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Sample records for respiratoire syncytial par

  1. Amelioration de la perfusion des organes vitaux par la valve d’impedance inspiratoire et le concept de pompe respiratoire: rationnel physiologique et application clinique (Improving Vital Organs Perfusion by the Respiratory Pump: Physiology and Clinical Use)

    Science.gov (United States)

    2013-09-01

    cœur vers le cerveau lors des compressions thoraciques et l’air est aspiré dans les poumons lors de la décompression active par traction sur la...maintenir une perfusion tissulaire adéquate. En nous basant sur ces observations dans le cœur et le cerveau , nous avons émis l’hypothèse que la...de la PIT pendant la phase de décompression avec une résistance inspiratoire double le débit sanguin vers le cœur et le cerveau , la PA et augmente

  2. Identification d’une nouvelle molécule d’intérêt chez le cheval atteint d’obstruction récurrente des voies respiratoires: La Pentraxine 3

    OpenAIRE

    Ramery, Eve

    2010-01-01

    L’ORVR ou obstruction récurrente des voies respiratoires (ORVR) est la cause la plus fréquente de maladie pulmonaire chronique chez le cheval adulte. La maladie se caractérise par une hyperréactivité bronchique, une production excessive de mucus et une inflammation neutrophilique pulmonaire qui ont pour effet de réduire la compliance dynamique du poumon et d’augmenter la résistance des voies respiratoires au débit aérien. Alors que la maladie est une entité documentée dans la littérature depu...

  3. Profil épidémiologique des pathologies respiratoires chez l’enfant à l’Hôpital d’Enfants de Rabat, Maroc

    Science.gov (United States)

    Benchekroun, Ilham; Boubkraoui, Mohamed El Mahdi; Mekaoui, Nour; Karboubi, Lamia; Mahraoui, Chafiq; Dakhama, Badr Sououd Benjelloun

    2017-01-01

    Introduction Les pathologies respiratoires représentent un motif fréquent d'hospitalisation en pédiatrie. L'objectif de cette étude était d'évaluer le profil épidémiologique des pathologies respiratoires chez l'enfant à l'hôpital d'enfants de Rabat, Maroc. Méthodes Il s'agit d'une étude observationnelle transversale qui a concerné tous les cas d'enfants âgés de 3 mois à 15 ans hospitalisés pour une pathologie respiratoire au service de pneumoallergologie et infectiologie pédiatriques de l'hôpital d'enfants de Rabat sur une période d'une année, du 1 janvier 2014 au 31 décembre 2014. Résultats Sur 3537 patients hospitalisés, 2493 (70,5%) l'ont été pour une pathologie respiratoire. Les hospitalisations pour exacerbation d'asthme (p < 0,001), bronchiolite aigüe (p < 0,001) et dyspnée laryngée (p = 0,004) étaient plus fréquentes chez le garçon alors que les hospitalisations pour pneumopathie aigüe (p = 0,005), pour inhalation de corps étranger (p = 0,007) et pour coqueluche (p = 0,020) étaient plus fréquentes chez la fille. Les hospitalisations pour pneumopathie aigüe (p < 0,001), exacerbation de séquelles graves de virose (p < 0,001) et pour coqueluche (p < 0,001) étaient plus fréquentes chez le nourrisson. Les hospitalisations pour pneumopathie aigüe (p < 0,001) et pour coqueluche (p = 0,015) étaient plus fréquentes en période automnohivernale. Conclusion Les motifs d'hospitalisation étaient dominés par les exacerbations d'asthme et la bronchiolite aigüe, lesquelles étaient plus fréquentes chez le garçon. Les infections respiratoires, représentées par les pneumopathies aigües et la coqueluche, étaient plus fréquentes en période automnohivernale et touchaient plus le nourrisson. PMID:29675122

  4. Respiratory Syncytial Virus

    Science.gov (United States)

    ... with facebook share with twitter share with linkedin Respiratory Syncytial Virus (RSV) Credit: CDC This is the ... the United States. Why Is the Study of Respiratory Syncytial Virus (RSV) a Priority for NIAID? In ...

  5. Respiratory syncytial virus (RSV)

    Science.gov (United States)

    RSV; Palivizumab; Respiratory syncytial virus immune globulin; Bronchiolitis - RSV ... Crowe JE. Respiratory syncytial virus. In: Kliegman RM, Stanton BF, St. Geme JW, Schor NF, eds. Nelson Textbook of Pediatrics . 20th ...

  6. Characteristics of breathing apparatus used in health physics; Caracteristiques de l'appareil respiratoire utilisables en radioprotection

    Energy Technology Data Exchange (ETDEWEB)

    Perissin-Pirasset, F. [Commissariat a l' Energie Atomique, Fontenay-aux-Roses (France). Centre d' Etudes Nucleaires

    1967-07-01

    The present state of knowledge makes it possible to envisage the calculation of doses absorbed by various parts of the respiration apparatus following inhalation of radio-active dusts contained in aerosols. After recalling some anatomical and histological considerations, the author presents various curves showing the deposition of dusts in the three parts of the breathing apparatus: - the rhino-pharynx - the trachea and wind-pipe - the pulmonary parenchyma. The dusts can be classified in three groups of biological solubility according to which the rates of elimination of the particles from the organs are different. A synthesis of these data is given in elimination diagrams. In order to calculate the doses it is necessary furthermore to know certain anatomical and physiological characteristics of a standard man. (author) [French] L'etat actuel des connaissances permet d'envisager le calcul des doses recues par les differentes parties de l'arbre respiratoire, a la suite d'inhalation de poussieres radioactives contenues dans des aerosols. Apres un rappel de notions anatomiques et histologiques, nous presentons differentes courbes de depot des poussieres dans les trois etages respiratoires: - le rhino-pharynx - la trachee et les bronches - le parenchyme pulmonaire. Les poussieres peuvent etre classees en trois groupes de solubilite biologique selon lesquels les vitesses d'elimination des particules a partir des organes sont differentes. Ceci peut etre synthetise dans des schemas d'elimination. Pour permettre le calcul des doses, il faut en outre disposer des caracteristiques d'un homme standard, du point de vue anatomique et physiologique. (auteur)

  7. Characteristics of breathing apparatus used in health physics; Caracteristiques de l'appareil respiratoire utilisables en radioprotection

    Energy Technology Data Exchange (ETDEWEB)

    Perissin-Pirasset, F [Commissariat a l' Energie Atomique, Fontenay-aux-Roses (France). Centre d' Etudes Nucleaires

    1967-07-01

    The present state of knowledge makes it possible to envisage the calculation of doses absorbed by various parts of the respiration apparatus following inhalation of radio-active dusts contained in aerosols. After recalling some anatomical and histological considerations, the author presents various curves showing the deposition of dusts in the three parts of the breathing apparatus: - the rhino-pharynx - the trachea and wind-pipe - the pulmonary parenchyma. The dusts can be classified in three groups of biological solubility according to which the rates of elimination of the particles from the organs are different. A synthesis of these data is given in elimination diagrams. In order to calculate the doses it is necessary furthermore to know certain anatomical and physiological characteristics of a standard man. (author) [French] L'etat actuel des connaissances permet d'envisager le calcul des doses recues par les differentes parties de l'arbre respiratoire, a la suite d'inhalation de poussieres radioactives contenues dans des aerosols. Apres un rappel de notions anatomiques et histologiques, nous presentons differentes courbes de depot des poussieres dans les trois etages respiratoires: - le rhino-pharynx - la trachee et les bronches - le parenchyme pulmonaire. Les poussieres peuvent etre classees en trois groupes de solubilite biologique selon lesquels les vitesses d'elimination des particules a partir des organes sont differentes. Ceci peut etre synthetise dans des schemas d'elimination. Pour permettre le calcul des doses, il faut en outre disposer des caracteristiques d'un homme standard, du point de vue anatomique et physiologique. (auteur)

  8. Adaptations respiratoires et circulatoires de l'esturgeon sibérien à une hypoxie environnementale

    Directory of Open Access Journals (Sweden)

    MAXIME V.

    1998-07-01

    Full Text Available Les adaptations respiratoires, acido-basiques et quelques effets circulatoires ont été étudiés chez l'esturgeon sibérien Acipenser baeri lors d'une hypoxie progressive ou d'un choc hypoxique, et du retour en normoxie. Au cours d'une hypoxie progressive, ce poisson est capable, en hyperventilant, de maintenir constante sa consommation d'oxygène jusqu'à une valeur critique de pression partielle d'oxygène dans l'eau située entre 20 et 40 mmHg. Le retour en normoxie est caractérisé par le paiement d'une dette d'oxygène, indiquant qu'un recours au métabolisme anaérobie a été nécessaire durant l'hypoxie. L'hypoxie progressive provoque initialement une alcalose ventilatoire associée ensuite à une acidose métabolique. Le choc hypoxique induit un état de stress comme en témoignent les valeurs élevées des taux plasmatiques de catécholamines. L'hyperventilation initiale est suivie d'une importante dépression ventilatoire. L'hypertension observée dans un premier temps, bien que modérée, représente un effet d'une augmentation du taux de catécholamines plasmatiques. Cet effet est ensuite atténué par une bradycardie d'origine vraisemblablement vagale, concomitante de l'hypoventilation. Les conséquences sur l'équilibre acido-basique, bien qu'amplifiées, sont comparables à celles d'une hypoxie progressive. Cependant, la libération très importante de lactate dans le sang lors du retour en normoxie n'entraîne qu'une faible diminution de pH du fait d'une augmentation concomitante du taux de sodium plasmatique. Ainsi l'esturgeon Acipenser baeri, bien que considéré comme un poisson archaïque, a développé les mêmes réponses adaptatives à l'hypoxie que les téléostéens.

  9. Distribution and removal of transuranic elements and cerium deposited by the inhalation route; Distribution et elimination des transuraniens et du cerium deposes par l'intermediaire des voies respiratoires; Raspredelenie transuranovykh ehlementov i tseriya, otkladyvayushchikhsya v rezul'tate vdykhaniya i ikh udalenie; Distribucion y eliminacion de elementos transuranicos y de cerio depositados por inhalacion

    Energy Technology Data Exchange (ETDEWEB)

    Bair, W. J.; Tombropoulos, E. G.; Park, J. F. [Hanford Atomic Products Operation, General Electric Company, Richland, WA (United States)

    1963-02-15

    forme chimique et les dimensions des particules des aerosols. Chez les chiens, 30 jours apres inhalation de nitrate de plutonium, 70% de la charge corporelle se trouvaient dans les poumons, 10% dans le foie et 15% dans le squelette. Apres inhalation d'aerosols de {sup 239}PuO{sub 2} ayant un diametre moyen de 0,12 {mu}, 71% de la charge corporelle se trouvaient dans les poumons, 3% dans les ganglions lymphatiques des bronches, 4,4% dans les muscles et 1,3% dans le squelette, tandis que 20% etaient distribues d'une maniere uniforme dans tous les autres tissus. Apres inhalation d'aerosols de {sup 239}PuO{sub 2} ayant un diametre moyen compris entre 0,3 et 0,6 {mu}, 98% etaient contenus dans les poumons, 1% environ dans les ganglions lymphatiques des bronches et 1% dans tous les autres tissus. Ces donnees ainsi que l'analyse de l'urine et des feces ont permis de definir l'importance relative des trois voies par lesquelles les radioisotopes inhales etaient evacues des poumons : mouvement ascendant dans la trachee par action ciliaire suivie d'excretion dans les feces, transporta travers la membrane alveolaire avec redistribution dans d'autres tissus et excretion graduelle dans l'urine, transfert aux ganglions lymphatiques des bronches ou sont accumulees les matieres insolubles inhalees. On a etudie divers agents therapeutiques qui pourraient favoriser l'evacuation des radioisotopes contenus dans les poumons par des voies qui eviteraient leur accumulation dans d'autres tissus, peut-etre plus radiosensibles. Parmi ces agents, il convient de citer les agents de chelation et d' humidification, les irritants, les sympathicomimetiques, les parasympathicomimetiques, les parasympathicolytiques et les antihistamines. L'acide diethylene-triamine penta-acetique (agent de chelation) administre en aerosols ou par voie intraperitoneale a rapidement elim ine, par excretion urinaire, le {sup 144}Ce-{sup 144}Pr des poumons et de l'organisme tout entier. Un mois apres avoir ete exposes a {sup

  10. Respiratoire infecties in Nederland: voorlopige resultaten NIVEL/RIVM surveillance Winter 1999/2000.

    NARCIS (Netherlands)

    Heijnen, M.L.A.; Pronk, J.D.D.; Bartelds, A.I.M.; Wilbrink, B.

    2000-01-01

    Vanaf winter 1992/93 voeren het NIVEL (Nederlands Instituut voor Onderzoek van de Gezondheidszorg) en het RIVM samen virologische surveillance van acute respiratoire infecties uit. Hier rapporteren we de voorlopige resultaten van deze surveillance voor winter 1999/2000. (aut.ref.)

  11. Respiratory Syncytial Virus (RSV)

    Centers for Disease Control (CDC) Podcasts

    Respiratory Syncytial Virus, or RSV, causes cold-like symptoms but can be serious for infants and older adults. In this podcast, CDC’s Dr. Eileen Schneider discusses this common virus and offers tips to prevent its spread.

  12. Respiratory Syncytial Virus (RSV)

    Centers for Disease Control (CDC) Podcasts

    2013-02-04

    Respiratory Syncytial Virus, or RSV, causes cold-like symptoms but can be serious for infants and older adults. In this podcast, CDC’s Dr. Eileen Schneider discusses this common virus and offers tips to prevent its spread.  Created: 2/4/2013 by National Center for Immunization and Respiratory Diseases (NCIRD), Division of Viral Diseases (DVD).   Date Released: 2/13/2013.

  13. Respiratory Syncytial Virus Vaccines

    OpenAIRE

    Dudas, Robert A.; Karron, Ruth A.

    1998-01-01

    Respiratory syncytial virus (RSV) is the most important cause of viral lower respiratory tract illness (LRI) in infants and children worldwide and causes significant LRI in the elderly and in immunocompromised patients. The goal of RSV vaccination is to prevent serious RSV-associated LRI. There are several obstacles to the development of successful RSV vaccines, including the need to immunize very young infants, who may respond inadequately to vaccination; the existence of two antigenically d...

  14. ARI-EL: een case-controle onderzoek naar Acute Respiratoire Infecties in de Eerste lijn. Tussenrapportage over okt. 2000 t/m sept. 2001

    NARCIS (Netherlands)

    van den Brandhof WE; Bartelds AIM; Peeters MF; Wilbrink B; Heijnen MLA; CIE; NIVEL; Streeklaboratorium voor de Volksgezondheid Tilburg; LIS

    2002-01-01

    Vanaf oktober 2000 is de Nederlandse influenza-surveillance tijdelijk uitgebreid tot een case-controle studie naar acute respiratoire infecties (ARI) bij huisartspatienten: de ARI-EL studie. Doel is inzicht verkrijgen in de incidentie en etiologie van ARI, risicofactoren voor ARI en in de zorgvraag

  15. Learn about Respiratory Syncytial Virus (RSV)

    Science.gov (United States)

    ... the Planet and Lung Health by Reducing Air Pollution Blog: JUUL: A Wolf in Sheep's Clothing '; } else { ... while processing XML file."); } }); } } --> Blank Section Header Lung Disease Lookup RSV Learn About Respiratory Syncytial Virus (RSV) RSV Symptoms, Causes & Risk Factors ...

  16. Epidémiologie et facteurs de risque des complications respiratoires majeures après chirurgie de l'aorte abdominale au CHU Ibn Sina, Maroc

    Science.gov (United States)

    Awab, Almahdi; Elahmadi, Brahim; Lamkinsi, Tarik; El Moussaoui, Rachid; El Hijri, Ahmed; Azzouzi, Abderrahim; Alilou, Mustapha

    2013-01-01

    Introduction L'incidence des complications respiratoires postopératoires (CRPO) reste très diversement appréciées selon les critères diagnostiques retenues dans les différentes études, ce qui la fait varier de 5 à plus de 50%. Les CRPO majeurs après chirurgie de l'aorte abdominale sont responsables d'une grande morbi-mortalité pouvant aller jusqu’à 36%, d'une durée d'hospitalisation et d'un coût plus importants. Ainsi dans l'optique d'améliorer notre prise en charge périopératoire de la chirurgie de l'aorte, nous avons décidé de mener une étude pour dresser le profil épidémiologique et déterminer les facteurs de risque des complications respiratoires dans notre contexte Méthodes Il s'agit d'une étude de cohorte rétrospective du mois de Janvier 2007 au mois de décembre 2011 portant sur l'ensemble des patients opérés pour pathologie aortique au bloc opératoire central de l'hôpital Ibn Sina de Rabat, Maroc. Résultats Cent vingt cinq patients ont été inclus dans notre étude, 24 patients ont été opérés pour anévrysme de l'aorte abdominale et 101 patients pour lésion occlusive aortoiliaque. Dans notre série 22 malades soit 17,6% ont présenté une complication respiratoire majeure avec, une reventilation dans 4,8% des cas, une difficulté de sevrage de la ventilation artificielle dans 3,2% des cas, une pneumopathie dans 4% des cas, un syndrome de détresse respiratoire aigue (SDRA) dans 4% des cas et une nécessité de fibroaspiration bronchique dans 1,6% des cas. En analyse univariée: l’âge, la présence d'une BPCO avec dyspnée stade 3 ou 4, la présence d'une anomalie à l'EFR préopératoire, la présence d'un stade avancé (III ou IV) de LOAI et la reprise chirurgicale étaient statistiquement associés à la survenue d'une complication respiratoire postopératoire. En analyse multivariée, seule une anomalie à l'EFR en préopératoire constituait un facteur de risque indépendant de survenue d'une complication

  17. Bovine respiratory syncytial virus (BRSV): A review

    DEFF Research Database (Denmark)

    Larsen, Lars Erik

    2000-01-01

    Bovine respiratory syncytial virus (BRSV) infection is the major cause of respiratory disease in calves during the first year of life. The study of the virus has been difficult because of its lability and very poor growth in cell culture. However, during the last decade, the introduction of new...... complex and unpredictable which makes the diagnosis and subsequent therapy very difficult. BRSV is closely related to human respiratory syncytial virus (HRSV) which is an important cause of respiratory disease in young children. In contrast to BRSV, the recent knowledge of HRSV is regularly extensively...

  18. Human Respiratory Syncytial Virus and Human Metapneumovirus

    OpenAIRE

    Luciana Helena Antoniassi da Silva; Fernando Rosado Spilki; Adriana Gut Lopes Riccetto; Emilio Elias Baracat; Clarice Weis Arns

    2009-01-01

    The human respiratory syncytial virus (hRSV) and the human metapneumovírus (hMPV) are main etiological agents of acute respiratory infections (ARI). The ARI is an important cause of childhood morbidity and mortality worldwide.  hRSV and hMPV are members of the Paramyxoviridae. They are enveloped, non-segmented viruses, with negative-sense single stranded genomes. Respiratory syncytial virus (hRSV) is the best characterized agent viral of this group, associated with respiratory diseases in...

  19. Respiratory syncytial virus neutralizing antibodies in cord blood, respiratory syncytial virus hospitalization, and recurrent wheeze

    DEFF Research Database (Denmark)

    Stensballe, Lone Graff; Ravn, Henrik; Kristensen, Kim

    2008-01-01

    BACKGROUND: Respiratory syncytial virus (RSV) hospitalization is associated with wheeze. OBJECTIVE: To examine the influence of maternally derived RSV neutralizing antibodies in cord blood on RSV hospitalization and recurrent wheeze in infancy. METHODS: Among children from the Danish National Birth...

  20. BIOLOGY OF HUMAN RESPIRATORY SYNCYTIAL VIRUS: A ...

    African Journals Online (AJOL)

    DR. AMINU

    membrane of the eyes, mouth, or nose and possibly through the ... transmembrane anchor near the C terminus. It is cleaved into two ... immunity induced by previous strains (Hall, 2001). Fluctuations in the .... isolation, and other serological techniques. Antigen .... Respiratory syncytial virus in B.N. fields, D.M. Knipe and.

  1. 21 CFR 866.3480 - Respiratory syncytial virus serological reagents.

    Science.gov (United States)

    2010-04-01

    ... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3480... respiratory syncytial viruses from clinical specimens or from tissue culture isolates derived from clinical...

  2. Hilar enlargement in respiratory syncytial virus pneumonia

    International Nuclear Information System (INIS)

    Odita, J.C.; Aghahowa, J.E.; Nwankwo, M.

    1989-01-01

    The clinical and radiographic features of ten children with hilar enlargement in association with proven Respiratory Syncytial Virus (RSV) infection are described. Hilar enlargement was seen in 10/35 children with RSV infection, and was invariably unilateral and right sided. It is recommended that RSV pneumonia be considered in children with unilateral hilar enlargement if tuberculosis has been excluded, and the onset of disease is rapid. (orig.)

  3. Human Respiratory Syncytial Virus and Human Metapneumovirus

    Directory of Open Access Journals (Sweden)

    Luciana Helena Antoniassi da Silva

    2009-08-01

    Full Text Available The human respiratory syncytial virus (hRSV and the human metapneumovírus (hMPV are main etiological agents of acute respiratory infections (ARI. The ARI is an important cause of childhood morbidity and mortality worldwide.  hRSV and hMPV are members of the Paramyxoviridae. They are enveloped, non-segmented viruses, with negative-sense single stranded genomes. Respiratory syncytial virus (hRSV is the best characterized agent viral of this group, associated with respiratory diseases in lower respiratory tract. Recently, a new human pathogen belonging to the subfamily Pneumovirinae was identified, the human metapneumovirus (hMPV, which is structurally similar to the hRSV, in genomic organization, viral structure, antigenicity and clinical symptoms.  The subfamily Pneumovirinae contains two genera: genus Pneumovirus contains hRSV, the bovine (bRSV, as well as the ovine and caprine respiratory syncytial virus and pneumonia virus of mice, the second genus Metapneumovirus, consists of avian metapneumovirus (aMPV and human metapneumovirus (hMPV. In this work, we present a brief narrative review of the literature on important aspects of the biology, epidemiology and clinical manifestations of infections by two respiratory viruses.

  4. Biology of human respiratory syncytial virus: a review | Aliyu | Bayero ...

    African Journals Online (AJOL)

    Acute lower respiratory tract infection is one of the major causes of mortality and morbidity in young children worldwide. Respiratory syncytial virus (RSV) is the single most important viral cause of lower respiratory tract infection during infancy and early childhood worldwide. Respiratory syncytial virus belongs to the ...

  5. Detection of contamination of the respiratory tracts by autoradiography of sputum (1963); Recherche de contaminations des voies respiratoires par l'autoradiographie des crachats (1963)

    Energy Technology Data Exchange (ETDEWEB)

    Andre, M; Hugot, G [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1963-07-01

    The sputum collected in the morning immediately after awakening is dissolved in mineral acids and then evaporated on a stainless steel plate. It is placed in contact with a nuclear emulsion plate and the number of traces appearing after 24 hrs, 48 hrs and 7 days exposure is counted. The conditions of exposure, development, and result interpretation are defined. (authors) [French] Le crachat recueilli le matin aussitot apres le reveil est mineralise puis evapore sur une plaque d'acier inoxydable. On met en contact avec une plaque d'emulsion nucleaire et on compte le nombre de traces apparues apres 24 h, 48 h et 7 jours d'exposition. Les conditions d'exposition, de developpement et l'interpretation des resultats sont definies. (auteurs)

  6. Respiratory Syncytial Virus Infection (RSV): Transmission and Prevention

    Science.gov (United States)

    ... of Search Controls Search Form Controls Cancel Submit Respiratory Syncytial Virus Infection (RSV) Note: Javascript is disabled ... 2018 Content source: National Center for Immunization and Respiratory Diseases (NCIRD) , Division of Viral Diseases Email Recommend ...

  7. Simultaneous detection of respiratory syncytial virus types A and B ...

    African Journals Online (AJOL)

    Tharwat Ezzat Deraz

    2012-02-28

    Feb 28, 2012 ... Abstract Background: Respiratory syncytial virus (RSV) types A and B and influenza A and B cause about .... plied Science, Mannheim, Germany; Cat. ..... detection of human rhinoviruses, paramyxoviruses, corona viruses, and ...

  8. Gold nanorod vaccine for respiratory syncytial virus

    International Nuclear Information System (INIS)

    Stone, John W; Thornburg, Natalie J; Blum, David L; Kuhn, Sam J; Crowe Jr, James E; Wright, David W

    2013-01-01

    Respiratory syncytial virus (RSV) is a major cause of pneumonia and wheezing in infants and the elderly, but to date there is no licensed vaccine. We developed a gold nanorod construct that displayed the major protective antigen of the virus, the fusion protein (F). Nanorods conjugated to RSV F were formulated as a candidate vaccine preparation by covalent attachment of viral protein using a layer-by-layer approach. In vitro studies using ELISA, electron microscopy and circular dichroism revealed that conformation-dependent epitopes were maintained during conjugation, and transmission electron microscopy studies showed that a dispersed population of particles could be achieved. Human dendritic cells treated with the vaccine induced immune responses in primary human T cells. These results suggest that this vaccine approach may be a potent method for immunizing against viruses such as RSV with surface glycoproteins that are targets for the human immune response. (paper)

  9. Respiratory Syncytial Virus (RSV) Test: MedlinePlus Lab Test Information

    Science.gov (United States)

    ... this page: https://medlineplus.gov/labtests/respiratorysyncytialvirusrsvtest.html Respiratory Syncytial Virus (RSV) Test To use the sharing ... is an RSV test? RSV , which stands for respiratory syncytial virus, is an infection that affects the ...

  10. : Effets respiratoires des nanoparticules

    OpenAIRE

    Andujar , Pascal; Lanone , Sophie; Brochard , Patrick; Boczkowski , Jorge

    2009-01-01

    International audience; Nanotechnology, defined as techniques aimed to design, characterize and produce materials on a nanometer scale, is a fast-growing field today. Nanomaterials are made of nanoobjects (nanoparticles, nanofibers, nanotubes...). The nanoscale confers on these materials their novel, hitherto unknown, chemical and physical properties by the laws of quantum physics which are essentially expressed on this scale. Nanotechnology applications are numerous (e.g., cosmetics, industr...

  11. Respiratory Syncytial Virus Bronchiolitis in Children.

    Science.gov (United States)

    Smith, Dustin K; Seales, Sajeewane; Budzik, Carol

    2017-01-15

    Bronchiolitis is a common lower respiratory tract infection in infants and young children, and respiratory syncytial virus (RSV) is the most common cause of this infection. RSV is transmitted through contact with respiratory droplets either directly from an infected person or self-inoculation by contaminated secretions on surfaces. Patients with RSV bronchiolitis usually present with two to four days of upper respiratory tract symptoms such as fever, rhinorrhea, and congestion, followed by lower respiratory tract symptoms such as increasing cough, wheezing, and increased respiratory effort. In 2014, the American Academy of Pediatrics updated its clinical practice guideline for diagnosis and management of RSV bronchiolitis to minimize unnecessary diagnostic testing and interventions. Bronchiolitis remains a clinical diagnosis, and diagnostic testing is not routinely recommended. Treatment of RSV infection is mainly supportive, and modalities such as bronchodilators, epinephrine, corticosteroids, hypertonic saline, and antibiotics are generally not useful. Evidence supports using supplemental oxygen to maintain adequate oxygen saturation; however, continuous pulse oximetry is no longer required. The other mainstay of therapy is intravenous or nasogastric administration of fluids for infants who cannot maintain their hydration status with oral fluid intake. Educating parents on reducing the risk of infection is one of the most important things a physician can do to help prevent RSV infection, especially early in life. Children at risk of severe lower respiratory tract infection should receive immunoprophylaxis with palivizumab, a humanized monoclonal antibody, in up to five monthly doses. Prophylaxis guidelines are restricted to infants born before 29 weeks' gestation, infants with chronic lung disease of prematurity, and infants and children with hemodynamically significant heart disease.

  12. Strategies for preventing respiratory syncytial virus.

    Science.gov (United States)

    Forbes, Michael

    2008-12-01

    Prevention of respiratory syncytial virus (RSV) infection-crucial for decreasing the burden associated with this disease-is discussed. Predictable outbreaks of RSV occur annually throughout the U.S. During these outbreaks, RSV infection spreads readily among children through close contact with infected individuals or contact with contaminated surfaces or objects. RSV is the leading cause of infant hospitalization and is associated with life-changing and life-threatening complications. Prevention is important for reducing the associated morbidity and mortality. The American Academy of Pediatrics (AAP) has outlined ways to prevent RSV transmission. According to the AAP, frequent hand washing is the most important strategy for reducing the burden of RSV disease. Other methods for controlling nosocomial spread of RSV include the use of gloves, frequent glove changes, and isolating or cohorting patients. General prevention measures that can be undertaken by family members include smoking cessation, breastfeeding, and avoiding situations, whenever possible, where exposure to RSV cannot be controlled. Passive immunoprophylaxis with palivizumab, the only agent approved by the FDA, reduces hospitalization in high-risk children. Palivizumab is currently the only agent approved by the FDA for the prevention of RSV infections in high-risk children. Not every child is equally at risk for serious RSV disease, and immunoprophylaxis is indicated only for certain high-risk children. The AAP has issued specific guidelines for RSV immunoprophylaxis with palivizumab. Other therapies are emerging for the prevention of RSV, including a new, enhanced-potency, humanized RSV monoclonal antibody and several different types of vaccines. RSV causes an annual, predictable epidemic. Treatment remains exclusively supportive. Prevention remains the cornerstone of disease management. The AAP has issued guidelines to protect those at high risk.

  13. Seasonal variation of maternally derived respiratory syncytial virus antibodies and association with infant hospitalizations for respiratory syncytial virus

    DEFF Research Database (Denmark)

    Stensballe, Lone Graff; Ravn, Henrik; Kristensen, Kim

    2009-01-01

    This study used 459 prospectively sampled cord blood samples to examine the association between maternally derived respiratory syncytial virus (RSV)-neutralizing antibodies and the RSV hospitalization season in Denmark. We found a clear temporal association and suggest that RSV-neutralizing antib......This study used 459 prospectively sampled cord blood samples to examine the association between maternally derived respiratory syncytial virus (RSV)-neutralizing antibodies and the RSV hospitalization season in Denmark. We found a clear temporal association and suggest that RSV......-neutralizing antibody level plays a role in the RSV seasonal pattern....

  14. Animal models of human respiratory syncytial virus disease

    NARCIS (Netherlands)

    Bem, Reinout A.; Domachowske, Joseph B.; Rosenberg, Helene F.

    2011-01-01

    Infection with the human pneumovirus pathogen, respiratory syncytial virus (hRSV), causes a wide spectrum of respiratory disease, notably among infants and the elderly. Laboratory animal studies permit detailed experimental modeling of hRSV disease and are therefore indispensable in the search for

  15. Coinfection pulmonaire par pneumocystis jirovecii et pseudomonas aeruginosa au cours du SIDA: à propos de deux cas

    Science.gov (United States)

    Mamoudou, Savadogo; Bellaud, Guillaume; Ana, Canestri; Gilles, Pialoux

    2015-01-01

    Rapporter deux cas cliniques de coinfections pulmonaires par Pneumocystis jirovecii et par Pseudomonas aeruginosa chez des patients vivant avec le VIH. Les deux patients étaient âgés respectivement de 32 ans et 46 ans. Un patient a été pris en charge à l'hôpital Yalgado Ouédraogo de Ouagadougou au Burkina Faso et l'autre a été pris en charge à l'hôpital Ténon de Paris, en France. Les deux souffraient de pneumopathie confirmée à la radiographie et à la tomodensitométrie. L'un des patients était sévèrement immuno déprimé, contrairement à l'autre. L'examen bactériologique dans les crachats avait permis d'isoler Pseudomonas aeruginosa et Pneumocystis jirovecii chez les deux patients. Sous traitement, l’évolution a été favorable. Les coinfections morbides sont relativement fréquentes chez les patients vivant avec le VIH. Devant une symptomatologie respiratoire du sujet vivant avec le VIH, il faut savoir rechercher en plus du Bacille de Koch, Pneumocystis jirovecii et Pseudomonas aeruginosa par un lavage broncho alvéolaire. PMID:26516396

  16. Increased concordance of severe respiratory syncytial virus infection in identical twins

    DEFF Research Database (Denmark)

    Thomsen, Simon Francis; Stensballe, Lone Graff; Skytthe, Axel

    2008-01-01

    (concordance rate: 0.66 vs 0.53), which suggests genetic influences on disease severity. Genetic factors accounted for 16%, family environment for 73%, and nonshared environment for 11% of the individual susceptibility to develop severe respiratory syncytial virus infection. CONCLUSIONS: The severity...... of respiratory syncytial virus infection is determined partly by genetic factors. This result should stimulate the search for genetic markers of disease severity.......OBJECTIVE: We estimated differences in the severity of respiratory syncytial virus infection attributable to genetic and environmental factors. METHODS: Record linkage data on hospitalizations attributable to respiratory syncytial virus infection were gathered on all twins (12,346 pairs) born...

  17. Management of the infant with respiratory syncytial virus.

    Science.gov (United States)

    Corey, M A; Clore, E R

    1991-04-01

    This article examines updated clinical information concerning respiratory syncytial virus (RSV) infection including epidemiology, pathology, clinical manifestations, diagnosis, treatment, nosocomial infection, and prognosis. Also presented is current information on ribavirin therapy, its side effects, and precautions. Research related to the most effective isolation methodology is discussed, as well as nursing diagnoses based on Gordon's Functional Health Patterns and interventions for the infant hospitalized with RSV bronchiolitis and/or pneumonia.

  18. Study of montelukast for the treatment of respiratory symptoms of post-respiratory syncytial virus bronchiolitis in children

    DEFF Research Database (Denmark)

    Bisgaard, H.; Flores-Nunez, A.; Goh, A.

    2008-01-01

    RATIONALE: A pilot study (Bisgaard H; Study Group on Montelukast and Respiratory Syncytial Virus. A randomized trial of montelukast in respiratory syncytial virus postbronchiolitis. Am J Respir Crit Care Med 2003;167:379-383) reported the efficacy of montelukast in post-respiratory syncytial viru...

  19. suPAR

    DEFF Research Database (Denmark)

    Hodges, Gethin W; Bang, Casper N; Wachtell, Kristian

    2015-01-01

    The fundamental role of inflammation in cardiovascular disease (CVD) has prompted interest in numerous biomarkers that detect subclinical levels of inflammation. Soluble urokinase plasminogen activator receptor (suPAR) is a novel biomarker that correlates significantly with cardiovascular events ...... comprehensive review of suPAR in CVD and explore its function and usefulness in predicting cardiovascular events....

  20. Intoxication aiguë sévère par les pesticides organophosphorés: à propos de 28 cas

    Directory of Open Access Journals (Sweden)

    Ali Derkaoui

    2011-03-01

    Full Text Available Les pesticides organophosphorés (POP sont des pesticides organiques de synthèse, largement utilisés en agriculture essentiellement comme insecticide, nemacide ou acaricide. Ce sont les produits agricoles, les plus incriminés dans les intoxications dans notre contexte. L’objectif de ce travail était de déterminer les caractéristiques cliniques, paracliniques, et évolutives de cette intoxication en milieu de réanimation. étude rétrospective portant sur les cas admis en réanimation (2003-2010. Les critères d’inclusion étaient d’ordre clinique, para clinique, thérapeutique et évolutif. 28 cas ont été recensés : 19 femmes et 9 hommes, âge moyen = 24,5 plus or minus 11 ans. La tentative de suicide était le principal motif d’intoxication (19cas. Le Glasgow coma score était en moyenne de 11 plus or minus 4. Le syndrome central, était présent chez 78% de nos patients, suivi du syndrome muscarinique 71% et le syndrome nicotinique dans 53% des cas. La prise en charge thérapeutique a consisté à la ventilation mécanique dans 50% des cas, l’usage des drogues vasoactives dans 14% des cas et l’administration d’un traitement antidotique dans 64% des cas. La mortalité globale était de 25%. Les pesticides organophosphorés sont les toxiques agricoles, le plus souvent incriminés dans notre contexte. Les symptômes résultent d’une importante accumulation d’Acétyle-choline (Ach dans l’organisme ; responsable de l’apparition des trois syndromes caractéristiques. Le diagnostic biologique se fait par le dosage de l’activité cholinestérasique dans le plasma. Le traitement associe des mesures symptomatiques qui reposent essentiellement sur la réanimation respiratoire et neurologique au traitement antidotique. L’évolution clinique dans ce type d’intoxication, est généralement favorable sous traitement avec régression des signes en quelques jours. Le décès est essentiellement, le fait d

  1. Identification of syncytial mutations in a clinical isolate of herpes simplex virus 2

    International Nuclear Information System (INIS)

    Muggeridge, Martin I.; Grantham, Michael L.; Johnson, F. Brent

    2004-01-01

    Small polykaryocytes resulting from cell fusion are found in herpes simplex virus (HSV) lesions in patients, but their significance for viral spread and pathogenesis is unclear. Although syncytial variants causing extensive fusion in tissue culture can be readily isolated from laboratory strains, they are rarely found in clinical isolates, suggesting that extensive cell fusion may be deleterious in vivo. Syncytial mutations have previously been identified for several laboratory strains, but not for clinical isolates of HSV type 2. To address this deficiency, we studied a recent syncytial clinical isolate, finding it to be a mixture of two syncytial and one nonsyncytial strain. The two syncytial strains have novel mutations in glycoprotein B, and in vitro cell fusion assays confirmed that they are responsible for syncytium formation. This panel of clinical strains may be ideal for examining the effect of increased cell fusion on pathogenesis

  2. Replication and clearance of respiratory syncytial virus - Apoptosis is an important pathway of virus clearance after experimental infection with bovine respiratory syncytial virus

    DEFF Research Database (Denmark)

    Viuff, B.; Tjørnehøj, Kirsten; Larsen, Lars Erik

    2002-01-01

    and clearance in a natural target animal. Replication of BRSV was demonstrated in the luminal part of the respiratory epithelial cells and replication in the upper respiratory tract preceded the replication in the lower respiratory tract. Virus excreted to the lumen of the respiratory tract was cleared...... and the infections with human respiratory syncytial. virus and BRSV have similar clinical, pathological, and epidemiological characteristics. In this study we used experimental BRSV infection in calves as a model of respiratory syncytial virus infection to demonstrate important aspects of viral replication......Human respiratory syncytial virus is an important cause of severe respiratory disease in young children, the elderly, and in immunocompromised adults. Similarly, bovine respiratory syncytial virus (BRSV) is causing severe, sometimes fatal, respiratory disease in calves. Both viruses are pneumovirus...

