tbuckley/cabot-search huggingface dataset:
The ambition of the European Respiratory Journal: chapter 2
Authors: M. Humbert
Journal: European Respiratory Journal (2013)

Last year, in my opening editorial as incoming Chief Editor, I stated that “the ambition of the Journal is […] to be the best possible publication available to help, inform and open new horizons to junior and established healthcare professionals and scientists who have an interest in (respiratory) medicine and science” [1]. At the beginning of 2014, I would like to share with you some thoughts about the future of our Journal.

The Editorial Board recognises that impact factor remains, among other criteria, an important indicator of quality in our academic world [1–3]. In this regard, we were delighted when the Journal’s impact factor reached an unprecedented level of 6.355 …
Airway epithelium expresses interleukin-18
Authors: L.a. Cameron, R.a. Taha, A Tsicopoulos, M Kurimoto, R. Olivenstein, B Wallaert, E.m. Minshall, Q.a. Hamid
Journal: European Respiratory Journal (1999)

Interleukin (IL)-18 is an interferon (IFN)-gamma-inducing cytokine suggested to be important in regulating inflammatory responses. This study investigated the pulmonary expression of IL-18 under conditions characterized by T-helper (Th)1 (lipopolysaccharide (LPS) treatment/sarcoidosis) and Th2 (ovalbumin (OVA) challenge/asthma) cytokine production. In situ hybridization and immunocytochemistry were used to determine the number of cells expressing IL-18, IFN-gamma, IL-5 and major basic protein (MBP) within lung tissue from Balb/c mice stimulated with LPS, OVA and in normal control mice. Bronchial biopsies from patients with sarcoidosis, asthma and control individuals were also examined. IL-18 was localized primarily to airway epithelium and mononuclear cells. Constitutive expression was observed within the lungs of control mice. Animals challenged with LPS exhibited more IL-18 messenger ribonucleic acid (mRNA)-positive and IFN-gamma immunoreactive cells, compared to control mice (p&lt;0.01). OVA-challenged mice had fewer IL-18 mRNA positive and more IL-5 and MBP immunoreactive cells, compared to control mice (p&lt;0.01). Similarly, constitutive expression of IL-18 protein was observed within the airway epithelium of control individuals, with more positive cells found within sarcoidosis tissue (p&lt;0.01) and fewer within asthmatic tissue (p&lt;0.01), compared to controls. These results demonstrate the expression of interleukin-18 within airway epithelium and the regulation of this cytokine under conditions of both T-helper1 and T-helper2 cytokine production.
Patient Safety in Cancer Care: A Time for Action
Authors: P. G. Norton, G. R. Baker
Journal: JNCI Journal of the National Cancer Institute (2007)

Retrospective chart audit studies of acute care in several countries have shown that between 3% and 16% of patients experience one or more harmful adverse events while hospitalized and that about half of these events are preventable ( 1 ). These studies indicate that medication treatment is an area of high risk. We still know relatively little about the incidence of adverse events in nonacute settings or for specific patient populations. In this issue of the Journal, Riechelmann et al. ( 2 ) begin to address this issue for cancer patients attending an outpatient oncology clinic. They surveyed patients concerning the medication that they had taken in the previous 4 weeks. From the information they received, they determined that 27% of the patients had the potential for one or more possibly serious drug interactions. The majority of these possible drug interactions involved not antineoplastic agents but rather drugs that were being administered for noncancer comorbidities. Although an incidence of 27% seems high, the results are consistent with what is known about the potential for adverse drug events in patients who have contact with several doctors. Indeed, Tamblyn et al. ( 3 ) concluded that “a single primary care physician and a single dispensing pharmacy may be ‘protective’ factors in preventing potentially inappropriate drug combinations.” This observation has been reinforced by Blendon et al. ( 4 ), who in 2002 carried out a random survey of more than 3800 adults in the United States, Australia, Canada, New Zealand, and the United Kingdom whose health had been defi ned as less than optimal based on their responses to a questionnaire. More than one-third of the 66% who regularly took one or more medications had not had their medications reviewed by the physician they relied on the most for the previous 2 years. Further, 15.8% of those seeing one or two doctors reported either a medication or medical error in the last 2 years, compared with 28.8% of those seeing three or more physicians.
Modifications of haematological series in patients co-infected with human immunodeficiency virus and hepatitis C virus during treatment with interferon and ribavirin: differences between pegylated and standard interferon
Authors: A. Arizcorreta, F. Brun, C. Fernández-Gutiérrez, R. García Juárez, F. Guerrero, E. Pérez-Guzmán, J.A. Girón-González
Journal: Clinical Microbiology and Infection (2004)
Blunted responsiveness of the neuronal activation marker Fos in brainstem cardiovascular nuclei of cirrhotic rats
Authors: D R Breitman, S. S. Lee
Journal: Hepatology (1997)

