tbuckley/cabot-search huggingface dataset:
UK should do more to cut teenage drinking and pregnancies, report urges
Authors: O. Mashta
Journal: BMJ (2009)

The UK government should target its spending on disadvantaged teenagers more effectively, says the Organisation for Economic Co-operation and Development, which published a report this week showing that rates of underage drinking and teenage pregnancy in the United Kingdom are among the highest in the industrialised world.

Relatively high public spending on child welfare and education in the UK is failing to produce results in many key areas, says the report, which compares the wellbeing of young people living in the 30 leading industrial economies.

The UK spends more on children than most other industrial countries, at just over £90 000 (€103 000; $150 000) per child …
Evidence That the Malignant Lymphoma of Sjögren's Syndrome Is a Monoclonal B-Cell Neoplasm
Authors: Jules Zulman, Ronald Jaffe, Norman Talal
Journal: New England Journal of Medicine (1978)

We studied the malignant lymphomas that developed in patients with Sjögren's syndrome and the antecedent benign salivary-gland lesions to determine their cellular characteristics. We used an immunoperoxidase technic that identified intracellular gamma, alpha and mu heavy chains and kappa and lambda light chains. In six of nine patients, the lymphomas were composed of cells containing intracytoplasmic immunoglobulin that was exclusively IgMK. The benign lymphoepithelial salivary-gland lesions preceding these malignant tumors consisted of approximately equal numbers of lymphoid cells containing either kappa or lambda light chains. Thus, in some patients with Sjögren's syndrome, there may be a progression in the lympho-proliferative lesions from a polyclonal infiltrate to a monoclonal neoplasm. Intracytoplasmic immunoglobulin identifies six of the nine cases as being B-cell in origin.
The 8q24 cancer risk variant rs6983267 shows long-range interaction with MYC in colorectal cancer
Authors: Mark M Pomerantz, Nasim Ahmadiyeh, Li Jia, Paula Herman, Michael P Verzi, Harshavardhan Doddapaneni, Christine A Beckwith, Jennifer A Chan, Adam Hills, Matt Davis, Keluo Yao, Sarah M Kehoe, Heinz-Josef Lenz, Christopher A Haiman, Chunli Yan, Brian E Henderson, Baruch Frenkel, Jordi Barretina, Adam Bass, Josep Tabernero, José Baselga, Meredith M Regan, J Robert Manak, Ramesh Shivdasani, Gerhard A Coetzee, Matthew L Freedman
Journal: Nature Genetics (2009)
SCL/TAL1 Interrupting Locus Derepresses GLI1 from the Negative Control of Suppressor-of-Fused in Pancreatic Cancer Cell
Authors: Kenji Kasai, Shingo Inaguma, Akiko Yoneyama, Kazuhiro Yoshikawa, Hiroshi Ikeda
Journal: Cancer Research (2008)

Abstract As a physically binding protein of GLI1 transcription factor, Suppressor-of-Fused (SUFU) has been placed in the center of negative regulation of Hedgehog (Hh) signaling. SUFU tethers GLI1 in cytoplasm, and in some circumstances, it moves into the nucleus in association with GLI1, leading to the suppression of GLI1 target gene expression by recruiting a corepressor complex. The activated transcriptional function of GLI1 is important for cellular proliferation in a variety of human cancers. However, it has not been revealed how GLI1 is derepressed from SUFU-mediated suppression. Here, we show SCL/TAL1 interrupting locus (SIL) product, a cytoplasmic protein overexpressed in pancreatic ductal adenocarcinoma (PDA), is responsible for the derepression of GLI1. We found SIL associated with the carboxyl terminus of SUFU, one of two distinct GLI1-binding domains, and this association was responsible for cytoplasmic tethering of SUFU. Overexpressed SIL attenuated SUFU-mediated cytoplasmic tethering and target gene suppression of GLI1. Knockdown of SIL in PDA cells conversely induced the nuclear accumulation of SUFU in association with GLI1 and the transcriptional suppression of GLI1 target genes. Importantly, we also showed that oncogenic K-RAS, and not Sonic hedgehog, enhanced the SIL association with the amino-terminus of SUFU, the other GLI1-binding domain that led to further increase of nuclear translocation of GLI1. These results uncover the role of SIL in derepressing GLI1 from the negative control of SUFU, which is a crucial step for activating Hh signaling in cancer cells. [Cancer Res 2008;68(19):7723–9]
NHS launches scheme to encourage diversity in top management posts
Authors: Jacqui Wise
Journal: BMJ (2007)

A new scheme to spot talented black and minority ethnic workers in the NHS and give them the opportunity to work at director level for 18 months was launched this week.

