tbuckley/cabot-search huggingface dataset:
Tracheal microvascular responses to beta-adrenergic stimulation in anesthetized rats.
Authors: M R Corboz, S T Ballard, S K Inglis, A E Taylor
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Previous study of adrenergic control of the tracheal vasculature in rats (1) demonstrated that beta-adrenergic blockade heightened arteriolar and large venular contractile responses to norepinephrine, a nonselective alpha-adrenergic agonist. The present study was undertaken to confirm the presence of functional beta-adrenergic receptors and to determine which beta-adrenergic receptor subtypes mediate vasodilation in this tissue. Tracheal adventitial arterioles (12.0 to 47.0 micro m initial diameter, n=39) and venules (48.0 to 98.5 micrometers initial diameter, n=44) were observed through a video microscope, and vessel diameters were measured. Vessels were preconstricted with 10(-4) M phenylephrine (PHE), a selective alpha 1-adrenergic agonist, to achieve sufficient tone for measurement of dilation responses. When vessels were treated only with PHE, arterioles and venules constricted to 55.9% and 67.6% of their initial diameter, respectively, after 15 min of suffusion. When preconstricted vessels were treated with the nonselective beta-adrenergic agonist isoproterenol (10(-5) M), both arterioles and venules significantly dilated from 63.4% to 82.9% and from 71.5% to 81.3% of their initial diameters. At high concentration (10(-5) M), the putative beta 2-adrenergic agonist terbutaline also caused preconstricted arterioles and venules to significantly dilate from 70.8% to 79.8% and from 71.5% to 83.4% of their initial diameters. The selective beta 1-adrenergic antagonist atenolol (10(-6) M) did not affect terbutaline-induced dilation in preconstricted arterioles, but greatly attenuated dilation in preconstricted venules. From these data, we conclude that beta 2-adrenergic receptors are present in and mediate dilation of tracheal arterioles, and also, that the dilation in large tracheal venules is mediated in large part through beta 1-adrenergic receptors.
Tumor-promoting immune-suppressive myeloid-derived suppressor cells in the multiple myeloma microenvironment in humans
Authors: Güllü Topal Görgün, Gregory Whitehill, Jennifer L. Anderson, Teru Hideshima, Craig Maguire, Jacob Laubach, Noopur Raje, Nikhil C. Munshi, Paul G. Richardson, Kenneth C. Anderson
Journal: Blood (2013)
Abstract 2014: Gene expression profiling identifies characteristic oncogenetic pathways in age-related Epstein-Barr virus (EBV)-positive B-cell lymphoproliferative disorders.
Authors: Harumi Kato, Kazuhito Yamamoto, Kennosuke Karube, Jun Takizawa, Shinobu Tsuzuki, Yasushi Yatabe, Teru Kanda, Miyuki Katayama, Yukiyasu Ozawa, Kenji Ishitsuka, Masataka Okamoto, Tomohiro Kinoshita, Koichi Oshima, Shigeo Nakamura, Yasuo Morishima, Masao Seto
Journal: Cancer Research (2013)

Abstract Age-related EBV-associated B-cell lymphoproliferative disorder (AR-EBVLPD) is newly classified as a subtype of diffuse large cell lymphoma (DLBCL) according to the WHO classification. AR-EBVLPD cases have poor prognosis compared to that of EBV-negative DLBCL patients. Until now, its molecular pathogenesis remains largely unknown. We investigated gene expression profiling to identify molecular genetic characterization of AR-EBVLPD. Total RNA was extracted from fresh-frozen tumor samples of five AR-EBVLPD and eight EBV-negative DLBCL cases. Expression profiling was studied using the Agilent 44K human oligonucleotide microarray. Genes highly expressed in AR-EBVLPD included inflammatory and immune-related genes. Gene set enrichment analysis and gene ontology analysis showed that gene sets of the JAK-STAT and NF-kB pathways were enriched in AR-EBVLPD cases. In vitro analysis showed that high activation of JAK-STAT and NF-kB pathways was induced by EBV infection into DLBCL cell lines. The immunoprecipitation assay confirmed that the NF-kB pathway was activated in EBV-infected cell lines compared to EBV-naïve cell lines. The protein expression level of phosphorylated STAT3 increased in an EBV-infected cell line according to western blot analysis. A total of 61 patients (25 AR-EBVLPD and 36 EBV-negative DLBCL) were analyzed immunohistochemically for pSTAT3. Protein expression of phospho-STAT3 was frequently observed in lymphoma cells of AR-EBVLPD clinical samples using immunohistochemistry [AR-EBVLPD: (80.0%, n=20/25) vs. EBV-negative DLBCL: (38.9%, n=22/36), p=0.001]. These results suggested that STAT3 and NF-kB activation was characteristic of AR-EBVLPD, which may reflect the nature of EBV-positive tumor cells. Targeting these pathways as therapies might improve clinical outcomes of AR-EBVLPD. Citation Format: Harumi Kato, Kazuhito Yamamoto, Kennosuke Karube, Jun Takizawa, Shinobu Tsuzuki, Yasushi Yatabe, Teru Kanda, Miyuki Katayama, Yukiyasu Ozawa, Kenji Ishitsuka, Masataka Okamoto, Tomohiro Kinoshita, Koichi Oshima, Shigeo Nakamura, Yasuo Morishima, Masao Seto. Gene expression profiling identifies characteristic oncogenetic pathways in age-related Epstein-Barr virus (EBV)-positive B-cell lymphoproliferative disorders. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2014. doi:10.1158/1538-7445.AM2013-2014
Quality of Life Among Long-Term Adolescent and Adult Survivors of Childhood Cancer
Authors: Elizabeth Maunsell, Lisa Pogany, Maru Barrera, Amanda K. Shaw, Kathy N. Speechley
Journal: Journal of Clinical Oncology (2006)