  3. Par Pond water balance

    International Nuclear Information System (INIS)

    Hiergesell, R.A.; Dixon, K.L.

    1996-06-01

    A water budget for the Par Pond hydrologic system was established in order to estimate the rate of groundwater influx to Par Pond. This estimate will be used in modeling exercises to predict Par Pond reservoir elevation and spillway discharge in the scenario where Savannah River water is no longer pumped and discharged into Par Pond. The principal of conservation of mass was used to develop the water budget, where water inflow was set equal to water outflow. Components of the water budget were identified, and the flux associated with each was determined. The water budget was considered balanced when inflow and outflow summed to zero. The results of this study suggest that Par Pond gains water from the groundwater system in the upper reaches of the reservoir, but looses water to the groundwater system near the dam. The rate of flux of groundwater from the water table aquifer into Par Pond was determined to be 13 cfs. The rate of flux from Par Pond to the water table aquifer near the dam was determined to be 7 cfs

  4. FooPar

    DEFF Research Database (Denmark)

    Hargreaves, F. P.; Merkle, D.

    2013-01-01

    We present FooPar, an extension for highly efficient Parallel Computing in the multi-paradigm programming language Scala. Scala offers concise and clean syntax and integrates functional programming features. Our framework FooPar combines these features with parallel computing techniques. Foo......, results based on a empirical analysis on two supercomputers are given. We achieve close-to-optimal performance wrt. theoretical peak performance. Based on this result we conclude that FooPar allows programmers to fully access Scalas design features without suffering from performance drops when compared...

  5. Live cell imaging of in vitro human trophoblast syncytialization.

    Science.gov (United States)

    Wang, Rui; Dang, Yan-Li; Zheng, Ru; Li, Yue; Li, Weiwei; Lu, Xiaoyin; Wang, Li-Juan; Zhu, Cheng; Lin, Hai-Yan; Wang, Hongmei

    2014-06-01

    Human trophoblast syncytialization, a process of cell-cell fusion, is one of the most important yet least understood events during placental development. Investigating the fusion process in a placenta in vivo is very challenging given the complexity of this process. Application of primary cultured cytotrophoblast cells isolated from term placentas and BeWo cells derived from human choriocarcinoma formulates a biphasic strategy to achieve the mechanism of trophoblast cell fusion, as the former can spontaneously fuse to form the multinucleated syncytium and the latter is capable of fusing under the treatment of forskolin (FSK). Live-cell imaging is a powerful tool that is widely used to investigate many physiological or pathological processes in various animal models or humans; however, to our knowledge, the mechanism of trophoblast cell fusion has not been reported using a live- cell imaging manner. In this study, a live-cell imaging system was used to delineate the fusion process of primary term cytotrophoblast cells and BeWo cells. By using live staining with Hoechst 33342 or cytoplasmic dyes or by stably transfecting enhanced green fluorescent protein (EGFP) and DsRed2-Nuc reporter plasmids, we observed finger-like protrusions on the cell membranes of fusion partners before fusion and the exchange of cytoplasmic contents during fusion. In summary, this study provides the first video recording of the process of trophoblast syncytialization. Furthermore, the various live-cell imaging systems used in this study will help to yield molecular insights into the syncytialization process during placental development. © 2014 by the Society for the Study of Reproduction, Inc.

  6. A randomized trial of montelukast in respiratory syncytial virus postbronchiolitis

    DEFF Research Database (Denmark)

    Bisgaard, Hans

    2003-01-01

    Infants often develop reactive airway disease after respiratory syncytial virus (RSV) bronchiolitis. Cysteinyl-leukotrienes (cys-LT) are released during RSV infection and may contribute to the inflammation. We hypothesized that a cys-LT receptor antagonist would ameliorate reactive airway disease...... subsequent to RSV bronchiolitis. One hundred and thirty infants who were 3 to 36 months old, hospitalized with acute RSV bronchiolitis, were randomized into a double-blind, parallel comparison of 5-mg montelukast chewable tablets or matching placebo given for 28 days starting within 7 days of symptom debut...

  7. It's quicker "Par Avignon"!

    CERN Multimedia

    2005-01-01

    For a few years, the CERN Library has been receiving books from the University of Hanover sent via Avignon, at least that's what it says on the envelope. Such a detour would mean that parcels were travelling 720 km more than the distance separating Geneva and Hanover, which would be a very strange state of affairs. The explanation lies in a spelling mistake. The sender has been stamping parcels with a stamp that says "Par Avignon prioritaire" (first-class via Avignon) instead of "Par Avion prioritaire" (First Class Air Mail), a source of much amusement to the librarians!

  8. Bovine respiratory syncytial virus ISCOMs - protection in the presence of maternal antibodies

    DEFF Research Database (Denmark)

    Hägglund, Sara; Hu, Ke-Fei; Larsen, Lars Erik

    2004-01-01

    The protection induced by immunostimulating complexes (ISCOMs) against bovine respiratory syncytial virus (BRSV) was evaluated and compared to that of a commercial inactivated vaccine (CV) in calves with BRSV-specific maternal antibodies. Following experimental challenge, controls (n = 4...

  9. Variation of respiratory syncytial virus and the relation with meteorological factors in different winter seasons.

    NARCIS (Netherlands)

    Meerhoff, T.J.; Paget, W.J.; Kimpen, J.L.; Schellevis, F.

    2009-01-01

    Background: Respiratory syncytial virus (RSV) is the most important viral agent causing severe respiratory disease in infants and children. In temperate climates, RSV activity typically peaks during winter. We have described the seasonal variation in RSV activity and investigated which

  10. Rapid antigen detection test for respiratory syncytial virus diagnosis as a diagnostic tool

    Directory of Open Access Journals (Sweden)

    Flávio da Silva Mesquita

    2017-05-01

    Conclusions: This study demonstrated that the QuickVue® RSV Test Kit can be effective in early detection of Respiratory syncytial virus in nasopharyngeal aspirate and is reliable for use as a diagnostic tool in pediatrics.

  11. Streptococcus pneumoniae enhances human respiratory syncytial virus infection in vitro and in vivo

    NARCIS (Netherlands)

    D.T. Nguyen (Tien); R.P.L. Louwen (Rogier); Elberse, K. (Karin); G. van Amerongen (Geert); S. Yüksel (Selma); A. Luijendijk (Ad); A.D.M.E. Osterhaus (Albert); W.P. Duprex (William Paul); R.L. de Swart (Rik)

    2015-01-01

    textabstractHuman respiratory syncytial virus (HRSV) and Streptococcus pneumoniae are important causative agents of respiratory tract infections. Both pathogens are associated with seasonal disease outbreaks in the pediatric population, and can often be detected simultaneously in infants

  12. Interference Between Respiratory Syncytial Virus and Human Rhinovirus Infection in Infancy

    NARCIS (Netherlands)

    Achten, Niek B.; Wu, Pingsheng; Bont, Louis; Blanken, Maarten O; Gebretsadik, Tebeb; Chappell, James D; Wang, Li; Yu, Chang; Larkin, Emma K; Carroll, Kecia N; Anderson, Larry J; Moore, Martin L; Sloan, Chantel D; Hartert, Tina V

    2017-01-01

    Background.: Respiratory syncytial virus (RSV) and human rhinovirus (HRV) are the most common viruses associated with acute respiratory tract infections in infancy. Viral interference is important in understanding respiratory viral circulation and the impact of vaccines. Methods.: To study viral

  13. Transmission of human respiratory syncytial virus in the immunocompromised ferret model

    NARCIS (Netherlands)

    de Waal, L. (Leon); S.L. Smits (Saskia); E.J.B. Veldhuis Kroeze (Edwin); G. van Amerongen (Geert); Pohl, M.O. (Marie O.); Osterhaus, A.D.M.E. (Albert D. M. E.); K.J. Stittelaar (Koert)

    2018-01-01

    textabstractHuman respiratory syncytial virus (HRSV) causes substantial morbidity and mortality in vulnerable patients, such as the very young, the elderly, and immunocompromised individuals of any age. Nosocomial transmission of HRSV remains a serious challenge in hospital settings, with

  14. Risk factors for admission and the role of respiratory syncytial virus ...

    African Journals Online (AJOL)

    disease and poor outcomes when exposed to the influenza virus. Studies of CTL responses ... (IL)8 and IL2) and human neutrophil elastase play a significant ~ role in the ..... Prophylaxis against respiratory syncytial virus in premature infants.

  15. Invasive pneumococcal and meningococcal disease : association with influenza virus and respiratory syncytial virus activity?

    NARCIS (Netherlands)

    Jansen, A G S C; Sanders, E A M; VAN DER Ende, A; VAN Loon, A M; Hoes, A W; Hak, E

    2008-01-01

    Few studies have examined the relationship between viral activity and bacterial invasive disease, considering both influenza virus and respiratory syncytial virus (RSV). This study aimed to assess the potential relationship between invasive pneumococcal disease (IPD), meningococcal disease (MD), and

  16. Respiratory syncytial virus (RSV) pneumonia in a southern muriqui (Brachyteles arachnoides).

    Science.gov (United States)

    Santos, S V; Strefezzi, R F; Pissinatti, A; Takakura, C F H; Kanamura, C; Duarte, M I S; Catão-Dias, J L

    2012-12-01

    An adult male Brachyteles arachanoides, kept in captivity since 1990, was found dead without apparent clinical evidence. Necropsy report, histopathology, immunohistochemistry, and ultrastructural examination were conducted. Pulmonary syncytial cells were positive for respiratory syncytial virus (RSV), and ultrastructural examination revealed viral particles inside macrophages compatible with the Paramyxoviridae family. Muriquis are susceptible to RSV pneumonia followed by respiratory distress syndrome and death. © 2012 John Wiley & Sons A/S.

  17. Neonatal respiratory syncytial virus infection: role of transplacentally and breast milk-acquired antibodies.

    OpenAIRE

    Wong, D T; Ogra, P L

    1986-01-01

    The effect of transplacentally and breast milk-acquired antibodies on respiratory syncytial virus infection was studied in neonatal and 2-month-old cotton rats. Adult female rats infected intranasally with live virus regularly produced virus-specific antibodies in the serum, colostrum, and breast milk. By using foster feeding techniques, we showed that both transplacentally and breast milk-acquired antibodies were effective in reducing the replication of respiratory syncytial virus in the lun...

  18. Bovine respiratory syncytial virus: first serological evidence in Uruguay.

    Science.gov (United States)

    Costa, M; García, L; Yunus, A S; Rockemann, D D; Samal, S K; Cristina, J

    2000-01-01

    Bovine respiratory syncytial virus (BRSV) is a major cause of respiratory disease in calves resulting in a substantial economic loss for the cattle industry worldwide. In order to determine the presence of BRSV in Uruguay, an immunoenzymatic test was set up, using a recombinant BRSV nucleocapsid (N) protein as the antigen. The N protein was produced in Sf9 insect cells by a recombinant baculovirus expressing the N protein. Serum samples collected from one hundred cattle from four different geographic regions of Uruguay were analyzed. Antibodies against the N protein of BRSV were detected in 95% of the serum samples analyzed. These results show for the first time the presence of BRSV antibodies and suggest a widespread BRSV infection in the cattle population of Uruguay.

  19. Respiratory syncytial virus mechanisms to interfere with type 1 interferons.

    Science.gov (United States)

    Barik, Sailen

    2013-01-01

    Respiratory syncytial virus (RSV) is a member of the Paramyxoviridae family that consists of viruses with nonsegmented negative-strand RNA genome. Infection by these viruses triggers the innate antiviral response of the host, mainly type I interferon (IFN). Essentially all other viruses of this family produce IFN suppressor functions by co-transcriptional RNA editing. In contrast, RSV has evolved two unique nonstructural proteins, NS1 and NS2, to effectively serve this purpose. Together, NS1 and NS2 degrade or sequester multiple signaling proteins that affect both IFN induction and IFN effector functions. While the mechanism of action of NS1 and NS2 is a subject of active research, their effect on adaptive immunity is also being recognized. In this review, we discuss various aspects of NS1 and NS2 function with implications for vaccine design.

  20. Need for a safe vaccine against respiratory syncytial virus infection

    Directory of Open Access Journals (Sweden)

    Joo-Young Kim

    2012-09-01

    Full Text Available Human respiratory syncytial virus (HRSV is a major cause of severe respiratory tract illnesses in infants and young children worldwide. Despite its importance as a respiratory pathogen, there is currently no licensed vaccine for HRSV. Following failure of the initial trial of formalin-inactivated virus particle vaccine, continuous efforts have been made for the development of safe and efficacious vaccines against HRSV. However, several obstacles persist that delay the development of HRSV vaccine, such as the immature immune system of newborn infants and the possible Th2-biased immune responses leading to subsequent vaccine-enhanced diseases. Many HRSV vaccine strategies are currently being developed and evaluated, including live-attenuated viruses, subunit-based, and vector-based candidates. In this review, the current HRSV vaccines are overviewed and the safety issues regarding asthma and vaccine-induced pathology are discussed.

  1. Overview of respiratory syncytial virus disease in young children

    Directory of Open Access Journals (Sweden)

    Hoopes JM

    2012-07-01

    Full Text Available J Michael Hoopes1, Veena R Kumar21Medical Information, 2Medical and Scientific Affairs, MedImmune, LLC, Gaithersburg, MD, USAAbstract: Respiratory tract illnesses associated with respiratory syncytial virus (RSV were first reported more than 160 years ago and gained acceptance as a major respiratory pathogen in the late 1950s. Annual epidemics show a seasonal pattern typically beginning in the late fall and ending in early spring, averaging 5 months in length, and varying in time of onset, offset, and duration depending on geographic location. Manifestations of RSV illness primarily involve the upper respiratory tract but can spread to the lower airways and lead to bronchiolitis and/or pneumonia. Initial infection occurs in approximately two-thirds of children during the first year of life; nearly all children are infected at least once by 2 years of age. Reinfection is common throughout life, but initial illness during infancy generally presents with the most severe symptoms. Medical risk conditions that consistently predispose young children to serious lower respiratory tract infection (LRTI include congenital heart disease, chronic lung disease, and premature birth. Serious LRTI due to RSV is the leading cause of hospitalization in infants and young children worldwide and annual mean hospital expenses have been estimated to exceed 1 billion dollars in the United States. Young children incur more inpatient and outpatient visits for RSV LRTI than for influenza. RSV has a greater impact than influenza on hospitalization in infants with respect to length of stay, severity/course of disease, and resultant needs for ancillary treatments. Unlike many other childhood illnesses, a vaccine is not currently available for preventing RSV disease.Keywords: bronchopulmonary dysplasia, infants, hospitalization, prematurity, respiratory syncytial virus

  2. Morphofunctional transformations of the yolk syncytial layer during zebrafish development.

    Science.gov (United States)

    Kondakova, Ekaterina Alexandrovna A; Efremov, Vladimir Ivanovich I

    2014-02-01

    The yolk syncytial layer (YSL) is a provisory extraembryonic structure of teleost fishes and representatives of some other taxa with meroblastic cleavage. The YSL of teleosts is a symplast with polymorphous polyploid nuclei. It is known to perform nutritional, morphogenetic, immune, and, probably, other functions. Data about the YSL organization, functioning and regulation is fragmentary. Although gene expression patterns and other aspects of YSL functioning have been studied in Danio rerio, the morphology of its YSL has not been described in detail. The study of zebrafish YSL structure on sequential developmental stages is necessary to recognize specific features of this important polyfunctional system in this model organism and to extend our knowledge about provisory systems. The thickness of the YSL and the distribution of its nuclei are not uniform on each stage and change during development. During oblong and sphere stages the internal YSL (I-YSL) is filled with yolk inclusions; interphase yolk syncytial nuclei (YSN) and mitotic asters can be seen. During doming and epiboly the external YSL (E-YSL) is thicker than I-YSL. On the subsequent stages the YSL is thickened caudally. The dorsal YSL part is thickened during early segmentation stages and becomes the thinnest YSL region later. The anterior part of the YSL is thin, but enlarges during larval period. The YSN of different size and diverse forms, from regular to lobed, are present and form clusters. The number of irregular-shaped nuclei increases during development. The YSL thickens in the end of endotrophic and in the course of endo-exotrophic period, and its cytoplasm contains numerous yolk inclusions. After yolk exhaustion the YSL is flat. As the YSL degrades, the YSN become pycnotic, and the YSL remnant probably is cleared by phagocytes. Copyright © 2013 Wiley Periodicals, Inc.

  3. La pelade par plaques

    Science.gov (United States)

    Spano, Frank; Donovan, Jeff C.

    2015-01-01

    Résumé Objectif Présenter aux médecins de famille des renseignements de base pour faire comprendre l’épidémiologie, la pathogenèse, l’histologie et l’approche clinique au diagnostic de la pelade par plaques. Sources des données Une recension a été effectuée dans PubMed pour trouver des articles pertinents concernant la pathogenèse, le diagnostic et le pronostic de la pelade par plaques. Message principal La pelade par plaques est une forme de perte pileuse auto-immune dont la prévalence durant une vie est d’environ 2 %. Des antécédents personnels ou familiaux de troubles auto-immuns concomitants, comme le vitiligo ou une maladie de la thyroïde, peuvent être observés dans un petit sous-groupe de patients. Le diagnostic peut souvent être posé de manière clinique en se fondant sur la perte de cheveux non cicatricielle et circulaire caractéristique, accompagnée de cheveux en « point d’exclamation » en périphérie chez ceux dont le problème en est aux premiers stades. Le diagnostic des cas plus complexes ou des présentations inhabituelles peut être facilité par une biopsie et un examen histologique. Le pronostic varie largement et de mauvais résultats sont associés à une apparition à un âge précoce, une perte importante, la variante ophiasis, des changements aux ongles, des antécédents familiaux ou des troubles auto-immuns concomitants. Conclusion La pelade par plaques est une forme auto-immune de perte de cheveux périodiquement observée en soins primaires. Les médecins de famille sont bien placés pour identifier la pelade par plaques, déterminer la gravité de la maladie et poser le diagnostic différentiel approprié. De plus, ils sont en mesure de renseigner leurs patients à propos de l’évolution clinique de la maladie ainsi que du pronostic général selon le sous-type de patients.

  4. Mise au point de l’analyse par séquençage à haut-débit du microbiote fongique et bactérien respiratoire chez les patients atteints de mucoviscidose

    OpenAIRE

    Nguyen , Do Ngoc Linh

    2016-01-01

    Chronic pulmonary infection results in an irreversible decline in lung function in patients with cystic fibrosis (CF). While several bacteria are known as main causes for these infections (for example: Pseudomonas aeruginosa, Staphylococcus aureus, Burkholderia cepacia, Achromobacter xylosoxidans...), more recently some fungal genera including filamentous fungi (such as Aspergillus, Scedosporium...) have also been identified as emerging or re-emerging pathogens able to cause invasive mycosis....

  5. Burden of Severe Respiratory Syncytial Virus Disease Among 33-35 Weeks' Gestational Age Infants Born During Multiple Respiratory Syncytial Virus Seasons.

    LENUS (Irish Health Repository)

    Anderson, Evan J

    2017-02-01

    Moderate-late preterm infants, 33-35 weeks\\' gestational age (wGA), are at increased risk for respiratory syncytial virus hospitalization (RSVH). The objective of this study is to quantify the burden of RSVH in moderate-late preterm infants.

  6. PROPHYLACTIC ADMINISTRATION OF RESPIRATORY SYNCYTIAL VIRUS IMMUNE GLOBULIN TO HIGH-RISK INFANTS AND YOUNG-CHILDREN

    NARCIS (Netherlands)

    GROOTHUIS, [No Value; SIMOES, EAF; LEVIN, MJ; HALL, CB; LONG, CE; RODRIGUEZ, WJ; ARROBIO, J; MEISSNER, HC; FULTON, DR; WELLIVER, RC; TRISTRAM, DA; SIBER, GR; PRINCE, GA; VANRADEN, M; HEMMING, VG

    1993-01-01

    Background. Infants with cardiac disease or prematurity are at risk for severe illness caused by respiratory syncytial virus. Immune globulin with a high titer of antibodies against respiratory syncytial virus may offer infants and young children at risk protection from this serious, common

  7. suPAR

    DEFF Research Database (Denmark)

    Eugen-Olsen, Jesper; Giamarellos-Bourboulis, Evangelos J

    2015-01-01

    Investigation of biomarkers that can promptly predict unfavourable outcome of critically illness is an emerging necessity taking into consideration the need for early intervention, the shortage of available beds in intensive care units and the considerable cost of hospitalisation. The most...... promising biomarker is soluble urokinase-type plasminogen activator receptor (suPAR). Three studies in large populations of critically ill patients and patients admitted to the emergency department have shown that concentrations >12ng/mL can safely predict unfavourable outcome. This review presents...

  8. Burden of Respiratory Syncytial Virus Hospitalizations in Canada

    Directory of Open Access Journals (Sweden)

    Ian Mitchell

    2017-01-01

    Full Text Available Objective. To examine the socioeconomic burden of respiratory syncytial virus (RSV disease for Canadian infants hospitalized for the condition. Data and Methods. The descriptive study used data collected in Alberta, Canada, during 2 consecutive RSV seasons. Infants (<1 year of age were included if they had not received palivizumab and were hospitalized with a confirmed diagnosis of RSV. Hospitalization resource use and parental time burden, out-of-pocket costs, lost work productivity, and stress and anxiety were assessed. Results. 13.4% of all infants (n = 67 had intensive care unit (ICU admission, and average ICU stay for these infants was 6.5 days. Families had average out-of-pocket expenses of 736.69 Canadian dollars (CAD $, and the average time both parents spent in hospital was nearly 7 days (164.0 hours. For working parents (n = 43, average absenteeism was 49% and overall work impairment was 77.8%. Parents also exhibited significant parental stress (3.6 on the Parental Stressor Scale: 43.9 state anxiety and 36.9 trait anxiety scores. Conclusions. Results indicate a high burden associated with the hospitalization of an infant due to RSV disease in terms of resource use, time, productivity, costs, and stress, even among a population of infants not considered to be at risk for the condition.

  9. Nosocomial infections by respiratory syncytial virus in children

    Directory of Open Access Journals (Sweden)

    Maren Karina Machado Echeverría

    2017-01-01

    Full Text Available Introduction: Acute lower respiratory infections cause high morbidity and mortality in children. Respiratory syncytial virus (RSV is the most prevalent agent. Some viruses cause serious nosocomial infections. In Uruguay, there is no knowledge about the morbidity and mortality of nosocomial infections by RSV. Objective: To determine the prevalence and characteristics of RSV nosocomial infections. Methodology: A descriptive study of acute lower respiratory infections caused by RSV in patients younger than two years, between 1/1/2005 and 31/12/2008 at the Hospital Pediátrico del Centro Hospitalario Pereira Rossell, was made. Results: Were identified 59 patients who represented an annual rate lower than 2/1000 discharges. The monthly distribution of cases was similar to the respiratory infections. No outbreaks were reported. The age of the patients had an average of 8.9 months, 39 were younger than one year, 23 had one or more risk factors for severe disease. Six patients required admission to intensive care unit, all required invasive ventilation, 3 died, none had chronic respiratory failure following the RSV nosocomial infection. Conclusions: During the study period, the RSV nosocomial infections showed a low prevalence, despite it highly contagiousness. They mainly affected young children, carriers of risk factors for severe ALRI. Their evolution was similar to that reported for RSV respiratory infections community acquired. It is important to maintain standards for the control of nosocomial infections, to prevent nosocomial transmission of RSV and prevent the onset of severe disease in hospitalized patients.

  10. Autonomic dysfunction with early respiratory syncytial virus-related infection.

    Science.gov (United States)

    Stock, Claire; Teyssier, Georges; Pichot, Vincent; Goffaux, Philippe; Barthelemy, Jean-Claude; Patural, Hugues

    2010-08-25

    Apparent life-threatening events (ALTE) and/or prolonged apnoea have been well-documented during respiratory syncytial virus (RSV) infection in infants less than 2 months of age but fundamental mechanisms remain unclear. The possibility of a central origin for the development of severe cardiac and respiratory events encouraged us, to explore the autonomic nervous system (ANS) profile of infected infants, since ANS activity may contribute to the constellation of symptoms observed during severe forms of RSV bronchiolitis. Eight infants (2 preterm and 6 full-term) less than 2 months of age and presenting with severe and apnoeic forms of RSV infection were evaluated using non-invasive electrophysiological monitoring obtained simultaneously for approximately 2 consecutive hours, including a quiet sleep period. Eight control subjects, paired for gestational and postnatal age, were also evaluated. ANS status was monitored using electrocardiogram recordings and quantified through a frequency-domain analysis of heart rate variability (HRV). This included sympathetic (VLF and LF) and parasympathetic (HF) indices as well as a measure of baroreflex sensitivity (BRS) obtained using non-invasive continuous arterial pressure. Regardless of gestational and postnatal age, heart rate variability components (Ptot, VLF, LF, and HF) and baroreflex components (alpha LF, alpha HF and sBR) were found to be significantly lower in the RSV-infected group than in the control group (pimportance of maintaining prolonged cardiopulmonary monitoring. Copyright 2010 Elsevier B.V. All rights reserved.

  11. [Respiratory syncytial virus infections in children in general practice].

    Science.gov (United States)

    Nielsen, Lisa Monica; Halgrener, Jørgen; Hansen, Bjarne V Lühr

    2003-06-30

    The aim of the study was to describe the course of respiratory syncytial virus (RSV) infections in children under two years of age seen in general practice. Children under two years of age presenting acute respiratory infection during the registration period on 59 GPs' lists participated in the study. The GPs recorded data on a registration chart and a questionnaire was sent to the parents of the children in question one month after the date of inclusion. The children were tested in general practice for the presence of RSV. The GPs' objective findings and choice of treatment as well as the parents' account of the course of disease were compared in children with and without the presence of RSV. A total of 221 children participated in the study. Fifty-seven children were found RSV positive (25.8%). Among the RSV positive children there were significantly more with wheezing audibly detected with examination by stethoscope than among the RSV negative. The remaining parameters (the GP's objective examination, treatment and course of the disease) were distributed independently of the result of the RSV analysis. The results showed that RSV infections in children under two years in general practice are frequent and that the clinical picture most often is uncomplicated.

  12. Respiratory syncytial virus tracking using internet search engine data.

    Science.gov (United States)

    Oren, Eyal; Frere, Justin; Yom-Tov, Eran; Yom-Tov, Elad

    2018-04-03

    Respiratory Syncytial Virus (RSV) is the leading cause of hospitalization in children less than 1 year of age in the United States. Internet search engine queries may provide high resolution temporal and spatial data to estimate and predict disease activity. After filtering an initial list of 613 symptoms using high-resolution Bing search logs, we used Google Trends data between 2004 and 2016 for a smaller list of 50 terms to build predictive models of RSV incidence for five states where long-term surveillance data was available. We then used domain adaptation to model RSV incidence for the 45 remaining US states. Surveillance data sources (hospitalization and laboratory reports) were highly correlated, as were laboratory reports with search engine data. The four terms which were most often statistically significantly correlated as time series with the surveillance data in the five state models were RSV, flu, pneumonia, and bronchiolitis. Using our models, we tracked the spread of RSV by observing the time of peak use of the search term in different states. In general, the RSV peak moved from south-east (Florida) to the north-west US. Our study represents the first time that RSV has been tracked using Internet data results and highlights successful use of search filters and domain adaptation techniques, using data at multiple resolutions. Our approach may assist in identifying spread of both local and more widespread RSV transmission and may be applicable to other seasonal conditions where comprehensive epidemiological data is difficult to collect or obtain.

  13. A role for airway remodeling during respiratory syncytial virus infection

    Directory of Open Access Journals (Sweden)

    Dimina Dawn M

    2005-10-01

    Full Text Available Abstract Background Severe respiratory syncytial virus infection (RSV during infancy has been shown to be a major risk factor for the development of subsequent wheeze. However, the reasons for this link remain unclear. The objective of this research was to determine the consequences of early exposure to RSV and allergen in the development of subsequent airway hyperreactivity (AHR using a developmental time point in the mouse that parallels that of the human neonate. Methods Weanling mice were sensitized and challenged with ovalbumin (Ova and/or infected with RSV. Eight days after the last allergen challenge, various pathophysiological endpoints were examined. Results AHR in response to methacholine was enhanced only in weanling mice exposed to Ova and subsequently infected with RSV. The increase in AHR appeared to be unrelated to pulmonary RSV titer. Total bronchoalveolar lavage cellularity in these mice increased approximately two-fold relative to Ova alone and was attributable to increases in eosinophil and lymphocyte numbers. Enhanced pulmonary pathologies including persistent mucus production and subepithelial fibrosis were observed. Interestingly, these data correlated with transient increases in TNF-α, IFN-γ, IL-5, and IL-2. Conclusion The observed changes in pulmonary structure may provide an explanation for epidemiological data suggesting that early exposure to allergens and RSV have long-term physiological consequences. Furthermore, the data presented here highlight the importance of preventative strategies against RSV infection of atopic individuals during neonatal development.

  14. The biennial cycle of respiratory syncytial virus outbreaks in Croatia

    Directory of Open Access Journals (Sweden)

    Drazenovic Vladimir

    2008-01-01

    Full Text Available Abstract The paper analyses the epidemic pattern of respiratory syncytial virus (RSV outbreaks in children in Croatia. Over a period of 11 consecutive winter seasons (1994–2005 3,435 inpatients from Zagreb County aged from infancy to 10 years who were hospitalised with acute respiratory tract infections were tested for RSV-infection. RSV was identified in nasopharyngeal secretions of patients by virus isolation in cell culture and by detection of viral antigen with monoclonal antibodies. In the Zagreb area, RSV outbreaks were proven to vary in a two-year cycle, which was repeated every 23–25 months. This biennial cycle comprised one larger and one smaller season. Climate factors correlated significantly with the number of RSV cases identified only in the large seasons, which suggests that the biennial cycle is likely to continue regardless of meteorological conditions. Knowledge of this biennial pattern should be useful in predicting the onset of RSV outbreaks in Croatia, and would facilitate planning for the prevention and control of RSV infections in the region.

  15. Sequential MRI, SPECT and PET in respiratory syncytial virus encephalitis

    International Nuclear Information System (INIS)

    Hirayama, K.; Sakazaki, Hiromi; Murakami, Seiko; Yonezawa, Sumiko; Fujimoto, Keiji; Seto, Toshiyuki; Tanaka, Katsuji; Hattori, Hideji; Matsuoka, Osamu; Murata, Ryosuke

    1999-01-01

    We report on a 3-year-old girl with respiratory syncytial virus (RSV) encephalitis manifested by disturbance of consciousness, conjugate eye deviation, anuria, truncal ataxia and intention tremor. T2-weighted magnetic resonance imaging (MRI) showed hyperintense areas in the cerebellar cortex. No lesion was detected in the cerebral cortex, pons or spinal cord. The hyperintense areas in the cerebellar cortex diminished with recovery from the clinical manifestations and had resolved 2 months after onset. The MRI lesions in the cerebellum were considered to be due to oedema. SPECT and positron emission tomography (PET), performed 3 months after onset, disclosed areas of hypoperfusion and hypometabolism at the same sites. One year after onset, MRI showed mild atrophy of the cerebellum. Hypoperfusion on SPECT and hypometabolism on PET remained. Neuroimaging showed that ataxia and tremor in this case were the result of cerebellitis. The patient has no neurological deficit except for mild truncal ataxia. This patient is a rare example of RSV encephalitis. (orig.)

  16. Occurrence of human respiratory syncytial virus in summer in Japan.

    Science.gov (United States)

    Shobugawa, Y; Takeuchi, T; Hibino, A; Hassan, M R; Yagami, R; Kondo, H; Odagiri, T; Saito, R

    2017-01-01

    In temperate zones, human respiratory syncytial virus (HRSV) outbreaks typically occur in cold weather, i.e. in late autumn and winter. However, recent outbreaks in Japan have tended to start during summer and autumn. This study examined associations of meteorological conditions with the numbers of HRSV cases reported in summer in Japan. Using data from the HRSV national surveillance system and national meteorological data for summer during the period 2007-2014, we utilized negative binomial logistic regression analysis to identify associations between meteorological conditions and reported cases of HRSV. HRSV cases increased when summer temperatures rose and when relative humidity increased. Consideration of the interaction term temperature × relative humidity enabled us to show synergistic effects of high temperature with HRSV occurrence. In particular, HRSV cases synergistically increased when relative humidity increased while the temperature was ⩾28·2 °C. Seasonal-trend decomposition analysis using the HRSV national surveillance data divided by 11 climate divisions showed that summer HRSV cases occurred in South Japan (Okinawa Island), Kyushu, and Nankai climate divisions, which are located in southwest Japan. Higher temperature and higher relative humidity were necessary conditions for HRSV occurrence in summer in Japan. Paediatricians in temperate zones should be mindful of possible HRSV cases in summer, when suitable conditions are present.

  17. Parálisis cerebral :

    OpenAIRE

    Cabrero Izquierdo, María del Carmen

    2012-01-01

    Se aborda el tema de la parálisis cerebral definiendo qué es, clasificando los tipos de parálisis dependiendo de la afectación y las características principales. Se explican algunos de sus tratamientos, se dan sistemas alternativos y/o aumentativos de comunicación para un alumno con PC (parálisis cerebral).

  18. Effect of human milk prostaglandins and lactoferrin on respiratory syncytial virus and rotavirus.

    Science.gov (United States)

    Grover, M; Giouzeppos, O; Schnagl, R D; May, J T

    1997-03-01

    The effect of lactoferrin and prostaglandins E and F2 alpha on the growth of rotavirus and respiratory syncytial virus in cell culture was investigated. Lactoferrin inhibited the growth of respiratory syncytial virus at a concentration tenfold lower than that normally present in human milk. The prostaglandins had no effect on either virus growth, even at a concentration of 100-fold more than that found in human milk. Lactoferrin may have some antiviral properties in human milk in addition to its known antibacterial functions.

  19. Genetic and antigenic analysis of the G attachment protein of bovine respiratory syncytial virus strains

    DEFF Research Database (Denmark)

    Elvander, M.; Vilcek, S.; Baule, C.

    1998-01-01

    Antigenic and genetic studies of bovine respiratory syncytial virus (BRSV) were made on isolates obtained from three continents over 27 years. Antigenic variation between eight isolates was initially determined using protein G-specific monoclonal antibodies. Four distinct reaction patterns were...... of a 731 nucleotide fragment in the G protein gene. Nine of the BRSV strains were analysed by direct sequencing of RT-PCR amplicons whereas sequences of 18 BRSV and three human respiratory syncytial virus (HRSV) strains were obtained from GenBank. The analysis revealed similarities of 88-100% among BRSV...

  20. Febrile status epilepticus due to respiratory syncytial virus infection.

    Science.gov (United States)

    Uda, Kazuhiro; Kitazawa, Katsuhiko

    2017-08-01

    Febrile status epilepticus can have neurological sequelae. The type of sequelae, however, depend on the etiology, including infection due to viral agents such as the influenza virus. Respiratory syncytial virus (RSV) infection in childhood may also contribute to this. The aim of this study was therefore to characterize febrile status epilepticus associated with RSV infection, and to determine whether this type of infection is a risk factor for neurological sequelae in febrile status epilepticus. We reviewed the medical records of children aged ≤3 years with febrile status epilepticus who were admitted to a tertiary hospital between January 2007 and December 2011. The differences between the RSV-positive and RSV-negative groups were evaluated according to the demographic and clinical data. A total of 99 patients with febrile status epilepticus who had been tested for RSV infection were identified. Three patients in the RSV-positive group (n = 19) and four in the RSV-negative group (n = 80) presented with bronchiolitis. The incidence of intubation and anti-seizure drug treatment in the RSV-positive group was significantly higher than in the -negative group. While all of the patients in the RSV-negative group recovered completely, six patients in the RSV-positive group developed encephalopathy and profound neurological sequelae. In five of the six patients, diffusion-weighted magnetic resonance imaging showed subcortical white matter lesions. RSV infection in the absence of bronchiolitis can initially present as febrile status epilepticus and subsequently develop into acute encephalopathy with profound neurological sequelae. © 2017 Japan Pediatric Society.