Cardiovascular function in cirrhosis is deranged, with indirect evidence of abnormal central cardiovascular regulation. We aimed to elucidate the role of brainstem cardiovascular nuclei in hemodynamic regulation by examining the protein product, Fos, of the immediate-early gene c-fos , in cirrhotic rats. Cirrhosis was induced by chronic bile duct ligation (BDL) of 25-days duration, while controls underwent a sham operation. To examine the effects of jaundice per se in the absence of cirrhosis, a third group of 5-day BDL rats was also studied. All rats were anesthetized with pentobarbital, and catheters were inserted to measure baseline blood pressure and heart rate. Separate groups were then subjected to volume manipulation by a hypotensive hemorrhage or isotonic saline infusion, or no challenge. Ninety minutes after the volume manipulation, the animals were killed and the medulla sectioned and stained for Fos by immunohistochemisty. The nucleus tractus solitarius (NTS) of the sham-operated unchallenged rats showed scant Fos immunoreactivity (27.8 ± 3.3 cells), but both hemorrhage and volume infusion significantly increased Fos staining (86.0 ± 3.7 and 95.2 ± 8.5, respectively). In contrast, the unchallenged cirrhotic rats showed markedly increased Fos in the NTS (154.6 ± 27.0), but neither hemorrhage nor volume infusion significantly changed the amount of Fos staining. Fos staining in the ventrolateral medulla (VLM) followed a similar pattern with low staining in the unchallenged sham rats and increased staining in the other groups, but no differences between the unchallenged and the volume-manipulated cirrhotic groups. The 5-day BDL jaundiced rats showed no baseline increase in Fos staining, nor any significant increase after hemorrhage. These results showing baseline activation of central neuronal regions responsible for blood pressure homeostasis, but completely blunted responsiveness in cirrhotic rats, confirm a central origin of disordered cardiovascular regulation. The presence of jaundice may also contribute to the central cardiovascular hyporesponsiveness.
VARIATION IN THE FUNCTIONAL POWER OF HUMAN SWEAT GLANDS
Authors: Vincent P. Dole, Jørn Hess Thaysen
Journal: The Journal of Experimental Medicine (1953)

A method has been worked out for the measurement of the volume of sweat produced by individual glands. A special paper, impregnated with iodine, absorbs water in a uniform way and shows the area of wetting by a sharply defined blue dot. Indirect calibrations showed that 1 cm.(3) of water would form a spot of 700 cm.(2) area, and that this relation of volume to area was a constant one over a wide range. The actual volumes encountered in prints of the sweat glands were from 5 x 10(-9) to 4 x 10(-6) cm.(3). The relative activity of glands at any instant of time can be expressed by the statistical distribution of log diameter of the dots on the print. This distribution, which might at first sight seem rather artificial, has the advantage of being unaffected by a proportionate change in the output of water from each gland. Thus it is independent of the duration of contact between print paper and skin, and of changes in the average flow from the field as a whole. It is sensitive only to changes in the activity of glands relative to each other. The methods of printing and statistical analysis were used to study the relative activity of glands in a field of 22 mm. diameter. Glands of the forearm and back were studied both under direct stimulation with mecholyl and under the reflex stimulation of environmental heat, similar results being obtained with the two kinds of stimuli. Glands of the abdomen and leg, stimulated with mecholyl, were studied in one experiment. Detailed comparison of the dots in consecutive prints showed that the large dots remained large and the small dots continued to be small. These persistent differences in the outflow of water from adjacent glands were interpreted as being due to differences in the functional power of the glands. Repeated prints of the glands during a period of 75 minutes, in which the sweat flow was declining, showed that the relative activity of the glands remained constant. This meant that the set of glands, although differing greatly in power, varied together as a functional unit. Different regions of the body show not only the variation of glandular power within each small area, but also marked differences in the average power of glands belonging to the different regions. Glands of the back, for instance, show a much greater outflow than glands of the forearm when stimulated equally with a local injection of mecholyl. Equal rates of outflow, therefore, do not mean equal states of functional activity, unless the regions being compared are of equal functional power.
Hotspot Mutations in H3F3A and IDH1 Define Distinct Epigenetic and Biological Subgroups of Glioblastoma
Authors: Dominik Sturm, Hendrik Witt, Volker Hovestadt, Dong-Anh Khuong-Quang, David T.W. Jones, Carolin Konermann, Elke Pfaff, Martje Tönjes, Martin Sill, Sebastian Bender, Marcel Kool, Marc Zapatka, Natalia Becker, Manuela Zucknick, Thomas Hielscher, Xiao-Yang Liu, Adam M. Fontebasso, Marina Ryzhova, Steffen Albrecht, Karine Jacob, Marietta Wolter, Martin Ebinger, Martin U. Schuhmann, Timothy van Meter, Michael C. Frühwald, Holger Hauch, Arnulf Pekrun, Bernhard Radlwimmer, Tim Niehues, Gregor von Komorowski, Matthias Dürken, Andreas E. Kulozik, Jenny Madden, Andrew Donson, Nicholas K. Foreman, Rachid Drissi, Maryam Fouladi, Wolfram Scheurlen, Andreas von Deimling, Camelia Monoranu, Wolfgang Roggendorf, Christel Herold-Mende, Andreas Unterberg, Christof M. Kramm, Jörg Felsberg, Christian Hartmann, Benedikt Wiestler, Wolfgang Wick, Till Milde, Olaf Witt, Anders M. Lindroth, Jeremy Schwartzentruber, Damien Faury, Adam Fleming, Magdalena Zakrzewska, Pawel P. Liberski, Krzysztof Zakrzewski, Peter Hauser, Miklos Garami, Almos Klekner, Laszlo Bognar, Sorana Morrissy, Florence Cavalli, Michael D. Taylor, Peter van Sluis, Jan Koster, Rogier Versteeg, Richard Volckmann, Tom Mikkelsen, Kenneth Aldape, Guido Reifenberger, V. Peter Collins, Jacek Majewski, Andrey Korshunov, Peter Lichter, Christoph Plass, Nada Jabado, Stefan M. Pfister
Journal: Cancer Cell (2012)
GIP: An Inconsequential Incretin or Not?
Authors: Richard E. Pratley
Journal: Diabetes Care (2010)

