointing to the core gene period 2 (per2) as a tumor suppressor. Circadian disruption has been epidemiologically linked to a raising number of estrogen dependent tumors identified in night-shift workers. In the present study, we investigate the signaling molecules that modulate the circadian expression of estrogen receptor alpha (ERa). ERa mRNA oscillates in a 24 h period and, unlike the circadian factor Per2, ERa peaks during the light phase of the day. Because up regulation of ER relates to tumor development, defining the mechanisms of ERa expression will contribute to our comprehension of cellular proliferation and regulation of normal developmental processes. Transcriptional activation of ERa was measured using a reporter system in Chinese Hamster Ovary and MCF-7 cell lines. Data show that Per2 influence ERa transcription through a non-canonical mechanism independent of its circadian counterparts. Promoter analysis using the Alibaba 2.0 suite revealed the presence of various putative novel partners. Among them, OCT-1 was found to directly interact with Per2 and with corresponding response element within the ERa promoter bit in vitro and endogenously in CHO and MCF-7 cells. The predicted binding site of OCT-1 is 867 bps downstream of the promoter. Pull-down assays were used to map direct interaction of various Per2 recombinant proteins and the DNA-binding domain of OCT-1. Radiolabeled OCT-1 was found to bind to the C-terminal end of Per2. Electrophoretic mobility shift assays were used to determine direct binding of OCT-1 to the promoter and chromatine immunoprecipitation validate the interactions in cells. Fluorescence anisotropy and surface plasmon resonance were employed to establish the binding affinity of OCT-1 to the ERa promoter and Per2. OCT-1 was found to have a high affinity for the ERa promoter (∼10 nM). Overall, our data points towards a direct regulation of estrogen receptor signaling by circadian modulators. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2125. doi:10.1158/1538-7445.AM2011-2125
An Exercise Test for Coronary Insufficiency
Authors: DAVID LITTMANN, MELVIN H. RODMAN
Journal: Circulation (1951)

Any exercise tolerance test is intended to record the objective accompaniments of coronary insufficiency. The test must therefore be stressful to effect such insufficiency. Described in this report is an exercise test which is considered specific in demonstrating coronary inadequacy when present, and reliable in ruling it out, provided that the effects of tachycardia on the electrocardiogram are recognized.
Subacute Combined System Degeneration With Folate Deficiency
Authors: Jonathan H. Pincus
Journal: JAMA (1972)

A 69-year-old woman with severe folate deficiency presented a clinical picture closely resembling that seen in classical prenicious anemia with neurologic involvement: megaloblastic anemia, dementia, impairment of posterior column functions, absent reflexes, and bilateral Babinski signs. All these abnormalities were resolved with folic acid therapy.
Moderate protein intake improves total and regional body composition and insulin sensitivity in overweight adults
Authors: Paul J. Arciero, Christopher L. Gentile, Roger Pressman, Meghan Everett, Michael J. Ormsbee, Jeff Martin, Jason Santamore, Liza Gorman, Patricia C. Fehling, Matthew D. Vukovich, Bradley C. Nindl
Journal: Metabolism (2008)
Philip Allan King-Lewis
Authors: P. Turnpenny
Journal: BMJ (2008)

Philip Allan King-Lewis worked in the NHS from 1964 to 1975, during his postgraduate training years, and again from 1988 until his retirement in 1998. However, the most significant part of his career took place between 1975 and 1988, when he worked as a physician and haematologist at the Nazareth Hospital, Israel—owned by the Edinburgh Medical Missionary Society (now EMMS Nazareth). It is quite possible he would have served longer in Nazareth had it not been for increasing immobility due to multiple sclerosis, diagnosed in 1979.