  1. Modifications de l'hémogramme au cours des maladies virales à expression digestive et/ou respiratoire chez le chien

    OpenAIRE

    Lavernhe, Elise

    2002-01-01

    Après un rappel bibliographique concernant les modifications de l'hémogramme au cours des trachéo-bronchites virales, de la maladie de Carré, de la pavovirose et des autres gastro-entérites virales, nous avons choisi d'étudier les hémogrammes de chiens atteints par ces maladies, présentés à la consultation de l'ENVT au cours de trois années scolaires successives. Les hémogrammes des chiens présentant une trachéo-bronchite virale sont peu modifiés. Les anomalies rencontrées sont de nombreuses ...

  2. Global respiratory syncytial virus-associated mortality in young children (RSV GOLD) : a retrospective case series

    NARCIS (Netherlands)

    Scheltema, Nienke M.; Gentile, Angela; Lucion, Florencia; Nokes, D. James; Munywoki, Patrick K.; Madhi, Shabir A.; Groome, Michelle J; Cohen, Cheryl; Moyes, Jocelyn; Thorburn, Kentigern; Thamthitiwat, Somsak; Oshitani, Hitoshi; Lupisan, Socorro P.; Gordon, Aubree; Sánchez, José F.; O'Brien, Katherine L.; Gessner, Bradford D.; Sutanto, Agustinus; Mejias, Asuncion; Ramilo, Octavio; Khuri-Bulos, Najwa; Halasa, Natasha; de-Paris, Fernanda; Pires, Márcia Rosane; Spaeder, Michael C.; Paes, Bosco A.; Simões, Eric A F; Leung, Ting F.; da Costa Oliveira, Maria Tereza; de Freitas Lázaro Emediato, Carla Cecília; Bassat, Quique; Butt, Warwick; Chi, Hsin; Aamir, Uzma Bashir; Ali, Asad; Lucero, Marilla G.; Fasce, Rodrigo A.; Lopez, Olga; Rath, Barbara A.; Polack, Fernando P.; Papenburg, Jesse; Roglić, Srđan; Ito, Hisato; Goka, Edward A.; Grobbee, Diederick E.; Nair, Harish; Bont, Louis J.

    2017-01-01

    Background Respiratory syncytial virus (RSV) infection is an important cause of pneumonia mortality in young children. However, clinical data for fatal RSV infection are scarce. We aimed to identify clinical and socioeconomic characteristics of children aged younger than 5 years with RSV-related

  3. Respiratory syncytial viral infections in young children : risk assessment and prevention

    NARCIS (Netherlands)

    E. Rietveld (Edwin)

    2003-01-01

    textabstractRespiratory syncytial virus is the main cause of lower respiratory tract infections in infants and young children. Although almost all children are infected before the age of two years, less than 2% develop severe disease necessitating hospitalisation. Risk factors for severe RSV

  4. Reduced Expression of HLA-DR on Monocytes During Severe Respiratory Syncytial Virus Infections

    NARCIS (Netherlands)

    Ahout, I.M.L.; Jans, J.; Haroutiounian, L.; Simonetti, E.R.; Gaast-de Jongh, C.E. van der; Diavatopoulos, D.A.; Jonge, M.I. de; Groot, R. de; Ferwerda, G.

    2016-01-01

    BACKGROUND: Respiratory syncytial virus (RSV) is a common cause of bronchiolitis in infants with a wide spectrum of disease severity. Besides environmental and genetic factors, it is thought that the innate immune system plays a pivotal role. The aim of this study was to investigate the expression

  5. Chronic diseases, chromosomal abnormalities, and congenital malformations as risk factors for respiratory syncytial virus hospitalization

    DEFF Research Database (Denmark)

    Kristensen, Kim; Hjuler, Thomas; Ravn, Henrik

    2012-01-01

    Little is known about how chronic conditions other than prematurity, heart disease, and Down syndrome affect the risk and severity of hospitalization for respiratory syncytial virus (RSV). We assess the risk and severity of RSV hospitalization in children with chronic conditions in this register...

  6. Seasonality of long term wheezing following respiratory syncytial virus lower respiratory tract infection

    NARCIS (Netherlands)

    Bont, L.; Steijn, M.; van Aalderen, W. M. C.; Brus, F.; Th Draaisma, J. M.; van Diemen-Steenvoorde, R. A. A. M.; Pekelharing-Berghuis, M.; Kimpen, J. L. L.

    2004-01-01

    Background: It is well known that respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) is associated with subsequent wheezing episodes, but the precise natural course of wheezing following RSV LRTI is not known. This study aimed to determine the continuous development of

  7. Seasonality of long term wheezing following respiratory syncytial virus lower respiratory tract infection

    NARCIS (Netherlands)

    Bont, L; Steijn, M; van Aalderen, WMC; Brus, F; Draaisma, JMT; Van Diemen-Steenvoorde, RAAM; Pekelharing-Berghuis, M; Kimpen, JLL

    Background: It is well known that respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) is associated with subsequent wheezing episodes, but the precise natural course of wheezing following RSV LRTI is not known. This study aimed to determine the continuous development of

  8. Heliox reduces respiratory system resistance in respiratory syncytial virus induced respiratory failure

    NARCIS (Netherlands)

    Kneyber, Martin C. J.; van Heerde, Marc; Twisk, Jos W. R.; Plotz, Frans B.; Markhors, Dick G.

    2009-01-01

    Introduction Respiratory syncytial virus (RSV) lower respiratory tract disease is characterised by narrowing of the airways resulting in increased airway resistance, air-trapping and respiratory acidosis. These problems might be overcome using helium-oxygen gas mixture. However, the effect of

  9. Radiological findings in children with respiratory syncytial virus infection: Relationship to clinical and bacteriological findings

    International Nuclear Information System (INIS)

    Eriksson, J.; Nordshus, T.; Westvik, J.; Carlsen, K.H.; Oerstadvik, I.; Eng, J.

    1986-01-01

    Respiratory syncytial virus (RSV) is a frequent cause of bronchiolitis leading to acute admission to hospital in the winter months. A wide range of findings accompanies this disease and the appearances are seldom completely diagnostic. Associated bacterial co-infections are common and we have shown an association with atelectasis among patients with pathogenic bacteria in the nasopharynx. (orig.)

  10. Heliox reduces respiratory system resistance in respiratory syncytial virus induced respiratory failure

    NARCIS (Netherlands)

    Kneijber, M.C.J.; van Heerde, M.; Twisk, J.W.R.; Plotz, F.; Markhorst, D.G.

    2009-01-01

    Introduction: Respiratory syncytial virus (RSV) lower respiratory tract disease is characterised by narrowing of the airways resulting in increased airway resistance, air-trapping and respiratory acidosis. These problems might be overcome using helium-oxygen gas mixture. However, the effect of

  11. Radiological features of lower respiratory infection by respiratory syncytial virus in infants and young children

    International Nuclear Information System (INIS)

    Kim, Woo Sun; Kim, In One; Yeon, Kyung Mo; Jang, Seong Hee; Lee, Hoan Jong

    1992-01-01

    Respiratory syncytial virus is the most common cause of lower respiratory infection (bronchiolitis and pneumonia) of infancy and early childhood. We analyzed clinical and radiological features of 76 patients with lower respiratory infections by respiratory syncytial virus, which were diagnosed by indirect immunofluorescent test or culture of nasal aspirate in Hep-2-cell monolayer, during the period of January- December, 1991. There were peaks of incidences in March-May and November- December, accounting for 87% of eases. Sixty-two cases (82%) were under 1 year of age. Fifty cases (66%) had underlying diseases. Major radiographical findings were overaeration (83%), parahilar peribronchial infiltrates (67%), segmental or subsegmental atelectasis (32%), and segmental or lobar consolidation (16%). In 15 cases (20%), overaeration was the only radiological findings. There was no evidence of pleural effusion or lymph node enlargement in all cases. By considering clinical features (symptoms, age, underlying diseases, epidemic seasons) in addition to the radiological findings, radiologists would be familiar with lower respiratory infection by respiratory syncytial virus. Air space consolidation, which is generally thought to represent bacterial pneumonia, is also observed not infrequently in respiratory syncytial virus infection

  12. Incidence and seasonality of respiratory syncytial virus hospitalisations in young children in Denmark, 2010 to 2015

    DEFF Research Database (Denmark)

    Jepsen, Martin T; Trebbien, Ramona; Emborg, Hanne Dorthe

    2018-01-01

    For future decisions on respiratory syncytial virus (RSV)-vaccination strategies and implementation into national immunisation-programmes, we used national registry data (hospitalisation, microbiology and vital statistics) to determine the age-specific incidence and direct medical costs of annual...

  13. Lower respiratory tract infection caused by respiratory syncytial virus : current management and new therapeutics

    NARCIS (Netherlands)

    Mazur, Natalie; Martinon-Torres, Federico; Baraldi, Eugenio; Fauroux, Brigitte; Greenough, Anne; Heikkinen, Terho; Manzoni, Paolo; Mejias, Asuncion; Nair, Harish; Papadopoulos, Nikolaos G.; Polack, Fernando P.; Ramilo, Octavio; Sharland, Mike; Stein, Renato; Madhi, Shabir A.; Bont, Louis

    2015-01-01

    Respiratory syncytial virus (RSV) is a major worldwide cause of morbidity and mortality in children under five years of age. Evidence-based management guidelines suggest that there is no effective treatment for RSV lower respiratory tract infection (LRTI) and that supportive care, ie, hydration and

  14. An ultrastructural study of the interaction of human eosinophils with respiratory syncytial virus

    NARCIS (Netherlands)

    Kimpen, JLL; Garofalo, R; Welliver, RC; Fujihara, K; Ogra, PL

    It was shown previously that eosinophils are activated in vivo and in vitro by respiratory syncytial virus (RSV) (Garofalo et al., J Pediatr 1992: 120: 28-32; Kimpen et al., Pediatr Res 1992: 32: 160-4). For study of the interaction of eosinophils and RSV on the ultrastructural level, normodense

  15. Pericarditis mediated by respiratory syncytial virus in a hematopoietic stem cell transplant patient.

    Science.gov (United States)

    Rubach, M P; Pavlisko, E N; Perfect, J R

    2013-08-01

    We describe a case of pericarditis and large pericardial effusion in a 63-year-old African-American man undergoing autologous hematopoietic stem cell transplant for multiple myeloma. Pericardial tissue biopsy demonstrated fibrinous pericarditis, and immunohistochemistry stains were positive for respiratory syncytial virus. The patient improved with oral ribavirin and intravenous immune globulin infusions. © 2013 John Wiley & Sons A/S.

  16. A randomized placebo controlled trial of ibuprofen for respiratory syncytial infection in a bovine model study

    Science.gov (United States)

    Background: Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis and hospital admission in infants. An analogous disease occurs in cattle and costs US agriculture a billion dollars a year. RSV causes much of its morbidity indirectly via adverse effects of the host response to ...

  17. Elusloom lennukiga puhkusele / Inge Parring

    Index Scriptorium Estoniae

    Parring, Inge

    2003-01-01

    Ilmunud ka: Delovõje Vedomosti 1. okt. lk. 13. Air Cargo Estonia/ACE Logisticsi müügijuht Inge Parring tutvustab elusloomade transpordivõimalusi. Vt. samas: Loomade transportimiseks vajalikud dokumendid

  18. Respiratory syncytial virus, pneumonia virus of mice, and influenza A virus differently affect respiratory allergy in mice

    NARCIS (Netherlands)

    Barends, M.; de Rond, L. G. H.; Dormans, J.; van Oosten, M.; Boelen, A.; Neijens, H. J.; Osterhaus, A. D. M. E.; Kimman, T. G.

    2004-01-01

    Respiratory viral infections in early childhood may interact with the immune system and modify allergen sensitization and/or allergic manifestations. In mice, respiratory syncytial virus (RSV) infection during allergic provocation aggravates the allergic T helper (Th) 2 immune response,

  19. Par Pond vegetation status 1996

    International Nuclear Information System (INIS)

    Mackey, H.E. Jr.; Riley, R.S.

    1996-12-01

    The water level of Par Pond was lowered approximately 20 feet in mid-1991 in order to protect downstream residents from possible dam failure suggested by subsidence on the downstream slope of the dam and to repair the dam. This lowering exposed both emergent and nonemergent macrophyte beds to drying conditions resulting in extensive losses. A survey of the newly emergent, shoreline aquatic plant communities of Par Pond began in June 1995, three months after the refilling of Par Pond to approximately 200 feet above mean sea level. These surveys continued in July, September, and late October, 1995, and into the early spring and late summer of 1996. Communities similar to the pre-drawdown, Par Pond aquatic plant communities continue to become re-established. Emergent beds of maidencane, lotus, waterlily, watershield, and Pontederia are extensive and well developed. Measures of percent cover, width of beds, and estimates of area of coverage with satellite data indicate regrowth within two years of from 40 to 60% of levels prior to the draw down. Cattail occurrence continued to increase during the summer of 1996, especially in the former warm arm of Par Pond, but large beds common to Par Pond prior to the draw down still have not formed. Lotus has invaded and occupies many of the areas formerly dominated by cattail beds. To track the continued development of macrophytes in Par Pond, future surveys through the summer and early fall of 1997, along with the evaluation of satellite data to map the extent of the macrophyte beds of Par Pond, are planned

  20. Effect of compounds with antibacterial activities in human milk on respiratory syncytial virus and cytomegalovirus in vitro.

    Science.gov (United States)

    Portelli, J; Gordon, A; May, J T

    1998-11-01

    The effect of some antibacterial compounds present in human milk were tested for antiviral activity against respiratory syncytial virus, Semliki Forest virus and cytomegalovirus. These included the gangliosides GM1, GM2 and GM3, sialyl-lactose, lactoferrin and chondroitin sulphate A, B and C, which were all tested for their ability to inhibit the viruses in cell culture. Of the compounds tested, only the ganglioside GM2, chondroitin sulphate B and lactoferrin inhibited the absorption and growth of respiratory syncytial virus in cell culture, and none inhibited the growth of Semliki Forest virus, indicating that lipid antiviral activity was not associated with any of the gangliosides. While the concentrations of these two compounds required to inhibit respiratory syncytial virus were in excess of those present in human milk, sialyl-lactose concentrations similar to those present in human milk increased the growth of cytomegalovirus. Lactoferrin was confirmed as inhibiting both respiratory syncytial virus and cytomegalovirus growth in culture even when used at lower concentrations than those present in human milk. The antiviral activities of GM2, chondroitin sulphate B and lactoferrin were tested when added to an infant formula. Lactoferrin continued to have antiviral activity against cytomegalovirus, but a lower activity against respiratory syncytial virus; ganglioside GM2 and chondroitin sulphate B still maintained antiviral activity against respiratory syncytial virus.

  1. Vote par sondage uniforme incorruptible

    OpenAIRE

    Blanchard , Nicolas

    2016-01-01

    International audience; Introduit en 2012 par David Chaum, le vote par sondage uniforme (random-sample voting) est un protocole de vote basé sur un choix d'une sous-population représentative , permettant de limiter les coûts tout en ayant de nombreux avantages, principalement lorsqu'il est couplé a d'autres techniques comme ThreeBallot. Nous analysons un problème de corruptibilité potentielle où les votants peuvent vendre leur vote au plus offrant et proposons une variation du protocole reméd...

  2. Maladie de Horton révélée par une dyspnée

    Science.gov (United States)

    Mahfoudhi, Madiha; Mamlouk, Habiba; Turki, Sami; Kheder, Adel

    2015-01-01

    Les manifestations pleuro-pulmonaires de la maladie de Horton sont rares et peu connues. Elles peuvent être inaugurales, à l'origine d'un retard à la prise en charge si elles sont méconnues. Il s'agissait d'un patient âgé de 75 ans, admis pour une dyspnée, une toux chronique et une fièvre. Il a reçu une antibiothérapie et a bénéficié d'une fibroscopie bronchique avec lavage broncho-alvéolaire à la recherche d'un germe, qui a révélé plutôt, une alvéolite lymphocytaire. L’évolution était marquée par la persistance des signes cliniques et du syndrome inflammatoire biologique. Un angio-scanner thoracique et une échographie cardiaque étaient sans anomalies. Une origine cardiaque, musculaire, hématologique, néoplasique, vasculaire ou métabolique de la dyspnée a été éliminée. Une maladie de Horton a été évoquée. La biopsie de l'artère temporale a confirmé le diagnostic d'une maladie de Horton. L’évolution sous corticothérapie était marquée par la disparition des signes cliniques et biologiques. Les manifestations pleuro-pulmonaires au cours de la maladie de Horton sont rares, et classiquement, rarement révélatrices de la maladie. La dyspnée peut initialement égarer le diagnostic vers d'autres étiologies notamment infectieuses. Le but de ce travail est d'insister sur le fait que la connaissance de ces différentes manifestations respiratoires au cours de la maladie de Horton (toux persistante, dyspnée, épanchement pleural) est utile au clinicien afin de prescrire une corticothérapie, chez un sujet le plus souvent âgé ayant un état fébrile et inflammatoire prolongé, permettant ainsi d’éviter l'apparition de complications. PMID:26161171

  3. Par Pond Fish, Water, and Sediment Chemistry

    Energy Technology Data Exchange (ETDEWEB)

    Paller, M.H. [Westinghouse Savannah River Company, AIKEN, SC (United States); Wike, L.D.

    1996-06-01

    The objectives of this report are to describe the Par Pond fish community and the impact of the drawdown and refill on the community, describe contaminant levels in Par Pond fish, sediments, and water and indicate how contaminant concentrations and distributions were affected by the drawdown and refill, and predict possible effects of future water level fluctuations in Par Pond.

  4. Par Pond Fish, Water, and Sediment Chemistry

    International Nuclear Information System (INIS)

    Paller, M.H.; Wike, L.D.

    1996-06-01

    The objectives of this report are to describe the Par Pond fish community and the impact of the drawdown and refill on the community, describe contaminant levels in Par Pond fish, sediments, and water and indicate how contaminant concentrations and distributions were affected by the drawdown and refill, and predict possible effects of future water level fluctuations in Par Pond

  5. The viral transcription group determines the HLA class I cellular immune response against human respiratory syncytial virus.

    Science.gov (United States)

    Johnstone, Carolina; Lorente, Elena; Barriga, Alejandro; Barnea, Eilon; Infantes, Susana; Lemonnier, François A; David, Chella S; Admon, Arie; López, Daniel

    2015-04-01

    The cytotoxic T-lymphocyte-mediated killing of virus-infected cells requires previous recognition of short viral antigenic peptides bound to human leukocyte antigen class I molecules that are exposed on the surface of infected cells. The cytotoxic T-lymphocyte response is critical for the clearance of human respiratory syncytial virus infection. In this study, naturally processed viral human leukocyte antigen class I ligands were identified with mass spectrometry analysis of complex human leukocyte antigen-bound peptide pools isolated from large amounts of human respiratory syncytial virus-infected cells. Acute antiviral T-cell response characterization showed that viral transcription determines both the immunoprevalence and immunodominance of the human leukocyte antigen class I response to human respiratory syncytial virus. These findings have clear implications for antiviral vaccine design. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. The Viral Transcription Group Determines the HLA Class I Cellular Immune Response Against Human Respiratory Syncytial Virus*

    Science.gov (United States)

    Johnstone, Carolina; Lorente, Elena; Barriga, Alejandro; Barnea, Eilon; Infantes, Susana; Lemonnier, François A.; David, Chella S.; Admon, Arie; López, Daniel

    2015-01-01

    The cytotoxic T-lymphocyte-mediated killing of virus-infected cells requires previous recognition of short viral antigenic peptides bound to human leukocyte antigen class I molecules that are exposed on the surface of infected cells. The cytotoxic T-lymphocyte response is critical for the clearance of human respiratory syncytial virus infection. In this study, naturally processed viral human leukocyte antigen class I ligands were identified with mass spectrometry analysis of complex human leukocyte antigen-bound peptide pools isolated from large amounts of human respiratory syncytial virus-infected cells. Acute antiviral T-cell response characterization showed that viral transcription determines both the immunoprevalence and immunodominance of the human leukocyte antigen class I response to human respiratory syncytial virus. These findings have clear implications for antiviral vaccine design. PMID:25635267

  7. Rapid antigen detection test for respiratory syncytial virus diagnosis as a diagnostic tool.

    Science.gov (United States)

    Mesquita, Flávio da Silva; Oliveira, Danielle Bruna Leal de; Crema, Daniela; Pinez, Célia Miranda Nunes; Colmanetti, Thaís Cristina; Thomazelli, Luciano Matsumia; Gilio, Alfredo Elias; Vieira, Sandra Elisabeth; Martinez, Marina Baquerizo; Botosso, Viviane Fongaro; Durigon, Edison Luiz

    The aim of this study was to evaluate the QuickVue ® RSV Test Kit (QUIDEL Corp, CA, USA) as a screening tool for respiratory syncytial virus in children with acute respiratory disease in comparison with the indirect immunofluorescence assay as gold standard. In Brazil, rapid antigen detection tests for respiratory syncytial virus are not routinely utilized as a diagnostic tool, except for the diagnosis of dengue and influenza. The authors retrospectively analyzed 486 nasopharyngeal aspirate samples from children under age 5 with acute respiratory infection, between December 2013 and August 2014, the samples were analyzed by indirect immunofluorescence assay and QuickVue ® RSV Test kit. Samples with discordant results were analyzed by real time PCR and nucleotide sequencing. From 313 positive samples by immunofluorescence assays, 282 (90%) were also positive by the rapid antigen detection test, two were positive only by rapid antigen detection test, 33 were positive only by immunofluorescence assays, and 171 were positive by both methods. The 35 samples with discordant results were analyzed by real time PCR; the two samples positive only by rapid antigen detection test and the five positive only by immunofluorescence assays were also positive by real time PCR. There was no relation between the negativity by QuickVue ® RSV Test and viral load or specific strain. The QuickVue ® RSV Test showed sensitivity of 90%, specificity of 98.8%, predictive positive value of 99.3%, and negative predictive value of 94.6%, with accuracy of 93.2% and agreement κ index of 0.85 in comparison to immunofluorescence assay. This study demonstrated that the QuickVue ® RSV Test Kit can be effective in early detection of Respiratory syncytial virus in nasopharyngeal aspirate and is reliable for use as a diagnostic tool in pediatrics. Copyright © 2016 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  8. Rapid antigen detection test for respiratory syncytial virus diagnosis as a diagnostic tool,

    Directory of Open Access Journals (Sweden)

    Flávio da Silva Mesquita

    Full Text Available Abstract Objective: The aim of this study was to evaluate the QuickVue® RSV Test Kit (QUIDEL Corp, CA, USA as a screening tool for respiratory syncytial virus in children with acute respiratory disease in comparison with the indirect immunofluorescence assay as gold standard. In Brazil, rapid antigen detection tests for respiratory syncytial virus are not routinely utilized as a diagnostic tool, except for the diagnosis of dengue and influenza. Methods: The authors retrospectively analyzed 486 nasopharyngeal aspirate samples from children under age 5 with acute respiratory infection, between December 2013 and August 2014, the samples were analyzed by indirect immunofluorescence assay and QuickVue® RSV Test kit. Samples with discordant results were analyzed by real time PCR and nucleotide sequencing. Results: From 313 positive samples by immunofluorescence assays, 282 (90% were also positive by the rapid antigen detection test, two were positive only by rapid antigen detection test, 33 were positive only by immunofluorescence assays, and 171 were positive by both methods. The 35 samples with discordant results were analyzed by real time PCR; the two samples positive only by rapid antigen detection test and the five positive only by immunofluorescence assays were also positive by real time PCR. There was no relation between the negativity by QuickVue® RSV Test and viral load or specific strain. The QuickVue® RSV Test showed sensitivity of 90%, specificity of 98.8%, predictive positive value of 99.3%, and negative predictive value of 94.6%, with accuracy of 93.2% and agreement κ index of 0.85 in comparison to immunofluorescence assay. Conclusions: This study demonstrated that the QuickVue® RSV Test Kit can be effective in early detection of Respiratory syncytial virus in nasopharyngeal aspirate and is reliable for use as a diagnostic tool in pediatrics.

  9. Computational Breakthrough of Natural Lead Hits from the Genus of Arisaema against Human Respiratory Syncytial Virus.

    Science.gov (United States)

    Kant, Kamal; Lal, Uma Ranjan; Ghosh, Manik

    2018-01-01

    To date, efforts for the prevention and treatment of human respiratory syncytial virus (RSV) infection have been still vain, and there is no safe and effective clinical accepted vaccine. Arisaema genus has claimed for various traditional bioactivities, but scientific assessments are quite limited. This encouraged us to carry out our present study on around 60 phytoconstituents of different Arisaema species as a natural inhibitor against the human RSV. Selected 60 phytochemical entities were evaluated on the docking behavior of human RSV receptor (PDB: 4UCC) using Maestro 9.3 (Schrödinger, LLC, Cambridge, USA). Furthermore, kinetic properties and toxicity nature of top graded ligands were analyzed through QikProp and ProTox tools. Notably, rutin (glide score: -8.49), schaftoside (glide score: -8.18) and apigenin-6,8-di-C-β-D-galactoside (glide score - 7.29) have resulted in hopeful natural lead hits with an ideal range of kinetic descriptors values. ProTox tool (oral rodent toxicity) has resulted in likely toxicity targets of apex-graded tested ligands. Finally, the whole efforts can be explored further as a model to confirm its anti-human RSV potential with wet laboratory experiments. Rutin, schaftoside, and apigenin-6,8-di-C-β-D-galactoside showed promising top hits docking profile against human respiratory syncytial virusMoreover, absorption, distribution, metabolism, excretion properties (QikProp) of top hits resulted within an ideal range of kinetic descriptorsProTox tool highlighted toxicity class ranges, LD 50 values, and possible toxicity targets of apex-graded tested ligands. Abbreviations used: RSV: Respiratory syncytial virus, PRRSV: Porcine respiratory and reproductive syndrome virus, ADME-T: Absorption, distribution, metabolism, excretion, and toxicity.

  10. A Case of Respiratory Syncytial Virus Infection in an HIV-Positive Adult

    Directory of Open Access Journals (Sweden)

    Aakriti Gupta

    2012-01-01

    Full Text Available Respiratory syncytial virus (RSV is commonly known to cause an influenza-like illness. However, it can also cause more severe disease in young children and older adults comprising of organ transplant patients with immunocompromised status. Till date, only four cases of RSV infections have been reported in HIV-positive adults. We describe here a case of HIV-positive female with relatively preserved immune function who presented with RSV infection requiring ventilation and showed improvement after prompt treatment with intravenous immunoglobulin.

  11. Human metapneumovirus and respiratory syncytial virus in hospitalized danish children with acute respiratory tract infection

    DEFF Research Database (Denmark)

    von Linstow, Marie-Louise; Henrik Larsen, Hans; Koch, Anders

    2004-01-01

    The newly discovered human metapneumovirus (hMPV) has been shown to be associated with respiratory illness. We determined the frequencies and clinical features of hMPV and respiratory syncytial virus (RSV) infections in 374 Danish children with 383 episodes of acute respiratory tract infection...... children 1-6 months of age. Asthmatic bronchitis was diagnosed in 66.7% of hMPV and 10.6% of RSV-infected children (p respiratory support. hMPV is present in young...

  12. Bovine respiratory syncytial virus (BRSV) pneumonia in beef calf herds despite vaccination

    DEFF Research Database (Denmark)

    Larsen, Lars Erik; Tegtmeier, C.; Pedersen, E.

    2001-01-01

    to the outbreak. The clinical signs comprised nasal discharge, pyrexia, cough and increased respiratory rates. A total of 28 calves died in the 2 herds. The laboratory investigations revealed that BRSV was involved and probably initiated both outbreaks. Furthermore, the serological results suggested...... beef herds failed to protect the calves against severe or even fatal BRSV mediated respiratory disease 2 months later.......The present report describes the clinical, pathological, serological and virological findings in calves from 2 larger Danish beef herds experiencing outbreaks of pneumonia. The calves had been vaccinated with an inactivated bovine respiratory syncytial virus (BRSV) vaccine 2 months prior...

  13. Prevention and treatment of respiratory syncytial virus bronchiolitis and postbronchiolitic wheezing

    Directory of Open Access Journals (Sweden)

    Kimpen Jan LL

    2002-06-01

    Full Text Available Abstract Respiratory syncytial virus (RSV is the primary cause of hospitalization for acute respiratory tract illness in general and specifically for bronchiolitis in young children. The link between RSV bronchiolitis and reactive airway disease is not completely understood, even though RSV bronchiolitis is frequently followed by recurrent episodes of wheezing. Therapy with ribavirin does not appear to significantly reduce long-term respiratory outcome of RSV lower respiratory tract infection, and corticosteroid or bronchodilator therapy may possibly improve outcomes only on a short-term basis. No vaccine against RSV is yet available. It is not known whether prophylaxis with RSV intravenous immune globulin or palivizumab can reduce postbronchiolitic wheezing.

  14. Directed and persistent movement arises from mechanochemistry of the ParA/ParB system.

    Science.gov (United States)

    Hu, Longhua; Vecchiarelli, Anthony G; Mizuuchi, Kiyoshi; Neuman, Keir C; Liu, Jian

    2015-12-22

    The segregation of DNA before cell division is essential for faithful genetic inheritance. In many bacteria, segregation of low-copy number plasmids involves an active partition system composed of a nonspecific DNA-binding ATPase, ParA, and its stimulator protein ParB. The ParA/ParB system drives directed and persistent movement of DNA cargo both in vivo and in vitro. Filament-based models akin to actin/microtubule-driven motility were proposed for plasmid segregation mediated by ParA. Recent experiments challenge this view and suggest that ParA/ParB system motility is driven by a diffusion ratchet mechanism in which ParB-coated plasmid both creates and follows a ParA gradient on the nucleoid surface. However, the detailed mechanism of ParA/ParB-mediated directed and persistent movement remains unknown. Here, we develop a theoretical model describing ParA/ParB-mediated motility. We show that the ParA/ParB system can work as a Brownian ratchet, which effectively couples the ATPase-dependent cycling of ParA-nucleoid affinity to the motion of the ParB-bound cargo. Paradoxically, this resulting processive motion relies on quenching diffusive plasmid motion through a large number of transient ParA/ParB-mediated tethers to the nucleoid surface. Our work thus sheds light on an emergent phenomenon in which nonmotor proteins work collectively via mechanochemical coupling to propel cargos-an ingenious solution shaped by evolution to cope with the lack of processive motor proteins in bacteria.

  15. Respiratoir falen soms toch door cardiale oorzaak

    NARCIS (Netherlands)

    van den Tol, D C; van der Werf, T S; Hamer, J P; Tulleken, J E; Ligtenberg, J J; Zijlstra, J G

    1998-01-01

    In two women aged 65 and 49 years and a man aged 64 years, severe respiratory failure developed and a pulmonary disease was suspected. They also had a minor systolic murmur. At further investigation no pulmonary cause for the disease could be established. Pulmonary artery catheterization revealed

  16. Recherche documentaire par titrage automatique

    OpenAIRE

    Lopez , Cédric; Prince , Violaine; Roche , Mathieu

    2011-01-01

    Nous proposons dans cet article un système facilitant la recherche d'information dans un ensemble de documents textuels, basé sur le titrage (et sous-titrage) automatique. Ce dernier peut se révéler crucial, par exemple, dans le cadre de la problématique de l'accessibilité des pages web (norme W3C). Notre processus de titrage automatique consiste à extraire des syntagmes nominaux pertinents dans les textes, pouvant constituer des titres ou sous-titres candidats. Une approche originale combina...

  17. BOVINE RESPIRATORY SYNCYTIAL VIRUS EPIDEMIOLOGY AND RISK FACTORS ON CATTLE HERDS OF CAMPECHE STATE, MEXICO

    Directory of Open Access Journals (Sweden)

    Lisandro Alberto Encalada Mena

    2016-12-01

    Full Text Available High seroprevalence in Yucatan and proximity to the state of Campeche make it necessary to determine the seroprevalence and risk factors of bovine respiratory syncytial virus (VRSB in the state of Campeche, Mexico. Thus the objective of the present work was to determine the seroprevalence and risk factors bovine respiratory syncytial virus (BRSV of the state of Campeche, Mexico. The sampled of 36 cattle herds (842 sera were analyzed by indirect ELISA kit, in the 11 municipalities of Campeche. A survey to obtain risk factors (sex, age of animals, number of animals grazing density, management system, presence of sheep on the farm and access to the roadside was applied and calculated X2 for each variable considered. Of the total number of samples analyzed (842, 273 were positive (32.47%. The prevalence ranges found ranged from 0% to 84%, so in 9 of the herds there were no positive samples, indicating a 75% (27/36 of dispersion of this virus. X2 analysis indicated that all variables were significant and are risk factors regarding with respect to the variable seroprevalence of BRSV. The results indicate a wide circulation of BRSV and we suggest implement recommendations that will enable a lower spread of this virus in the cattle population.

  18. Functional organization of cytoplasmic inclusion bodies in cells infected by respiratory syncytial virus.

    Science.gov (United States)

    Rincheval, Vincent; Lelek, Mickael; Gault, Elyanne; Bouillier, Camille; Sitterlin, Delphine; Blouquit-Laye, Sabine; Galloux, Marie; Zimmer, Christophe; Eleouet, Jean-François; Rameix-Welti, Marie-Anne

    2017-09-15

    Infection of cells by respiratory syncytial virus induces the formation of cytoplasmic inclusion bodies (IBs) where all the components of the viral RNA polymerase complex are concentrated. However, the exact organization and function of these IBs remain unclear. In this study, we use conventional and super-resolution imaging to dissect the internal structure of IBs. We observe that newly synthetized viral mRNA and the viral transcription anti-terminator M2-1 concentrate in IB sub-compartments, which we term "IB-associated granules" (IBAGs). In contrast, viral genomic RNA, the nucleoprotein, the L polymerase and its cofactor P are excluded from IBAGs. Live imaging reveals that IBAGs are highly dynamic structures. Our data show that IBs are the main site of viral RNA synthesis. They further suggest that shortly after synthesis in IBs, viral mRNAs and M2-1 transiently concentrate in IBAGs before reaching the cytosol and suggest a novel post-transcriptional function for M2-1.Respiratory syncytial virus (RSV) induces formation of inclusion bodies (IBs) sheltering viral RNA synthesis. Here, Rincheval et al. identify highly dynamic IB-associated granules (IBAGs) that accumulate newly synthetized viral mRNA and the viral M2-1 protein but exclude viral genomic RNA and RNA polymerase complexes.

  19. The impact of laboratory characteristics on molecular detection of respiratory syncytial virus in a European multicentre quality control study

    NARCIS (Netherlands)

    Meerhoff, T. J.; MacKay, W. G.; Meijer, A.; Paget, W. J.; Niesters, H. G. M.; Kimpen, J. L. L.; Schellevis, F.

    2008-01-01

    The performance of nucleic acid amplification techniques for detecting respiratory syncytial virus (RSV) was evaluated in 25 laboratories across Europe by an external quality assessment study. In addition, factors related to the diagnostic performance of laboratories were explored. The results of

  20. Serological indication for persistence of bovine respiratory syncytial virus in cattle and attempts to detect the virus

    NARCIS (Netherlands)

    Poel, van der W.H.M.; Langedijk, J.P.M.; Kramps, J.A.; Middel, W.G.J.; Brand, A.; Oirschot, van J.T.

    1997-01-01

    To identify putative persistent bovine respiratory syncytial virus (BRSV) infections in cattle, seven cattle that had experienced BRSV infections were treated with corticosteroids for two periods of 5 days. During the 5-day periods and the 3 weeks after treatment, attempts were made to isolate BRSV

  1. Codetection of Respiratory Syncytial Virus in Habituated Wild Western Lowland Gorillas and Humans During a Respiratory Disease Outbreak

    Czech Academy of Sciences Publication Activity Database

    Grützmacher, K. S.; Köndgen, S.; Keil, V.; Todd, A.; Feistner, A.; Herbinger, I.; Petrželková, Klára Judita; Fuh, T.; Leendertz, S. A.; Calvignac-Spencer, S.; Leendertz, F. H.

    2016-01-01

    Roč. 13, č. 3 (2016), s. 499-510 ISSN 1612-9202 Institutional support: RVO:60077344 Keywords : respiratory disease * respiratory syncytial virus * enterovirus * western lowland gorillas * great apes * noninvasive detection Subject RIV: EE - Microbiology, Virology Impact factor: 2.252, year: 2016

  2. Codetection of respiratory syncytial virus in habituated wild western lowland gorillas and humans during a respiratory disease outbreak

    Czech Academy of Sciences Publication Activity Database

    Grützmacher, K. S.; Köndgen, S.; Keil, V.; Todd, A.; Feistner, A.; Herbinger, I.; Petrželková, Klára Judita; Fuh, T.; Leendertz, S. A.; Calvignac-Spencer, S.; Leendertz, F. H.