The “incretin effect” refers to the enhancement of insulin secretion in response to an oral glucose load relative to that of an isoglycemic intravenous glucose challenge (1). In humans, the incretin effect is mediated by two peptide hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which are secreted from enteroendocrine cells in response to nutrients entering the gut. GLP-1 secretion from L-cells, found in highest density in the distal ileum but also throughout the small and large intestine, is stimulated by glucose, amino acids, and fat. GIP, in contrast, is produced by the K-cells in the proximal duodenum; its secretion is also stimulated by glucose, but is particularly enhanced by fat (2). Both GLP-1 and GIP are derived from prohormones (proglucagon and pro-GIP, respectively) and secreted as active hormones. The effects of both GLP-1 and GIP are mediated by specific G protein–coupled receptors present on the plasma membrane of β-cells and other target tissues. GLP-1 and GIP increase insulin secretion from β-cells in a glucose-dependent manner. In rodents, GLP-1 and GIP also enhance β-cell mass by increasing rates of proliferation and decreasing rates of apoptosis. Many physiological effects of GLP-1 and GIP do not overlap, however. GLP-1 suppresses glucagon secretion, slows gastric emptying, and has central nervous system effects to regulate appetite, whereas GIP does not. GIP, on the other hand, has direct effects on adipocytes to promote triglyceride storage (1). The incretin system, therefore, facilitates integrated physiological responses to meals of different size and composition allowing ingested nutrients to be optimally metabolized.

The incretin effect is an important determinant of glucose tolerance. In patients with type 2 diabetes, the incretin effect …
Ischemic Preconditioning Attenuates Cardiac Sympathetic Nerve Injury via ATP-Sensitive Potassium Channels During Myocardial Ischemia
Authors: Toshiro Miura, Shuji Kawamura, Hironari Tatsuno, Yasuhiro Ikeda, Shunsuke Mikami, Hiroshi Iwamoto, Takayuki Okamura, Mitsuo Iwatate, Masayasu Kimura, Yuka Dairaku, Tsuyoshi Maekawa, Masunori Matsuzaki
Journal: Circulation (2001)