Philip went up to New College, Oxford, in 1958 and proceeded to the Middlesex Hospital for his clinical studies, from where he graduated in 1965, and house jobs. His junior postgraduate years were spent in a variety of posts that included Farnborough (Kent) and Billericay Hospitals, and he obtained the DRCOG besides the MRCP. En route to …
Adding psychotherapy to antidepressant medication in depression and anxiety disorders: a meta-analysis
Authors: Pim Cuijpers, Marit Sijbrandij, Sander L. Koole, Gerhard Andersson, Aartjan T. Beekman, Charles F. Reynolds
Journal: World Psychiatry (2014)

We conducted a meta-analysis of randomized trials in which the effects of treatment with antidepressant medication were compared to the effects of combined pharmacotherapy and psychotherapy in adults with a diagnosed depressive or anxiety disorder. A total of 52 studies (with 3,623 patients) met inclusion criteria, 32 on depressive disorders and 21 on anxiety disorders (one on both depressive and anxiety disorders). The overall difference between pharmacotherapy and combined treatment was Hedges' g = 0.43 (95% CI: 0.31-0.56), indicating a moderately large effect and clinically meaningful difference in favor of combined treatment, which corresponds to a number needed to treat (NNT) of 4.20. There was sufficient evidence that combined treatment is superior for major depression, panic disorder, and obsessive-compulsive disorder (OCD). The effects of combined treatment compared with placebo only were about twice as large as those of pharmacotherapy compared with placebo only, underscoring the clinical advantage of combined treatment. The results also suggest that the effects of pharmacotherapy and those of psychotherapy are largely independent from each other, with both contributing about equally to the effects of combined treatment. We conclude that combined treatment appears to be more effective than treatment with antidepressant medication alone in major depression, panic disorder, and OCD. These effects remain strong and significant up to two years after treatment. Monotherapy with psychotropic medication may not constitute optimal care for common mental disorders.
Standards of care in research
Authors: Zulfiqar Bhutta
Journal: BMJ (2004)

Should reflect local conditions and not the best western standards 

T he interpretation of “standard of care” in research has generated a lot of controversy among researchers. It has underpinned much of the debate on the use of placebos in randomised controlled trials such as the one around the zidovudine trials, which were proposed to prevent mother to child transmission of HIV infection in Africa. These trials entailed an evaluation of a short course treatment regimen in comparison with a control population receiving nothing.1–3 A high profile debate ensued that led to a reconsideration of guidelines on international research as well and spurred initiatives to make low cost antiretroviral treatment available in developing countries.4 5

In October 2000, the World Medical Association modified the Helsinki declaration to state that “the benefits, risks, burdens and effectiveness of a new method should be tested against those of the best current prophylactic, diagnostic, and therapeutic methods.”6 The Council for …
Management of portal hypertensive gastropathy and other bleeding
Authors: Woo Jin Chung
Journal: Clinical and Molecular Hepatology (2014)

A major cause of cirrhosis related morbidity and mortality is the development of variceal bleeding, a direct consequence of portal hypertension. Less common causes of gastrointestinal bleeding are peptic ulcers, malignancy, angiodysplasia, etc. Upper gastrointestinal bleeding has been classified according to the presence of a variceal or non-variceal bleeding. Although non-variceal gastrointestinal bleeding is not common in cirrhotic patients, gastroduodenal ulcers may develop as often as non-cirrhotic patients. Ulcers in cirrhotic patients may be more severe and less frequently associated with chronic intake of non-steroidal anti-inflammatory drugs, and may require more frequently endoscopic treatment. Portal hypertensive gastropathy (PHG) refers to changes in the mucosa of the stomach in patients with portal hypertension. Patients with portal hypertension may experience bleeding from the stomach, and pharmacologic or radiologic interventional procedure may be useful in preventing re-bleeding from PHG. Gastric antral vascular ectasia (GAVE) seems to be different disease entity from PHG, and endoscopic ablation can be the first-line treatment. Keywords: Gastric antral vascular ectasia; Liver cirrhosis; Portal hypertensive gastropathy
Variations in Maximal Oxygen Intake with Physical Activity in Middle-Aged Men
Authors: JOHN R. MCDONOUGH, FUSAKO KUSUMI, ROBERT A. BRUCE
Journal: Circulation (1970)