    2016-01-01

    Roč. 13, č. 3 (2016), s. 499-510 ISSN 1612-9202 Institutional support: RVO:68081766 Keywords : respiratory disease * respiratory syncytial virus * enterovirus * western lowland gorillas * great apes * noninvasive detection Subject RIV: GJ - Animal Vermins ; Diseases, Veterinary Medicine Impact factor: 2.252, year: 2016

  3. GENETIC SUSCEPTIBILITY TO RESPIRATORY SYNCYTIAL VIRUS BRONCHIOLITIS IN PRETERM CHILDREN IS ASSOCIATED WITH AIRWAY REMODELING GENES AND INNATE IMMUNE GENES

    NARCIS (Netherlands)

    Siezen, Christine L. E.; Bont, Louis; Hodemaekers, Hennie M.; Ermers, Marieke J.; Doornbos, Gerda; van't Slot, Ruben; Wijmenga, Ciska; van Hottwelingen, Hans C.; Kimpen, Jan L. L.; Kimman, Tjeerd G.; Hoebee, Barbara; Janssen, Riny

    Prematurity is a risk factor for severe respiratory syncytial virus bronchiolitis. We show that genetic factors in innate immune genes (IFNA13, IFNAR2, STAT2. IL27, NFKBIA, C3, IL1RN, TLR5), in innate and adaptive immunity (IFNG), and in airway remodeling genes (ADAM33 and TGFBR1), affect disease

  4. Defining the Risk and Associated Morbidity and Mortality of Severe Respiratory Syncytial Virus Infection Among Infants with Chronic Lung Disease

    NARCIS (Netherlands)

    Paes, Bosco; Fauroux, Brigitte; Figueras-Aloy, Josep; Bont, Louis; Checchia, Paul A; Simões, Eric A F; Manzoni, Paolo; Carbonell-Estrany, Xavier

    2016-01-01

    INTRODUCTION: The REGAL (RSV evidence-a geographical archive of the literature) series provide a comprehensive review of the published evidence in the field of respiratory syncytial virus (RSV) in Western countries over the last 20 years. This third publication covers the risk and burden of RSV

  5. A Model of the Costs of Community and Nosocomial Pediatric Respiratory Syncytial Virus Infections in Canadian Hospitals

    Directory of Open Access Journals (Sweden)

    Philip Jacobs

    2013-01-01

    Full Text Available BACKGROUND: Approximately one in 10 hospitalized patients will acquire a nosocomial infection (NI after admission to hospital, of which 71% are due to respiratory viruses, including the respiratory syncytial virus (RSV. NIs are concerning and lead to prolonged hospitalizations. The economics of NIs are typically described in generalized terms and specific cost data are lacking.

  6. Prospective validation of a prognostic model for respiratory syncytial virus bronchiolitis in late preterm infants: a multicenter birth cohort study

    NARCIS (Netherlands)

    Blanken, M.O.; Koffijberg, H.; Nibbelke, E.E.; Rovers, M.M.; Bont, L.; Liem, K.D.; et al.,

    2013-01-01

    OBJECTIVES: This study aimed to update and validate a prediction rule for respiratory syncytial virus (RSV) hospitalization in preterm infants 33-35 weeks gestational age (WGA). STUDY DESIGN: The RISK study consisted of 2 multicenter prospective birth cohorts in 41 hospitals. Risk factors were

  7. SECHAGE DE PRODUITS GRANULAIRES PAR DESHYDRATATION PAR DETENTES SUCCESSIVES (DDS)

    OpenAIRE

    Abdulla , Galal; Mellouk , Hamid; Belghit , Abdelhamid; Allaf , Karim

    2009-01-01

    International audience; Dans cette étude, nous avons évalué les performances d'un nouveau procédé de séchage dans le cas du liège en granulés. Ce procédé (La déshydratation par détentes successives : DDS) consiste à soumettre le matériau liège dans une chambre hermétique aux variations cycliques de la pression. Chaque cycle est composé d'une compression et d'une décompression. La phase de compression est réalisée en injectant de l'air comprimé à température ambiante provenant d'un compresseur...

  8. La preuve par le nombre

    Directory of Open Access Journals (Sweden)

    Hélène Verdier

    2012-04-01

    Full Text Available S’il en était besoin, la question des usages et de la finalité des résultats de l’inventaire général pourrait être abordée par le nombre : nombre d’œuvres répertoriées, de communes inventoriées, de clichés photographiques réalisés, de dossiers, de consultations des notices dans les bases de données… Les additions aujourd’hui sont éloquentes, mais elles laissent dans l’ombre le rôle de l’inventaire qui, en mettant en œuvre une démarche systématique de connaissance, participe à l’ identificatio...

  9. Par Pond vegetation status Summer 1995 -- Summary

    International Nuclear Information System (INIS)

    Mackey, H.E. Jr.; Riley, R.S.

    1996-01-01

    The water level of Par Pond was lowered approximately 20 feet in mid-1991 in order to protect downstream residents from possible dam failure suggested by subsidence on the downstream slope of the dam and to repair the dam. This lowering exposed both emergent and nonemergent macrophyte beds to drying conditions resulting in extensive losses. A survey of the newly emergent, shoreline aquatic plant communities of Par Pond began in June 1995, three months after the refilling of Par Pond to approximately 200 feet above mean sea level. These surveys continued in July, September, and late October, 1995. Communities similar to the pre-drawdown, Par Pond aquatic plant communities are becoming re-established. Emergent beds of maidencane, lotus, waterlily, and watershield are extensive and well developed. Cattail occurrence continued to increase during the summer, but large beds common to Par Pond prior to the drawdown have not formed. Estimates from SPOT HRV, remote sensing satellite data indicated that as much as 120 hectares of emergent wetlands vegetation may have been present along the Par Pond shoreline by early October, 1995. To track the continued development of macrophytes in Par Pond, future surveys throughout 1996 and 1997, along with the continued evaluation of satellite data to map the areal extent of the macrophyte beds of Par Pond, are planned

  10. Respiratory syncytial virus subunit vaccine based on a recombinant fusion protein expressed transiently in mammalian cells.

    Science.gov (United States)

    Nallet, Sophie; Amacker, Mario; Westerfeld, Nicole; Baldi, Lucia; König, Iwo; Hacker, David L; Zaborosch, Christiane; Zurbriggen, Rinaldo; Wurm, Florian M

    2009-10-30

    Although respiratory syncytial virus (RSV) causes severe lower respiratory tract infection in infants and adults at risk, no RSV vaccine is currently available. In this report, efforts toward the generation of an RSV subunit vaccine using recombinant RSV fusion protein (rRSV-F) are described. The recombinant protein was produced by transient gene expression (TGE) in suspension-adapted human embryonic kidney cells (HEK-293E) in 4 L orbitally shaken bioreactors. It was then purified and formulated in immunostimulating reconstituted influenza virosomes (IRIVs). The candidate vaccine induced anti-RSV-F neutralizing antibodies in mice, and challenge studies in cotton rats are ongoing. If successful in preclinical and clinical trials, this will be the first recombinant subunit vaccine produced by large-scale TGE in mammalian cells.

  11. The human cathelicidin LL-37 has antiviral activity against respiratory syncytial virus.

    Directory of Open Access Journals (Sweden)

    Silke M Currie

    Full Text Available Respiratory syncytial virus is a leading cause of lower respiratory tract illness among infants, the elderly and immunocompromised individuals. Currently, there is no effective vaccine or disease modifying treatment available and novel interventions are urgently required. Cathelicidins are cationic host defence peptides expressed in the inflamed lung, with key roles in innate host defence against infection. We demonstrate that the human cathelicidin LL-37 has effective antiviral activity against RSV in vitro, retained by a truncated central peptide fragment. LL-37 prevented virus-induced cell death in epithelial cultures, significantly inhibited the production of new infectious particles and diminished the spread of infection, with antiviral effects directed both against the viral particles and the epithelial cells. LL-37 may represent an important targetable component of innate host defence against RSV infection. Prophylactic modulation of LL-37 expression and/or use of synthetic analogues post-infection may represent future novel strategies against RSV infection.

  12. Validation of a pediatric caregiver diary to measure symptoms of postacute respiratory syncytial virus bronchiolitis

    DEFF Research Database (Denmark)

    Santanello, Nancy C; Norquist, Josephine M; Nelsen, Linda M

    2005-01-01

    consistent, supporting a unidimensional scale structure. Test-retest reliabilities for the percentage of SFD and CSS were above the recommended cut point of 0.70. Cross-sectional and longitudinal correlations were sizeable and statistically significant, demonstrating construct validity. Hypothesized known......Acute respiratory syncytial virus (RSV)-induced bronchiolitis is often associated with continuing respiratory symptoms following hospitalization. To date, there is no validated objective measure to evaluate symptoms of RSV-induced bronchiolitis. We report on the reliability, validity...... the 4-week treatment period of the reported prospective, placebo-controlled trial of montelukast for treatment of postacute RSV were used to assess reliability (internal consistency and test-retest), construct validity (cross-sectional and longitudinal correlations), discriminant validity (known...

  13. Excretion patterns of human metapneumovirus and respiratory syncytial virus among young children

    DEFF Research Database (Denmark)

    von Linstow, Marie-Louise; Eugen-Olsen, Jesper; Koch, A

    2006-01-01

    of the infected children showed to have an upper respiratory tract infection when following up. CONCLUSION: Viral RNA was present in nasal secretions, saliva, sweat, and faeces, but whether or not the virions were infectious and constitute a potential mode of transmission remains to be shown in future studies.......BACKGROUND: As respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) cause serious respiratory tract infections, the routes of transmission of these viruses are important to elucidate. We examined the modes of virus shedding and shedding duration of RSV and hMPV in young children....... METHODS: From each child in a group of 44 children (37 RSV-positive, 6 hMPV-positive, and 1 co-infected child), aged between 0.5-38 months, hospitalised at Hvidovre Hospital, Copenhagen, Denmark, one nasopharyngeal aspirate (NPA), saliva, urine, and faeces sample were collected at inclusion and weekly...

  14. Respiratory Syncytial Virus Pneumonia Treated with Lower-Dose Palivizumab in a Heart Transplant Recipient

    Directory of Open Access Journals (Sweden)

    J. L. Grodin

    2012-01-01

    Full Text Available Respiratory syncytial virus (RSV is an important community-acquired pathogen that can cause significant morbidity and mortality in patients who have compromised pulmonary function, are elderly, or are immunosuppressed. This paper describes a 70-year-old man with a remote history of heart transplantation who presented with signs and symptoms of pneumonia. Chest computed tomography (CT imaging demonstrated new patchy ground glass infiltrates throughout the upper and lower lobes of the left lung, and the RSV direct fluorescence antibody (DFA was positive. The patient received aerosolized ribavirin, one dose of intravenous immunoglobulin, and one dose of palivizumab. After two months of followup, the patient had improved infiltrates on chest CT, improved pulmonary function testing, and no evidence of graft rejection or dysfunction. There are few data on RSV infections in heart transplant patients, but this case highlights the importance of considering this potentially serious infection and introduces a novel method of treatment.

  15. The causal direction in the association between respiratory syncytial virus hospitalization and asthma

    DEFF Research Database (Denmark)

    Stensballe, Lone Graff; Simonsen, Jacob Brunbjerg; Thomsen, Simon Francis

    2009-01-01

    BACKGROUND: Earlier studies have reported an increased risk of asthma after respiratory syncytial virus (RSV) hospitalization. Other studies found that asthmatic disposition and propensity to wheeze increase the risk of RSV hospitalization. OBJECTIVE: The current study examined the causal direction......; and asthma is associated with a long-term increased susceptibility for severe RSV disease, suggesting a host factor being responsible for the severe response to RSV infection. This suggests that severe RSV infection and asthma may share a common genetic predisposition and/or environmental exposure....... was increased as much as 6-fold to 8-fold during the first 2 months after RSV hospitalization but was no longer increased 1 year later. Asthma increased the risk of RSV hospitalization by 3-fold, and the risk was not time-dependent. Analyzing these associations on the basis of asthma defined from use of inhaled...

  16. Gene-gun DNA vaccination aggravates respiratory syncytial virus-induced pneumonitis

    DEFF Research Database (Denmark)

    Bartholdy, Christina; Olszewska, Wieslawa; Stryhn, Anette

    2004-01-01

    elicited with recombinant vaccinia virus expressing the complete RSV M2 protein, but stronger than those induced by a similar DNA construct without the beta2m gene. DNA vaccination led to enhanced pulmonary disease after RSV challenge, with increased weight loss and cell recruitment to the lung. Depletion......A CD8+ T-cell memory response to respiratory syncytial virus (RSV) was generated by using a DNA vaccine construct encoding the dominant Kd-restricted epitope from the viral transcription anti-terminator protein M2 (M2(82-90)), linked covalently to human beta2-microglobulin (beta2m). Cutaneous gene...... of CD8+ T cells reduced, but did not abolish, enhancement of disease. Mice vaccinated with a construct encoding a class I-restricted lymphocytic choriomeningitis virus epitope and beta2m suffered more severe weight loss after RSV infection than unvaccinated RSV-infected mice, although RSV-specific CD8...

  17. Human metapneumovirus and respiratory syncytial virus in hospitalized danish children with acute respiratory tract infection

    DEFF Research Database (Denmark)

    von Linstow, Marie-Louise; Larsen, Hans Henrik; Eugen-Olsen, Jesper

    2004-01-01

    The newly discovered human metapneumovirus (hMPV) has been shown to be associated with respiratory illness. We determined the frequencies and clinical features of hMPV and respiratory syncytial virus (RSV) infections in 374 Danish children with 383 episodes of acute respiratory tract infection...... children 1-6 months of age. Asthmatic bronchitis was diagnosed in 66.7% of hMPV and 10.6% of RSV-infected children (p infected children required respiratory support. hMPV is present in young.......6%) ARTI episodes by real-time reverse transcription-polymerase chain reaction using primers targeting the hMPV N gene and the RSV L gene. Two children were co-infected with hMPV and RSV. They were excluded from statistical analysis. Hospitalization for ARTI caused by hMPV was restricted to very young...

  18. Respiratory syncytial virus infection facilitates acute colonization of Pseudomonas aeruginosa in mice

    DEFF Research Database (Denmark)

    de Vrankrijker, Angélica M M; Wolfs, Tom F W; Ciofu, Oana

    2009-01-01

    virus infections in facilitating colonization and infection with P. aeruginosa. A study was undertaken to determine whether respiratory syncytial virus (RSV) infection could facilitate the initiation of an acute infection with P. aeruginosa in vivo. Balb/c mice were infected intranasally with P......Pseudomonas aeruginosa causes opportunistic infections in immunocompromised individuals and patients ventilated mechanically and is the major pathogen in patients with cystic fibrosis, in which it causes chronic infections. Epidemiological, in vitro and animal data suggest a role for respiratory....... These results suggest that RSV can facilitate the initiation of acute P. aeruginosa infection without the RSV infection being clinically apparent. This could have implications for treatment strategies to prevent opportunistic P. aeruginosa lung infection....

  19. The influence of diurnal temperature range on the incidence of respiratory syncytial virus in Japan.

    Science.gov (United States)

    Onozuka, D

    2015-03-01

    The incidence of respiratory syncytial virus (RSV) has been reported to exhibit seasonal variation. However, the impact of diurnal temperature range (DTR) on RSV has not been investigated. After acquiring data related to cases of RSV and weather parameters of DTR in Fukuoka, Japan, between 2006 and 2012, we used negative binomial generalized linear models and distributed lag nonlinear models to assess the possible relationship between DTR and RSV cases, adjusting for confounding factors. Our analysis revealed that the weekly number of RSV cases increased with a relative risk of 3·30 (95% confidence interval 1·65-6·60) for every 1°C increase in DTR. Our study provides quantitative evidence that the number of RSV cases increased significantly with increasing DTR. We suggest that preventive measures for limiting the spread of RSV should be considered during extended periods of high DTR.

  20. Establishing Correlates of Protection for Vaccine Development: Considerations for the Respiratory Syncytial Virus Vaccine Field.

    Science.gov (United States)

    Kulkarni, Prasad S; Hurwitz, Julia L; Simões, Eric A F; Piedra, Pedro A

    2018-03-01

    Correlates of protection (CoPs) can play a significant role in vaccine development by assisting the selection of vaccine candidates for clinical trials, supporting clinical trial design and implementation, and simplifying tests of vaccine modifications. Because of this important role in vaccine development, it is essential that CoPs be defined by well-designed immunogenicity and efficacy studies, with attention paid to benefits and limitations. The respiratory syncytial virus (RSV) field is unique in that a great deal of information about the humoral response is available from basic research and clinical studies. Polyclonal and monoclonal antibodies have been used routinely in the clinic to protect vulnerable infants from infection, providing a wealth of information about correlations between neutralizing antibodies and disease prevention. Considerations for the establishment of future CoPs to support RSV vaccine development in different populations are therefore discussed.

  1. A Two-Dimensional Human Minilung System (Model for Respiratory Syncytial Virus Infections

    Directory of Open Access Journals (Sweden)

    Esmeralda Magro-Lopez

    2017-12-01

    Full Text Available Human respiratory syncytial virus (HRSV is a major cause of serious pediatric respiratory diseases that lacks effective vaccine or specific therapeutics. Although our understanding about HRSV biology has dramatically increased during the last decades, the need for adequate models of HRSV infection is compelling. We have generated a two-dimensional minilung from human embryonic stem cells (hESCs. The differentiation protocol yielded at least six types of lung and airway cells, although it is biased toward the generation of distal cells. We show evidence of HRSV replication in lung cells, and the induction of innate and proinflammatory responses, thus supporting its use as a model for the study of HRSV–host interactions.

  2. Extensive sequence divergence among bovine respiratory syncytial viruses isolated during recurrent outbreaks in closed herds

    DEFF Research Database (Denmark)

    Larsen, Lars Erik; Tjørnehøj, Kirsten; Viuff, B.

    2000-01-01

    and veal calf production units) in different years and from all confirmed outbreaks in Denmark within a short period. The results showed that identical viruses were isolated within a herd during outbreaks and that viruses from recurrent infections varied by up to 11% in sequence even in closed herds......The nucleotides coding for the extracellular part of the G glycoprotein and the full SH protein of bovine respiratory syncytial virus (BRSV) were sequenced from viruses isolated from numerous outbreaks of BRSV infection. The isolates included viruses isolated from the same herd (closed dairy farms....... It is possible that a quasispecies variant swarm of BRSV persisted in some of the calves in each herd and that a new and different highly fit virus type (master and consensus sequence) became dominant and spread from a single animal in connection with each new outbreak. Based on the high level of diversity...

  3. Systemic signature of the lung response to respiratory syncytial virus infection.

    Directory of Open Access Journals (Sweden)

    Jeroen L A Pennings

    Full Text Available Respiratory Syncytial Virus is a frequent cause of severe bronchiolitis in children. To improve our understanding of systemic host responses to RSV, we compared BALB/c mouse gene expression responses at day 1, 2, and 5 during primary RSV infection in lung, bronchial lymph nodes, and blood. We identified a set of 53 interferon-associated and innate immunity genes that give correlated responses in all three murine tissues. Additionally, we identified blood gene signatures that are indicative of acute infection, secondary immune response, and vaccine-enhanced disease, respectively. Eosinophil-associated ribonucleases were characteristic for the vaccine-enhanced disease blood signature. These results indicate that it may be possible to distinguish protective and unfavorable patient lung responses via blood diagnostics.

  4. Control apparatus for radioactive contamination of the filtering device adapted on the protection apparatus of the respiratory tracts (1961); Appareil de controle de la contamination radioactive des dispositifs filtrants adaptes sur les appareils de protection des voies respiratoires (1961)

    Energy Technology Data Exchange (ETDEWEB)

    Dujancourt, S; Roche, J [Commissariat a l' Energie Atomique, Centre de Production de Plutonium, Marcoule (France). Centre d' Etudes Nucleaires

    1961-07-01

    That apparatus allows to detect and localize the radioactive contamination of the mask cartridge, for alpha, beta and gamma radiations, concerning external contamination, and for beta and gamma radiations, concerning internal contamination. It consists of lead coffin, in which the cartridge is inserted for control. Halogen counters are in contact with it. Operation conditions (Geiger or proportional) and their position on regard to the cartridge are controlled from outside. A sealer counts the pulses, given by the different counters. (authors) [French] Cet appareil permet de detecter et de localiser la contamination radioactive de cartouches filtrantes de masques, en {alpha}, {beta} et {gamma}, en ce qui concerne la contamination exterieure, et en {beta} et {gamma} en ce qui concerne la contamination interieure. Il est constitue par un coffre en plomb dans lequel est introduite la cartouche a controler. Des compteurs halogenes sont au contact de celle-ci. Leur regime de fonctionnement (Geiger ou proportionnel) et leur position par rapport a la cartouche sont commandes de l'exterieur. Une echelle de comptage compte les impulsions donnees par les differents compteurs. (auteurs)

  5. ¡París!

    Directory of Open Access Journals (Sweden)

    Beatriz Caballero

    2003-01-01

    Full Text Available El día no le alcanzaba para caminarlo. Conocía cada puente, cada calle,plaza, museo, rincón, iglesia, café, y la mesa con el mejor ángulo para mirar siempre una iglesia, ojalá Saint-Germain-des-Pres, o Notre-Dame. Siempre contaba la impresión que le había causado a Bolívar ver allí cuando el papa coronó a Napoleón. Él se iba para la oficina todos los días, Luis a un taller a pintar, Antonio a estudiar ciencias políticas, yo al colegio y mamá hacía las cosas prácticas. Aprendíamos francés todos al tiempo y por la noche nos contábamos lo nuevo que cada uno había aprendido. Mamá después, cuando ya se quería volver, decía que París nos había maleado a todos. Estaba en pleno furor el cine francés de la "nueva ola", pero ella sólo me llevaba a ver películas de vaqueros pues no se fiaba de la clasificación de los periódicos.

  6. Contribution to the study of the reduction of sulfate by the yolk sac of the chicken embryo; Contribution a l'etude de la reduction du sulfate par le sac vitellin de l'embryon de poulet

    Energy Technology Data Exchange (ETDEWEB)

    Bourgeois, Claude

    1958-11-15

    des oxydations respiratoires. L'inhibition par le cyanure de potassium, qui n'est pas totale, meme a la concentration de 5.10{sup -3} M, et qui est nettement moins marquee que l'inhibition respiratoire simultanee correspond sans doute egalement a une action sur la synthese de donateurs d'hydrogene necessaires a la reduction du sulfate. La reduction du sulfate en sulfite par l'embryon de poulet est tres differente de la reduction catabolique realisee par Desulfovibrio; elle s'apparente par sa signification anabolique a la reduction realisee par d'autres bacteries et par les vegetaux.

  7. C9.A/14 steelwork joints de poutres par plaque frontale : assemblages par gousset

    CERN Document Server

    2015-01-01

    Les Tables de résistances ultimes des assemblages boulonnés par plaque frontale et par gousset, complétées par une description des modèles de calcul et des exemples d’application, ont pour but de faciliter la tâche de l'ingénieur et du constructeur. Cette première partie C9.A/14 contient les chapitres suivants: - Joints de poutres par plaque frontale en acier S235 et S355 - Assemblages par gousset en acier S235 et S355 Les Tables contiennent des données relatives à la géométrie ainsi que les valeurs de calcul correspondantes des résistances ultimes des assemblages ; elles remplacent le chapitre « Assemblages par plaques frontales et boulons HR » des anciennes Tables C9.1 de 1983 / 2002. Le calcul de ces assemblages par plaque frontale est basé sur les hypothèses du modèle de la méthode des composants décrite dans la norme SN EN 1993-1-8. Les vérifications sont effectuées selon la norme SIA 263:2013. Les assemblages par gousset remplacent les assemblages par double cornière, (telle...

  8. Curcumin modified silver nanoparticles for highly efficient inhibition of respiratory syncytial virus infection

    Science.gov (United States)

    Yang, Xiao Xi; Li, Chun Mei; Huang, Cheng Zhi

    2016-01-01

    Interactions between nanoparticles and viruses have attracted increasing attention due to the antiviral activity of nanoparticles and the resulting possibility to be employed as biomedical interventions. In this contribution, we developed a very simple route to prepare uniform and stable silver nanoparticles (AgNPs) with antiviral properties by using curcumin, which is a member of the ginger family isolated from rhizomes of the perennial herb Curcuma longa and has a wide range of biological activities like antioxidant, antifungal, antibacterial and anti-inflammatory effects, and acts as reducing and capping agents in this synthetic route. The tissue culture infectious dose (TCID50) assay showed that the curcumin modified silver nanoparticles (cAgNPs) have a highly efficient inhibition effect against respiratory syncytial virus (RSV) infection, giving a decrease of viral titers about two orders of magnitude at the concentration of cAgNPs under which no toxicity was found to the host cells. Mechanism investigations showed that cAgNPs could prevent RSV from infecting the host cells by inactivating the virus directly, indicating that cAgNPs are a novel promising efficient virucide for RSV.Interactions between nanoparticles and viruses have attracted increasing attention due to the antiviral activity of nanoparticles and the resulting possibility to be employed as biomedical interventions. In this contribution, we developed a very simple route to prepare uniform and stable silver nanoparticles (AgNPs) with antiviral properties by using curcumin, which is a member of the ginger family isolated from rhizomes of the perennial herb Curcuma longa and has a wide range of biological activities like antioxidant, antifungal, antibacterial and anti-inflammatory effects, and acts as reducing and capping agents in this synthetic route. The tissue culture infectious dose (TCID50) assay showed that the curcumin modified silver nanoparticles (cAgNPs) have a highly efficient inhibition

  9. Protease-activated receptor (PAR)-2 is required for PAR-1 signalling in pulmonary fibrosis

    NARCIS (Netherlands)

    Lin, Cong; von der Thüsen, Jan; Daalhuisen, Joost; ten Brink, Marieke; Crestani, Bruno; van der Poll, Tom; Borensztajn, Keren; Spek, C. Arnold

    2015-01-01

    Idiopathic pulmonary fibrosis is the most devastating diffuse fibrosing lung disease of unknown aetiology. Compelling evidence suggests that both protease-activated receptor (PAR)-1 and PAR-2 participate in the development of pulmonary fibrosis. Previous studies have shown that bleomycin-induced

  10. The respiratory syncytial virus polymerase has multiple RNA synthesis activities at the promoter.

    Directory of Open Access Journals (Sweden)

    Sarah L Noton

    Full Text Available Respiratory syncytial virus (RSV is an RNA virus in the Family Paramyxoviridae. Here, the activities performed by the RSV polymerase when it encounters the viral antigenomic promoter were examined. RSV RNA synthesis was reconstituted in vitro using recombinant, isolated polymerase and an RNA oligonucleotide template representing nucleotides 1-25 of the trailer complement (TrC promoter. The RSV polymerase was found to have two RNA synthesis activities, initiating RNA synthesis from the +3 site on the promoter, and adding a specific sequence of nucleotides to the 3' end of the TrC RNA using a back-priming mechanism. Examination of viral RNA isolated from RSV infected cells identified RNAs initiated at the +3 site on the TrC promoter, in addition to the expected +1 site, and showed that a significant proportion of antigenome RNAs contained specific nucleotide additions at the 3' end, demonstrating that the observations made in vitro reflected events that occur during RSV infection. Analysis of the impact of the 3' terminal extension on promoter activity indicated that it can inhibit RNA synthesis initiation. These findings indicate that RSV polymerase-promoter interactions are more complex than previously thought and suggest that there might be sophisticated mechanisms for regulating promoter activity during infection.

  11. Respiratory syncytial virus infection enhances Pseudomonas aeruginosa biofilm growth through dysregulation of nutritional immunity.

    Science.gov (United States)

    Hendricks, Matthew R; Lashua, Lauren P; Fischer, Douglas K; Flitter, Becca A; Eichinger, Katherine M; Durbin, Joan E; Sarkar, Saumendra N; Coyne, Carolyn B; Empey, Kerry M; Bomberger, Jennifer M

    2016-02-09

    Clinical observations link respiratory virus infection and Pseudomonas aeruginosa colonization in chronic lung disease, including cystic fibrosis (CF) and chronic obstructive pulmonary disease. The development of P. aeruginosa into highly antibiotic-resistant biofilm communities promotes airway colonization and accounts for disease progression in patients. Although clinical studies show a strong correlation between CF patients' acquisition of chronic P. aeruginosa infections and respiratory virus infection, little is known about the mechanism by which chronic P. aeruginosa infections are initiated in the host. Using a coculture model to study the formation of bacterial biofilm formation associated with the airway epithelium, we show that respiratory viral infections and the induction of antiviral interferons promote robust secondary P. aeruginosa biofilm formation. We report that the induction of antiviral IFN signaling in response to respiratory syncytial virus (RSV) infection induces bacterial biofilm formation through a mechanism of dysregulated iron homeostasis of the airway epithelium. Moreover, increased apical release of the host iron-binding protein transferrin during RSV infection promotes P. aeruginosa biofilm development in vitro and in vivo. Thus, nutritional immunity pathways that are disrupted during respiratory viral infection create an environment that favors secondary bacterial infection and may provide previously unidentified targets to combat bacterial biofilm formation.

  12. ACUTE RESPIRATORY SYNCYTIAL VIRUS INFECTION IN CHILDREN IN THE AGE ASPECT

    Directory of Open Access Journals (Sweden)

    V. B. Rovny

    2013-01-01

    Full Text Available The clinical features of laboratory-confirmed acute respiratory syncytial virus infection (ARSVI are described in 221 children of the age from 1 month to 5 years. Febrile fever has been recorded in 76% of patients with ARSVI, and significantly more often in children in the second year of life (92%, but the difference in the temerature or duration has not been found. 98% of children have had symptoms of the lower respiratory tract lesions. The most common ARSVI manifestations in the patients of the first year of life were obstructive diseases of the lower respiratory tract (obstructive bronchitis in 53% and bronchiolitis in 11% of children, in the patients of the second year of life — pneumonia (28%, p < 0,05 and catarrhal otitis (26%; p < 0,05. Bronchial obstruction syndrome in children of the first year of life was characterized by the significantly higher frequency (73% and the maximal duration (9,7 ± 1,08 days. The largest number of cases of the severe respiratory failure has been recorded among patients of the second year of life (3 degree of respiratory failure in 22% of patients, p < 0,05.

  13. Respiratory syncytial virus M2-1 protein induces the activation of nuclear factor kappa B

    Energy Technology Data Exchange (ETDEWEB)

    Reimers, Kerstin [Klinik fuer Plastische, Hand-und Wiederherstellungschirurgie, Podbielskistrasse 380, D-30659 Hannover (Germany); Buchholz, Katja [Institut fuer Medizinische Mikrobiologie, Otto-von-Guericke-Universitaet Magdeburg, Leipzigerstrasse 44, D-39120 Magdeburg (Germany); Werchau, Hermann [Institut fuer Medizinische Mikrobiologie, Otto-von-Guericke-Universitaet Magdeburg, Leipzigerstrasse 44, D-39120 Magdeburg (Germany)

    2005-01-20

    Respiratory syncytial virus (RSV) induces the production of a number of cytokines and chemokines by activation of nuclear factor kappa B (NF-{kappa}B). The activation of NF-{kappa}B has been shown to depend on viral replication in the infected cells. In this study, we demonstrate that expression of RSV M2-1 protein, a transcriptional processivity and anti-termination factor, is sufficient to activate NF-{kappa}B in A549 cells. Electromobility shift assays show increased NF-{kappa}B complexes in the nuclei of M2-1-expressing cells. M2-1 protein is found in nuclei of M2-1-expressing cells and in RSV-infected cells. Co-immunoprecipitations of nuclear extracts of M2-1-expressing cells and of RSV-infected cells revealed an association of M2-1 with Rel A protein. Furthermore, the activation of NF-{kappa}B depends on the C-terminus of the RSV M2-1 protein, as shown by NF-{kappa}B-induced gene expression of a reporter gene construct.

  14. Down syndrome as risk factor for respiratory syncytial virus hospitalization: A prospective multicenter epidemiological study.

    Science.gov (United States)

    Sánchez-Luna, Manuel; Medrano, Constancio; Lirio, Julián

    2017-03-01

    Respiratory syncytial virus (RSV) infection in childhood, particularly in premature infants, is associated with significant morbidity and mortality. To compare the hospitalization rates due to RSV infection and severity of disease between infants with and without Down syndrome (DS) born at term and without other associated risk factors for severe RSV infection. In a prospective multicentre epidemiological study, 93 infants were included in the DS cohort and 68 matched by sex and data of birth (±1 week) and were followed up to 1 year of age and during a complete RSV season. The hospitalization rate for all acute respiratory infection was significantly higher in the DS cohort than in the non-DS cohort (44.1% vs 7.7%, P<.0001). Hospitalizations due to RSV were significantly more frequent in the DH cohort than in the non-DS cohort (9.7% vs 1.5%, P=.03). RSV prophylaxis was recorded in 33 (35.5%) infants with DS. The rate of hospitalization according to presence or absence of RSV immunoprophylaxis was 3.0% vs 15%, respectively. Infants with DS showed a higher rate of hospitalization due to acute lower respiratory tract infection and RSV infection compared to non-DS infants. Including DS infants in recommendations for immunoprophylaxis of RSV disease should be considered. © 2016 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

  15. Memory CD8 T cells mediate severe immunopathology following respiratory syncytial virus infection.

    Directory of Open Access Journals (Sweden)

    Megan E Schmidt

    2018-01-01

    Full Text Available Memory CD8 T cells can provide protection from re-infection by respiratory viruses such as influenza and SARS. However, the relative contribution of memory CD8 T cells in providing protection against respiratory syncytial virus (RSV infection is currently unclear. To address this knowledge gap, we utilized a prime-boost immunization approach to induce robust memory CD8 T cell responses in the absence of RSV-specific CD4 T cells and antibodies. Unexpectedly, RSV infection of mice with pre-existing CD8 T cell memory led to exacerbated weight loss, pulmonary disease, and lethal immunopathology. The exacerbated disease in immunized mice was not epitope-dependent and occurred despite a significant reduction in RSV viral titers. In addition, the lethal immunopathology was unique to the context of an RSV infection as mice were protected from a normally lethal challenge with a recombinant influenza virus expressing an RSV epitope. Memory CD8 T cells rapidly produced IFN-γ following RSV infection resulting in elevated protein levels in the lung and periphery. Neutralization of IFN-γ in the respiratory tract reduced morbidity and prevented mortality. These results demonstrate that in contrast to other respiratory viruses, RSV-specific memory CD8 T cells can induce lethal immunopathology despite mediating enhanced viral clearance.

  16. Phosphorylation of human respiratory syncytial virus P protein at serine 54 regulates viral uncoating

    International Nuclear Information System (INIS)

    Asenjo, Ana; Gonzalez-Armas, Juan C.; Villanueva, Nieves

    2008-01-01

    The human respiratory syncytial virus (HRSV) structural P protein, phosphorylated at serine (S) and threonine (T) residues, is a co-factor of viral RNA polymerase. The phosphorylation of S54 is controlled by the coordinated action of two cellular enzymes: a lithium-sensitive kinase, probably glycogen synthetase kinase (GSK-3) β and protein phosphatase 2A (PP2A). Inhibition of lithium-sensitive kinase, soon after infection, blocks the viral growth cycle by inhibiting synthesis and/or accumulation of viral RNAs, proteins and extracellular particles. P protein phosphorylation at S54 is required to liberate viral ribonucleoproteins (RNPs) from M protein, during the uncoating process. Kinase inhibition, late in infection, produces a decrease in genomic RNA and infectious viral particles. LiCl, intranasally applied to mice infected with HRSV A2 strain, reduces the number of mice with virus in their lungs and the virus titre. Administration of LiCl to humans via aerosol should prevent HRSV infection, without secondary effects

  17. Respiratory Syncytial Virus Disease Is Mediated by Age-Variable IL-33.

    Directory of Open Access Journals (Sweden)

    Jordy Saravia

    2015-10-01

    Full Text Available Respiratory syncytial virus (RSV is the most common cause of infant hospitalizations and severe RSV infections are a significant risk factor for childhood asthma. The pathogenic mechanisms responsible for RSV induced immunopathophysiology remain elusive. Using an age-appropriate mouse model of RSV, we show that IL-33 plays a critical role in the immunopathogenesis of severe RSV, which is associated with higher group 2 innate lymphoid cells (ILC2s specifically in neonates. Infection with RSV induced rapid IL-33 expression and an increase in ILC2 numbers in the lungs of neonatal mice; this was not observed in adult mice. Blocking IL-33 with antibodies or using an IL-33 receptor knockout mouse during infection was sufficient to inhibit RSV immunopathogenesis (i.e., airway hyperresponsiveness, Th2 inflammation, eosinophilia, and mucus hyperproduction; whereas administration of IL-33 to adult mice during RSV infection was sufficient to induce RSV disease. Additionally, elevated IL-33 and IL-13 were observed in nasal aspirates from infants hospitalized with RSV; these cytokines declined during convalescence. In summary, IL-33 is necessary, either directly or indirectly, to induce ILC2s and the Th2 biased immunopathophysiology observed following neonatal RSV infection. This study provides a mechanism involving IL-33 and ILC2s in RSV mediated human asthma.

  18. Transmission of Human Respiratory Syncytial Virus in the Immunocompromised Ferret Model

    Science.gov (United States)

    de Waal, Leon; Smits, Saskia L.; Veldhuis Kroeze, Edwin J. B.; van Amerongen, Geert; Pohl, Marie O.; Osterhaus, Albert D. M. E.; Stittelaar, Koert J.