Background During myocardial ischemia, massive norepinephrine (NE) is released from the cardiac sympathetic nerve terminals, reflecting the sympathetic nerve injury. A brief preceding ischemia can reduce infarct size; this is known as ischemic preconditioning (PC). The effect of PC on sympathetic nerves, however, including its underlying mechanisms in dog hearts, has remained unclear. Thus, this study was designed to elucidate whether the activation of ATP-sensitive potassium (K ATP ) channels is involved in the mechanism of cardiac sympathetic nerve protection conferred by PC. Methods and Results Interstitial NE concentration was measured by the in situ cardiac microdialysis method in 45 anesthetized dogs. Five minutes of ischemia followed by 5 minutes of reperfusion was performed as PC. In the controls, the dialysate NE concentration (dNE) increased 15-fold after the 40-minute ischemia. PC decreased dNE at 40-minute ischemia by 59% ( P &lt;0.01), which was reversed by glibenclamide. A K ATP channel opener, nicorandil (25 μg · kg −1 · min −1 IV), decreased dNE at 40 minutes of ischemia by 76% ( P &lt;0.01), which was also reversed by glibenclamide. During the PC procedure, no significant increase in dNE was detected, even with the uptake-1 inhibitor desipramine. Conclusions Cardiac sympathetic nerve injury during myocardial ischemia was attenuated by PC via the activation of K ATP channels, but the trigger of the PC effect is unlikely to be NE release in dog hearts.
SPARC mediates metastatic cooperation between CSC and non-CSC prostate cancer cell subpopulations
Authors: Francesca Mateo, Óscar Meca-Cortés, Toni Celià-Terrassa, Yolanda Fernández, Ibane Abasolo, Lourdes Sánchez-Cid, Raquel Bermudo, Amaia Sagasta, Leonardo Rodríguez-Carunchio, Mònica Pons, Verónica Cánovas, Mercedes Marín-Aguilera, Lourdes Mengual, Antonio Alcaraz, Simó Schwartz, Begoña Mellado, Kristina Y Aguilera, Rolf Brekken, Pedro L Fernández, Rosanna Paciucci, Timothy M Thomson
Journal: Molecular Cancer (2014)

Tumor cell subpopulations can either compete with each other for nutrients and physical space within the tumor niche, or co-operate for enhanced survival, or replicative or metastatic capacities. Recently, we have described co-operative interactions between two clonal subpopulations derived from the PC-3 prostate cancer cell line, in which the invasiveness of a cancer stem cell (CSC)-enriched subpopulation (PC-3M, or M) is enhanced by a non-CSC subpopulation (PC-3S, or S), resulting in their accelerated metastatic dissemination. M and S secretomes were compared by SILAC (Stable Isotope Labeling by Aminoacids in Cell Culture). Invasive potential in vitro of M cells was analyzed by Transwell-Matrigel assays. M cells were co-injected with S cells in the dorsal prostate of immunodeficient mice and monitored by bioluminescence for tumor growth and metastatic dissemination. SPARC levels were determined by immunohistochemistry and real-time RT-PCR in tumors and by ELISA in plasma from patients with metastatic or non-metastatic prostate cancer. Comparative secretome analysis yielded 213 proteins differentially secreted between M and S cells. Of these, the protein most abundantly secreted in S relative to M cells was SPARC. Immunodepletion of SPARC inhibited the enhanced invasiveness of M induced by S conditioned medium. Knock down of SPARC in S cells abrogated the capacity of its conditioned medium to enhance the in vitro invasiveness of M cells and compromised their potential to boost the metastatic behavior of M cells in vivo. In most primary human prostate cancer samples, SPARC was expressed in the epithelial tumoral compartment of metastatic cases. The matricellular protein SPARC, secreted by a prostate cancer clonal tumor cell subpopulation displaying non-CSC properties, is a critical mediator of paracrine effects exerted on a distinct tumor cell subpopulation enriched in CSC. This paracrine interaction results in an enhanced metastatic behavior of the CSC-enriched tumor subpopulation. SPARC is expressed in the neoplastic cells of primary prostate cancer samples from metastatic cases, and could thus constitute a tumor progression biomarker and a therapeutic target in advanced prostate cancer.
The effect of increased hepatic sitosterol on the regulation of 3-hydroxy-3-methylglutaryl—coenzyme a reductase and cholesterol 7α-hydroxylase in the rat and sitosterolemic homozygotes
Authors: Sarah Shefer, Gerald Salen, John Bullock, Lien B. Nguyen, Gene C. Ness, Zhihong Vhao, Peter F. Belamarich, Indu Chowdhary, Susan Lerner, Ashok K. Batta, Stephen G. Tint
Journal: Hepatology (1994)