The “national breaking through top talent programme,” part of the NHS Institute for Innovation and Improvement, aims to develop senior black and minority ethnic staff and help them break through the glass ceiling.

There are 193 000 NHS employees from black and minority ethnic backgrounds, but less than 2% work at an executive director level or higher. 

Cynthia Bower, chief executive …
Modifying the Proliferative State of Target Cells to Control DNA Expression and Identifying Cell Types Transfected In Vivo
Authors: Kathryn W Riddle, Hyun-Joon Kong, J Kent Leach, Claudia Fischbach, Charles Cheung, Kristi S Anseth, David J Mooney
Journal: Molecular Therapy (2007)

Although the majority of current gene transfer techniques have focused on increasing the ability of the DNA to enter the cell, it is possible that changing the proliferative and migratory state of cells will influence the cells ability to take up and express plasmid DNA. This study was designed to test the hypothesis that growth factors (basic fibroblast growth factor (bFGF) and hepatocyte growth factor/scatter factor (HGF/SF)) used to alter the proliferative and migratory state of cells can alter plasmid DNA uptake and expression. <i>In vitro</i> studies indicate that enhancing cell proliferation with growth factor exposure enhances plasmid DNA uptake and expression. Furthermore, dual localized delivery of bFGF and plasmid DNA <i>in vivo</i> increases the expression, 3–6 times over control, as compared to plasmid delivery alone. Dual delivery of a factor promoting cell proliferation and a plasmid led to a further increase in the expression of the plasmid encoding bone morphogenetic protein-2 in a rat cranial defect by specific cell populations. The results of these studies suggest that increasing the proliferative state of target cell populations can enhance non-viral gene transfer.
Dermatofibrosarcoma protuberans with<i>COL1A1</i>(exon 18) -<i>PDGFB</i>(exon 2) fusion transcript
Authors: H. Saeki, H. Ohmatsu, T. Hoashi, N. Asano, T. Idezuki, Y. Kawabata, A. Asahina, K. Kikuchi, K. Tamaki
Journal: British Journal of Dermatology (2003)

Journal Article Dermatofibrosarcoma protuberans with COL1A1 (exon 18) –PDGFB (exon 2) fusion transcript Get access H. Saeki, H. Saeki Department of Dermatology, Faculty of Medicine, University of Tokyo, Hongo 7‐3‐1, Bunkyo‐ku, Tokyo 113‐8655, Japan Hidehisa Saeki MD, Faculty of Medicine, University of Tokyo, Hongo 7‐3‐1, Bunkyo‐ku, Tokyo 113‐8655, Japan. E‐mail: saeki‐der@h.u‐tokyo.ac.jp Search for other works by this author on: Oxford Academic Google Scholar H. Ohmatsu, H. Ohmatsu Department of Dermatology, Faculty of Medicine, University of Tokyo, Hongo 7‐3‐1, Bunkyo‐ku, Tokyo 113‐8655, Japan Search for other works by this author on: Oxford Academic Google Scholar T. Hoashi, T. Hoashi Department of Dermatology, Faculty of Medicine, University of Tokyo, Hongo 7‐3‐1, Bunkyo‐ku, Tokyo 113‐8655, Japan Search for other works by this author on: Oxford Academic Google Scholar N. Asano, N. Asano Department of Dermatology, Faculty of Medicine, University of Tokyo, Hongo 7‐3‐1, Bunkyo‐ku, Tokyo 113‐8655, Japan Search for other works by this author on: Oxford Academic Google Scholar T. Idezuki, T. Idezuki Department of Dermatology, Faculty of Medicine, University of Tokyo, Hongo 7‐3‐1, Bunkyo‐ku, Tokyo 113‐8655, Japan Search for other works by this author on: Oxford Academic Google Scholar Y. Kawabata, Y. Kawabata Department of Dermatology, Faculty of Medicine, University of Tokyo, Hongo 7‐3‐1, Bunkyo‐ku, Tokyo 113‐8655, Japan Search for other works by this author on: Oxford Academic Google Scholar A. Asahina, A. Asahina Department of Dermatology, Faculty of Medicine, University of Tokyo, Hongo 7‐3‐1, Bunkyo‐ku, Tokyo 113‐8655, Japan Search for other works by this author on: Oxford Academic Google Scholar K. Kikuchi, K. Kikuchi Department of Dermatology, Faculty of Medicine, University of Tokyo, Hongo 7‐3‐1, Bunkyo‐ku, Tokyo 113‐8655, Japan Search for other works by this author on: Oxford Academic Google Scholar K. Tamaki K. Tamaki Department of Dermatology, Faculty of Medicine, University of Tokyo, Hongo 7‐3‐1, Bunkyo‐ku, Tokyo 113‐8655, Japan Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 148, Issue 5, 1 May 2003, Pages 1028–1031, https://doi.org/10.1046/j.1365-2133.2003.05367.x Published: 01 May 2003 Article history Accepted: 18 December 2002 Published: 01 May 2003
Phosphodiesterase 1 Upregulation in Pulmonary Arterial Hypertension
Authors: Ralph Theo Schermuly, Soni Savai Pullamsetti, Grazyna Kwapiszewska, Rio Dumitrascu, Xia Tian, Norbert Weissmann, Hossein Ardeschir Ghofrani, Christina Kaulen, Torsten Dunkern, Christian Schudt, Robert Voswinckel, Jiang Zhou, Arun Samidurai, Walter Klepetko, Renate Paddenberg, Wolfgang Kummer, Werner Seeger, Friedrich Grimminger
Journal: Circulation (2007)