    2018-01-01

    Human respiratory syncytial virus (HRSV) causes substantial morbidity and mortality in vulnerable patients, such as the very young, the elderly, and immunocompromised individuals of any age. Nosocomial transmission of HRSV remains a serious challenge in hospital settings, with intervention strategies largely limited to infection control measures, including isolation of cases, high standards of hand hygiene, cohort nursing, and use of personal protective equipment. No vaccines against HRSV are currently available, and treatment options are largely supportive care and expensive monoclonal antibody or antiviral therapy. The limitations of current animal models for HRSV infection impede the development of new preventive and therapeutic agents, and the assessment of their potential for limiting HRSV transmission, in particular in nosocomial settings. Here, we demonstrate the efficient transmission of HRSV from immunocompromised ferrets to both immunocompromised and immunocompetent contact ferrets, with pathological findings reproducing HRSV pathology in humans. The immunocompromised ferret-HRSV model represents a novel tool for the evaluation of intervention strategies against nosocomial transmission of HRSV. PMID:29301313

  19. Nucleic acid-based vaccines targeting respiratory syncytial virus: Delivering the goods.

    Science.gov (United States)

    Smith, Trevor R F; Schultheis, Katherine; Broderick, Kate E

    2017-11-02

    Respiratory syncytial virus (RSV) is a massive medical burden on a global scale. Infants, children and the elderly represent the vulnerable populations. Currently there is no approved vaccine to protect against the disease. Vaccine development has been hindered by several factors including vaccine enhanced disease (VED) associated with formalin-inactivated RSV vaccines, inability of target populations to raise protective immune responses after vaccination or natural viral infection, and a lack of consensus concerning the most appropriate virus-associated target antigen. However, with recent advances in the molecular understanding of the virus, and design of highly characterized vaccines with enhanced immunogenicity there is new belief a RSV vaccine is possible. One promising approach is nucleic acid-based vaccinology. Both DNA and mRNA RSV vaccines are showing promising results in clinically relevant animal models, supporting their transition into humans. Here we will discuss this strategy to target RSV, and the ongoing studies to advance the nucleic acid vaccine platform as a viable option to protect vulnerable populations from this important disease.

  20. Comparative epidemiology of human metapneumovirus- and respiratory syncytial virus-associated hospitalizations in Guatemala

    Science.gov (United States)

    McCracken, John P; Arvelo, Wences; Ortíz, José; Reyes, Lissette; Gray, Jennifer; Estevez, Alejandra; Castañeda, Oscar; Langley, Gayle; Lindblade, Kim A

    2014-01-01

    Background Human metapneumovirus (HMPV) is an important cause of acute respiratory infections (ARI), but little is known about how it compares with respiratory syncytial virus (RSV) in Central America. Objectives In this study, we describe hospitalized cases of HMPV- and RSV-ARI in Guatemala. Methods We conducted surveillance at three hospitals (November 2007–December 2012) and tested nasopharyngeal and oropharyngeal swab specimens for HMPV and RSV using real-time reverse transcription-polymerase chain reaction. We calculated incidence rates, and compared the epidemiology and outcomes of HMPV-positive versus RSV-positive and RSV-HMPV-negative cases. Results We enrolled and tested specimens from 6288 ARI cases; 596 (9%) were HMPV-positive and 1485 (24%) were RSV-positive. We observed a seasonal pattern of RSV but not HMPV. The proportion HMPV-positive was low (3%) and RSV-positive high (41%) for age Guatemala, but HMPV hospitalizations are less frequent than RSV and, in young children, less severe than other etiologies. Preventive interventions should take into account the wide variation in incidence by age and unpredictable timing of incidence peaks. PMID:24761765

  1. Severity of viral coinfection in hospitalized infants with respiratory syncytial virus infection.

    Science.gov (United States)

    De Paulis, Milena; Gilio, Alfredo Elias; Ferraro, Alexandre Archanjo; Ferronato, Angela Esposito; do Sacramento, Patrícia Rossi; Botosso, Viviane Fongaro; Oliveira, Danielle Bruna Leal de; Marinheiro, Juliana Cristina; Hársi, Charlotte Marianna; Durigon, Edison Luiz; Vieira, Sandra Elisabete

    2011-01-01

    To compare the severity of single respiratory syncytial virus (RSV) infections with that of coinfections. A historical cohort was studied, including hospitalized infants with acute RSV infection. Nasopharyngeal aspirate samples were collected from all patients to detect eight respiratory viruses using molecular biology techniques. The following outcomes were analyzed: duration of hospitalization and of oxygen therapy, intensive care unit admission and need of mechanical ventilation. Results were adjusted for confounding factors (prematurity, age and breastfeeding). A hundred and seventy six infants with bronchiolitis and/or pneumonia were included in the study. Their median age was 4.5 months. A hundred and twenty one had single RSV infection and 55 had coinfections (24 RSV + adenovirus, 16 RSV + human metapneumovirus and 15 other less frequent viral associations). The four severity outcomes under study were similar in the group with single RSV infection and in the coinfection groups, independently of what virus was associated with RSV. Virus coinfections do not seem to affect the prognosis of hospitalized infants with acute RSV infection.

  2. Rapid antigen detection test for respiratory syncytial virus diagnosis as a diagnostic tool

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    Flávio da Silva Mesquita

    2017-05-01

    Full Text Available Objective: The aim of this study was to evaluate the QuickVue® RSV Test Kit (QUIDEL Corp, CA, USA as a screening tool for respiratory syncytial virus in children with acute respiratory disease in comparison with the indirect immunofluorescence assay as gold standard. In Brazil, rapid antigen detection tests for respiratory syncytial virus are not routinely utilized as a diagnostic tool, except for the diagnosis of dengue and influenza. Methods: The authors retrospectively analyzed 486 nasopharyngeal aspirate samples from children under age 5 with acute respiratory infection, between December 2013 and August 2014, the samples were analyzed by indirect immunofluorescence assay and QuickVue® RSV Test kit. Samples with discordant results were analyzed by real time PCR and nucleotide sequencing. Results: From 313 positive samples by immunofluorescence assays, 282 (90% were also positive by the rapid antigen detection test, two were positive only by rapid antigen detection test, 33 were positive only by immunofluorescence assays, and 171 were positive by both methods. The 35 samples with discordant results were analyzed by real time PCR; the two samples positive only by rapid antigen detection test and the five positive only by immunofluorescence assays were also positive by real time PCR. There was no relation between the negativity by QuickVue® RSV Test and viral load or specific strain. The QuickVue® RSV Test showed sensitivity of 90%, specificity of 98.8%, predictive positive value of 99.3%, and negative predictive value of 94.6%, with accuracy of 93.2% and agreement κ index of 0.85 in comparison to immunofluorescence assay. Conclusions: This study demonstrated that the QuickVue® RSV Test Kit can be effective in early detection of Respiratory syncytial virus in nasopharyngeal aspirate and is reliable for use as a diagnostic tool in pediatrics. Resumo: Objetivo: Avaliar o teste QuickVue® RSV Test Kit (QUIDEL Corp, CA, EUA para o diagn

  3. Respiratory Syncytial Virus (RSV RNA loads in peripheral blood correlates with disease severity in mice

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    Torres Juan

    2010-09-01

    Full Text Available Abstract Background Respiratory Syncytial Virus (RSV infection is usually restricted to the respiratory epithelium. Few studies have documented the presence of RSV in the systemic circulation, however there is no consistent information whether virus detection in the blood correlates with disease severity. Methods Balb/c mice were inoculated with live RSV, heat-inactivated RSV or medium. A subset of RSV-infected mice was treated with anti-RSV antibody 72 h post-inoculation. RSV RNA loads were measured by PCR in peripheral blood from day 1-21 post-inoculation and were correlated with upper and lower respiratory tract viral loads, the systemic cytokine response, lung inflammation and pulmonary function. Immunohistochemical staining was used to define the localization of RSV antigens in the respiratory tract and peripheral blood. Results RSV RNA loads were detected in peripheral blood from day 1 to 14 post-inoculation, peaked on day 5 and significantly correlated with nasal and lung RSV loads, airway obstruction, and blood CCL2 and CXCL1 expression. Treatment with anti-RSV antibody reduced blood RSV RNA loads and improved airway obstruction. Immunostaining identified RSV antigens in alveolar macrophages and peripheral blood monocytes. Conclusions RSV RNA was detected in peripheral blood upon infection with live RSV, followed a time-course parallel to viral loads assessed in the respiratory tract and was significantly correlated with RSV-induced airway disease.

  4. Interaction between human BAP31 and respiratory syncytial virus small hydrophobic (SH) protein

    International Nuclear Information System (INIS)

    Li, Yan; Jain, Neeraj; Limpanawat, Suweeraya; To, Janet; Quistgaard, Esben M.; Nordlund, Par; Thanabalu, Thirumaran; Torres, Jaume

    2015-01-01

    The small hydrophobic (SH) protein is a short channel-forming polypeptide encoded by the human respiratory syncytial virus (hRSV). Deletion of SH protein leads to the viral attenuation in mice and primates, and delayed apoptosis in infected cells. We have used a membrane-based yeast two-hybrid system (MbY2H) and a library from human lung cDNA to detect proteins that bind SH protein. This led to the identification of a membrane protein, B-cell associated protein 31 (BAP31). Transfected SH protein co-localizes with transfected BAP31 in cells, and pulls down endogenous BAP31. Titration of purified C-terminal endodomain of BAP31 against isotopically labeled SH protein in detergent micelles suggests direct interaction between the two proteins. Given the key role of BAP31 in protein trafficking and its critical involvement in pro- and anti-apoptotic pathways, this novel interaction may constitute a potential drug target. - Highlights: • A yeast two-hybrid system (MbY2H) detected BAP31 as a binder of RSV SH protein. • Transfected SH and BAP31 co-localize in lung epithelial cells. • Endogenous BAP31 is pulled down by RSV SH protein. • BAP31 endodomain interacts with the N-terminal α-helix of SH protein in micelles. • This interaction is proposed to be a potential drug target

  5. Interaction between human BAP31 and respiratory syncytial virus small hydrophobic (SH) protein

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    Li, Yan; Jain, Neeraj; Limpanawat, Suweeraya; To, Janet [School of Biological Sciences, Nanyang Technological University, 637551 (Singapore); Quistgaard, Esben M. [Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm (Sweden); Nordlund, Par [School of Biological Sciences, Nanyang Technological University, 637551 (Singapore); Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm (Sweden); Thanabalu, Thirumaran [School of Biological Sciences, Nanyang Technological University, 637551 (Singapore); Torres, Jaume, E-mail: jtorres@ntu.edu.sg [School of Biological Sciences, Nanyang Technological University, 637551 (Singapore)

    2015-08-15

    The small hydrophobic (SH) protein is a short channel-forming polypeptide encoded by the human respiratory syncytial virus (hRSV). Deletion of SH protein leads to the viral attenuation in mice and primates, and delayed apoptosis in infected cells. We have used a membrane-based yeast two-hybrid system (MbY2H) and a library from human lung cDNA to detect proteins that bind SH protein. This led to the identification of a membrane protein, B-cell associated protein 31 (BAP31). Transfected SH protein co-localizes with transfected BAP31 in cells, and pulls down endogenous BAP31. Titration of purified C-terminal endodomain of BAP31 against isotopically labeled SH protein in detergent micelles suggests direct interaction between the two proteins. Given the key role of BAP31 in protein trafficking and its critical involvement in pro- and anti-apoptotic pathways, this novel interaction may constitute a potential drug target. - Highlights: • A yeast two-hybrid system (MbY2H) detected BAP31 as a binder of RSV SH protein. • Transfected SH and BAP31 co-localize in lung epithelial cells. • Endogenous BAP31 is pulled down by RSV SH protein. • BAP31 endodomain interacts with the N-terminal α-helix of SH protein in micelles. • This interaction is proposed to be a potential drug target.

  6. Respiratory syncytial virus in adults with severe acute respiratory illness in a high HIV prevalence setting.

    Science.gov (United States)

    Moyes, Jocelyn; Walaza, Sibongile; Pretorius, Marthi; Groome, Michelle; von Gottberg, Anne; Wolter, Nicole; Haffejee, Sumayya; Variava, Ebrahim; Cohen, Adam L; Tempia, Stefano; Kahn, Kathleen; Dawood, Halima; Venter, Marietjie; Cohen, Cheryl; Madhi, Shabir A

    2017-10-01

    There are limited data on the epidemiology of respiratory syncytial virus (RSV) illness in HIV-infected adults or the elderly in Africa. We studied the epidemiology of RSV-associated severe acute respiratory illness (SARI) hospitalizations in adults in South Africa from 2009 through 2013. Individuals admitted to sentinel surveillance hospitals were investigated by respiratory tract swabs for RSV, using a multiplex real-time polymerase chain reaction assay. The incidence of RSV-associated SARI was calculated for the one site with population denominators. Of 7796 participants investigated, 329 (4%) tested positive for RSV. On multivariable analysis, HIV-infected individuals with RSV-associated SARI had greater odds of being in the age groups 18-44 and 45-64 years (odd ratios (OR) 26.3; 95% confidence interval (CI) 6.2-112.1 and OR 11.4; 95% CI 2.6-50.0) compared with those ≥65 years and being female (OR 2.7; 95% CI 1.4-5.4). The relative risk of hospitalization with RSV-associated SARI was 12-18 times higher in HIV infected individual compared to that of HIV-uninfected. The incidence of RSV-associated SARI was higher in HIV-infected individuals and those aged 65 years and older. Further studies are warranted to describe the disease association of RSV detected in adults with SARI. Copyright © 2017 The British Infection Association. All rights reserved.

  7. Human respiratory syncytial virus load normalized by cell quantification as predictor of acute respiratory tract infection.

    Science.gov (United States)

    Gómez-Novo, Miriam; Boga, José A; Álvarez-Argüelles, Marta E; Rojo-Alba, Susana; Fernández, Ana; Menéndez, María J; de Oña, María; Melón, Santiago

    2018-05-01

    Human respiratory syncytial virus (HRSV) is a common cause of respiratory infections. The main objective is to analyze the prediction ability of viral load of HRSV normalized by cell number in respiratory symptoms. A prospective, descriptive, and analytical study was performed. From 7307 respiratory samples processed between December 2014 to April 2016, 1019 HRSV-positive samples, were included in this study. Low respiratory tract infection was present in 729 patients (71.54%). Normalized HRSV load was calculated by quantification of HRSV genome and human β-globin gene and expressed as log10 copies/1000 cells. HRSV mean loads were 4.09 ± 2.08 and 4.82 ± 2.09 log10 copies/1000 cells in the 549 pharyngeal and 470 nasopharyngeal samples, respectively (P respiratory tract infection and 4.22 ± 2.28 log10 copies/1000 cells with upper respiratory tract infection or febrile syndrome (P < 0.05). A possible cut off value to predict LRTI evolution was tentatively established. Normalization of viral load by cell number in the samples is essential to ensure an optimal virological molecular diagnosis avoiding that the quality of samples affects the results. A high viral load can be a useful marker to predict disease progression. © 2018 Wiley Periodicals, Inc.

  8. Cholesterol is required for stability and infectivity of influenza A and respiratory syncytial viruses.

    Science.gov (United States)

    Bajimaya, Shringkhala; Frankl, Tünde; Hayashi, Tsuyoshi; Takimoto, Toru

    2017-10-01

    Cholesterol-rich lipid raft microdomains in the plasma membrane are considered to play a major role in the enveloped virus lifecycle. However, the functional role of cholesterol in assembly, infectivity and stability of respiratory RNA viruses is not fully understood. We previously reported that depletion of cellular cholesterol by cholesterol-reducing agents decreased production of human parainfluenza virus type 1 (hPIV1) particles by inhibiting virus assembly. In this study, we analyzed the role of cholesterol on influenza A virus (IAV) and respiratory syncytial virus (RSV) production. Unlike hPIV1, treatment of human airway cells with the agents did not decrease virus particle production. However, the released virions were less homogeneous in density and unstable. Addition of exogenous cholesterol to the released virions restored virus stability and infectivity. Collectively, these data indicate a critical role of cholesterol in maintaining IAV and RSV membrane structure that is essential for sustaining viral stability and infectivity. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Factors Affecting the Immunity to Respiratory Syncytial Virus: From Epigenetics to Microbiome

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    Wendy Fonseca

    2018-02-01

    Full Text Available Respiratory syncytial virus (RSV is a common pathogen that infects virtually all children by 2 years of age and is the leading cause of hospitalization of infants worldwide. While most children experience mild symptoms, some children progress to severe lower respiratory tract infection. Those children with severe disease have a much higher risk of developing childhood wheezing later in life. Many risk factors are known to result in exacerbated disease, including premature birth and early age of RSV infection, when the immune system is relatively immature. The development of the immune system before and after birth may be altered by several extrinsic and intrinsic factors that could lead to severe disease predisposition in children who do not exhibit any currently known risk factors. Recently, the role of the microbiome and the resulting metabolite profile has been an area of intense study in the development of lung disease, including viral infection and asthma. This review explores both known risk factors that can lead to severe RSV-induced disease as well as emerging topics in the development of immunity to RSV and the long-term consequences of severe infection.

  10. Respiratory syncytial virus increases lung cellular bioenergetics in neonatal C57BL/6 mice

    International Nuclear Information System (INIS)

    Alsuwaidi, Ahmed R.; Albawardi, Alia; Almarzooqi, Saeeda; Benedict, Sheela; Othman, Aws R.; Hartwig, Stacey M.; Varga, Steven M.; Souid, Abdul-Kader

    2014-01-01

    We have previously reported that lung cellular bioenergetics (cellular respiration and ATP) increased in 4–10 week-old BALB/c mice infected with respiratory syncytial virus (RSV). This study examined the kinetics and changes in cellular bioenergetics in ≤2-week-old C57BL/6 mice following RSV infection. Mice (5–14 days old) were inoculated intranasally with RSV and the lungs were examined on days 1–10 post-infection. Histopathology and electron microscopy revealed preserved pneumocyte architectures and organelles. Increased lung cellular bioenergetics was noted from days 1–10 post-infection. Cellular GSH remained unchanged. These results indicate that the increased lung cellular respiration (measured by mitochondrial O 2 consumption) and ATP following RSV infection is independent of either age or genetic background of the host. - Highlights: • RSV infection increases lung cellular respiration and ATP in neonatal C57BL/6 mice. • Increased lung cellular bioenergetics is a biomarker of RSV infection. • Lung cellular glutathione remains unchanged in RSV infection

  11. [Respiratory infections caused by respiratory syncytial virus in the adult population: description of 16 cases].

    Science.gov (United States)

    Reina, Jordi; López, Carla

    2013-08-17

    Respiratory infections of viral etiology are frequent in the adult population. Those caused by respiratory syncytial virus (RSV) are a little known entity. The aim of this study was to determine the clinical and epidemiological characteristics of adult patients with respiratory infection due to RSV. We performed a prospective study from October 2012 to March 2013 on respiratory infections caused by RSV. Viral detection was performed using a technique of reverse transcription polymerase chain reaction genomic amplification in real time. We diagnosed 16 patients, 12 (75%) requiring hospitalization. Patients were grouped into immunocompromised (7 [43.7%]) and immunocompetent cases (9 cases 56.3%]). The first group included 3 patients with HIV infection (42.8%) and 4 hematologic patients (57.2%). The second group included those who had a baseline disease, 5 cases (55.5%), and those who lacked it, 4 cases (44.4%), and did not require hospitalization. The main clinical manifestations of patients prompting them to attend the Emergency Department were cough (50%), dyspnea (43.5%), fever (25%), expectoration (25%) and flu symptoms (25%). The most frequent diagnoses at discharge were pneumonia (37.5%) and flu syndrome (31.2%). Respiratory infections caused by RSV represent a rare condition that mainly affects immunocompromised patients. The underlying pathology determines the evolution of the process, which is favorable except in cases of severe immunosuppression. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  12. Ameliorating Effect of Dietary Xylitol on Human Respiratory Syncytial Virus (hRSV) Infection.

    Science.gov (United States)

    Xu, Mei Ling; Wi, Ga Ram; Kim, Hyoung Jin; Kim, Hong-Jin

    2016-01-01

    Human respiratory syncytial virus (hRSV) is the most common cause of bronchiolitis and pneumonia in infants. The lack of proper prophylactics and therapeutics for controlling hRSV infection has been of great concern worldwide. Xylitol is a well-known sugar substitute and its effect against bacteria in the oral cavity is well known. However, little is known of its effect on viral infections. In this study, the effect of dietary xylitol on hRSV infection was investigated in a mouse model for the first time. Mice received xylitol for 14 d prior to virus challenge and for a further 3 d post challenge. Significantly larger reductions in lung virus titers were observed in the mice receiving xylitol than in the controls receiving phosphate-buffered saline (PBS). In addition, fewer CD3(+) and CD3(+)CD8(+) lymphocytes, whose numbers reflect inflammatory status, were recruited in the mice receiving xylitol. These results indicate that dietary xylitol can ameliorate hRSV infections and reduce inflammation-associated immune responses to hRSV infection.

  13. Immunological Features of Respiratory Syncytial Virus-Caused Pneumonia—Implications for Vaccine Design

    Directory of Open Access Journals (Sweden)

    Emma Rey-Jurado

    2017-03-01

    Full Text Available The human respiratory syncytial virus (hRSV is the causative agent for high rates of hospitalizations due to viral bronchiolitis and pneumonia worldwide. Such a disease is characterized by an infection of epithelial cells of the distal airways that leads to inflammation and subsequently to respiratory failure. Upon infection, different pattern recognition receptors recognize the virus and trigger the innate immune response against the hRSV. Further, T cell immunity plays an important role for virus clearance. Based on animal studies, it is thought that the host immune response to hRSV is based on a biased T helper (Th-2 and Th17 T cell responses with the recruitment of T cells, neutrophils and eosinophils to the lung, causing inflammation and tissue damage. In contrast, human immunity against RSV has been shown to be more complex with no definitive T cell polarization profile. Nowadays, only a humanized monoclonal antibody, known as palivizumab, is available to protect against hRSV infection in high-risk infants. However, such treatment involves several injections at a significantly high cost. For these reasons, intense research has been focused on finding novel vaccines or therapies to prevent hRSV infection in the population. Here, we comprehensively review the recent literature relative to the immunological features during hRSV infection, as well as the new insights into preventing the disease caused by this virus.

  14. Local interleukin-10 production during respiratory syncytial virus bronchiolitis is associated with post-bronchiolitis wheeze

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    Hodemaekers Hennie M

    2011-09-01

    Full Text Available Abstract Background Respiratory syncytial virus (RSV is the most common cause of bronchiolitis in infants. Following RSV bronchiolitis, 50% of children develop post-bronchiolitis wheeze (PBW. Animal studies have suggested that interleukin (IL-10 plays a critical role in the pathogenesis of RSV bronchiolitis and subsequent airway hyperresponsiveness. Previously, we showed that ex vivo monocyte IL-10 production is a predictor of PBW. Additionally, heterozygosity of the single-nucleotide polymorphism (SNP rs1800872 in the IL10 promoter region was associated with protection against RSV bronchiolitis. Methods This study aimed to determine the in vivo role of IL-10 in RSV pathogenesis and recurrent wheeze in a new cohort of 235 infants hospitalized for RSV bronchiolitis. IL-10 levels in nasopharyngeal aspirates (NPAs were measured at the time of hospitalization and the IL10 SNP rs1800872 genotype was determined. Follow-up data were available for 185 children (79%. Results Local IL-10 levels during RSV infection turned out to be higher in infants that later developed physician diagnosed PBW as compared to infants without PBW in the first year after RSV infection (958 vs 692 pg/ml, p = 0.02. The IL10 promoter SNP rs1800872 was not associated with IL-10 concentration in NPAs. Conclusion The relationship between high local IL-10 levels during the initial RSV infection and physician diagnosed PBW provides further evidence of the importance of the IL-10 response during RSV bronchiolitis.

  15. Influenza and Respiratory Syncytial viral infections in Malaysia: Demographic and Clinical perspective.

    Science.gov (United States)

    Rahman, M M; Wong, K K; Hanafiah, A; Isahak, I

    2014-01-01

    Respiratory infections represent a major public health problem worldwide. The study aimed to determine the prevalence of respiratory syncytial and influenza virus infections and analyzed in respect to demography and clinical perspective. Methods : The specimens were processed by cell culture and immunofluorescent assay (IFA) and real-time reverse transcriptase-PCR (rRT-PCR) for detection of respiratory viruses. Results : Out of 505 specimens 189 (37.8%) were positive, in which RSV was positive in 124(24.8%) cases and influenza A was positive in 65(13%) cases. Positive cases for influenza virus A and RSV were analyzed based on demography: age, gender, ethnicity and clinical symptoms. There were no significant differences among gender, ethnicity and clinical symptoms in both RSV and influenza A virus infections. It was observed that children below 3 years of ages were more prone to RSV infections. On the contrary, influenza virus A infected all age groups of humans. RSV infects mostly child below 3 years of age and influenza virus infects all age group. No specificity of RSV and influenza infection in relation to demography.

  16. A review of palivizumab and emerging therapies for respiratory syncytial virus.

    Science.gov (United States)

    Shadman, Kristin A; Wald, Ellen R

    2011-11-01

    Respiratory syncytial virus (RSV) is an important pathogen in children and adults; however, current treatment options are primarily supportive. Palivizumab, the only approved specific monoclonal antibody for RSV is used prophylactically to reduce morbidity in a select population of high-risk children. The development and current use of palivizumab; the potential role of palivizumab as preventive therapy in patients with cystic fibrosis, asthma and compromised immune systems; and explores the limited research in which palivizumab has been used for treatment of RSV. The modified recommendations for the use of palivizumab espoused by the American Academy of Pediatrics and research on the cost-effectiveness of this product are presented. In addition, the authors discuss the development of enhanced monoclonal antibodies including motavizumab, which was recently denied FDA approval for preventative therapy. The authors explore the historical and current efforts to develop a vaccine targeting RSV. The current status of antiviral drug development is also reviewed. The literature search included RSV-Ig, palivizumab, and emerging drugs and vaccines for the treatment of RSV as keywords and titles from 1997 to 2011. Although there are potential drugs and vaccines in development to prevent or reduce the effects of RSV infection, palivizumab remains the only licensed product to reduce the severity of disease in high-risk pediatric patients.

  17. Detection of an untyped strain of bovine respiratory syncytial virus in a dairy herd

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    Ingrid Bortolin Affonso

    2014-10-01

    Full Text Available Bovine respiratory syncytial virus (BRSV causes important lower respiratory tract illness in calves. According to F and G proteins genetic sequences, three BRSV subgroups have been reported and characterized in several countries, showing differences in its distribution. In Brazil, the virus is widely disseminated throughout the herds and the few characterized isolates revealed the solely occurrence of the subgroup B. This study describes the detection and characterization of an untyped BRSV strain from a twenty-days-old calf from a herd without clinical respiratory disease. Nasal swabs were analyzed by RT-nested PCR for the F and G proteins genes. One sample has amplified the F protein gene. Sequencing and subsequent phylogenetic reconstruction were accomplished, revealing that the strain could not be grouped with any other BRSV subgroups reported. This result may suggest that the BRSV is in constantly evolution, even in Brazil, where the vaccination is not a common practice. More detailed studies about BRSV characterization are necessary to know the virus subgroups distribution among the Brazilian herds to recommend appropriated immunoprophylaxis.

  18. Syncytial Hepatitis of Tilapia ( Oreochromis niloticus L.) is Associated With Orthomyxovirus-Like Virions in Hepatocytes.

    Science.gov (United States)

    Del-Pozo, J; Mishra, N; Kabuusu, R; Cheetham, S; Eldar, A; Bacharach, E; Lipkin, W I; Ferguson, H W

    2017-01-01

    Using transmission electron microscopy (TEM), the presented work expands on the ultrastructural findings of an earlier report on "syncytial hepatitis," a novel disease of tilapia (SHT). Briefly, TEM confirmed the presence of an orthomyxovirus-like virus within the diseased hepatocytes but not within the endothelium. This was supported by observing extracellular and intracellular (mostly intraendosomal), 60-100 nm round virions with a trilaminar capsid containing up to 7 electron-dense aggregates. Other patterns noted included enveloped or filamentous virions and virion-containing cytoplasmic membrane folds, suggestive of endocytosis. Patterns atypical for orthymyxovirus included the formation of syncytia and the presence of virions within the perinuclear cisternae (suspected to be the Golgi apparatus). The ultrastructural morphology of SHT-associated virions is similar to that previously reported for tilapia lake virus (TiLV). A genetic homology was investigated using the available reverse transcriptase polymerase chain reaction (RT-PCR) probes for TiLV and comparing clinically sick with clinically normal fish and negative controls. By RT-PCR analysis, viral nucleic acid was detected only in diseased fish. Taken together, these findings strongly suggest that a virus is causally associated with SHT, that this virus shares ultrastructural features with orthomyxoviruses, and it presents with partial genetic homology with TiLV (190 nucleotides).

  19. Human airway epithelial cell cultures for modeling respiratory syncytial virus infection.

    Science.gov (United States)

    Pickles, Raymond J

    2013-01-01

    Respiratory syncytial virus (RSV) is an important human respiratory pathogen with narrow species tropism. Limited availability of human pathologic specimens during early RSV-induced lung disease and ethical restrictions for RSV challenge studies in the lower airways of human volunteers has slowed our understanding of how RSV causes airway disease and greatly limited the development of therapeutic strategies for reducing RSV disease burden. Our current knowledge of RSV infection and pathology is largely based on in vitro studies using nonpolarized epithelial cell-lines grown on plastic or in vivo studies using animal models semipermissive for RSV infection. Although these models have revealed important aspects of RSV infection, replication, and associated inflammatory responses, these models do not broadly recapitulate the early interactions and potential consequences of RSV infection of the human columnar airway epithelium in vivo. In this chapter, the pro et contra of in vitro models of human columnar airway epithelium and their usefulness in respiratory virus pathogenesis and vaccine development studies will be discussed. The use of such culture models to predict characteristics of RSV infection and the correlation of these findings to the human in vivo situation will likely accelerate our understanding of RSV pathogenesis potentially identifying novel strategies for limiting the severity of RSV-associated airway disease.

  20. Respiratory syncytial virus increases lung cellular bioenergetics in neonatal C57BL/6 mice

    Energy Technology Data Exchange (ETDEWEB)

    Alsuwaidi, Ahmed R., E-mail: alsuwaidia@uaeu.ac.ae [Departments of Pediatrics, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain (United Arab Emirates); Albawardi, Alia, E-mail: alia.albawardi@uaeu.ac.ae [Departments of Pathology, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain (United Arab Emirates); Almarzooqi, Saeeda, E-mail: saeeda.almarzooqi@uaeu.ac.ae [Departments of Pathology, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain (United Arab Emirates); Benedict, Sheela, E-mail: sheela.benedict@uaeu.ac.ae [Departments of Pediatrics, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain (United Arab Emirates); Othman, Aws R., E-mail: aws.rashad@uaeu.ac.ae [Departments of Pediatrics, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain (United Arab Emirates); Hartwig, Stacey M., E-mail: stacey-hartwig@uiowa.edu [Department of Microbiology, Department of Pathology and Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242 (United States); Varga, Steven M., E-mail: steven-varga@uiowa.edu [Department of Microbiology, Department of Pathology and Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242 (United States); Souid, Abdul-Kader, E-mail: asouid@uaeu.ac.ae [Departments of Pediatrics, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain (United Arab Emirates)

    2014-04-15

    We have previously reported that lung cellular bioenergetics (cellular respiration and ATP) increased in 4–10 week-old BALB/c mice infected with respiratory syncytial virus (RSV). This study examined the kinetics and changes in cellular bioenergetics in ≤2-week-old C57BL/6 mice following RSV infection. Mice (5–14 days old) were inoculated intranasally with RSV and the lungs were examined on days 1–10 post-infection. Histopathology and electron microscopy revealed preserved pneumocyte architectures and organelles. Increased lung cellular bioenergetics was noted from days 1–10 post-infection. Cellular GSH remained unchanged. These results indicate that the increased lung cellular respiration (measured by mitochondrial O{sub 2} consumption) and ATP following RSV infection is independent of either age or genetic background of the host. - Highlights: • RSV infection increases lung cellular respiration and ATP in neonatal C57BL/6 mice. • Increased lung cellular bioenergetics is a biomarker of RSV infection. • Lung cellular glutathione remains unchanged in RSV infection.

  1. Short term effect of urban air pollution on respiratory disease, especially chronic obstructive pulmonary disease (COPD). Analysis of studies published from 1962 to january 2000; Impact a court terme de la pollution atmospherique urbaine sur l'insuffisance respiratoire par bronchopneumopathie chronique obstructive (BPCO). Synthese des etudes, publiees de 1962 a janvier 2000

    Energy Technology Data Exchange (ETDEWEB)

    Desqueyroux, H.; Momas, I. [Universite Rene Descartes, Faculte des Sciences Pharmaceutiques et Biologiques, Lab. d' Hygiene et de Sante Publique, 75 - Paris (France)

    2001-02-01

    This review presents a synthesis of studies published from 1962 to 2000 on the relations between air pollution and chronic obstructive pulmonary disease (COPD): 12 ecological epidemiological studies, 6 epidemiological panel studies, and 11 controlled human exposure trials. The controlled trials, ecological time-based epidemiological studies and panels are examined successively followed by a discussion of their methodology and results. The controlled trials either do no highlight effects or show effects having no clinical significance since variations are similar to physiological variability. For epidemiological studies reporting individual data, the results point to a particle effect (two studies). This effect of particles is found in ecological studies which also describe an impact of ozone, sometimes of sulfur dioxide and less often of nitrogen dioxide. In conclusion, patients suffering from COPD are generally regarded as a group sensitive to air pollution, as suggested by the results of numerous ecological epidemiological studies. Rare individual studies provide a few arguments supporting this assumption. (authors)

  2. Environmental exposure of primary care personnel to ribavirin aerosol when supervising treatment of infants with respiratory syncytial virus infections.

    Science.gov (United States)

    Rodriguez, W J; Bui, R H; Connor, J D; Kim, H W; Brandt, C D; Parrott, R H; Burch, B; Mace, J

    1987-01-01

    The potential exposure to ribavirin aerosol in the environment was assessed in nurses caring for infants and children with severe lower respiratory tract infections due to respiratory syncytial virus. Ribavirin aerosol was administered via a ventilator, oxygen tent, or oxygen hood. Participants worked directly with infants receiving ribavirin for 20.0 to 35.0 h over a 3-day period. No toxic or adverse effects of ribavirin aerosol were observed in any of the 19 nurses studied, and ribavirin was not detected in erythrocytes, plasma, or urine collected after the potential exposure period. PMID:3662474

  3. Molecular epidemiology of the SH (small hydrophobic) gene of human respiratory syncytial virus (HRSV), over 2 consecutive years.

    Science.gov (United States)

    Lima, Hildenêr Nogueira; Botosso, Viviane Fongaro; Oliveira, Danielle Bruna Leal; Campos, Angélica Cristine de Almeida; Leal, Andrea Lima; Silva, Tereza Souza; Bosso, Patrícia Alves Ramos; Moraes, Claudia Trigo Pedroso; Filho, Claudionor Gomes da Silva; Vieira, Sandra Elisabete; Gilio, Alfredo Elias; Stewien, Klaus Eberhard; Durigon, Edison Luiz

    2012-01-01

    Human respiratory syncytial virus (HRSV) strains were isolated from nasopharyngeal aspirates collected from 965 children between 2004 and 2005, yielding 424 positive samples. We sequenced the small hydrophobic protein (SH) gene of 117 strains and compared them with other viruses identified worldwide. Phylogenetic analysis showed a low genetic variability among the isolates but allowed us to classify the viruses into different genotypes for both groups, HRSVA and HRSVB. It is also shown that the novel BA-like genotype was well segregated from the others, indicating that the mutations are not limited to the G gene. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. Respiratory syncytial virus groups A and B in Porto Alegre, Brazil, from 1990 to 1995 and 1998

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    Straliotto Selir M

    2001-01-01

    Full Text Available We analyzed the respiratory syncytial virus (RSV groups and their epidemiological pattern that were detected over the course of seven years in southern Brazil. The two RSV groups co-circulated each year, but frequencies of groups A and B varied both between and within yearly outbreaks. In 1991, group A predominated over group B (p=0.0016. RSV outbreaks analyzed showed a temperature-dependent pattern and no association with rainfall, similarly to other countries from southern South America. Knowledge of the variants is important in terms of both diagnosis and definition of a vaccine composition.