ABSTRACT We investigated hepatic cholesterol homeostasis in four homozygous sitosterolemic subjects from two unrelated families who showed enhanced absorption, diminished removal and increased tissue and plasma concentrations of sitosterol (24–ethyl cholesterol). Measurements of hepatic 3–hydroxy–3–methylglutaryl coenzyme A reductase activities were correlated with steady state messenger RNA levels and related to cholesterol 7α–hydroxylase activities in the sitosterolemic homozygotes and nine controls. Similar determinations were made in rats infused intravenously with sitosterol so that hepatic and plasma sitosterol concentrations increased to about 10% of total sterols to resemble the human disease sitosterolemia. In the four sitosterolemic homozygotes, hepatic 3–hydroxy–3–methylglutaryl coenzyme A reductase activities were markedly reduced (12% of normal), and steady state 3–hydroxy–3–methylglutaryl coenzyme A reductase messenger RNA levels barely detected. In contrast, hepatic 3–hydroxy–3–methylglutaryl coenzyme A reductase activities and messenger RNA levels were not decreased in rats with similarly elevated hepatic sitosterol concentrations. However, hepatic cholesterol 7α–hydroxylase activity was inhibited 30% in both the sitosterolemic homozygotes and rats with high liver sitosterol concentrations. Plasma cholesterol concentrations increased 120% in the sitosterol–infused rats and 29% in the untreated human homozygotes. These results demonstrate that high–tissue sitosterol concentrations do not inhibit hepatic 3–hydroxy–3–methylglutaryl coenzyme A reductase activity or steady state messenger RNA levels and that they competitively block cholesterol 7α–hydroxylase activity and raise plasma cholesterol levels. Thus the deficiency of 3–hydroxy–3–methylglutaryl coenzyme A reductase in the liver of sitosterolemic homozygotes is inherited and not due to the hepatic accumulation of sitosterol. In distinction, elevated hepatic sitosterol concentrations increase plasma cholesterol levels by competitively suppressing cholesterol 7α–hydroxylase activity. (Hepatology 1994;20:213–219.).
BUILD-3: A Randomized, Controlled Trial of Bosentan in Idiopathic Pulmonary Fibrosis
Authors: Talmadge E. King, Kevin K. Brown, Ganesh Raghu, Roland M. du Bois, David A. Lynch, Fernando Martinez, Dominique Valeyre, Isabelle Leconte, Adele Morganti, Sébastien Roux, Juergen Behr
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

A previous trial of bosentan in idiopathic pulmonary fibrosis (IPF) showed a trend to delayed IPF worsening or death. Also, improvements in some measures of dyspnea and health-related quality of life were observed.To demonstrate that bosentan delays IPF worsening or death.Prospective, randomized (2:1), double-blind, placebo-controlled, event-driven, parallel-group, morbidity-mortality trial of bosentan in adults with IPF of less than 3 years' duration, confirmed by surgical lung biopsy, and without extensive honeycombing on high-resolution computed tomography. The primary endpoint was time to IPF worsening (a confirmed decrease from baseline in FVC ≥ 10% and diffusing capacity of the lung for carbon monoxide ≥ 15%, or acute exacerbation of IPF) or death up to End of Study. Effects of bosentan on health-related quality of life, dyspnea, and the safety and tolerability of bosentan were investigated.Six hundred sixteen patients were randomized to bosentan (n=407) or placebo (=209). No significant difference between treatment groups was observed in the primary endpoint analysis (hazard ratio, 0.85; 95% confidence interval, 0.66-1.10; P=0.2110). No treatment effects were observed on health-related quality of life or dyspnea. Some effects of bosentan treatment were observed in changes from baseline to 1 year in FVC and diffusing capacity of the lung for carbon monoxide. The safety profile for bosentan was similar to that observed in other trials.The primary objective in the Bosentan Use in Interstitial Lung Disease-3 trial was not met. Bosentan was well tolerated. Clinical trial registered with www.clinicaltrials.gov (NCT 00391443).
Comparison of drug survival rates for adalimumab, etanercept and infliximab in patients with psoriasis vulgaris
Authors: R. Gniadecki, K. Kragballe, T.N. Dam, L. Skov
Journal: British Journal of Dermatology (2011)

Journal Article Comparison of drug survival rates for adalimumab, etanercept and infliximab in patients with psoriasis vulgaris Get access R. Gniadecki, R. Gniadecki Department of Dermatology, Bispebjerg University Hospital, 2200 Copenhagen N, Denmark Robert Gniadecki. E‐mail: r.gniadecki@gmail.com Search for other works by this author on: Oxford Academic Google Scholar K. Kragballe, K. Kragballe Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark Search for other works by this author on: Oxford Academic Google Scholar T.N. Dam, T.N. Dam Department of Dermatology, Roskilde Hospital, Roskilde, Denmark Search for other works by this author on: Oxford Academic Google Scholar L. Skov L. Skov Department of Dermato‐Allergology, Gentofte University Hospital, Copenhagen, Denmark Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 164, Issue 5, 1 May 2011, Pages 1091–1096, https://doi.org/10.1111/j.1365-2133.2011.10213.x Published: 01 May 2011