Pulmonary arterial hypertension (PAH) is a life-threatening disease, characterized by vascular smooth muscle cell hyperproliferation. The calcium/calmodulin-dependent phosphodiesterase 1 (PDE1) may play a major role in vascular smooth muscle cell proliferation.We investigated the expression of PDE1 in explanted lungs from idiopathic PAH patients and animal models of PAH and undertook therapeutic intervention studies in the animal models. Strong upregulation of PDE1C in pulmonary arterial vessels in the idiopathic PAH lungs compared with healthy donor lungs was noted on the mRNA level by laser-assisted vessel microdissection and on the protein level by immunohistochemistry. In chronically hypoxic mouse lungs and lungs from monocrotaline-injected rats, PDE1A upregulation was detected in the structurally remodeled arterial muscular layer. Long-term infusion of the PDE1 inhibitor 8-methoxymethyl 3-isobutyl-1-methylxanthine in hypoxic mice and monocrotaline-injected rats with fully established pulmonary hypertension reversed the pulmonary artery pressure elevation, structural remodeling of the lung vasculature (nonmuscularized versus partially muscularized versus fully muscularized small pulmonary arteries), and right heart hypertrophy.Strong upregulation of the PDE1 family in pulmonary artery smooth muscle cells is noted in human idiopathic PAH lungs and lungs from animal models of PAH. Inhibition of PDE1 reverses structural lung vascular remodeling and right heart hypertrophy in 2 animal models. The PDE1 family may thus offer a new target for therapeutic intervention in pulmonary hypertension.
Effect of Atrial Stimulation Site on the Electrophysiological Properties of the Atrioventricular Node in Man
Authors: WILLIAM P. BATSFORD, MASOOD AKHTAR, ANTONIO R. CARACTA, MARK E. JOSEPHSON, STUART F. SEIDES, ANTHONY N. DAMATO
Journal: Circulation (1974)

The electrophysiological properties of the atrioventricular conduction system were compared in 16 patients using stimulation of the high right atrium (HRA) and a site within the coronary sinus (CS). The site of atrial stimulation significantly altered A-V nodal conduction time and refractoriness in eight patients (Group A) and did not change A-V nodal properties in the remaining patients. His-Purkinje conduction time and refractoriness were not affected by changing the atrial stimulation site. The atrial stimulation site may influence A-V nodal function by changing the site and/or mode of entry of the impulse into the A-V node.
The First Derivative Thoracic Impedance Cardiogram
Authors: ZUHDI LABABIDI, D. A. EHMKE, ROBERT E. DURNIN, PAUL E. LEAVERTON, RONALD M. LAUER
Journal: Circulation (1970)

When an alternating current of high frequency is applied to the thorax, the first derivative of the impedance to this current is affected by the cardiac cycle resulting in a characteristic wave form. Phonocardiograms, electrocardiograms, and first derivative thoracic impedance cardiograms were recorded simultaneously in 91 subjects. The first derivative thoracic impedance cardiograms were found to have sharply demarcated points which occur synchronously with the first heart sound, aortic second sound, pulmonic second sound, mitral opening snap, third heart sound, and fourth heart sound. The first derivative thoracic impedance cardiogram may thus be used not only as a reference tracing to help identify heart sounds on the phonocardiogram, but also for directly timing the intervals within the cardiac cycle.
Effect of Cigarette Smoking on Competence of the Pylorus: Preliminary Study
Authors: N. W. Read, P. Grech
Journal: BMJ (1973)