Data on maximal exercise performance are presented for normal middle-aged men free of cardiovascular disease. Maximal oxygen intake, oxygen pulse, heart rate, and lactate levels all decrease with increasing age. Physical activity defined by habitual running of any amount had a highly significant effect on maximal oxygen consumption. The enhanced effect of physical activity was found equivalent to nearly 10 years of age effect on maximal aerobic capacity. Multivariate analysis revealed significant association between maximal oxygen intake and several coronary risk factors; specifically, physical activity, vital capacity, cigarette smoking, and body weight. Notably lacking in significance were other known risk factors, serum cholesterol, and blood pressure. Data for maximal oxygen intake on healthy men aged 40 to 70 years are presented by age group and physical activity class; and regression equations are provided for estimation of maximal oxygen intake from age, physical activity status, and duration of the multistage treadmill test. These data should prove useful as normal standards for assessment of aerobic capacity in middle-aged men until such time as larger numbers of data on maximal exercise testing become available.
Risk Factors for Suicide in Multiple Sclerosis
Authors: Elsebeth Nylev Stenager, Nils Koch-Henriksen, Egon Stenager
Journal: Psychotherapy and Psychosomatics (1996)

Background: The purpose of the present study was to identify risk factors for suicide in patients with multiple sclerosis (MS). Methods: The study is based on available information about MS patients identified in the Danish MS Registry (DMSR) with onset in the period 1950–1985. We compared the MS suicides with the 1950-1985 onset cohort patients in the DSMR as to distribution of age at onset, presenting symptoms, and time from onset to diagnosis. We reviewed sociodemographic data, age of onset, the course of the disease, recent deterioration, type of deterioration, Kurtzke Disability Status Scale (DSS) score, previous mental disorder, type of mental disorder, previous suicide attempts, expression of suicidal intentions, circumstances at suicide, and suicide method for all MS patients who had committed suicide. In order to characterize MS suicides with respect to risk factors, comparisons were made for male and female suicides and for various groups of MS suicides according to disability status. Results: The male suicide patients were characterized by a tendency to commit suicide in the age interval 40–49 years, by the use of a violent suicide method, by previous suicidal behaviour, by a previous mental disorder, by recent deterioration of MS, and by a moderate disability. For women the characteristics were less distinct. Patients with a severe course of MS had been subjected to more risk factors before the suicide than patients with a moderate course of the disease. Conclusion: Careful counselling and good information on all aspects of the disease, especially in the first stages and at time of progression, could be an instrument of prevention of suicides in MS patients. Furthermore, recognition and treatment of depression and pain is important.
"CLINICAL ROENTGENOLOGY OF PREGNANCY"
Authors: William Snow
Journal: JAMA (1942)

<h3>To the Editor:—</h3> Please be advised that the reviewer's statement regarding my book that a good number of the one hundred and nineteen illustrations had been "touched up" is not sufficiently clear. None of the photographs or reproductions were retouched. The differentiation of the soft tissues of pregnancy were elicited by relative overexposure of the film and the use of a very bright spotlight later. This is becoming a common and useful practice in many branches of roentgenology. The reviewer evidently considered the superimposed guidelines on the pelvimetry photographic reproductions as "touched up." To these he took objection. However, it is my carefully considered opinion that these guidelines are absolutely essential for the reader if the book is to be used as a working manual for practicing measurements on these illustrations.
P342Lamin A/C mutations associated with different laminopathies affect differentiation of mesenchimal stem cells
Authors: M A Bogdanova, A A Kostareva, A B Malashicheva
Journal: Cardiovascular Research (2014)