  5. ParA and ParB coordinate chromosome segregation with cell elongation and division during Streptomyces sporulation

    Science.gov (United States)

    Donczew, Magdalena; Mackiewicz, Paweł; Wróbel, Agnieszka; Flärdh, Klas; Zakrzewska-Czerwińska, Jolanta

    2016-01-01

    In unicellular bacteria, the ParA and ParB proteins segregate chromosomes and coordinate this process with cell division and chromosome replication. During sporulation of mycelial Streptomyces, ParA and ParB uniformly distribute multiple chromosomes along the filamentous sporogenic hyphal compartment, which then differentiates into a chain of unigenomic spores. However, chromosome segregation must be coordinated with cell elongation and multiple divisions. Here, we addressed the question of whether ParA and ParB are involved in the synchronization of cell-cycle processes during sporulation in Streptomyces. To answer this question, we used time-lapse microscopy, which allows the monitoring of growth and division of single sporogenic hyphae. We showed that sporogenic hyphae stop extending at the time of ParA accumulation and Z-ring formation. We demonstrated that both ParA and ParB affect the rate of hyphal extension. Additionally, we showed that ParA promotes the formation of massive nucleoprotein complexes by ParB. We also showed that FtsZ ring assembly is affected by the ParB protein and/or unsegregated DNA. Our results indicate the existence of a checkpoint between the extension and septation of sporogenic hyphae that involves the ParA and ParB proteins. PMID:27248800

  6. Contamination potentielle des aliments par des ...

    African Journals Online (AJOL)

    SARA Computers

    la notion de la pollution et de l'exposition aux PCBs, lorsque 77% n'ont pas conscience de cette situation de risque ... 2018). Quoique la contamination par les. PCBs soit de faible niveau, elle est ...... Université Paris-Est, Paris, France ; 183.

  7. Elevation of Serum Acid Sphingomyelinase Activity in Children with Acute Respiratory Syncytial Virus Bronchiolitis.

    Science.gov (United States)

    Yoshida, Shuichiro; Noguchi, Atsuko; Kikuchi, Wataru; Fukaya, Hiroshi; Igarashi, Kiyoshi; Takahashi, Tsutomu

    2017-12-01

    Acid sphingomyelinase (ASM) is a lysosomal enzyme that hydrolyzes sphingomyelin into ceramide, a bioactive lipid to regulate cellular physiological functions. Thus, ASM activation has been reported as a key event in pathophysiological reactions including inflammation, cytokine release, oxidative stress, and endothelial damage in human diseases. Since ASM activation is associated with extracellular ASM secretion through unknown mechanisms, it can be detected by recognizing the elevation of secretory ASM (S-ASM) activity. Serum S-ASM activity has been reported to increase in chronic diseases, acute cardiac diseases, and systemic inflammatory diseases. However, the serum S-ASM has not been investigated in common acute illness. This study was designed to evaluate serum S-ASM activity in children with common acute illness. Fifty children with common acute illness and five healthy children were included in this study. The patients were categorized into five groups based on clinical diagnoses: acute respiratory syncytial virus (RSV) bronchiolitis, adenovirus infection, streptococcal infection, asthma, and other infections due to unknown origin. The serum S-ASM activity was significantly elevated at 6.9 ± 1.6 nmol/0.1 mL/6 h in the group of acute RSV bronchiolitis patients compared with healthy children who had a mean level of 1.8 ± 0.8 nmol/0.1 mL/6 h (p ASM activity was not significantly elevated. The results suggest an association of ASM activation with RSV infection, a cause for common acute illness. This is the first report to describe the elevation of serum S-ASM activity in respiratory tract infection.

  8. Functional Impairment of Mononuclear Phagocyte System by the Human Respiratory Syncytial Virus

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    Karen Bohmwald

    2017-11-01

    Full Text Available The mononuclear phagocyte system (MPS comprises of monocytes, macrophages (MΦ, and dendritic cells (DCs. MPS is part of the first line of immune defense against a wide range of pathogens, including viruses, such as the human respiratory syncytial virus (hRSV. The hRSV is an enveloped virus that belongs to the Pneumoviridae family, Orthopneumovirus genus. This virus is the main etiological agent causing severe acute lower respiratory tract infection, especially in infants, children and the elderly. Human RSV can cause bronchiolitis and pneumonia and it has also been implicated in the development of recurrent wheezing and asthma. Monocytes, MΦ, and DCs significantly contribute to acute inflammation during hRSV-induced bronchiolitis and asthma exacerbation. Furthermore, these cells seem to be an important component for the association between hRSV and reactive airway disease. After hRSV infection, the first cells encountered by the virus are respiratory epithelial cells, alveolar macrophages (AMs, DCs, and monocytes in the airways. Because AMs constitute the predominant cell population at the alveolar space in healthy subjects, these cells work as major innate sentinels for the recognition of pathogens. Although adaptive immunity is crucial for viral clearance, AMs are required for the early immune response against hRSV, promoting viral clearance and controlling immunopathology. Furthermore, exposure to hRSV may affect the phagocytic and microbicidal capacity of monocytes and MΦs against other infectious agents. Finally, different studies have addressed the roles of different DC subsets during infection by hRSV. In this review article, we discuss the role of the lung MPS during hRSV infection and their involvement in the development of bronchiolitis.

  9. Surfactant protein B polymorphisms are associated with severe respiratory syncytial virus infection, but not with asthma

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    Heinzmann Andrea

    2007-05-01

    Full Text Available Abstract Background Surfactant proteins (SP are important for the innate host defence and essential for a physiological lung function. Several linkage and association studies have investigated the genes coding for different surfactant proteins in the context of pulmonary diseases such as chronic obstructive pulmonary disease or respiratory distress syndrome of preterm infants. In this study we tested whether SP-B was in association with two further pulmonary diseases in children, i. e. severe infections caused by respiratory syncytial virus and bronchial asthma. Methods We chose to study five polymorphisms in SP-B: rs2077079 in the promoter region; rs1130866 leading to the amino acid exchange T131I; rs2040349 in intron 8; rs3024801 leading to L176F and rs3024809 resulting in R272H. Statistical analyses made use of the Armitage's trend test for single polymorphisms and FAMHAP and FASTEHPLUS for haplotype analyses. Results The polymorphisms rs3024801 and rs3024809 were not present in our study populations. The three other polymorphisms were common and in tight linkage disequilibrium with each other. They did not show association with bronchial asthma or severe RSV infection in the analyses of single polymorphisms. However, haplotypes analyses revealed association of SP-B with severe RSV infection (p = 0.034. Conclusion Thus our results indicate a possible involvement of SP-B in the genetic predisposition to severe RSV infections in the German population. In order to determine which of the three polymorphisms constituting the haplotypes is responsible for the association, further case control studies on large populations are necessary. Furthermore, functional analysis need to be conducted.

  10. Sub-nucleocapsid nanoparticles: a nasal vaccine against respiratory syncytial virus.

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    Xavier Roux

    Full Text Available BACKGROUND: Bronchiolitis caused by the respiratory syncytial virus (RSV in infants less than two years old is a growing public health concern worldwide, and there is currently no safe and effective vaccine. A major component of RSV nucleocapsid, the nucleoprotein (N, has been so far poorly explored as a potential vaccine antigen, even though it is a target of protective anti-viral T cell responses and is remarkably conserved between human RSV A and B serotypes. We recently reported a method to produce recombinant N assembling in homogenous rings composed of 10-11 N subunits enclosing a bacterial RNA. These nanoparticles were named sub-nucleocapsid ring structure (N SRS. METHODOLOGY AND PRINCIPAL FINDINGS: The vaccine potential of N SRS was evaluated in a well-characterized and widely acknowledged mouse model of RSV infection. BALB/c adult mice were immunized intranasally with N SRS adjuvanted with the detoxified E. coli enterotoxin LT(R192G. Upon RSV challenge, vaccinated mice were largely protected against virus replication in the lungs, with a mild inflammatory lymphocytic and neutrophilic reaction in their airways. Mucosal immunization with N SRS elicited strong local and systemic immunity characterized by high titers of IgG1, IgG2a and IgA anti-N antibodies, antigen-specific CD8(+ T cells and IFN-gamma-producing CD4(+ T cells. CONCLUSIONS/SIGNIFICANCE: This is the first report of using nanoparticles formed by the recombinant nucleocapsid protein as an efficient and safe intra-nasal vaccine against RSV.

  11. [Quantitative fluorogenic real-time PCR assay for respiratory syncytial virus detection].

    Science.gov (United States)

    Zhang, Qi-wei; You, Shang-you; Sun, Ji-min; Wu, Qi; Yu, Chun-hua; Zhang, Chu-yu

    2005-07-01

    To Establish a rapid and objective quantitative fluorogenic real-time PCR assay for early detection of human respiratory syncytial virus (hRSV). Two pairs of primers and one TaqMan Fluorogenic probe that are specific for the recognition of the most conservative N gene of hRSV for virus detection with LighCycler PCR in 93 nasopharyngeal secretion specimens collected from infants and young children. The assay was compared with virus isolation, routine PCR, nested PCR, and enzyme-linked immunosorbent assay (ELISA). This TaqMan assay had a sensitivity of 1 x 10(2) cDNA copies/microl with a dynamic range between 1 x 10(2) and 1 x 10(7) cDNA copies/microl, which was the same as that of nested PCR, but 10 times more sensitive than routine PCR. The specificity of the assay was evaluated by comparing hRSV with polivirus type 1, coxsackie virus type 2, influenza A, influenza B and adenovirus type 7. A PCR product of the expected size (195 bp) was produced and fluorescence signal detected for hRSV, but not for any of the other viruses. The results in LightCycler and Rotor-Gene instrument were consistent. Forty-four specimens (43.9%) were hRSV-positive with this assay and 4 (4/93,4.3%) were hRSV-positive with ELISA, showing rather low correlation between the two methods. No visible relation was found between the concentration of hRSV RNA and severity of the disease. This assay is rapid, sensitive, specific and quantitative, and has the potential of wide application for early diagnosis of hRSV infection and evaluation of the therapeutic effect.

  12. Phylogeny and population dynamics of respiratory syncytial virus (Rsv) A and B.

    Science.gov (United States)

    Martinelli, Marianna; Frati, Elena Rosanna; Zappa, Alessandra; Ebranati, Erika; Bianchi, Silvia; Pariani, Elena; Amendola, Antonella; Zehender, Gianguglielmo; Tanzi, Elisabetta

    2014-08-30

    Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections in infants and young children. RSV is characterised by high variability, especially in the G glycoprotein, which may play a significant role in RSV pathogenicity by allowing immune evasion. To reconstruct the origin and phylodynamic history of RSV, we evaluated the genetic diversity and evolutionary dynamics of RSV A and RSV B isolated from children under 3 years old infected in Italy from 2006 to 2012. Phylogenetic analysis revealed that most of the RSV A sequences clustered with the NA1 genotype, and RSV B sequences were included in the Buenos Aires genotype. The mean evolutionary rates for RSV A and RSV B were estimated to be 2.1 × 10(-3) substitutions (subs)/site/year and 3.03 × 10(-3) subs/site/year, respectively. The time of most recent common ancestor for the tree root went back to the 1940s (95% highest posterior density-HPD: 1927-1951) for RSV A and the 1950s (95%HPD: 1951-1960) for RSV B. The RSV A Bayesian skyline plot (BSP) showed a decrease in transmission events ending in about 2005, when a sharp growth restored the original viral population size. RSV B BSP showed a similar trend. Site-specific selection analysis identified 10 codons under positive selection in RSV A sequences and only one site in RSV B sequences. Although RSV remains difficult to control due to its antigenic diversity, it is important to monitor changes in its coding sequences, to permit the identification of future epidemic strains and to implement vaccine and therapy strategies. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Role of Bibersteinia trehalosi, respiratory syncytial virus, and parainfluenza-3 virus in bighorn sheep pneumonia.

    Science.gov (United States)

    Dassanayake, Rohana P; Shanthalingam, Sudarvili; Subramaniam, Renuka; Herndon, Caroline N; Bavananthasivam, Jegarubee; Haldorson, Gary J; Foreyt, William J; Evermann, James F; Herrmann-Hoesing, Lynn M; Knowles, Donald P; Srikumaran, Subramaniam

    2013-02-22

    Pneumonic bighorn sheep (BHS) have been found to be culture- and/or sero-positive for Bibersteinia trehalosi, respiratory syncytial virus (RSV), and parainfluenza-3 virus (PI-3). The objective of this study was to determine whether these pathogens can cause fatal pneumonia in BHS. In the first study, two groups of four BHS each were intra-tracheally administered with leukotoxin-positive (Group I) or leukotoxin-negative (Group II) B. trehalosi. All four animals in Group I developed severe pneumonia, and two of them died within 3 days. The other two animals showed severe pneumonic lesions on euthanasia and necropsy. Animals in Group II neither died nor showed gross pneumonic lesions on necropsy, suggesting that leukotoxin-positive, but not leukotoxin-negative, B. trehalosi can cause fatal pneumonia in BHS. In the second study, two other groups of four BHS (Groups III and IV) were intra-nasally administered with a mixture of RSV and PI-3. Four days later, RSV/PI-3-inoculated Group IV and another group of four BHS (Group V, positive control) were intra-nasally administered with Mannheimia haemolytica, the pathogen that consistently causes fatal pneumonia in BHS. All four animals in group III developed pneumonia, but did not die during the study period. However all four animals in Group IV, and three animals in Group V developed severe pneumonia and died within two days of M. haemolytica inoculation. The fourth animal in Group V showed severe pneumonic lesions on euthanasia and necropsy. These findings suggest that RSV/PI-3 can cause non-fatal pneumonia, but are not necessary predisposing agents for M. haemolytica-caused pneumonia of BHS. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. Macrophages are required for dendritic cell uptake of respiratory syncytial virus from an infected epithelium.

    Science.gov (United States)

    Ugonna, Kelechi; Bingle, Colin D; Plant, Karen; Wilson, Kirsty; Everard, Mark L

    2014-01-01

    We have previously shown that the respiratory syncytial virus [RSV] can productively infect monocyte derived dendritic cells [MoDC] and remain dormant within the same cells for prolonged periods. It is therefore possible that infected dendritic cells act as a reservoir within the airways of individuals between annual epidemics. In the present study we explored the possibility that sub-epithelial DCs can be infected with RSV from differentiated bronchial epithelium and that in turn RSV from DCs can infect the epithelium. A dual co-culture model was established in which a differentiated primary airway epithelium on an Air Liquid Interface (ALI) was cultured on a transwell insert and MoDCs were subsequently added to the basolateral membrane of the insert. Further experiments were undertaken using a triple co-culture model in which in which macrophages were added to the apical surface of the differentiated epithelium. A modified RSV [rr-RSV] expressing a red fluorescent protein marker of replication was used to infect either the MoDCs or the differentiated epithelium and infection of the reciprocal cell type was assessed using confocal microscopy. Our data shows that primary epithelium became infected when rr-RSV infected MoDCs were introduced onto the basal surface of the transwell insert. MoDCs located beneath the epithelium did not become infected with virus from infected epithelial cells in the dual co-culture model. However when macrophages were present on the apical surface of the primary epithelium infection of the basal MoDCs occurred. Our data suggests that RSV infected dendritic cells readily transmit infection to epithelial cells even when they are located beneath the basal layer. However macrophages appear to be necessary for the transmission of infection from epithelial cells to basal dendritic cells.

  15. Multicenter Clinical Evaluation of the Alere i Respiratory Syncytial Virus Isothermal Nucleic Acid Amplification Assay.

    Science.gov (United States)

    Hassan, Ferdaus; Hays, Lindsay M; Bonner, Aleta; Bradford, Bradley J; Franklin, Ruffin; Hendry, Phyllis; Kaminetsky, Jed; Vaughn, Michael; Cieslak, Kristin; Moffatt, Mary E; Selvarangan, Rangaraj

    2018-03-01

    The Alere i respiratory syncytial virus (RSV) assay is an isothermal nucleic acid amplification test capable of detecting RSV directly from respiratory specimens, with results being available in ≤13 min after test initiation. The objective of this study was to evaluate the performance characteristics of the Alere i RSV assay in a point-of-care setting by using direct nasopharyngeal (NP) swab specimens (direct NP) and nasopharyngeal swab specimens eluted and transported in viral transport medium (VTM NP). The study was a prospective, multicenter, clinical trial conducted at 9 sites across the United States to evaluate the clinical performance of the Alere i RSV assay with respiratory specimens obtained from both children (age, 60 years). The performance of the Alere i RSV assay was compared with that of the reference method, the Prodesse ProFlu+ real-time reverse transcriptase PCR (RT-PCR) assay. All specimens with discrepant test results were tested further by a second FDA-cleared PCR assay (the Verigene respiratory virus plus nucleic acid test; Luminex Inc., TX). A total of 554 subjects with signs and symptoms of respiratory infections were enrolled, and respiratory samples were collected in this study. In comparison with the ProFlu+ real-time RT-PCR, the overall sensitivity and specificity of Alere i RSV assay for the detection of RSV were 98.6% (95% confidence interval [CI], 94.4 to 99.7%) and 98.0% (95% CI, 95.8 to 99.1%), respectively, for direct NP and 98.6% (95% CI, 94.4 to 99.7%) and 97.8% (95% CI, 95.5 to 98.9%), respectively, for VTM NP. The Alere i RSV is a highly sensitive and specific molecular assay ideal for rapid RSV detection in patients in the point-of-care setting due to its minimal hands-on time and rapid result availability. Copyright © 2018 American Society for Microbiology.

  16. Exposure of neonates to Respiratory Syncytial Virus is critical in determining subsequent airway response in adults

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    Daly Melissa

    2006-08-01

    Full Text Available Abstract Background Respiratory syncytial virus (RSV is the most common cause of acute bronchiolitis in infants and the elderly. Furthermore, epidemiological data suggest that RSV infection during infancy is a potent trigger of subsequent wheeze and asthma development. However, the mechanism by which RSV contributes to asthma is complex and remains largely unknown. A recent study indicates that the age of initial RSV infection is a key factor in determining airway response to RSV rechallenge. We hypothesized that severe RSV infection during neonatal development significantly alters lung structure and the pulmonary immune micro-environment; and thus, neonatal RSV infection is crucial in the development of or predisposition to allergic inflammatory diseases such as asthma. Methods To investigate this hypothesis the present study was conducted in a neonatal mouse model of RSV-induced pulmonary inflammation and airway dysfunction. Seven-day-old mice were infected with RSV (2 × 105 TCID50/g body weight and allowed to mature to adulthood. To determine if neonatal RSV infection predisposed adult animals to enhanced pathophysiological responses to allergens, these mice were then sensitized and challenged with ovalbumin. Various endpoints including lung function, histopathology, cytokine production, and cellularity in bronchoalveolar lavage were examined. Results RSV infection in neonates alone led to inflammatory airway disease characterized by airway hyperreactivity, peribronchial and perivascular inflammation, and subepithelial fibrosis in adults. If early RSV infection was followed by allergen exposure, this pulmonary phenotype was exacerbated. The initial response to neonatal RSV infection resulted in increased TNF-α levels in bronchoalveolar lavage. Interestingly, increased levels of IL-13 and mucus hyperproduction were observed almost three months after the initial infection with RSV. Conclusion Neonatal RSV exposure results in long term

  17. [Respiratory syncytial virus outbreak in a tertiary hospital Neonatal Intensive Care Unit].

    Science.gov (United States)

    Moreno Parejo, Carlos; Morillo García, Aurea; Lozano Domínguez, Carmen; Carreño Ochoa, Concepción; Aznar Martín, Javier; Conde Herrera, Manuel

    2016-09-01

    Investigation and control of a respiratory syncytial virus (RSV) outbreak that affected the Neonatal Intensive Care Unit (NICU) of a university hospital from October to December 2012. Cohort study of children admitted to the NICU. The infection attack rate was calculated. A descriptive analysis of the cases and a multivariate analysis was performed using the variables that were shown to be risk factors for RSV infection. Preventive measures taken were: contact isolation; hand hygiene training and observation; exclusivity of a health team of nurses and physicians for positive cases, restrictions on visitor numbers; surveillance RSV testing, and palivizumab prophylaxis. The outbreak had three epidemic waves and 20 positive cases out of a total of 48 children admitted. The overall attack rate was 42%. Half of positive cases were children, with a median age of 36 days (p25=22, p75=58). The independent risk factors for RSV infection were birth weight below 1000 grams (OR=23.5; P=.002) and to have another nosocomial infection the week before the diagnosis of RSV infection (OR=19.98; P=.016). It was an outbreak with a high number of cases, due to the delay in notification, prolonged RSV carrier status, and low adherence to hand hygiene practice, which favoured the cross-transmission of infection. The most effective preventive measures were direct observation of hand hygiene and supervision of isolation measures. Copyright © 2015 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  18. Respiratory syncytial virus, adenoviruses, and mixed acute lower respiratory infections in children in a developing country.

    Science.gov (United States)

    Rodríguez-Martínez, Carlos E; Rodríguez, Diego Andrés; Nino, Gustavo

    2015-05-01

    There is growing evidence suggesting greater severity and worse outcomes in children with mixed as compared to single respiratory virus infections. However, studies that assess the risk factors that may predispose a child to a mixture of respiratory syncytial virus (RSV) and adenoviral infections, are scarce. In a retrospective cohort study, the study investigated the epidemiology of RSV and adenovirus infections and predictors of mixed RSV-adenoviral infections in young children hospitalized with acute lower respiratory infection in Bogota, Colombia, South America, over a 2-year period 2009-2011. Of a total of 5,539 children admitted with a diagnosis of acute lower respiratory infection, 2,267 (40.9%) who were positive for RSV and/or adenovirus were selected. Out the total number of cases, 1,416 (62.5%) infections occurred during the 3-month period from March to May, the first rainy season of Bogota, Colombia. After controlling for gender, month when the nasopharyngeal sample was taken, and other pre-existing conditions, it was found that an age greater than 6 months (OR:1.74; CI 95%:1.05-2.89; P = 0.030) and malnutrition as a comorbidity (OR:9.92; CI 95%:1.01-100.9; P = 0.049) were independent predictors of mixed RSV-adenoviral infections in the sample of patients. In conclusion, RSV and adenovirus are significant causes of acute lower respiratory infection in infants and young children in Bogota, Colombia, especially during the first rainy season. The identified predictors of mixed RSV-adenoviral infections should be taken into account when planning intervention, in order to reduce the burden of acute lower respiratory infection in young children living in the country. © 2015 Wiley Periodicals, Inc.

  19. Molecular Characterization of Human Respiratory Syncytial Virus in the Philippines, 2012-2013.

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    Rungnapa Malasao

    Full Text Available Human respiratory syncytial virus (HRSV is a major cause of acute lower respiratory tract infections in infants and children worldwide. We performed molecular analysis of HRSV among infants and children with clinical diagnosis of severe pneumonia in four study sites in the Philippines, including Biliran, Leyte, Palawan, and Metro Manila from June 2012 to July 2013. Nasopharyngeal swabs were collected and screened for HRSV using real-time polymerase chain reaction (PCR. Positive samples were tested by conventional PCR and sequenced for the second hypervariable region (2nd HVR of the G gene. Among a total of 1,505 samples, 423 samples were positive for HRSV (28.1%, of which 305 (72.1% and 118 (27.9% were identified as HRSV-A and HRSV-B, respectively. Two genotypes of HRSV-A, NA1 and ON1, were identified during the study period. The novel ON1 genotype with a 72-nucleotide duplication in 2nd HVR of the G gene increased rapidly and finally became the predominant genotype in 2013 with an evolutionary rate higher than the NA1 genotype. Moreover, in the ON1 genotype, we found positive selection at amino acid position 274 (p<0.05 and massive O- and N-glycosylation in the 2nd HVR of the G gene. Among HRSV-B, BA9 was the predominant genotype circulating in the Philippines. However, two sporadic cases of GB2 genotype were found, which might share a common ancestor with other Asian strains. These findings suggest that HRSV is an important cause of severe acute respiratory infection among children in the Philippines and revealed the emergence and subsequent predominance of the ON1 genotype and the sporadic detection of the GB2 genotype. Both genotypes were detected for the first time in the Philippines.

  20. Clinical Presentation and Birth Outcomes Associated with Respiratory Syncytial Virus Infection in Pregnancy.

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    Helen Y Chu

    Full Text Available Respiratory syncytial virus (RSV is the most important cause of viral pneumonia in children worldwide. A maternal vaccine may protect both the mother and infant from RSV illness. The epidemiology and clinical presentation of RSV in pregnant and postpartum women is not well-described.Data were collected from a prospective, randomized trial of influenza immunization in pregnant women in rural southern Nepal. Women were enrolled in their second trimester of pregnancy and followed until six months postpartum. Active weekly home-based surveillance for febrile respiratory illness was performed. Mid-nasal swabs collected with episodes of respiratory illness were tested for RSV by real-time polymerase chain reaction.RSV was detected in 14 (0.4% illness episodes in 3693 women over 3554 person-years of surveillance from 2011-2014. RSV incidence was 3.9/1000 person-years overall, and 11.8/1000 person-years between September and December. Seven (50% women sought care for RSV illness; none died. Of the 7 (50% illness episodes during pregnancy, all had live births with 2 (29% preterm births and a median birthweight of 3060 grams. This compares to 469 (13% preterm births and a median birthweight of 2790 grams in women without RSV during pregnancy. Of the 7 mothers with postpartum RSV infection, RSV was detected in 4 (57% of their infants.RSV was an uncommon cause of febrile respiratory illness in mothers during pregnancy in Nepal. These data will inform prevention and therapeutic strategies against RSV in resource-limited settings.

  1. Respiratory Syncytial Virus Aggravates Renal Injury through Cytokines and Direct Renal Injury

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    Songhui Zhai

    2016-09-01

    Full Text Available The purpose of this study was to investigate the relationship between renal injury and reinfection that is caused by respiratory syncytial virus (RSV and to analyze the mechanism of renal injury. Rats were repeatedly infected with RSV on days 4, 8, 14, and 28, then sacrificed and examined on day 56 after the primary infection. Renal injury was examined by transmission electron microscopy and histopathology. The F protein of RSV was detected in the renal tissue by indirect immunofluorescence. Proteinuria and urinary glycosaminoglycans (GAGs, serum levels of albumin, urea nitrogen, and creatinine, secretion of cytokines, T lymphocyte population and subsets, and dendritic cell (DC activation state were examined. The results showed that renal injury was more serious in the reinfection group than in the primary infection group. At a higher infection dose, 6×106 PFU, the renal injury was more severe, accompanied by higher levels of proteinuria and urinary GAGs excretion, and lower levels of serum albumin. Podocyte foot effacement was more extensive, and hyperplasia of mesangial cells and proliferation of mesangial matrix were observed. The maturation state of DCs was specific, compared with the primary infection. There was also a decrease in the ratio of CD4+ to CD8+T lymphocytes, due to an increase in the percentage of CD8+T lymphocytes and a decrease in the percentage of CD4+T lymphocytes, and a dramatic increase in the levels of IL-6 and IL-17. In terms of the different reinfection times, the day 14 reinfection group yielded the most serious renal injury and the most significant change in immune function. RSV F protein was still expressed in the glomeruli 56 days after RSV infection. Altogether, these results reveal that RSV infection could aggravate renal injury, which might be due to direct renal injury caused by RSV and the inflammatory lesions caused by the anti-virus response induced by RSV.

  2. Development and clinical applications of novel antibodies for prevention and treatment of respiratory syncytial virus infection.

    Science.gov (United States)

    Mejias, Asuncion; Garcia-Maurino, Cristina; Rodriguez-Fernandez, Rosa; Peeples, Mark E; Ramilo, Octavio

    2017-01-11

    Respiratory syncytial virus (RSV) remains a significant cause of morbidity and mortality in infants and young children, immunocompromised patients and the elderly. Despite the high disease burden, an effective and safe vaccine is lacking, although several candidates are currently in development. Current treatment for RSV infection remains largely supportive and RSV-specific options for prophylaxis are limited to palivizumab. In the past few years, novel therapeutic options including nanobodies, polyclonal and monoclonal antibodies have emerged and there are several products in preclinical and Phase-I, -II or -III clinical trials. The major target for antiviral drug development is the surface fusion (F) glycoprotein, which is crucial for the infectivity and pathogenesis of the virus. Solving the structures of the two conformations of the RSV F protein, the prefusion and postfusion forms, has revolutionized RSV research. It is now known that prefusion F is highly superior in inducing neutralizing antibodies. In this section we will review the stages of development and availability of different antibodies directed against RSV for the prevention and also for treatment of acute RSV infections. Some of these newer anti-RSV agents have shown enhanced potency, are being explored through alternative routes of administration, have improved pharmacokinetic profiles with an extended half-life, and may reduce design and manufacturing costs. Management strategies will require targeting not only high-risk populations (including adults or immunocompromised patients), but also previously healthy children who, in fact, represent the majority of children hospitalized with RSV infection. Following treated patients longitudinally is essential for determining the impact of these strategies on the acute disease as well as their possible long-term benefits on lung morbidity. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Respiratory syncytial virus infections enhance cigarette smoke induced COPD in mice.

    Directory of Open Access Journals (Sweden)

    Robert F Foronjy

    Full Text Available Respiratory syncytial viral (RSV infections are a frequent cause of chronic obstructive pulmonary disease (COPD exacerbations, which are a major factor in disease progression and mortality. RSV is able to evade antiviral defenses to persist in the lungs of COPD patients. Though RSV infection has been identified in COPD, its contribution to cigarette smoke-induced airway inflammation and lung tissue destruction has not been established. Here we examine the long-term effects of cigarette smoke exposure, in combination with monthly RSV infections, on pulmonary inflammation, protease production and remodeling in mice. RSV exposures enhanced the influx of macrophages, neutrophils and lymphocytes to the airways of cigarette smoke exposed C57BL/6J mice. This infiltration of cells was most pronounced around the vasculature and bronchial airways. By itself, RSV caused significant airspace enlargement and fibrosis in mice and these effects were accentuated with concomitant smoke exposure. Combined stimulation with both smoke and RSV synergistically induced cytokine (IL-1α, IL-17, IFN-γ, KC, IL-13, CXCL9, RANTES, MIF and GM-CSF and protease (MMP-2, -8, -12, -13, -16 and cathepsins E, S, W and Z expression. In addition, RSV exposure caused marked apoptosis within the airways of infected mice, which was augmented by cigarette smoke exposure. RSV and smoke exposure also reduced protein phosphatase 2A (PP2A and protein tyrosine phosphates (PTP1B expression and activity. This is significant as these phosphatases counter smoke-induced inflammation and protease expression. Together, these findings show for the first time that recurrent RSV infection markedly enhances inflammation, apoptosis and tissue destruction in smoke-exposed mice. Indeed, these results indicate that preventing RSV transmission and infection has the potential to significantly impact on COPD severity and progression.

  4. When to perform urine cultures in respiratory syncytial virus-positive febrile older infants?

    Science.gov (United States)

    Kaluarachchi, Dinushan; Kaldas, Virginia; Erickson, Evelyn; Nunez, Randolph; Mendez, Magda

    2014-09-01

    Respiratory syncytial virus (RSV) infections are associated with clinically significant rate of urinary tract infections (UTIs) in young infants. Previous research investigating RSV infections and UTIs has been performed mainly in infants younger than 2 to 3 months and has not focused on the risk of UTI in infants 3 to 12 months. This study aimed to assess the rate of UTIs in febrile RSV-positive older infants admitted as inpatients and identify predictors of UTI in febrile RSV-positive older infants. This is a retrospective comparative study of febrile RSV-positive infants 0 to 12 months of age admitted to the inpatient pediatric unit of Lincoln Medical and Mental Health Center, Bronx, from September through April 2006 to 2012. Infants 3 to 12 months were considered the cases, and infants 0 to 3 months were the comparative group. The rate of UTIs between the 2 groups was compared. Univariate tests and multiple logistic regression were used to identify demographic/clinical factors associated with UTI in febrile RSV-positive older infants. A total of 414 RSV-positive febrile infants were enrolled including 297 infants 3 to 12 months of age. The rate of UTI in older infants was 6.1% compared with 6.8% in infants younger than 3 months. Positive urinalysis finding was an independent predictor of UTI (P = 0.003) in older infants. All 11 boys with UTI were uncircumcised, and none of the 51 circumcised boys had UTI. Demographic (race, sex, and age) and clinical factors (temperature, white blood cell count, and absolute neutrophil count) were not associated with UTI. Febrile older infants who are RSV positive have a clinically significant rate of UTIs. It seems prudent to examine the urine of these older infants. Positive urinalysis finding was a predictive factor of UTI. Circumcised boys are at a decreased risk of UTI, compared with uncircumcised boys.

  5. A Randomized Placebo Controlled Trial of Ibuprofen for Respiratory Syncytial Virus Infection in a Bovine Model.

    Directory of Open Access Journals (Sweden)

    Paul Walsh

    Full Text Available Respiratory syncytial virus (RSV is the most common cause of bronchiolitis and hospital admission in infants. An analogous disease occurs in cattle and costs US agriculture a billion dollars a year. RSV causes much of its morbidity indirectly via adverse effects of the host response to the virus. RSV is accompanied by elevated prostaglandin E2 (PGE2 which is followed by neutrophil led inflammation in the lung. Ibuprofen is a prototypical non-steroidal anti-inflammatory drug that decreases PGE2 levels by inhibiting cyclooxygenase.We hypothesized that treatment of RSV with ibuprofen would decrease PGE2 levels, modulate the immune response, decrease clinical illness, and decrease the histopathological lung changes in a bovine model of RSV. We further hypothesized that viral replication would be unaffected.We performed a randomized placebo controlled trial of ibuprofen in 16 outbred Holstein calves that we infected with RSV. We measured clinical scores, cyclooxygenase, lipoxygenase and endocannabinoid products in plasma and mediastinal lymph nodes and interleukin (Il-4, Il-13, Il-17 and interferon-γ in mediastinal lymph nodes. RSV shedding was measured daily and nasal Il-6, Il-8 and Il-17 every other day. The calves were necropsied on Day 10 post inoculation and histology performed.One calf in the ibuprofen group required euthanasia on Day 8 of infection for respiratory distress. Clinical scores (p<0.01 and weight gain (p = 0.08 seemed better in the ibuprofen group. Ibuprofen decreased cyclooxygenase, lipoxygenase, and cytochrome P450 products, and increased monoacylglycerols in lung lymph nodes. Ibuprofen modulated the immune response as measured by narrowed range of observed Il-13, Il-17 and IFN-γ gene expression in mediastinal lymph nodes. Lung histology was not different between groups, and viral shedding was increased in calves randomized to ibuprofen.Ibuprofen decreased PGE2, modulated the immune response, and improved clinical outcomes

  6. Characterization of a viral phosphoprotein binding site on the surface of the respiratory syncytial nucleoprotein.

    Science.gov (United States)

    Galloux, Marie; Tarus, Bogdan; Blazevic, Ilfad; Fix, Jenna; Duquerroy, Stéphane; Eléouët, Jean-François

    2012-08-01

    The human respiratory syncytial virus (HRSV) genome is composed of a negative-sense single-stranded RNA that is tightly associated with the nucleoprotein (N). This ribonucleoprotein (RNP) complex is the template for replication and transcription by the viral RNA-dependent RNA polymerase. RNP recognition by the viral polymerase involves a specific interaction between the C-terminal domain of the phosphoprotein (P) (P(CTD)) and N. However, the P binding region on N remains to be identified. In this study, glutathione S-transferase (GST) pulldown assays were used to identify the N-terminal core domain of HRSV N (N(NTD)) as a P binding domain. A biochemical characterization of the P(CTD) and molecular modeling of the N(NTD) allowed us to define four potential candidate pockets on N (pocket I [PI] to PIV) as hydrophobic sites surrounded by positively charged regions, which could constitute sites complementary to the P(CTD) interaction domain. The role of selected amino acids in the recognition of the N-RNA complex by P was first screened for by site-directed mutagenesis using a polymerase activity assay, based on an HRSV minigenome containing a luciferase reporter gene. When changed to Ala, most of the residues of PI were found to be critical for viral RNA synthesis, with the R132A mutant having the strongest effect. These mutations also reduced or abolished in vitro and in vivo P-N interactions, as determined by GST pulldown and immunoprecipitation experiments. The pocket formed by these residues is critical for P binding to the N-RNA complex, is specific for pneumovirus N proteins, and is clearly distinct from the P binding sites identified so far for other nonsegmented negative-strand viruses.

  7. Matrix expansion and syncytial aggregation of syndecan-1+ cells underpin villous atrophy in coeliac disease.

    Directory of Open Access Journals (Sweden)

    Camilla Salvestrini

    Full Text Available We studied the expression of sulphated glycosaminoglycans (GAGs in coeliac disease (CD mucosa, as they are critical determinants of tissue volume, which increases in active disease. We also examined mucosal expression of IL-6, which stimulates excess GAG synthesis in disorders such as Grave's ophthalmopathy.We stained archival jejunal biopsies from 5 children with CD at diagnosis, on gluten-free diet and challenge for sulphated GAGs. We then examined duodenal biopsies from 9 children with CD compared to 9 histological normal controls, staining for sulphated GAGs, heparan sulphate proteoglycans (HSPG, short-chain HSPG (Δ-HSPG and the proteoglycan syndecan-1 (CD138, which is expressed on epithelium and plasma cells. We confirmed findings with a second monoclonal in another 12 coeliac children. We determined mucosal IL-6 expression by immunohistochemistry and PCR in 9 further cases and controls, and used quantitative real time PCR for other Th17 pathway cytokines in an additional 10 cases and controls.In CD, HSPG expression was lost in the epithelial compartment but contrastingly maintained within an expanded lamina propria. Within the upper lamina propria, clusters of syndecan-1(+ plasma cells formed extensive syncytial sheets, comprising adherent plasma cells, lysed cells with punctate cytoplasmic staining and shed syndecan ectodomains. A dense infiltrate of IL-6(+ mononuclear cells was detected in active coeliac disease, also localised to the upper lamina propria, with significantly increased mRNA expression of IL-6 and IL-17A but not IL-23 p19.Matrix expansion, through syndecan-1(+ cell recruitment and lamina propria GAG increase, underpins villous atrophy in coeliac disease. The syndecan-1(+ cell syncytia and excess GAG production recapitulate elements of the invertebrate encapsulation reaction, itself dependent on insect transglutaminase and glutaminated early response proteins. As in other matrix expansion disorders, IL-6 is upregulated and

  8. Matrix Expansion and Syncytial Aggregation of Syndecan-1+ Cells Underpin Villous Atrophy in Coeliac Disease

    Science.gov (United States)

    Salvestrini, Camilla; Lucas, Mark; Lionetti, Paolo; Torrente, Franco; James, Sean; Phillips, Alan D.; Murch, Simon H.