The competence of the pylorus was studied in 13 normal volunteers and nine dyspeptic patients by means of a radiological technique involving intubation of the duodenum. The pylorus was found to be competent in most normal individuals and in fewer than half of the dyspeptic patients. However, on smoking a cigarette, appreciable increase in duodenogastric reflux was seen in nine out of the 13 normal volunteers and in seven out of the nine dyspeptic patients. Such induced pyloric incompetence and the resultant regurgitation of duodenal juices may explain the increased incidence of gastritis and gastric ulceration in heavy smokers.
Multiple organ pathology, metabolic abnormalities and impaired homeostasis of reactive oxygen species in Epas1−/− mice
Authors: Marzia Scortegagna, Kan Ding, Yavuz Oktay, Arti Gaur, Frederick Thurmond, Liang-Jun Yan, Brett T Marck, Alvin M Matsumoto, John M Shelton, James A Richardson, Michael J Bennett, Joseph A Garcia
Journal: Nature Genetics (2003)
Deleterious cardiac effects of captopril during acute myocardial ischaemia in the dog
Authors: S. Alam, S. Rezkalla, P. Farkas, Z. G Turi
Journal: Cardiovascular Research (1992)

Journal Article Deleterious cardiac effects of captopril during acute myocardial ischaemia in the dog Get access Samir Alam, Samir Alam Correspondence to Dr Turi (Cardiac Catheterization Laboratory). Search for other works by this author on: Oxford Academic PubMed Google Scholar Shereif Rezkalla, Shereif Rezkalla Search for other works by this author on: Oxford Academic PubMed Google Scholar Peter Farkas, Peter Farkas Search for other works by this author on: Oxford Academic PubMed Google Scholar Zoltan G Turi Zoltan G Turi Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 26, Issue 3, March 1992, Pages 232–236, https://doi.org/10.1093/cvr/26.3.232 Published: 01 March 1992 Article history Received: 03 May 1991 Accepted: 19 September 1991 Published: 01 March 1992
934 DEFECTIVE CD39 EXPRESSION BY Tregs IN AUTOIMMUNE HEPATITIS PREVENTS SUPPRESSION OF IL17 PRODUCTION AND IS ASSOCIATED WITH IMPAIRED ATP-HYDROLYSIS
Authors: C.R. Grant, R. Liberal, B.S. Holder, Y. Ma, S.C. Robson, G. Mieli-Vergani, D. Vergani, M.S. Longhi
Journal: Journal of Hepatology (2013)
Treatment of Scoliosis
Authors: Edward J. Riseborough
Journal: New England Journal of Medicine (1967)

ALTHOUGH a considerable amount of research is being done on the causes of idiopathic scoliosis, very little has been discovered concerning the underlying pathologic process. Despite this failure, many advances have been made in the treatment of this condition during the past decade.1 With the development of the Milwaukee brace,2 Harrington instruments3 and the more effective cast technics described by Bisser,4 an aggressive approach to the treatment of scoliosis has replaced the time-honored "watchful-waiting" method. Watching scoliosis gradually progress in children is no longer tenable.Milwaukee BracePerhaps the greatest advance in the treatment of scoliosis in recent years has . . .
Genetic evidence for a common pathway mediating oxidative stress, inflammatory gene induction, and aortic fatty streak formation in mice.
Authors: F Liao, A Andalibi, J H Qiao, H Allayee, A M Fogelman, A J Lusis
Journal: Journal of Clinical Investigation (1994)

In a previous survey of inbred mouse strains on an atherogenic diet, we observed that the susceptibility to aortic atherosclerotic lesion formation was associated with the accumulation of lipid peroxidation products, induction of inflammatory genes, and the activation of NF-kB-like transcription factors (Liao, F., A. Andalibi, F. C. deBeer, A. M. Fogelman, and A.J. Lusis. 1993. J. Clin. Invest. 91:2572-2579). We hypothesized that the inflammation-related processes were stimulated by oxidized lipids, since injection of minimally oxidized LDL (MM-LDL) activated the same set of genes. We now report that the induction of inflammatory genes and activation of NF-kB-like transcription factors cosegregate with aortic atherosclerotic lesion formation in BXH recombinant inbred strains derived from parental C57BL/6J (susceptible) and C3H/HeJ (resistant) mice. In addition, the accumulation of hepatic conjugated dienes exhibited a significant correlation with inflammatory gene activation. These results provide strong evidence for the role of inflammatory mediators inducible by oxidative stress in atherogenesis. They also suggest that a major gene contributing to aortic lesion development in this mouse model, designated Ath-1, may control either the accumulation of lipid peroxides in tissues or the cellular responses to such lipid peroxides.
What and what not to conclude from the results of the LEGS study?
Authors: Andreas G Helg
Journal: Annals of the Rheumatic Diseases (2014)