Nuclear lamins are the major proteins of nuclear envelope and provide the strength of nuclear membrane as well as the interaction of extra-nuclear structures with components of cell nucleus. Recently, it became clear that lamins not only play a structural role in the cell, but could also regulate cell fate, for example lamins could influence cell differentiation via interaction with components of Notch signaling pathway. The best known modification of lamin A/C is progerin. It causes a very rare and severe syndrome of premature aging, or progeria. More often human mutations in LMNA encoding lamin A/C lead to diseases commonly referred to as laminopathies. In these diseases different mutations cause tissue specific phenotypes that affect predominantly a tissue of mesenchimal origin such as myocardium, skeletal muscle, adipose and bone tissues. The nature of this phenomenon, as well as the mechanisms by which lamins A/C regulate cell differentiation remain poorly understood. The aim of this study was to investigate the effect of different mutations of LMNA on human mesenchimal stem cell (MSC) osteogenic differentiation, and to explore a possible interaction of lamins A/C and Notch signaling pathway. We modified human mesenchimal stem cells (MSC) with several variants of mutant LMNA bearing known mutations with tissue specific phenotype associated with different laminopathies and then analyzed effects of different mutations on the efficiency of osteogenic differentiation. Efficiency of differentiation was evaluated by the number of differentiated MSC through 21 days after the induction of differentiation and by assessing the level of expression of specific osteogenic markers: SPP1, IBSP, BGLAP. We have shown that mutations associated with different types of laminopathies have different effects on the efficiency of MSC osteogenic differentiation at the morphological level and at the level of the expression of specific osteogenic markers. Different LMNA mutations increased or reduced the efficiency of differentiation. Our results explain why different mutations in the same gene could lead to a broad spectrum of phenotypes seen in different laminopathies. Mutant LMNA impaired the function of Notch signaling pathway and also changed HDAC activity in modified MSC comparing to MSC bearing wt LMNA. Thus, we have shown that a mechanism involved in the regulation of MSC differentiation may be an interaction of lamins A/C with components of Notch signaling and also epigenetic mechanisms.
S23 Multidimensional phenotypes of asthma
Authors: TSC Hinks, XY Zhou, P Lum, KJ Staples, B Dimitrov, C Smith, J Ward, PH Howarth, AF Walls, SD Gadola, R Djukanovic
Journal: Thorax (2013)

<h3>Introduction and Objectives</h3> Asthma is a complex disease involving many cell types including CD4+ and CD8+ T cells, eosinophils, basophils and mast cells, and their soluble mediators. Poor understanding of disease heterogeneity and mechanisms underlying distinct clinico-pathological endotypes limits progress. We hypothesised that identification of distinct multidimensional endotypes using combined clinical and pathological parameters would enable a better understanding of asthma mechanisms and phenotypes. We undertook to analyse a range of cell types and mediators across a wide clinical spectrum of asthma and health with application of a novel analytical approach: topological data analysis (TDA). <h3>Methods</h3> 76 adult subjects underwent extensive phenotyping, using clinical assessment, lung function, methacholine challenge, sputum induction, phlebotomy, and bronchoscopy. Samples were analysed for measurement of CD4+, CD8+ and invariant T cell subsets, of T cell cytokines, of mast cell and basophil mediators, bradykinin and vitamin D, using 9-colour flow-cytometry, RT-PCR, multiplex ELISA and mass spectrometry. We used Bayesian network analysis (BNA) to define the inter-connectivity between the key biological parameters investigated and TDA to identify novel multi-dimensional endotypes of asthma. <h3>Results</h3> We generated a Bayesian belief network using 37 key parameters on a subset of 62 subjects with the most complete data (figure), revealing asthma severity as a multidimensional feature, influenced by a wide variety of parameters, including Th2 inflammation, mast cells and basophils. A TDA network generated using only pathological features revealed distinct pathological endotypes including i) mast cell / basophil mediated ii) severe, obese, high bradykinin iii) minimal inflammation, without allergic rhinitis iv) Th2 mediated, milder disease. Significant differences were observed between clusters in carboxypeptidase, bradykinin, basogranulin, Th2 cells, and IL-4,-5,-12p70. A TDA network generated using only clinical features revealed a clear dichotomy between steroid responsive and steroid refractory disease. Differences were observed between clinical groups in tryptase, chymase, eosinophils and Th2 and mucosal associated invariant T (MAIT) cells. <h3>Conclusions</h3> This study highlights the diversity of aberrant immune responses associated with different clinical and pathological phenotypes of asthma. Attention should focus on further defining these distinct subtypes using such unbiased techniques and characterising under-researched pathways such as CD8+ T cells, basophils and bradykinin.
Are ATP sensitive potassium channels involved in the pronounced antiarrhythmic effects of preconditioning?
Authors: A. Vegh, J. G. Papp, L. Szekeres, J. R Parratt
Journal: Cardiovascular Research (1993)