    2014-01-01

    Background We studied the expression of sulphated glycosaminoglycans (GAGs) in coeliac disease (CD) mucosa, as they are critical determinants of tissue volume, which increases in active disease. We also examined mucosal expression of IL-6, which stimulates excess GAG synthesis in disorders such as Grave's ophthalmopathy. Methods We stained archival jejunal biopsies from 5 children with CD at diagnosis, on gluten-free diet and challenge for sulphated GAGs. We then examined duodenal biopsies from 9 children with CD compared to 9 histological normal controls, staining for sulphated GAGs, heparan sulphate proteoglycans (HSPG), short-chain HSPG (Δ-HSPG) and the proteoglycan syndecan-1 (CD138), which is expressed on epithelium and plasma cells. We confirmed findings with a second monoclonal in another 12 coeliac children. We determined mucosal IL-6 expression by immunohistochemistry and PCR in 9 further cases and controls, and used quantitative real time PCR for other Th17 pathway cytokines in an additional 10 cases and controls. Results In CD, HSPG expression was lost in the epithelial compartment but contrastingly maintained within an expanded lamina propria. Within the upper lamina propria, clusters of syndecan-1+ plasma cells formed extensive syncytial sheets, comprising adherent plasma cells, lysed cells with punctate cytoplasmic staining and shed syndecan ectodomains. A dense infiltrate of IL-6+ mononuclear cells was detected in active coeliac disease, also localised to the upper lamina propria, with significantly increased mRNA expression of IL-6 and IL-17A but not IL-23 p19. Conclusions Matrix expansion, through syndecan-1+ cell recruitment and lamina propria GAG increase, underpins villous atrophy in coeliac disease. The syndecan-1+ cell syncytia and excess GAG production recapitulate elements of the invertebrate encapsulation reaction, itself dependent on insect transglutaminase and glutaminated early response proteins. As in other matrix expansion disorders

  9. A Randomized Placebo Controlled Trial of Ibuprofen for Respiratory Syncytial Virus Infection in a Bovine Model

    Science.gov (United States)

    Walsh, Paul; Behrens, Nicole; Carvallo Chaigneau, Francisco R.; McEligot, Heather; Agrawal, Karan; Newman, John W.; Anderson, Mark; Gershwin, Laurel J.

    2016-01-01

    Background Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis and hospital admission in infants. An analogous disease occurs in cattle and costs US agriculture a billion dollars a year. RSV causes much of its morbidity indirectly via adverse effects of the host response to the virus. RSV is accompanied by elevated prostaglandin E2 (PGE2) which is followed by neutrophil led inflammation in the lung. Ibuprofen is a prototypical non-steroidal anti-inflammatory drug that decreases PGE2 levels by inhibiting cyclooxygenase. Hypotheses We hypothesized that treatment of RSV with ibuprofen would decrease PGE2 levels, modulate the immune response, decrease clinical illness, and decrease the histopathological lung changes in a bovine model of RSV. We further hypothesized that viral replication would be unaffected. Methods We performed a randomized placebo controlled trial of ibuprofen in 16 outbred Holstein calves that we infected with RSV. We measured clinical scores, cyclooxygenase, lipoxygenase and endocannabinoid products in plasma and mediastinal lymph nodes and interleukin (Il)-4, Il-13, Il-17 and interferon-γ in mediastinal lymph nodes. RSV shedding was measured daily and nasal Il-6, Il-8 and Il-17 every other day. The calves were necropsied on Day 10 post inoculation and histology performed. Results One calf in the ibuprofen group required euthanasia on Day 8 of infection for respiratory distress. Clinical scores (pibuprofen group. Ibuprofen decreased cyclooxygenase, lipoxygenase, and cytochrome P450 products, and increased monoacylglycerols in lung lymph nodes. Ibuprofen modulated the immune response as measured by narrowed range of observed Il-13, Il-17 and IFN-γ gene expression in mediastinal lymph nodes. Lung histology was not different between groups, and viral shedding was increased in calves randomized to ibuprofen. Conclusions Ibuprofen decreased PGE2, modulated the immune response, and improved clinical outcomes. However lung

  10. Respiratory syncytial virus-related encephalitis: magnetic resonance imaging findings with diffusion-weighted study

    International Nuclear Information System (INIS)

    Park, Arim; Suh, Sang-il; Seol, Hae-Young; Son, Gyu-Ri; Lee, Nam-Joon; Lee, Young Hen; Seo, Hyung Suk; Eun, Baik-Lin

    2014-01-01

    Respiratory syncytial virus (RSV) is a common pathogen causing acute respiratory infection in children. Herein, we describe the incidence and clinical and magnetic resonance imaging (MRI) findings of RSV-related encephalitis, a major neurological complication of RSV infection. We retrospectively reviewed the medical records and imaging findings of the patients over the past 7 years who are admitted to our medical center and are tested positive for RSV-RNA by reverse transcriptase PCR. In total, 3,856 patients were diagnosed with RSV bronchiolitis, and 28 of them underwent brain MRI for the evaluation of neurologic symptoms; 8 of these 28 patients had positive imaging findings. Five of these 8 patients were excluded because of non-RSV-related pathologies, such as subdural hemorrhage, brain volume loss due to status epilepticus, periventricular leukomalacia, preexisting ventriculomegaly, and hypoxic brain injury. The incidence of RSV-related encephalitis was as follows: 3/3,856 (0.08 %) of the patients are positive for RSV RNA, 3/28 (10.7 %) of the patient underwent brain MRI for neurological symptom, and 3/8 (37.5 %) of patients revealed abnormal MR findings. The imaging findings were suggestive of patterns of rhombenmesencephalitis, encephalitis with acute disseminated encephalomyelitis, and limbic encephalitis. They demonstrated no diffusion abnormality on diffusion-weighted image and symptom improvement on the follow-up study. Encephalitis with RSV bronchiolitis occurs rarely. However, on brain MRI performed upon suspicion of neurologic involvement, RSV encephalitis is not infrequently observed among the abnormal MR findings and may mimic other viral and limbic encephalitis. Physicians should be aware of this entity to ensure proper diagnosis and neurologic care of RSV-positive patients. (orig.)

  11. Respiratory syncytial virus-related encephalitis: magnetic resonance imaging findings with diffusion-weighted study

    Energy Technology Data Exchange (ETDEWEB)

    Park, Arim; Suh, Sang-il; Seol, Hae-Young [Korea University College of Medicine, Department of Radiology, Korea University Guro Hospital, Seoul (Korea, Republic of); Son, Gyu-Ri; Lee, Nam-Joon [Korea University College of Medicine, Department of Radiology, Korea University Anam Hospital, Seoul (Korea, Republic of); Lee, Young Hen; Seo, Hyung Suk [Korea University College of Medicine, Department of Radiology, Korea University Ansan Hospital, Gyeonggi-do (Korea, Republic of); Eun, Baik-Lin [Korea University College of Medicine, Department of Pediatrics, Korea University Guro Hospital, Seoul (Korea, Republic of)

    2014-02-15

    Respiratory syncytial virus (RSV) is a common pathogen causing acute respiratory infection in children. Herein, we describe the incidence and clinical and magnetic resonance imaging (MRI) findings of RSV-related encephalitis, a major neurological complication of RSV infection. We retrospectively reviewed the medical records and imaging findings of the patients over the past 7 years who are admitted to our medical center and are tested positive for RSV-RNA by reverse transcriptase PCR. In total, 3,856 patients were diagnosed with RSV bronchiolitis, and 28 of them underwent brain MRI for the evaluation of neurologic symptoms; 8 of these 28 patients had positive imaging findings. Five of these 8 patients were excluded because of non-RSV-related pathologies, such as subdural hemorrhage, brain volume loss due to status epilepticus, periventricular leukomalacia, preexisting ventriculomegaly, and hypoxic brain injury. The incidence of RSV-related encephalitis was as follows: 3/3,856 (0.08 %) of the patients are positive for RSV RNA, 3/28 (10.7 %) of the patient underwent brain MRI for neurological symptom, and 3/8 (37.5 %) of patients revealed abnormal MR findings. The imaging findings were suggestive of patterns of rhombenmesencephalitis, encephalitis with acute disseminated encephalomyelitis, and limbic encephalitis. They demonstrated no diffusion abnormality on diffusion-weighted image and symptom improvement on the follow-up study. Encephalitis with RSV bronchiolitis occurs rarely. However, on brain MRI performed upon suspicion of neurologic involvement, RSV encephalitis is not infrequently observed among the abnormal MR findings and may mimic other viral and limbic encephalitis. Physicians should be aware of this entity to ensure proper diagnosis and neurologic care of RSV-positive patients. (orig.)

  12. CFD analysis of PAR performance as function of inlet design

    Energy Technology Data Exchange (ETDEWEB)

    Park, Kweonha, E-mail: khpark@kmou.ac.kr [Division of Mechanical and Energy systems Engineering, Korea Maritime University, Dongsam-dong, Yeongdo-gu, Busan 606-791 (Korea, Republic of); Khor, Chong Lee, E-mail: itachi_829@hotmail.com [Department of Mechanical Engineering, Korea Maritime University (Korea, Republic of)

    2016-01-15

    Highlights: • The new concept of PAR (passive autocatalytic recombiner) was proposed and analyzed. • Guidance wall was added at the bottom of PAR to enhance the flow rate through the catalyst. • The new concept of PAR was proved to have a better hydrogen removal performance. - Abstract: Passive autocatalytic recombiner (PAR) is very useful hydrogen mitigation measurement. It is widely implemented in the current and advanced light water reactors (ALWRs). The design of the PARs should be optimized for the specific use under severe accident scenarios. Several techniques and innovations have been fused into the PAR, as an effort to increase its efficiency of hydrogen mitigation. This study proposes different concepts of PAR, which applied some changes to the honeycomb catalyst PAR made by the Korea Nuclear Technology (KNT) Inc. Two slices of plate are added to the bottom of PAR model, which intended to act as a reflection wall and promote the gas flow into PAR. Hydrogen volume fraction was given 4 vol. % which tested by KNT to investigate the performance of PAR in different direction gas flow conditions to see maximum hydrogen recombination rate. The new concept of PAR was proved to have a better hydrogen removal performance compared to the original honeycomb catalyst PAR.

  13. CFD analysis of PAR performance as function of inlet design

    International Nuclear Information System (INIS)

    Park, Kweonha; Khor, Chong Lee

    2016-01-01

    Highlights: • The new concept of PAR (passive autocatalytic recombiner) was proposed and analyzed. • Guidance wall was added at the bottom of PAR to enhance the flow rate through the catalyst. • The new concept of PAR was proved to have a better hydrogen removal performance. - Abstract: Passive autocatalytic recombiner (PAR) is very useful hydrogen mitigation measurement. It is widely implemented in the current and advanced light water reactors (ALWRs). The design of the PARs should be optimized for the specific use under severe accident scenarios. Several techniques and innovations have been fused into the PAR, as an effort to increase its efficiency of hydrogen mitigation. This study proposes different concepts of PAR, which applied some changes to the honeycomb catalyst PAR made by the Korea Nuclear Technology (KNT) Inc. Two slices of plate are added to the bottom of PAR model, which intended to act as a reflection wall and promote the gas flow into PAR. Hydrogen volume fraction was given 4 vol. % which tested by KNT to investigate the performance of PAR in different direction gas flow conditions to see maximum hydrogen recombination rate. The new concept of PAR was proved to have a better hydrogen removal performance compared to the original honeycomb catalyst PAR.

  14. SAFARI 2000 PAR Measurements, Kalahari Transect, Botswana, Wet Season 2000

    Data.gov (United States)

    National Aeronautics and Space Administration — Ceptometer data from a Decagon AccuPAR (Model PAR-80) were collected at four sites in Botswana during the SAFARI 2000 Kalahari Transect Wet Season Campaign (March,...

  15. Radiographic and radionuclide lung perfusion imaging in healthy calves and calves naturally infected with bovine respiratory syncytial virus

    International Nuclear Information System (INIS)

    Verhoeff, J.; Brom, W.E. van den; Ingh, T.S.G.A.M. van den

    1992-01-01

    Nine calves between three and 18 weeks old with serologically confirmed natural bovine respiratory syncytial virus infection were examined clinically, radiographically and by radionuclide lung perfusion imaging. The results were compared with those from seven healthy calves. The diseased calves were euthanased and examined pathologically, virologically and bacteriologically. The clinical signs indicated that the disease was in an acute stage. Radiography of the diseased animals revealed cysts, corresponding morphologically with bullous emphysema, and infiltrations roughly corresponding in distribution with atelectatic and, or, pneumonic areas. Radionuclide lung perfusion imaging revealed no perfusion shifts between the left and right lungs and a normal perfusion pattern in five of the nine diseased calves. The abnormalities in the perfusion patterns of three calves were probably caused by anatomical disorders such as cysts and pleural adhesions, but no cause of the abnormality could be found in one calf. These findings suggest that in calves infected with bovine respiratory syncytial virus, the normal perfusion pattern is maintained until anatomical disorders occur. The pathological examination and radiography revealed that the cranioventral lung fields were particularly poorly ventilated. This finding and the normal perfusion pattern indicate that these parts of the lungs are probably the sites where shuntings and perfusion-ventilation mismatchings occur

  16. An experimental infection model for reproduction of calf pneumonia with bovine respiratory syncytial virus (BRSV) based on one combined exposure of calves

    DEFF Research Database (Denmark)

    Tjørnehøj, Kirsten; Uttenthal, Åse; Viuff, B.

    2003-01-01

    Bovine respiratory syncytial virus (BRSV) has been recognised as an important pathogen in calf pneumonia for 30 years, but surprisingly few effective infection models for studies of the immune response and the pathogenesis in the natural host have been established. We present a reproducible...... disease. This model is a valuable tool for the study of the pathogenesis of BRSV and for vaccine efficacy studies....

  17. The reorganization of root anatomy and ultrastructure of syncytial cells in tomato (Lycopersicon esculentum Mill. infected with potato cyst nematode (Globodera rostochiensis Woll.

    Directory of Open Access Journals (Sweden)

    Sylwia Fudali

    2011-01-01

    Full Text Available The sequence of anatomical and ultrastructural events leading to the syncytium development in tomato roots infected with Globodera rostochiensis was examined. The syncytia were preferentially induced in cortical or pericyclic cells in the elongation zone of root. They developed towards the vascular cylinder by incorporation of new cells via local cell wall breakdown. After surrounding primary phloem bundle and reaching xylem tracheary elements syncytia spread along vascular cylinder. Roots in primary state of growth seemed to be the best place for syncytium induction as syncytia formed in the zone of secondary growth were less hypertrophied. At the ultrastructural level syncytial elements were characterized by strong hypertrophy, breakdown of central vacuole, increased volume of cytoplasm, proliferation of organelles, and enlargement of nuclei. On the syncytial wall adjoining vessels the cell wall ingrowths were formed, while the syncytial walls at interface of phloem were considerably thickened. They lacked of functional plasmodesmata and did not form any ingrowths. Using immunofluorescent-labelling and immunogold-labelling methods tomato expansin 5 protein was localized in nematode infected roots. The distribution of LeEXP A5 was restricted only to the walls of syncytia. The protein distribution pattern indicated that LeEXP A5 could mediates cell wall expansion during hypertrophy of syncytial elements.

  18. A bovine respiratory syncytial virus strain with mutations in subgroup-specific antigenic domains of the G protein induces partial heterologous protection in cattle

    NARCIS (Netherlands)

    Schrijver, R.S.; Langedijk, J.P.M.; Middel, W.G.J.; Kramps, J.A.; Rijsewijk, F.A.M.; Oirschot, van J.T.

    1998-01-01

    Bovine respiratory syncytial virus (BRSV) strains are tentatively divided in subgroups A, AB and B, based on antigenic differences of the G protein. A Dutch BRSV strain (Waiboerhoeve: WBH), could not be assigned to one of the subgroups, because the strain did not react with any monoclonal antibody

  19. Characterization of the CD8(+)T cell responses directed against respiratory syncytial virus during primary and secondary infection in C57BL/6 mice

    NARCIS (Netherlands)

    Lukens, M.V.; Claassen, E.A.W.; Graaff, de P.M.A.; Dijk, van M.E.A.; Hoogerhout, P.; Toebes, M.; Schumacher, T.N.; Most, van der R.G.; Kimpen, J.L.L.; Bleek, van G.M.

    2006-01-01

    The BALB/c mouse model for human respiratory syncytial virus infection has contributed significantly to our understanding of the relative role for CD4+ and CD8+ T cells to immune protection and pathogenic immune responses. To enable comparison of RSV-specific T cell responses in different mouse

  20. Investigation of the presence of human or bovine respiratory syncytial virus in the lungs of mink (Neovison vison) with hemorrhagic pneumonia due to Pseudomonas aeruginosa

    DEFF Research Database (Denmark)

    Salomonsen, Charlotte Mark; Breum, Solvej Østergaard; Larsen, Lars Erik

    2012-01-01

    Background Hemorrhagic pneumonia is a disease of farmed mink (Neovison vison) caused by Pseudomonas aeruginosa. The disease is highly seasonal in Danish mink with outbreaks occurring almost exclusively in the autumn. Human respiratory syncytial virus (RSV) has been shown to augment infection with...

  1. High Incidence of Recurrent Wheeze in Children With Down Syndrome With and Without Previous Respiratory Syncytial Virus Lower Respiratory Tract Infection

    NARCIS (Netherlands)

    Bloemers, B.; van Furth, A.M.; Weijerman, M.E.; Gemke, R.J.B.J.; Broers, C.J.M.; Kimpen, J.L.L.; Bont, L.

    2010-01-01

    Background: Respiratory syncytial virus (RSV)-induced lower respiratory tract infection (LRTI) is associated with the subsequent development of recurrent wheeze. In a recent study, we found a high incidence (9.9%) of hospitalization for RSV-induced LRTI among children with Down syndrome (DS),

  2. Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015 : A systematic review and modelling study

    NARCIS (Netherlands)

    Shi, Ting; McAllister, David A.; O'Brien, Katherine L.; Simoes, Eric A. F.; Madhi, Shabir A.; Gessner, Bradford D.; Polack, Fernando P.; Balsells, Evelyn; Acacio, Sozinho; Aguayo, Claudia; Alassani, Issifou; Ali, Asad; Antonio, Martin; Awasthi, Shally; Awori, Juliet O.; Azziz-Baumgartner, Eduardo; Baggett, Henry C.; Baillie, Vicky L.; Balmaseda, Angel; Barahona, Alfredo; Basnet, Sudha; Bassat, Quique; Basualdo, Wilma; Bigogo, Godfrey; Bont, Louis; Breiman, Robert F.; Brooks, W. Abdullah; Broor, Shobha; Bruce, Nigel; Bruden, Dana; Buchy, Philippe; Campbell, Stuart; Carosone-Link, Phyllis; Chadha, Mandeep; Chipeta, James; Chou, Monidarin; Clara, Wilfrido; Cohen, Cheryl; de Cuellar, Elizabeth; Dang, Duc Anh; Dash-yandag, Budragchaagiin; Deloria-Knoll, Maria; Dherani, Mukesh; Eap, Tekchheng; Ebruke, Bernard E.; Echavarria, Marcela; de Freitas Lázaro Emediato, Carla Cecília; Fasce, Rodrigo A.; Feikin, Daniel R.; Feng, Luzhao; Gentile, Angela; Gordon, Aubree; Goswami, Doli; Goyet, Sophie; Groome, Michelle J; Halasa, Natasha; Hirve, Siddhivinayak; Homaira, Nusrat; Howie, Stephen R.C.; Jara, Jorge; Jroundi, Imane; Kartasasmita, Cissy B.; Khuri-Bulos, Najwa; Kotloff, Karen L.; Krishnan, Anand; Libster, Romina; Lopez, Olga; Lucero, Marilla G.; Lucion, Florencia; Lupisan, Socorro P.; Marcone, Debora N.; McCracken, John P.; Mejia, Mario; Moisi, Jennifer C.; Montgomery, Joel M.; Moore, David P.; Moraleda, Cinta; Moyes, Jocelyn; Munywoki, Patrick; Mutyara, Kuswandewi; Nicol, Mark P.; Nokes, D. James; Nymadawa, Pagbajabyn; da Costa Oliveira, Maria Tereza; Oshitani, Histoshi; Pandey, Nitin; Paranhos-Baccalà, Gláucia; Phillips, Lia N.; Picot, Valentina Sanchez; Rahman, Mustafizur; Rakoto-Andrianarivelo, Mala; Rasmussen, Zeba A.; Rath, Barbara A.; Robinson, Annick; Romero, Candice; Russomando, Graciela; Salimi, Vahid; Sawatwong, Pongpun; Scheltema, Nienke; Schweiger, Brunhilde; Scott, J. Anthony G.; Seidenberg, Phil; Shen, Kunling; Singleton, Rosalyn; Sotomayor, Viviana; Strand, Tor A.; Sutanto, Agustinus; Sylla, Mariam; Tapia, Milagritos D.; Thamthitiwat, Somsak; Thomas, Elizabeth D.; Tokarz, Rafal; Turner, Claudia; Venter, Marietjie; Waicharoen, Sunthareeya; Wang, Jianwei; Watthanaworawit, Wanitda; Yoshida, Lay Myint; Yu, Hongjie; Zar, Heather J.; Campbell, Harry; Nair, Harish

    2017-01-01

    Background: We have previously estimated that respiratory syncytial virus (RSV) was associated with 22% of all episodes of (severe) acute lower respiratory infection (ALRI) resulting in 55 000 to 199 000 deaths in children younger than 5 years in 2005. In the past 5 years, major research activity on

  3. Plasma suPAR is lowered by smoking cessation

    DEFF Research Database (Denmark)

    Eugen-Olsen, Jesper; Ladelund, Steen; Sørensen, Lars Tue

    2016-01-01

    BACKGROUND: Soluble urokinase plasminogen activator receptor (suPAR) is a stable inflammatory biomarker. In patients, suPAR is a marker of disease presence, severity and prognosis. In the general population, suPAR is predictive of disease development, such as diabetes and cardiovascular disease a...

  4. Copenhagen uPAR prostate cancer (CuPCa) database

    DEFF Research Database (Denmark)

    Lippert, Solvej; Berg, Kasper D; Høyer-Hansen, Gunilla

    2016-01-01

    AIM: Urokinase plasminogen activator receptor (uPAR) plays a central role during cancer invasion by facilitating pericellular proteolysis. We initiated the prospective 'Copenhagen uPAR Prostate Cancer' study to investigate the significance of uPAR levels in prostate cancer (PCa) patients. METHODS...

  5. The inflammatory marker suPAR after cardiac arrest

    DEFF Research Database (Denmark)

    Rundgren, Malin; Lyngbaek, Stig; Fisker, Helle

    2015-01-01

    . This pilot study aimed at investigating suPAR levels in relation to outcome after CA and mild induced hypothermia. METHODS: suPAR levels were measured at 6, 36, and 72 hours in patients treated with hypothermia after CA. suPAR levels were analyzed in relation to survival after 6 months. Receiver operating...

  6. Phosphorylation of Mycobacterium tuberculosis ParB participates in regulating the ParABS chromosome segregation system.

    Science.gov (United States)

    Baronian, Grégory; Ginda, Katarzyna; Berry, Laurence; Cohen-Gonsaud, Martin; Zakrzewska-Czerwińska, Jolanta; Jakimowicz, Dagmara; Molle, Virginie

    2015-01-01

    Here, we present for the first time that Mycobacterium tuberculosis ParB is phosphorylated by several mycobacterial Ser/Thr protein kinases in vitro. ParB and ParA are the key components of bacterial chromosome segregation apparatus. ParB is a cytosolic conserved protein that binds specifically to centromere-like DNA parS sequences and interacts with ParA, a weak ATPase required for its proper localization. Mass spectrometry identified the presence of ten phosphate groups, thus indicating that ParB is phosphorylated on eight threonines, Thr32, Thr41, Thr53, Thr110, Thr195, and Thr254, Thr300, Thr303 as well as on two serines, Ser5 and Ser239. The phosphorylation sites were further substituted either by alanine to prevent phosphorylation or aspartate to mimic constitutive phosphorylation. Electrophoretic mobility shift assays revealed a drastic inhibition of DNA-binding by ParB phosphomimetic mutant compared to wild type. In addition, bacterial two-hybrid experiments showed a loss of ParA-ParB interaction with the phosphomimetic mutant, indicating that phosphorylation is regulating the recruitment of the partitioning complex. Moreover, fluorescence microscopy experiments performed in the surrogate Mycobacterium smegmatis ΔparB strain revealed that in contrast to wild type Mtb ParB, which formed subpolar foci similar to M. smegmatis ParB, phoshomimetic Mtb ParB was delocalized. Thus, our findings highlight a novel regulatory role of the different isoforms of ParB representing a molecular switch in localization and functioning of partitioning protein in Mycobacterium tuberculosis.

  7. Phosphorylation of Mycobacterium tuberculosis ParB participates in regulating the ParABS chromosome segregation system.

    Directory of Open Access Journals (Sweden)

    Grégory Baronian

    Full Text Available Here, we present for the first time that Mycobacterium tuberculosis ParB is phosphorylated by several mycobacterial Ser/Thr protein kinases in vitro. ParB and ParA are the key components of bacterial chromosome segregation apparatus. ParB is a cytosolic conserved protein that binds specifically to centromere-like DNA parS sequences and interacts with ParA, a weak ATPase required for its proper localization. Mass spectrometry identified the presence of ten phosphate groups, thus indicating that ParB is phosphorylated on eight threonines, Thr32, Thr41, Thr53, Thr110, Thr195, and Thr254, Thr300, Thr303 as well as on two serines, Ser5 and Ser239. The phosphorylation sites were further substituted either by alanine to prevent phosphorylation or aspartate to mimic constitutive phosphorylation. Electrophoretic mobility shift assays revealed a drastic inhibition of DNA-binding by ParB phosphomimetic mutant compared to wild type. In addition, bacterial two-hybrid experiments showed a loss of ParA-ParB interaction with the phosphomimetic mutant, indicating that phosphorylation is regulating the recruitment of the partitioning complex. Moreover, fluorescence microscopy experiments performed in the surrogate Mycobacterium smegmatis ΔparB strain revealed that in contrast to wild type Mtb ParB, which formed subpolar foci similar to M. smegmatis ParB, phoshomimetic Mtb ParB was delocalized. Thus, our findings highlight a novel regulatory role of the different isoforms of ParB representing a molecular switch in localization and functioning of partitioning protein in Mycobacterium tuberculosis.

  8. [Ambroise Paré in French literature].

    Science.gov (United States)

    Dumaitre, P

    1995-01-01

    The 16th century by its passionate side has been the favourite one of authors of historical novels in which among the heroes of "cloak and dagger stories" appears sometime Ambroise Paré. Alexandre Dumas (the father) has shown him at the court of Charles IX in La Reine Margot (1845) where he does not however play a great role. On the contrary, Balzac in Le Martyr calviniste (1842) has given him a capital part close to the dying François II, whom he intended to trepanize but had to give up this idea as a consequence of the opposition of the queen-mother Catherine de Médicis. In the present century, Robert Merle in Paris ma bonne ville (Fortune de France, 3, 1980) shows Paré at the time of the Saint Barthélemy.

  9. Par Pond refill water quality sampling

    International Nuclear Information System (INIS)

    Koch, J.W. II; Martin, F.D.; Westbury, H.M.

    1996-08-01

    This study was designed to document anoxia and its cause in the event that the anoxia caused a fish kill. However, no fish kill was observed during this study, and dissolved oxygen and nutrient concentrations generally remained within the range expected for southeastern reservoirs. Par Pond water quality monitoring will continue during the second summer after refill as the aquatic macrophytes become reestablished and nutrients in the sediments are released to the water column

  10. Induction and Subversion of Human Protective Immunity: Contrasting Influenza and Respiratory Syncytial Virus

    Science.gov (United States)

    Ascough, Stephanie; Paterson, Suzanna; Chiu, Christopher

    2018-01-01

    Respiratory syncytial virus (RSV) and influenza are among the most important causes of severe respiratory disease worldwide. Despite the clinical need, barriers to developing reliably effective vaccines against these viruses have remained firmly in place for decades. Overcoming these hurdles requires better understanding of human immunity and the strategies by which these pathogens evade it. Although superficially similar, the virology and host response to RSV and influenza are strikingly distinct. Influenza induces robust strain-specific immunity following natural infection, although protection by current vaccines is short-lived. In contrast, even strain-specific protection is incomplete after RSV and there are currently no licensed RSV vaccines. Although animal models have been critical for developing a fundamental understanding of antiviral immunity, extrapolating to human disease has been problematic. It is only with recent translational advances (such as controlled human infection models and high-dimensional technologies) that the mechanisms responsible for differences in protection against RSV compared to influenza have begun to be elucidated in the human context. Influenza infection elicits high-affinity IgA in the respiratory tract and virus-specific IgG, which correlates with protection. Long-lived influenza-specific T cells have also been shown to ameliorate disease. This robust immunity promotes rapid emergence of antigenic variants leading to immune escape. RSV differs markedly, as reinfection with similar strains occurs despite natural infection inducing high levels of antibody against conserved antigens. The immunomodulatory mechanisms of RSV are thus highly effective in inhibiting long-term protection, with disturbance of type I interferon signaling, antigen presentation and chemokine-induced inflammation possibly all contributing. These lead to widespread effects on adaptive immunity with impaired B cell memory and reduced T cell generation and

  11. Induction and Subversion of Human Protective Immunity: Contrasting Influenza and Respiratory Syncytial Virus

    Directory of Open Access Journals (Sweden)

    Stephanie Ascough

    2018-03-01

    Full Text Available Respiratory syncytial virus (RSV and influenza are among the most important causes of severe respiratory disease worldwide. Despite the clinical need, barriers to developing reliably effective vaccines against these viruses have remained firmly in place for decades. Overcoming these hurdles requires better understanding of human immunity and the strategies by which these pathogens evade it. Although superficially similar, the virology and host response to RSV and influenza are strikingly distinct. Influenza induces robust strain-specific immunity following natural infection, although protection by current vaccines is short-lived. In contrast, even strain-specific protection is incomplete after RSV and there are currently no licensed RSV vaccines. Although animal models have been critical for developing a fundamental understanding of antiviral immunity, extrapolating to human disease has been problematic. It is only with recent translational advances (such as controlled human infection models and high-dimensional technologies that the mechanisms responsible for differences in protection against RSV compared to influenza have begun to be elucidated in the human context. Influenza infection elicits high-affinity IgA in the respiratory tract and virus-specific IgG, which correlates with protection. Long-lived influenza-specific T cells have also been shown to ameliorate disease. This robust immunity promotes rapid emergence of antigenic variants leading to immune escape. RSV differs markedly, as reinfection with similar strains occurs despite natural infection inducing high levels of antibody against conserved antigens. The immunomodulatory mechanisms of RSV are thus highly effective in inhibiting long-term protection, with disturbance of type I interferon signaling, antigen presentation and chemokine-induced inflammation possibly all contributing. These lead to widespread effects on adaptive immunity with impaired B cell memory and reduced T cell

  12. [Risk factors for acute respiratory syncytial virus infection of lower respiratory tract in hospitalized infants].