We assessed effects of childhood or adolescent cancer on quality of life among adolescent and adult cancer survivors, a group who are thought to be at particular risk for adverse late effects.We studied 1,334 survivors and 1,477 age- and sex-matched, general population controls from across Canada using a mailed questionnaire which included the Short Form-36 (SF-36) and measures of self-esteem, optimism, and life satisfaction. General linear models and logistic regression were used. Survivor-control differences corresponding to an effect size (ES) > or = 0.5 were considered clinically important.Participants were age 15 years to 37 years. Most survivors (83.8%) were diagnosed > or = 10 years earlier. Fewer survivors (62.1%) than controls (71.1%) reported very good or excellent general health (adjusted odds ratio, 0.6; 95% CI, 0.5 to 0.7). However, quality of life differences between survivors and controls were small, and for the most part probably not clinically important. Three clinical characteristics-having had CNS or bone cancer, more than one treatment series, and > or = two organs with a dysfunction at treatment end-were independently associated with poorer quality of life in the physical dimensions. Only survivors with > or = two organs with dysfunction (8.7%) reported poorer quality of life in both physical and psychosocial domains, with several clinically important ES. The largest ES for the SF-36 physical summary scores were found in the 8% of survivors with two or three of these characteristics simultaneously, compared with those survivors who had none (-0.79 and -1.13, respectively).Overall, a sizeable majority of adolescent and adult long-term survivors of childhood cancer in Canada appear to have adapted well.
Catecholamines Regulate the Activity, Secretion, and Synthesis of Renalase
Authors: Guoyong Li, Jianchao Xu, Peili Wang, Heino Velazquez, Yanyan Li, Yanling Wu, Gary V. Desir
Journal: Circulation (2008)

We previously identified renalase, a secreted novel amine oxidase that specifically degrades circulating catecholamines. Parenteral administration of either native or recombinant renalase lowers blood pressure, heart rate, and cardiac contractility by metabolizing circulating catecholamines. Renalase plasma levels are markedly reduced in patients with chronic kidney disease. It is not known whether endogenous renalase contributes to the regulation of catecholamines.We show here that circulating renalase lacks significant amine oxidase activity under basal conditions (prorenalase) but that a brief surge of epinephrine lasting <2 minutes causes renalase activity to increase from 48+/-18 to 2246+/-98 arbitrary units (n=3; P<0.002). Enzyme activation is detectable within 30 seconds and sustained for at least 60 minutes. Analysis of epinephrine-mediated hemodynamic changes in normotensive rats indicates that prorenalase becomes maximally activated when systolic pressure increases by >5 mm Hg. The catecholamine surge also leads to a 2.8-fold increase in plasma renalase concentration. Cultured cells exposed to dopamine upregulate steady-state renalase gene expression by >10-fold. The time course of prorenalase activation is abnormal in rats with chronic kidney disease.These data identify a novel mechanism for the regulation of circulating catecholamines. In the renalase pathway, excess catecholamine facilitates the conversion of prorenalase, an inactive plasma amine oxidase, to renalase, which can degrade catecholamines. Excess catecholamines not only regulate the activation of prorenalase but also promote its secretion and synthesis. Because chronic kidney disease is associated with a number of systemic abnormalities, including activation of the sympathetic nervous system, increased catecholamines levels, cardiac hypertrophy, and hypertension, renalase replacement is an attractive therapeutic modality owing to its role in catecholamine metabolism.
A Statewide Approach to Graduate Medical Education
Authors: Jeoffrey K. Stross, Roland G. Hiss, Joseph A. Rinaldo, Calvin J. Dykman, Neal A. Vanselow
Journal: New England Journal of Medicine (1974)