Journal Article Are ATP sensitive potassium channels involved in the pronounced antiarrhythmic effects of preconditioning? Get access Agnes Vegh, Agnes Vegh Department of Pharmacology, Albert Szent-Gyorgi Medical University, Dom ter 12, Szeged, Hungary: A Vegh, J G Papp, L Szekeres; Department of Physiology and Pharmacology, University of Strathclyde, Glasgow G1 1 XW, United Kingdom: J R Parratt. Correspondence to Professor Parratt. Search for other works by this author on: Oxford Academic PubMed Google Scholar Julius Gy Papp, Julius Gy Papp Department of Pharmacology, Albert Szent-Gyorgi Medical University, Dom ter 12, Szeged, Hungary: A Vegh, J G Papp, L Szekeres; Department of Physiology and Pharmacology, University of Strathclyde, Glasgow G1 1 XW, United Kingdom: J R Parratt. Search for other works by this author on: Oxford Academic PubMed Google Scholar Laszlo Szekeres, Laszlo Szekeres Department of Pharmacology, Albert Szent-Gyorgi Medical University, Dom ter 12, Szeged, Hungary: A Vegh, J G Papp, L Szekeres; Department of Physiology and Pharmacology, University of Strathclyde, Glasgow G1 1 XW, United Kingdom: J R Parratt. Search for other works by this author on: Oxford Academic PubMed Google Scholar James R Parratt James R Parratt Department of Pharmacology, Albert Szent-Gyorgi Medical University, Dom ter 12, Szeged, Hungary: A Vegh, J G Papp, L Szekeres; Department of Physiology and Pharmacology, University of Strathclyde, Glasgow G1 1 XW, United Kingdom: J R Parratt. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 27, Issue 4, April 1993, Pages 638–643, https://doi.org/10.1093/cvr/27.4.638 Published: 01 April 1993 Article history Received: 27 August 1992 Accepted: 12 November 1992 Published: 01 April 1993
Clinical Nuclear Medicine
Authors: Thomas P. Haynie
Journal: JAMA (1969)

Textbooks on the clinical use of radioisotopes, or nuclear medicine, as it is now called, are generally of three types. The first combines the authorship of a clinician and a physicist. These were among the first textbooks available. Secondly, as the field has grown more complex, the multiple-authored textbook, with as many as 35 authors, has appeared more recently. Finally, and this also appears to be a recent trend, a single clinician who has been involved in the clinical use of radioisotopes for many years and has gained experience in a broad range of medical diseases, writes a solo textbook.<i>Clinical Nuclear Medicine</i>, by Maynard, is an example of the third type. As one would expect, the book does not have the emphasis and content of the first two types. The explanation of nuclear phenomena and the fundamentals of radioisotopes is missing. And then, the individual topics as they relate
Acute Gastric Anisakiasis
Authors: Keizo Sugimachi
Journal: JAMA (1985)

From 1969 to 1984, we treated 178 patients with acute gastric anisakiasis caused by gastric mucosal penetration of the<i>Anisakis</i>larvae. Because the larvae of<i>Anisakis</i>can always be observed by endoscopy and removed with biopsy forceps, early performance of endoscopy is highly recommended for patients in whom acute gastric anisakiasis is suspected and for those who have eaten raw fish within 12 hours before onset of the gastric symptoms. Endoscopic removal is essential to relieve the intolerable pain; after relief, the administration of antacids will repair the damaged gastric mucosa. Ulcer formation is rare. (<i>JAMA</i>1985;253:1012-1013)