Like probably many others, we have been waiting eagerly for the results of the Long-term Evaluation of Glucosamine Sulfate (LEGS) study.1 The expectation was that this trial would shed light onto the ongoing controversy about the value of chondroitin, glucosamine and their combination in the treatment of osteoarthritis (OA) of the knee, and provide answers to several open questions. The LEGS study fully met this expectation as to the structure-modifying effect of the combination of chondroitin sulfate and glucosamine sulfate. However, what do the results of this trial tell us about the structure-modifying effect of chondroitin sulfate or glucosamine sulfate alone, or about the symptomatic effect of chondroitin sulfate, glucosamine sulfate or the combination thereof? Unfortunately, the results of the LEGS study add very little to this question as we will point out subsequently.

Symptomatic effect: The main symptomatic outcome measure in the LEGS study was changed from the use of non-steroidal anti-inflammatory drugs (NSAIDs) to self-reported pain when the authors realised that only about 20% of the patients recruited till that point in time were taking NSAIDs. The alternative primary outcome measure to assess the symptomatic effect was the maximum score of pain ‘at its worst’ recorded daily in a 7-day diary that the participants had to complete every 2 months. There are several problems with this alternative outcome measure: (1) It seems not to have been validated, that is, we have not found any relevant validation study. (2) Experiences with it are lacking, that is, we are not aware of any other trial in which this measure had been used. (3) Pain due to knee OA is activity-related (depending on the activity), that is, a patient with knee OA may not suffer from pain while walking, but may do so when descending stairs. We do not know what …
Systemic Therapy of Advanced Bronchioloalveolar Cell Carcinoma: Challenges and Opportunities
Authors: Vincent A. Miller, Fred R. Hirsch, David H. Johnson
Journal: Journal of Clinical Oncology (2005)

Bronchioloalveolar cell carcinoma (BAC) has fascinated physicians with its unique epidemiology, pathology, clinical manifestations, and natural history when compared with other non–small-cell lung cancer (NSCLC) subtypes. However, the relative rarity of pure BAC as defined by the WHO, and the inconsistent definitions used in various series, has limited systematic study of this entity. Retrospective and prospective studies suggest that patients with BAC treated with cytotoxic chemotherapy have a longer median survival than those with other subtypes of NSCLC. However, the widely accepted view that BAC is less chemosensitive than other NSCLCs is not clearly supported by the small body of available literature. Antitumor activity of cytotoxic agents and the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors has been documented in phase II trials but no phase III trials have been conducted in this disease. The observation that profound responses to gefitinib and erlotinib often occurred in NSCLC patients with BAC, and that EGFR tyrosine kinase domain mutations were identified in large part by careful study of such patients, serves as a paradigm for translational research in this disease. The recognition that pure BAC and adenocarcinoma with BAC features behave similarly and as such represent a relatively common entity will facilitate accrual to BAC specific studies. Alternatively, stratification of these histologic subtypes in broader clinical trials in NSCLC is warranted. However, for either strategy to succeed in advancing our understanding of the molecular biology of BAC, it must be accompanied by central pathologic review with detailed classification of such, and of adequate tissue for measurement of known or putative targets of action of the agent under study.
PROTEUS VULGARIS AS GAS PRODUCER IN DIABETES
Authors: Harold L. Leder
Journal: JAMA (1942)

<h3>To the Editor:—</h3> InThe Journal, Dec. 27, 1941 Carl L. Gillies reported 4 cases of interstitial emphysema in diabetes caused by the colon bacillus. It seems worth while at this time to call attention to the fact that Proteus vulgaris may also be a producer of gas in cases of diabetes. In August 1939, in Joseph Tenopyr's service at Kings County Hospital, Brooklyn, I attended a young diabetic Negress who had a painful, large, hard, cracked callosity on the heel. While she was in the hospital an area of cellulitis adjacent to the callus appeared, associated with a decided elevation of the pulse rate and of the temperature. A dirty brownish serous discharge with a "musty" odor oozed from the crack, and a few days later an area of crepitation in the tissues surrounding the heel was noted, which soon spread to involve similarly the entire lower extremity. Roentgen