Abstract Graduate medical education in the United States has been criticized for fragmentation of responsibility, inadequate funding, variation in quality, inadequate response to physician manpower needs, lack of inservice evaluation, and use of foreign medical graduates. One solution is to establish a graduate-medical-education system that is organized, controlled, and financed on a statewide basis. Such a system could centralize responsibility, adequately finance the educational component of training, respond to the needs of the individual states, and standardize the content and evaluation of the educational programs. A widely representative governing board could determine the nature of the program and work with appropriate state fiscal organizations to handle budgetary needs. Such a system, if implemented, might have certain disadvantages, but would, on balance, greatly mitigate the problems now besetting graduate medical education. (N Engl J Med 291:701–706, 1974)
Inhibition of the Interaction Between NS3 Protease and HCV IRES With a Small Peptide: A Novel Therapeutic Strategy
Authors: Upasana Ray, Chaitrali L Roy, Anuj Kumar, Prashant Mani, Agnel P Joseph, G Sudha, Debi P Sarkar, N Srinivasan, Saumitra Das
Journal: Molecular Therapy (2012)

Recently, we have demonstrated that the protease domain of NS3 alone can bind specifically to hepatitis C virus (HCV) internal ribosome entry site (IRES) near the initiator AUG, dislodges human La protein and inhibits translation in favor of viral RNA replication. Here, by using a computational approach, the contact points of the protease on the HCV IRES were putatively mapped. A 30-mer NS3 peptide was designed from the predicted RNA-binding region that retained RNA-binding ability and also inhibited IRES-mediated translation. This peptide was truncated to 15 mer and this also demonstrated ability to inhibit HCV RNA-directed translation as well as replication. More importantly, its activity was tested in an in vivo mouse model by encapsulating the peptide in Sendai virus virosomes followed by intravenous delivery. The study demonstrates for the first time that the HCV NS3-IRES RNA interaction can be selectively inhibited using a small peptide and reports a strategy to deliver the peptide into the liver. Recently, we have demonstrated that the protease domain of NS3 alone can bind specifically to hepatitis C virus (HCV) internal ribosome entry site (IRES) near the initiator AUG, dislodges human La protein and inhibits translation in favor of viral RNA replication. Here, by using a computational approach, the contact points of the protease on the HCV IRES were putatively mapped. A 30-mer NS3 peptide was designed from the predicted RNA-binding region that retained RNA-binding ability and also inhibited IRES-mediated translation. This peptide was truncated to 15 mer and this also demonstrated ability to inhibit HCV RNA-directed translation as well as replication. More importantly, its activity was tested in an in vivo mouse model by encapsulating the peptide in Sendai virus virosomes followed by intravenous delivery. The study demonstrates for the first time that the HCV NS3-IRES RNA interaction can be selectively inhibited using a small peptide and reports a strategy to deliver the peptide into the liver.
THE DEPENDENCE OF NEUROLOGY ON INTERNAL MEDICINEA PLEA FOR THE ESTABLISHMENT OF NEUROLOGIC HOSPITALS, AND OF NEUROLOGIC WARDS IN GENERAL HOSPITALS
Authors: JOSEPH COLLINS
Journal: JAMA (1910)

The practice of establishing institutions for special research, with endowments sufficient to secure them from the motives which influence the conduct of establishments on a commercial foundation, is rapidly gaining substantial recognition in America. We have had no war indemnities applicable to scientific purposes, but fortunately we have scores of wealthy men and women who are showing themselves disposed to lay those financial foundations which must henceforth underly the up-building of the natural sciences. They have initiated a movement which has already done more for us than herald a coming greatness. They have stimulated interest in medical progress, both in the profession and out of it, and already practical results are at hand. <h3>NEUROLOGY NEGLECTED</h3> Our achievements in surgery, in medicine, in public hygiene, in the widening scope of medical education, are all products of the spirit of inquiry which is fostered in the endowed laboratory; and such laboratories are
CSF-1 signaling mediates recovery from acute kidney injury
Authors: Ming-Zhi Zhang, Bing Yao, Shilin Yang, Li Jiang, Suwan Wang, Xiaofeng Fan, Huiyong Yin, Karlton Wong, Tomoki Miyazawa, Jianchun Chen, Ingrid Chang, Amar Singh, Raymond C. Harris
Journal: Journal of Clinical Investigation (2012)

Renal tubule epithelia represent the primary site of damage in acute kidney injury (AKI), a process initiated and propagated by the infiltration of macrophages. Here we investigated the role of resident renal macrophages and dendritic cells in recovery from AKI after ischemia/reperfusion (I/R) injury or a novel diphtheria toxin–induced (DT-induced) model of selective proximal tubule injury in mice. DT-induced AKI was characterized by marked renal proximal tubular cell apoptosis. In both models, macrophage/dendritic cell depletion during the recovery phase increased functional and histologic injury and delayed regeneration. After I/R-induced AKI, there was an early increase in renal macrophages derived from circulating inflammatory (M1) monocytes, followed by accumulation of renal macrophages/dendritic cells with a wound-healing (M2) phenotype. In contrast, DT-induced AKI only generated an increase in M2 cells. In both models, increases in M2 cells resulted largely from in situ proliferation in the kidney. Genetic or pharmacologic inhibition of macrophage colony-stimulating factor (CSF-1) signaling blocked macrophage/dendritic cell proliferation, decreased M2 polarization, and inhibited recovery. These findings demonstrated that CSF-1–mediated expansion and polarization of resident renal macrophages/dendritic cells is an important mechanism mediating renal tubule epithelial regeneration after AKI.
Evolutionary Toxicology: Population-Level Effects of Chronic Contaminant Exposure on the Marsh Frogs ( <i>Rana ridibunda</i> ) of Azerbaijan
Authors: Cole W. Matson, Megan M. Lambert, Thomas J. McDonald, Robin L. Autenrieth, Kirby C. Donnelly, Arif Islamzadeh, Dmitri I. Politov, John W. Bickham
Journal: Environmental Health Perspectives (2005)

We used molecular methods and population genetic analyses to study the effects of chronic contaminant exposure in marsh frogs from Sumgayit, Azerbaijan. Marsh frogs inhabiting wetlands in Sumgayit are exposed to complex mixtures of chemical contaminants, including petroleum products, pesticides, heavy metals, and many other industrial chemicals. Previous results documented elevated estimates of genetic damage in marsh frogs from the two most heavily contaminated sites. Based on mitochondrial DNA (mtDNA) control region sequence data, the Sumgayit region has reduced levels of genetic diversity, likely due to environmental degradation. The Sumgayit region also acts as an ecological sink, with levels of gene flow into the region exceeding gene flow out of the region. Additionally, localized mtDNA heteroplasmy and diversity patterns suggest that one of the most severely contaminated sites in Sumgayit is acting as a source of new mutations resulting from an increased mutation rate. This study provides an integrated method for assessing the cumulative population impacts of chronic contaminant exposure by studying both population genetic and evolutionary effects.
Activation of the fibrinolytic system and utilization of the coagulation inhibitors in sepsis: comparison with severe sepsis and septic shock
Authors: Antonis C. Mavrommatis, Thodoris Theodoridis, Michael Economou, Anastasia Kotanidou, Mahmoud El Ali, Vana Christopoulou-Kokkinou, Spyros G. Zakynthinos
Journal: Intensive Care Medicine (2001)
Tackling the next influenza pandemic
Authors: Ran D Balicer, Michael Huerta, Itamar Grotto
Journal: BMJ (2004)

“Ring” prophylaxis of close contacts with antivirals may be an effective strategy 

Recent efforts have been directed towards preparing rapid effective responses to epidemics of smallpox and severe acute respiratory syndrome (SARS). We must now hasten the preparations for another inevitable threat—the next global influenza pandemic. Currently contingency plans are largely based on rapid vaccination of susceptible populations; other measures, such as treatment with antiviral drugs, serve only as adjuncts.1 In practice, however, technical constraints on vaccine production—foremost among these the time required to initiate mass vaccine production during a pandemic—will limit the effectiveness of this measure in the first stages of the pandemic.2 Recently a systematic review by Cooper et al addressed the effectiveness of neuraminidase inhibitors in the treatment and prevention of influenza.3 The authors concluded that the prophylactic use of these drugs can lead to a reduction of 70-90% in the risk of laboratory confirmed symptomatic flu, depending on the strategy adopted and the population studied. Neuraminidase inhibitors have also shown efficacy in preventing transmission of influenza in institutions and community settings.3 4 The availability of a highly effective supplement to vaccination opens to debate the appropriate role …
NURSING WARD THERAPY AS AN ALTERNATIVE FOR RESTRAINT
Authors: KAREL PLANANSKY, ROY JOHNSTON
Journal: American Journal of Psychiatry (1961)

1. The use of mechanical restraint was virtually eliminated on a psychiatric ward of acutely disturbed, combative patients. 2. This was accomplished in a research setting through successive stages designed to be of educational value to the participants. 3. At first, the nurses tended to substitute chemical sedation for mechanical controls. 4. Through a number of informal talks and formal devices (restraint graphs, obligatory written memoranda for all restraint, etc.), Nursing Ward Therapy techniques were finally substituted for both mechanical and chemical restraint. As a result, the ward nurse perceived herself as shifting from a primarily medical role to the role of a psychiatric nursing specialist. 5. Nursing Ward Therapy is presented as the alternative of choice in handling emergencies in large mental institutions.
Common variants in P2RY11 are associated with narcolepsy
Authors: Birgitte R Kornum, Minae Kawashima, Juliette Faraco, Ling Lin, Thomas J Rico, Stephanie Hesselson, Robert C Axtell, Hedwich Kuipers, Karin Weiner, Alexandra Hamacher, Matthias U Kassack, Fang Han, Stine Knudsen, Jing Li, Xiaosong Dong, Juliane Winkelmann, Giuseppe Plazzi, Sona Nevsimalova, Seung-Chul Hong, Yutaka Honda, Makoto Honda, Birgit Högl, Thanh G N Ton, Jacques Montplaisir, Patrice Bourgin, David Kemlink, Yu-Shu Huang, Simon Warby, Mali Einen, Jasmin L Eshragh, Taku Miyagawa, Alex Desautels, Elisabeth Ruppert, Per Egil Hesla, Francesca Poli, Fabio Pizza, Birgit Frauscher, Jong-Hyun Jeong, Sung-Pil Lee, Kingman P Strohl, William T Longstreth, Mark Kvale, Marie Dobrovolna, Maurice M Ohayon, Gerald T Nepom, H-Erich Wichmann, Guy A Rouleau, Christian Gieger, Douglas F Levinson, Pablo V Gejman, Thomas Meitinger, Paul Peppard, Terry Young, Poul Jennum, Lawrence Steinman, Katsushi Tokunaga, Pui-Yan Kwok, Neil Risch, Joachim Hallmayer, Emmanuel Mignot
Journal: Nature Genetics (2010)
EXPERIMENTAL RICKETS IN RATS
Authors: H. C. Sherman, A. M. Pappenheimer
Journal: The Journal of Experimental Medicine (1921)

1. A simple diet is presented which regularly induced rickets in young rats. 2. The substitution of 0.4 per cent secondary potassium phosphate for a small part of calcium lactate in this diet completely inhibited the development of rickets. 3. Quantitative determinations of calcium in the bodies of parallel rats showed a marked increase of calcium content in the rats receiving the added phosphate over those which developed rickets. 4. While it is thus shown by x-rays and by histological examinations and by quantitative chemical analysis that added potassium phosphate increased the assimilation and normal deposition of calcium, it may be the quantitative relationship between the inorganic ions rather than actual deficiency of any one of them which was here the determining factor in the cause or prevention of rickets. Our experiments and conclusions do not exclude the possibility of other causes of rickets than those here discussed.
A First Brush with Professional Courtesy
Authors: Jules Hirsch
Journal: Annals of Internal Medicine (2005)

On Being a Doctor18 October 2005A First Brush with Professional CourtesyJules Hirsch, MDJules Hirsch, MDFrom The Rockefeller University, New York, NY 10021-6399.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-143-8-200510180-00014 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Some time ago, a colleague showed me a letter from the new financial manager of a distinguished academic hospital where he had served as a housestaff officer. All alumni were warned that giving special assistance to fellow physicians or their families, sometimes called professional courtesy, could be too costly in these times of health care penury. I always thought that the injunction of the Hippocratic Oath “to consider dear to me as my parents him who taught me this art” was a good lesson in kindness to be shown to those who practiced my “art” and their families. I shared ... Author, Article, and Disclosure InformationAffiliations: From The Rockefeller University, New York, NY 10021-6399.Corresponding Author: Jules Hirsch, MD, The Rockefeller University, 1230 York Avenue, New York, NY 10021-6399; e-mail, [email protected]edu. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 18 October 2005Volume 143, Issue 8Page: 613KeywordsAlumniBehaviorFearGastroenterology and hepatologyGratitudeHealth careHereditary nonpolyposis colorectal cancerNauseaShouldersStomach ePublished: 18 October 2005 Issue Published: 18 October 2005 Copyright & PermissionsCopyright © 2005 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...