    Science.gov (United States)

    Zhang, Xiaobo; Liu, Lijuan; Shi, Peng; Jiang, Gaoli; Jia, Pin; Wang, Chuankai; Wang, Libo; Qian, Liling

    2014-05-01

    To investigate the clinical epidemiologic characteristics and analyze risk factors for acute respiratory syncytial virus (RSV) infection in hospitalized infants with acute lower respiratory tract infection (ALRI). ALRI infants admitted to Children's Hospital of Fudan University from March 1st, 2011 to February 29th, 2012, were enrolled in this study. Patient information included demographic characteristics, feeding history, family status, clinical presentation, accessory examination, treatment and prognosis. According to the etiology of ALRI infants, we compared the seasonal distribution, demographic characteristics, household characteristics and underlying diseases between RSV-positive patients and RSV-negative patients. Univariate and multiple Logistic regression analyses were used to determine factors that were associated with risk of RSV infection. Among 1 726 ALRI infants, there were 913 RSV-positive infants (52.9%). The occurrence of RSV infection had a seasonal variation, with a peak in winter (59.1%). The median (P25, P75) age of RSV infants was 64 (21-155) days. The gestational age (GA) and body weight (BW) was (37.5 ± 2.4) weeks and (3.07 ± 0.66) kg, respectively. The male/female ratio among these was 1.9: 1. RSV infection was more popular among infants in the families with smoking members, crowded living conditions, history of atopic mother. Differences of the proportion of patients with underlying disease between RSV-positive and negative groups were statistically significant (59.4% vs. 54.2%, P infection were: GAinfection (OR = 1.351, 95%CI: 1.024-1.783; OR = 1.713, 95%CI: 1.332-2.204). Multivariate logistic regression determined the factors increasing the risk of RSV infection were: underlying CHD (OR = 1.298, 95%CI: 1.002-1.681), mother with atopic diseases (OR = 1.766, 95%CI: 1.237-2.520), autumn or winter infection (OR = 1.481, 95%CI: 1.105-1.985; OR = 1.766, 95%CI: 1.358-2.296). The prevalence of RSV infection was the highest in winter, while

  13. Antibody-Induced Internalization of the Human Respiratory Syncytial Virus Fusion Protein.

    Science.gov (United States)

    Leemans, A; De Schryver, M; Van der Gucht, W; Heykers, A; Pintelon, I; Hotard, A L; Moore, M L; Melero, J A; McLellan, J S; Graham, B S; Broadbent, L; Power, U F; Caljon, G; Cos, P; Maes, L; Delputte, P

    2017-07-15

    Respiratory syncytial virus (RSV) infections remain a major cause of respiratory disease and hospitalizations among infants. Infection recurs frequently and establishes a weak and short-lived immunity. To date, RSV immunoprophylaxis and vaccine research is mainly focused on the RSV fusion (F) protein, but a vaccine remains elusive. The RSV F protein is a highly conserved surface glycoprotein and is the main target of neutralizing antibodies induced by natural infection. Here, we analyzed an internalization process of antigen-antibody complexes after binding of RSV-specific antibodies to RSV antigens expressed on the surface of infected cells. The RSV F protein and attachment (G) protein were found to be internalized in both infected and transfected cells after the addition of either RSV-specific polyclonal antibodies (PAbs) or RSV glycoprotein-specific monoclonal antibodies (MAbs), as determined by indirect immunofluorescence staining and flow-cytometric analysis. Internalization experiments with different cell lines, well-differentiated primary bronchial epithelial cells (WD-PBECs), and RSV isolates suggest that antibody internalization can be considered a general feature of RSV. More specifically for RSV F, the mechanism of internalization was shown to be clathrin dependent. All RSV F-targeted MAbs tested, regardless of their epitopes, induced internalization of RSV F. No differences could be observed between the different MAbs, indicating that RSV F internalization was epitope independent. Since this process can be either antiviral, by affecting virus assembly and production, or beneficial for the virus, by limiting the efficacy of antibodies and effector mechanism, further research is required to determine the extent to which this occurs in vivo and how this might impact RSV replication. IMPORTANCE Current research into the development of new immunoprophylaxis and vaccines is mainly focused on the RSV F protein since, among others, RSV F-specific antibodies are

  14. Structure-Based Design of Head-Only Fusion Glycoprotein Immunogens for Respiratory Syncytial Virus.

    Directory of Open Access Journals (Sweden)

    Jeffrey C Boyington

    Full Text Available Respiratory syncytial virus (RSV is a significant cause of severe respiratory illness worldwide, particularly in infants, young children, and the elderly. Although no licensed vaccine is currently available, an engineered version of the metastable RSV fusion (F surface glycoprotein-stabilized in the pre-fusion (pre-F conformation by "DS-Cav1" mutations-elicits high titer RSV-neutralizing responses. Moreover, pre-F-specific antibodies, often against the neutralization-sensitive antigenic site Ø in the membrane-distal head region of trimeric F glycoprotein, comprise a substantial portion of the human response to natural RSV infection. To focus the vaccine-elicited response to antigenic site Ø, we designed a series of RSV F immunogens that comprised the membrane-distal head of the F glycoprotein in its pre-F conformation. These "head-only" immunogens formed monomers, dimers, and trimers. Antigenic analysis revealed that a majority of the 70 engineered head-only immunogens displayed reactivity to site Ø-targeting antibodies, which was similar to that of the parent RSV F DS-Cav1 trimers, often with increased thermostability. We evaluated four of these head-only immunogens in detail, probing their recognition by antibodies, their physical stability, structure, and immunogenicity. When tested in naïve mice, a head-only trimer, half the size of the parent RSV F trimer, induced RSV titers, which were statistically comparable to those induced by DS-Cav1. When used to boost DS-Cav1-primed mice, two head-only RSV F immunogens, a dimer and a trimer, boosted RSV-neutralizing titers to levels that were comparable to those boosted by DS-Cav1, although with higher site Ø-directed responses. Our results provide proof-of-concept for the ability of the smaller head-only RSV F immunogens to focus the vaccine-elicited response to antigenic site Ø. Decent primary immunogenicity, enhanced physical stability, potential ease of manufacture, and potent

  15. Quantitative trait loci associated with the immune response to a bovine respiratory syncytial virus vaccine.

    Directory of Open Access Journals (Sweden)

    Richard J Leach

    Full Text Available Infectious disease is an important problem for animal breeders, farmers and governments worldwide. One approach to reducing disease is to breed for resistance. This linkage study used a Charolais-Holstein F2 cattle cross population (n = 501 which was genotyped for 165 microsatellite markers (covering all autosomes to search for associations with phenotypes for Bovine Respiratory Syncytial Virus (BRSV specific total-IgG, IgG1 and IgG2 concentrations at several time-points pre- and post-BRSV vaccination. Regions of the bovine genome which influenced the immune response induced by BRSV vaccination were identified, as well as regions associated with the clearance of maternally derived BRSV specific antibodies. Significant positive correlations were detected within traits across time, with negative correlations between the pre- and post-vaccination time points. The whole genome scan identified 27 Quantitative Trait Loci (QTL on 13 autosomes. Many QTL were associated with the Thymus Helper 1 linked IgG2 response, especially at week 2 following vaccination. However the most significant QTL, which reached 5% genome-wide significance, was on BTA 17 for IgG1, also 2 weeks following vaccination. All animals had declining maternally derived BRSV specific antibodies prior to vaccination and the levels of BRSV specific antibody prior to vaccination were found to be under polygenic control with several QTL detected.Heifers from the same population (n = 195 were subsequently immunised with a 40-mer Foot-and-Mouth Disease Virus peptide (FMDV in a previous publication. Several of these QTL associated with the FMDV traits had overlapping peak positions with QTL in the current study, including the QTL on BTA23 which included the bovine Major Histocompatibility Complex (BoLA, and QTL on BTA9 and BTA24, suggesting that the genes underlying these QTL may control responses to multiple antigens. These results lay the groundwork for future investigations to identify the

  16. Elevated temperature triggers human respiratory syncytial virus F protein six-helix bundle formation

    International Nuclear Information System (INIS)

    Yunus, Abdul S.; Jackson, Trent P.; Crisafi, Katherine; Burimski, Irina; Kilgore, Nicole R.; Zoumplis, Dorian; Allaway, Graham P.; Wild, Carl T.; Salzwedel, Karl

    2010-01-01

    Human respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract infection in infants, immunocompromised patients, and the elderly. The RSV fusion (F) protein mediates fusion of the viral envelope with the target cell membrane during virus entry and is a primary target for antiviral drug and vaccine development. The F protein contains two heptad repeat regions, HR1 and HR2. Peptides corresponding to these regions form a six-helix bundle structure that is thought to play a critical role in membrane fusion. However, characterization of six-helix bundle formation in native RSV F protein has been hindered by the fact that a trigger for F protein conformational change has yet to be identified. Here we demonstrate that RSV F protein on the surface of infected cells undergoes a conformational change following exposure to elevated temperature, resulting in the formation of the six-helix bundle structure. We first generated and characterized six-helix bundle-specific antibodies raised against recombinant peptides modeling the RSV F protein six-helix bundle structure. We then used these antibodies as probes to monitor RSV F protein six-helix bundle formation in response to a diverse array of potential triggers of conformational changes. We found that exposure of 'membrane-anchored' RSV F protein to elevated temperature (45-55 deg. C) was sufficient to trigger six-helix bundle formation. Antibody binding to the six-helix bundle conformation was detected by both flow cytometry and cell-surface immunoprecipitation of the RSV F protein. None of the other treatments, including interaction with a number of potential receptors, resulted in significant binding by six-helix bundle-specific antibodies. We conclude that native, untriggered RSV F protein exists in a metastable state that can be converted in vitro to the more stable, fusogenic six-helix bundle conformation by an increase in thermal energy. These findings help to better define the mechanism of

  17. Intoxication par la paraphényléne-diamine (takaout au Maroc: à propos de 24 cas

    Directory of Open Access Journals (Sweden)

    Ali Derkaoui

    2011-03-01

    Full Text Available La paraphénylène-diamine (PPD est une amine aromatique dérivée de l’aniline, utilisée depuis 1863 par les femmes dans un but cosmétique comme teinture capillaire noire ou adjuvant de henné dans plusieurs pays d’Afrique et de Moyen Orient. Le but de notre travail était de décrire les caractéristiques cliniques, paracliniques et évolutives de nos patients et de les comparer avec les données de la littérature. Il s’agissait d’une étude rétrospective portant sur les cas admis en réanimation (2003-2010. Les critères d’inclusion étaient d’ordre clinique, paraclinique, thérapeutique et évolutif. Durant la période de l’étude 24 patients ont été inclus provenant de la région de Fés-Boulmane. L’intoxication à la (PPD représentait 26% de l’ensemble des intoxications admises au cours de la même période. L âge moyen était de 23,6 plus or minus 11 ,6 ans. Il existait une prédominance féminine avec un sex-ratio de 4,7. L’intoxication était volontaire dans 82,6 %, accidentelle dans 8,6 %, et criminelle dans 4,3%. Le syndrome de rhabdomyolyse caractéristique de cette intoxication était retrouvé chez 60% de nos patients, l’atteinte respiratoire chez 56,5%, l’atteinte cardiaque était présente dans 30% des cas et 17,4% des patients avaient présentés une insuffisance rénale. La prise en charge thérapeutique se basait sur l’apport volémique massif, alcalinisation des urines ainsi que l’administration de corticoïdes et de diurétiques. Le recours à une trachéotomie de sauvetage était nécessaire chez 7 patients. Trois de nos patients avaient bénéficié d’une épuration extra rénale. L’évolution était fatale chez 47,8% des cas. La PPD représente ainsi la principale cause de mortalité toxique dans notre contexte. L’intoxication à la PPD, représente la première cause de rhabdomyolyse toxique dans notre contexte. Elle est responsable d’une mortalité très élevée. Ce qui

  18. Centromere pairing by a plasmid-encoded type I ParB protein

    DEFF Research Database (Denmark)

    Ringgaard, Simon; Löwe, Jan; Gerdes, Kenn

    2007-01-01

    The par2 locus of Escherichia coli plasmid pB171 encodes two trans-acting proteins, ParA and ParB, and two cis-acting sites, parC1 and parC2, to which ParB binds cooperatively. ParA is related to MinD and oscillates in helical structures and thereby positions ParB/parC-carrying plasmids regularly......, hence identifying the N terminus of ParB as a requirement for ParB-mediated centromere pairing. These observations suggest that centromere pairing is an important intermediate step in plasmid partitioning mediated by the common type I loci....

  19. Characterization of oligosaccharide structures on a chimeric respiratory syncytial virus protein expressed in insect cell line Sf9

    International Nuclear Information System (INIS)

    Wathen, M.W.; Aeed, P.A.; Elhammer, A.P.

    1991-01-01

    The oligosaccharide structures added to a chimeric protein (FG) composed of the extracellular domains of respiratory syncytial virus F and G proteins, expressed in the insect cell line Sf9, were investigated. Cells were labeled in vivo with [ 3 H]glucosamine and infected wit a recombinant baculovirus containing the FG gene. The secreted chimeric protein was isolated by immunoprecipitation and subjected to oligosaccharide analysis. The FG protein contains two types of O-linked oligosaccharides: GalNAc and Galβ1-3GalNAc constituting 17 and 66% of the total number of structures respectively. Only one type of N-linked oligosaccharide, constituting the remaining 17% of the structures on FG, was detected: a trimannosyl core structure with a fucose residue linked α1-6 to the asparagine-linked N-acetylglucosamine

  20. Antibody Tracing, Seroepidemiology and Risk Factors of Bovine Respiratory Syncytial Virus and Bovine Adenovirus-3 in Dairy Holstein Farms

    Directory of Open Access Journals (Sweden)

    Mahsa FARZINPOUR

    2016-01-01

    Full Text Available Antibody tracing, risk factors and seroepidemiology of bovine respiratory syncytial virus and bovine adenovirus-3 were investigated in 22 Industrial and Semi-Industrial dairy Holstein farms. Serum samples (n=736 from various ages of unvaccinated cows were collected from May to September 2012. Risk factors including age, past history of respiratory diseases, amount of milk production, husbandry type and herd size were considered. Data were analyzed by Chi-square and logistic regression. Results indicated that the infection with some of individual viruses was related to past history of respiratory disease and herd size. No specific pattern was seen on the effect of level of milk production on seropositivity of animals. The seroprevalence for BRSV and BAV-3 were 89.1% and 88%, respectively. The present study indicates that infections of bovine respiratory viruses frequently occur in cattle of Fars province and the main viral cause of primary occurrence of respiratory diseases may be due to aforementioned viruses.

  1. A multi-tiered time-series modelling approach to forecasting respiratory syncytial virus incidence at the local level.

    Science.gov (United States)

    Spaeder, M C; Fackler, J C

    2012-04-01

    Respiratory syncytial virus (RSV) is the most common cause of documented viral respiratory infections, and the leading cause of hospitalization, in young children. We performed a retrospective time-series analysis of all patients aged Forecasting models of weekly RSV incidence for the local community, inpatient paediatric hospital and paediatric intensive-care unit (PICU) were created. Ninety-five percent confidence intervals calculated around our models' 2-week forecasts were accurate to ±9·3, ±7·5 and ±1·5 cases/week for the local community, inpatient hospital and PICU, respectively. Our results suggest that time-series models may be useful tools in forecasting the burden of RSV infection at the local and institutional levels, helping communities and institutions to optimize distribution of resources based on the changing burden and severity of illness in their respective communities.

  2. A safe and efficient BCG vectored vaccine to prevent the disease caused by the human Respiratory Syncytial Virus.

    Science.gov (United States)

    Rey-Jurado, Emma; Soto, Jorge; Gálvez, Nicolás; Kalergis, Alexis M

    2017-09-02

    The human Respiratory Syncytial Virus (hRSV) causes lower respiratory tract infections including pneumonia and bronchiolitis. Such infections also cause a large number of hospitalizations and affects mainly newborns, young children and the elderly worldwide. Symptoms associated with hRSV infection are due to an exacerbated immune response characterized by low levels of IFN-γ, recruitment of neutrophils and eosinophils to the site of infection and lung damage. Although hRSV is a major health problem, no vaccines are currently available. Different immunization approaches have been developed to achieve a vaccine that activates the immune system, without triggering an unbalanced inflammation. These approaches include live attenuated vaccine, DNA or proteins technologies, and the use of vectors to express proteins of the virus. In this review, we discuss the host immune response to hRSV and the immunological mechanisms underlying an effective and safe BCG vectored vaccine against hRSV.

  3. Increase of CTGF mRNA expression by respiratory syncytial virus infection is abrogated by caffeine in lung epithelial cells.

    Science.gov (United States)

    Kunzmann, Steffen; Krempl, Christine; Seidenspinner, Silvia; Glaser, Kirsten; Speer, Christian P; Fehrholz, Markus

    2018-04-16

    Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract infection in early childhood. Underlying pathomechanisms of elevated pulmonary morbidity in later infancy are largely unknown. We found that RSV-infected H441 cells showed increased mRNA expression of connective tissue growth factor (CTGF), a key factor in airway remodeling. Additional dexamethasone treatment led to further elevated mRNA levels, indicating additive effects. Caffeine treatment prevented RSV-mediated increase of CTGF mRNA. RSV may be involved in airway remodeling processes by increasing CTGF mRNA expression. Caffeine might abrogate these negative effects and thereby help to restore lung homeostasis. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  4. Experiments toward the development of a radioimmunoassay for the detection of serum antibodies for the respiratory syncytial virus

    International Nuclear Information System (INIS)

    Heizmann, W.R.

    1982-01-01

    In order to detect an infection by the respiratory syncytial virus (RSV) quickly and safely, a radioimmunassay (RIA) should be developed. Various antigen preparations were compared to one another. The immune serums used in the RIA came from guinea pigs with a RSV antibody titer of up to 320 in the complement binding reaction. A number of observations lead to the discussion of the possibility of the formation (incomplete) of cross-reactive antibodies between virus and host cell. This hypothesis could be well supported through references in the literature. Under the assumption of the existence of cross-reactive antibodies, a further model of the pathogenesis of the RSV illness allows itself to be developed, which could be preceived as an illness with autoimmune components. With this model the varying courses of this disease in different age groups can be easily explained. (orig.) [de

  5. Analysis of the interaction between respiratory syncytial virus and lipid-rafts in Hep2 cells during infection

    International Nuclear Information System (INIS)

    Brown, Gaie; Jeffree, Chris E.; McDonald, Terence; McL Rixon, Helen W.; Aitken, James D.; Sugrue, Richard J.

    2004-01-01

    The assembly of respiratory syncytial virus (RSV) in lipid-rafts was examined in Hep2 cells. Confocal and electron microscopy showed that during RSV assembly, the cellular distribution of the complement regulatory proteins, decay accelerating factor (CD55) and CD59, changes and high levels of these cellular proteins are incorporated into mature virus filaments. The detergent-solubility properties of CD55, CD59, and the RSV fusion (F) protein were found to be consistent with each protein being located predominantly within lipid-raft structures. The levels of these proteins in cell-released virus were examined by immunoelectronmicroscopy and found to account for between 5% and 15% of the virus attachment (G) glycoprotein levels. Collectively, our findings suggest that an intimate association exists between RSV and lipid-raft membranes and that significant levels of these host-derived raft proteins, such as those regulating complement activation, are subsequently incorporated into the envelope of mature virus particles

  6. Syncytial giant-cell hepatitis due to autoimmune hepatitis type II (LKM1+) presenting as subfulminant hepatitis.

    Science.gov (United States)

    Ben-Ari, Z; Broida, E; Monselise, Y; Kazatsker, A; Baruch, J; Pappo, O; Skappa, E; Tur-Kaspa, R

    2000-03-01

    Giant cell hepatitis (GCH) in adults is a rare event. The diagnosis of GCH is based on findings of syncytial giant hepatocytes. It is commonly associated with either viral infection or autoimmune hepatitis type I. A patient with GCH due to autoimmune hepatitis type II (LKM1+) is described, a combination that has not been previously reported. Corticosteroid therapy was effective in decreasing serum liver enzymes; however, the patient deteriorated rapidly and developed subfulminant hepatic failure. Although an emergency orthotopic liver transplantation was performed, the patient died because of reperfusion injury. Interestingly, only a few giant hepatocytes were noted in the explanted liver. This case stresses the association of GCH with autoimmune disorders, the possible immune mechanism involved in the formation of giant cell hepatocytes, and illustrates the rapidly progressive course and unfavorable prognosis that these patients can develop.

  7. Childhood Pars Planitis; Clinical Features and Outcomes

    Directory of Open Access Journals (Sweden)

    Homayoon Nikkhah

    2011-01-01

    Full Text Available Purpose: To evaluate the demographic and clinical features of childhood pars planitis, and to determine the therapeutic and visual outcomes of the disease. Methods: Medical records of pediatric patients (less than 16 years of age at diagnosis with pars planitis and at least 6 months of follow-up who were referred to Labbafinejad Medical Center, Tehran, Iran over a 22 year period were reviewed. Results: Overall, 117 eyes of 61 patients including 51 (83.6% male subjects were included. Mean age at the time of diagnosis was 7.8΁3.2 (range, 3-16 years. Mean best corrected visual acuity (BCVA was 0.88΁0.76 logMAR at presentation which improved to 0.39΁0.51 logMAR at final visit (P<0.001. Endotheliitis was present in 23 (19.6% eyes and was significantly more prevalent in subjects younger than 9 years (P=0.025. Cataract formation (41.9% and cystoid macular edema (19.7% were the most prevalent complications. Univariate regression analysis showed that better baseline visual acuity (OR=0.38, 95%CI 0.21-0.70, P=0.002, age older than 5 years at disease onset (OR=0.36, 95%CI 0.14-0.9, P=0.029, absence of endotheliitis (OR=0.39, 95%CI 0.15-0.99, P=0.047 and female gender (OR=3.77, 95%CI 1.03-13.93, P=0.046 were significantly associated with final BCVA of 20/40 or better. Conclusion: Childhood pars planitis was much more common among male subjects. Endotheliitis may be a sign of inflammation spillover and is more prevalent in younger patients. Visual prognosis is favorable in most patients with appropriate treatment.

  8. Accouchement par forceps: indications et pronostic materno-foetal ...

    African Journals Online (AJOL)

    L'accouchement par voie basse, peut être parfois compromis par des facteurs maternels, foetaux ou materno-foetaux nécessitant des moyens thérapeutiques comme le forceps pour achever l'accouchement par voie naturelle. Le forceps, une méthode qui n'est pas sans risque pour la mère et le nouveau-né. Nous avons ...

  9. Prospective and retrospective evaluation of the Cepheid Xpert® Flu/RSV XC assay for rapid detection of influenza A, influenza B, and respiratory syncytial virus.

    Science.gov (United States)

    Salez, Nicolas; Nougairede, Antoine; Ninove, Laetitia; Zandotti, Christine; de Lamballerie, Xavier; Charrel, Remi N

    2015-04-01

    A total of 281 clinical specimens (nasal swabs and nasopharyngeal aspirates) were tested with the Xpert® Flu/RSV XC. The results were compared to those obtained with the real-time retro transcriptase-polymerase chain reaction assays routinely used in our laboratory. The Xpert® Flu/RSV XC showed sensitivity/specificity of 97.8%/100% and 97.9%/100% for flu and respiratory syncytial virus, respectively. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. PAR1 activation affects the neurotrophic properties of Schwann cells.

    Science.gov (United States)

    Pompili, Elena; Fabrizi, Cinzia; Somma, Francesca; Correani, Virginia; Maras, Bruno; Schininà, Maria Eugenia; Ciraci, Viviana; Artico, Marco; Fornai, Francesco; Fumagalli, Lorenzo

    2017-03-01

    Protease-activated receptor-1 (PAR1) is the prototypic member of a family of four G-protein-coupled receptors that signal in response to extracellular proteases. In the peripheral nervous system, the expression and/or the role of PARs are still poorly investigated. High PAR1 mRNA expression was found in the rat dorsal root ganglia and the signal intensity of PAR1 mRNA increased in response to sciatic nerve transection. In the sciatic nerve, functional PAR1 receptor was reported at the level of non-compacted Schwann cell myelin microvilli of the nodes of Ranvier. Schwann cells are the principal population of glial cells of the peripheral nervous system which myelinate axons playing an important role during axonal regeneration and remyelination. The present study was undertaken in order to determine if the activation of PAR1 affects the neurotrophic properties of Schwann cells. Our results suggest that the stimulation of PAR1 could potentiate the Schwann cell ability to favour nerve regeneration. In fact, the conditioned medium obtained from Schwann cell cultures challenged with a specific PAR1 activating peptide (PAR1 AP) displays increased neuroprotective and neurotrophic properties with respect to the culture medium from untreated Schwann cells. The proteomic analysis of secreted proteins in untreated and PAR1 AP-treated Schwann cells allowed the identification of factors differentially expressed in the two samples. Some of them (such as macrophage migration inhibitory factor, matrix metalloproteinase-2, decorin, syndecan 4, complement C1r subcomponent, angiogenic factor with G patch and FHA domains 1) appear to be transcriptionally regulated after PAR1 AP treatment as shown by RT-PCR. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Taare Zameen Par and dyslexic savants.

    Science.gov (United States)

    Chakravarty, Ambar

    2009-04-01

    The film Taare Zameen Par (Stars upon the Ground) portrays the tormented life at school and at home of a child with dyslexia and his eventual success after his artistic talents are discovered by his art teacher at the boarding school. The film hints at a curious neurocognitive phenomenon of creativity in the midst of language disability, as exemplified in the lives of people like Leonardo da Vinci and Albert Einstein, both of whom demonstrated extraordinary creativity even though they were probably affected with developmental learning disorders. It has been hypothesized that a developmental delay in the dominant hemisphere most likely 'disinhibits' the nondominant parietal lobe, unmasking talents-artistic or otherwise-in some such individuals. It has been suggested that, in remedial training, children with learning disorders be encouraged to develop such hidden talents to full capacity, rather than be subjected to the usual overemphasis on the correction of the disturbed coded symbol operations.

  12. Soudage de bois feuillus par friction rotationnelle

    OpenAIRE

    Belleville, Benoît

    2012-01-01

    Les différentes colles utilisées actuellement par l’industrie du meuble au Canada nécessitent des temps de polymérisation constituant un goulot dans la production des meubles et limitant l’atteinte de la production unitaire. Ces adhésifs synthétiques généralement issus de la pétrochimie nécessitent énormément d’énergie lors de leur confection. L’utilisation de connecteurs métalliques ou plastiques, quant à elle, limite les phases de découpage et sablage subséquentes. La présence d’adhésifs et...

  13. TMS suppression of right pars triangularis, but not pars opercularis, improves naming in aphasia

    Science.gov (United States)

    Naeser, Margaret A.; Martin, Paula I.; Theoret, Hugo; Kobayashi, Masahito; Fregni, Felipe; Nicholas, Marjorie; Tormos, Jose M.; Steven, Megan S.; Baker, Errol H.; Pascual-Leone, Alvaro

    2011-01-01

    This study sought to discover if an optimum 1 cm2 area in the non-damaged right hemisphere (RH) was present, which could temporarily improve naming in chronic, nonfluent aphasia patients when suppressed with repetitive transcranial magnetic stimulation (rTMS). Ten minutes of slow, 1 Hz rTMS was applied to suppress different RH ROIs in eight aphasia cases. Picture naming and response time (RT) were examined before, and immediately after rTMS. In aphasia patients, suppression of right pars triangularis (PTr) led to significant increase in pictures named, and significant decrease in RT. Suppression of right pars opercularis (POp), however, led to significant increase in RT, but no change in number of pictures named. Eight normals named all pictures correctly; similar to aphasia patients, RT significantly decreased following rTMS to suppress right PTr, versus right POp. Differential effects following suppression of right PTr versus right POp suggest different functional roles for these regions. PMID:21864891

  14. ParABS system in chromosome partitioning in the bacterium Myxococcus xanthus.

    Directory of Open Access Journals (Sweden)

    Antonio A Iniesta

    Full Text Available Chromosome segregation is an essential cellular function in eukaryotic and prokaryotic cells. The ParABS system is a fundamental player for a mitosis-like process in chromosome partitioning in many bacterial species. This work shows that the social bacterium Myxococcus xanthus also uses the ParABS system for chromosome segregation. Its large prokaryotic genome of 9.1 Mb contains 22 parS sequences near the origin of replication, and it is shown here that M. xanthus ParB binds preferentially to a consensus parS sequence in vitro. ParB and ParA are essential for cell viability in M. xanthus as in Caulobacter crescentus, but unlike in many other bacteria. Absence of ParB results in anucleate cells, chromosome segregation defects and loss of viability. Analysis of ParA subcellular localization shows that it clusters at the poles in all cells, and in some, in the DNA-free cell division plane between two chromosomal DNA masses. This ParA localization pattern depends on ParB but not on FtsZ. ParB inhibits the nonspecific interaction of ParA with DNA, and ParA colocalizes with chromosomal DNA only when ParB is depleted. The subcellular localization of ParB suggests a single ParB-parS complex localized at the edge of the nucleoid, next to a polar ParA cluster, with a second ParB-parS complex migrating after the replication of parS takes place to the opposite nucleoid edge, next to the other polar ParA cluster.

  15. Concerning the dynamic instability of actin homolog ParM

    International Nuclear Information System (INIS)

    Popp, David; Yamamoto, Akihiro; Iwasa, Mitsusada; Narita, Akihiro; Maeda, Kayo; Maeda, Yuichiro

    2007-01-01

    Using in vitro TIRF- and electron-microscopy, we reinvestigated the dynamics of native ParM, a prokaryotic DNA segregation protein and actin homolog. In contrast to a previous study, which used a cysteine ParM mutant, we find that the polymerization process of wild type ATP-ParM filaments consists of a polymerization phase and a subsequent steady state phase, which is dynamically unstable, like that of microtubules. We find that the apparent bidirectional polymerization of ParM, is not due to the intrinsic nature of this filament, but results from ParM forming randomly oriented bundles in the presence of crowding agents. Our results imply, that in the bacterium, ParM filaments spontaneously form bipolar bundles. Due to their intrinsic dynamic instability, ParM bundles can efficiently 'search' the cytoplasmic lumen for DNA, bind it equally well at the bipolar ends and segregate it approximately symmetrically, by the insertion of ParM subunits at either end

  16. The protein kinase SIK downregulates the polarity protein Par3

    DEFF Research Database (Denmark)

    Vanlandewijck, Michael; Dadras, Mahsa Shahidi; Lomnytska, Marta

    2018-01-01

    on Par3. Functionally, this mechanism impacts on tight junction downregulation. Furthermore, SIK contributes to the loss of epithelial polarity and examination of advanced and invasive human cancers of diverse origin displayed high levels of SIK expression and a corresponding low expression of Par3...

  17. Recombination in the human Pseudoautosomal region PAR1.

    Directory of Open Access Journals (Sweden)

    Anjali G Hinch

    2014-07-01

    Full Text Available The pseudoautosomal region (PAR is a short region of homology between the mammalian X and Y chromosomes, which has undergone rapid evolution. A crossover in the PAR is essential for the proper disjunction of X and Y chromosomes in male meiosis, and PAR deletion results in male sterility. This leads the human PAR with the obligatory crossover, PAR1, to having an exceptionally high male crossover rate, which is 17-fold higher than the genome-wide average. However, the mechanism by which this obligatory crossover occurs remains unknown, as does the fine-scale positioning of crossovers across this region. Recent research in mice has suggested that crossovers in PAR may be mediated independently of the protein PRDM9, which localises virtually all crossovers in the autosomes. To investigate recombination in this region, we construct the most fine-scale genetic map containing directly observed crossovers to date using African-American pedigrees. We leverage recombination rates inferred from the breakdown of linkage disequilibrium in human populations and investigate the signatures of DNA evolution due to recombination. Further, we identify direct PRDM9 binding sites using ChIP-seq in human cells. Using these independent lines of evidence, we show that, in contrast with mouse, PRDM9 does localise peaks of recombination in the human PAR1. We find that recombination is a far more rapid and intense driver of sequence evolution in PAR1 than it is on the autosomes. We also show that PAR1 hotspot activities differ significantly among human populations. Finally, we find evidence that PAR1 hotspot positions have changed between human and chimpanzee, with no evidence of sharing among the hottest hotspots. We anticipate that the genetic maps built and validated in this work will aid research on this vital and fascinating region of the genome.

  18. PARs for combustible gas control in advanced light water reactors

    International Nuclear Information System (INIS)

    Hosler, J.; Sliter, G.

    1997-01-01

    This paper discusses the progress being made in the United States to introduce passive autocatalytic recombiner (PAR) technology as a cost-effective alternative to electric recombiners for controlling combustible gas produced in postulated accidents in both future Advanced Light Water Reactors (ALWRs) and certain U. S. operating nuclear plants. PARs catalytically recombine hydrogen and oxygen, gradually producing heat and water vapor. They have no moving parts and are self-starting and self-feeding, even under relatively cold and wet containment conditions. Buoyancy of the hot gases they create sets up natural convective flow that promotes mixing of combustible gases in a containment. In a non-inerted ALWR containment, two approaches each employing a combination of PARs and igniters are being considered to control hydrogen in design basis and severe accidents. In pre-inerted ALWRs, PARs alone control radiolytic oxygen produced in either accident type. The paper also discusses regulatory feedback regarding these combustible gas control approaches and describes a test program being conducted by the Electric Power Research Institute (EPRI) and Electricite de France (EdF) to supplement the existing PAR test database with performance data under conditions of interest to U.S. plants. Preliminary findings from the EPRI/EdF PAR model test program are included. Successful completion of this test program and confirmatory tests being sponsored by the U. S. NRC are expected to pave the way for use of PARs in ALWRs and operating plants. (author)

  19. Respiratory Syncytial Virus Nonstructural Proteins Upregulate SOCS1 and SOCS3 in the Different Manner from Endogenous IFN Signaling

    Directory of Open Access Journals (Sweden)

    Junwen Zheng

    2015-01-01

    Full Text Available Respiratory syncytial virus (RSV infection upregulates genes of the suppressor of cytokine signaling (SOCS family, which utilize a feedback loop to inhibit type I interferon dependent antiviral signaling pathway. Here, we reconstituted RSV nonstructural (NS protein expression plasmids (pNS1, pNS2, and pNS1/2 and tested whether NS1 or NS2 would trigger SOCS1 and SOCS3 protein expression. These NS proteins inhibited interferon- (IFN- α signaling through a mechanism involving the induction of SOCS1 and SOCS3, which appeared to be different from autocrine IFN dependent. NS1 induced both SOCS1 and SOCS3 upregulation, while NS2 only induced SOCS1 expression. The induced expression of SOCS1 and SOCS3 preceded endogenous IFN-signaling activation and inhibited the IFN-inducible antiviral response as well as chemokine induction. Treatments with INF-α and NS proteins both induced SOCS1 expression; however, they had opposing effects on IFN-α-dependent antiviral gene expression. Our results indicate that NS1 and NS2, which induce the expression of SOCS1 or SOCS3, might represent an independent pathway of stimulating endogenous IFN signaling.

  20. Respiratory syncytial virus fusion glycoprotein expressed in insect cells form protein nanoparticles that induce protective immunity in cotton rats.

    Directory of Open Access Journals (Sweden)

    Gale Smith

    Full Text Available Respiratory Syncytial Virus (RSV is an important viral agent causing severe respiratory tract disease in infants and children as well as in the elderly and immunocompromised individuals. The lack of a safe and effective RSV vaccine represents a major unmet medical need. RSV fusion (F surface glycoprotein was modified and cloned into a baculovirus vector for efficient expression in Sf9 insect cells. Recombinant RSV F was glycosylated and cleaved into covalently linked F2 and F1 polypeptides that formed homotrimers. RSV F extracted and purified from insect cell membranes assembled into 40 nm protein nanoparticles composed of multiple RSV F oligomers arranged in the form of rosettes. The immunogenicity and protective efficacy of purified RSV F nanoparticles was compared to live and formalin inactivated RSV in cotton rats. Immunized animals induced neutralizing serum antibodies, inhibited virus replication in the lungs, and had no signs of disease enhancement in the respiratory track of challenged animals. RSV F nanoparticles also induced IgG competitive for binding of palivizumab neutralizing monoclonal antibody to RSV F antigenic site II. Antibodies to this epitope are known to protect against RSV when passively administered in high risk infants. Together these data provide a rational for continued development a recombinant RSV F nanoparticle vaccine candidate.

  1. Molecular Characterization of Respiratory Syncytial Virus in Children with Repeated Infections with Subgroup B in the Philippines.

    Science.gov (United States)

    Okamoto, Michiko; Dapat, Clyde P; Sandagon, Ann Marie D; Batangan-Nacion, Leilanie P; Lirio, Irene C; Tamaki, Raita; Saito, Mayuko; Saito-Obata, Mariko; Lupisan, Socorro P; Oshitani, Hitoshi

    2018-05-02

    Human respiratory syncytial virus (RSV) is the leading cause of severe acute respiratory infection in infants and young children, which is characterized by repeated infections. However, the role of amino acid substitutions in repeated infections remains unclear. Hence, this study aimed to elucidate the genetic characteristics of RSV in children with repeated infections using molecular analyses of F and G genes. We conducted a cohort study for children younger than 5 years in the Philippines. We collected nasopharyngeal swabs from children with acute respiratory symptoms and compared F and G sequences between prior and subsequent RSV infections. We examined 1,802 children from May 2014 to January 2016 and collected 3,471 samples. Repeated infections were observed in 25 children, including 4 with homologous RSV-B reinfections. Viruses from the 4 pairs of homologous reinfections had amino acid substitutions in the G protein mostly at O-glycosylation sites, whereas changes in the F protein were identified at antigenic sites V (L173S) and θ (Q209K), considered essential epitopes for the prefusion conformation of the F protein. Amino acid substitutions in G and F proteins of RSV-B might have led to antigenic changes, potentially contributing to homologous reinfections observed in this study.

  2. Ferrets as a Novel Animal Model for Studying Human Respiratory Syncytial Virus Infections in Immunocompetent and Immunocompromised Hosts

    Science.gov (United States)

    Stittelaar, Koert J.; de Waal, Leon; van Amerongen, Geert; Veldhuis Kroeze, Edwin J.B.; Fraaij, Pieter L.A.; van Baalen, Carel A.; van Kampen, Jeroen J.A.; van der Vries, Erhard; Osterhaus, Albert D.M.E.; de Swart, Rik L.

    2016-01-01

    Human respiratory syncytial virus (HRSV) is an important cause of severe respiratory tract disease in immunocompromised patients. Animal models are indispensable for evaluating novel intervention strategies in this complex patient population. To complement existing models in rodents and non-human primates, we have evaluated the potential benefits of an HRSV infection model in ferrets (Mustela putorius furo). Nine- to 12-month-old HRSV-seronegative immunocompetent or immunocompromised ferrets were infected with a low-passage wild-type strain of HRSV subgroup A (105 TCID50) administered by intra-tracheal or intra-nasal inoculation. Immune suppression was achieved by bi-daily oral administration of tacrolimus, mycophenolate mofetil, and prednisolone. Throat and nose swabs were collected daily and animals were euthanized four, seven, or 21 days post-infection (DPI). Virus loads were determined by quantitative virus culture and qPCR. We observed efficient HRSV replication in both the upper and lower respiratory tract. In immunocompromised ferrets, virus loads reached higher levels and showed delayed clearance as compared to those in immunocompetent animals. Histopathological evaluation of animals euthanized 4 DPI demonstrated that the virus replicated in the respiratory epithelial cells of the trachea, bronchi, and bronchioles. These animal models can contribute to an assessment of the efficacy and safety of novel HRSV intervention strategies. PMID:27314379

  3. Ferrets as a Novel Animal Model for Studying Human Respiratory Syncytial Virus Infections in Immunocompetent and Immunocompromised Hosts

    Directory of Open Access Journals (Sweden)

    Koert J. Stittelaar

    2016-06-01

    Full Text Available Human respiratory syncytial virus (HRSV is an important cause of severe respiratory tract disease in immunocompromised patients. Animal models are indispensable for evaluating novel intervention strategies in this complex patient population. To complement existing models in rodents and non-human primates, we have evaluated the potential benefits of an HRSV infection model in ferrets (Mustela putorius furo. Nine- to 12-month-old HRSV-seronegative immunocompetent or immunocompromised ferrets were infected with a low-passage wild-type strain of HRSV subgroup A (105 TCID50 administered by intra-tracheal or intra-nasal inoculation. Immune suppression was achieved by bi-daily oral administration of tacrolimus, mycophenolate mofetil, and prednisolone. Throat and nose swabs were collected daily and animals were euthanized four, seven, or 21 days post-infection (DPI. Virus loads were determined by quantitative virus culture and qPCR. We observed efficient HRSV replication in both the upper and lower respiratory tract. In immunocompromised ferrets, virus loads reached higher levels and showed delayed clearance as compared to those in immunocompetent animals. Histopathological evaluation of animals euthanized 4 DPI demonstrated that the virus replicated in the respiratory epithelial cells of the trachea, bronchi, and bronchioles. These animal models can contribute to an assessment of the efficacy and safety of novel HRSV intervention strategies.

  4. Positive selection results in frequent reversible amino acid replacements in the G protein gene of human respiratory syncytial virus.

    Science.gov (United States)

    Botosso, Viviane F; Zanotto, Paolo M de A; Ueda, Mirthes; Arruda, Eurico; Gilio, Alfredo E; Vieira, Sandra E; Stewien, Klaus E; Peret, Teresa C T; Jamal, Leda F; Pardini, Maria I de M C; Pinho, João R R; Massad, Eduardo; Sant'anna, Osvaldo A; Holmes, Eddie C; Durigon, Edison L

    2009-01-01

    Human respiratory syncytial virus (HRSV) is the major cause of lower respiratory tract infections in children under 5 years of age and the elderly, causing annual disease outbreaks during the fall and winter. Multiple lineages of the HRSVA and HRSVB serotypes co-circulate within a single outbreak and display a strongly temporal pattern of genetic variation, with a replacement of dominant genotypes occurring during consecutive years. In the present study we utilized phylogenetic methods to detect and map sites subject to adaptive evolution in the G protein of HRSVA and HRSVB. A total of 29 and 23 amino acid sites were found to be putatively positively selected in HRSVA and HRSVB, respectively. Several of these sites defined genotypes and lineages within genotypes in both groups, and correlated well with epitopes previously described in group A. Remarkably, 18 of these positively selected tended to revert in time to a previous codon state, producing a "flip-flop" phylogenetic pattern. Such frequent evolutionary reversals in HRSV are indicative of a combination of frequent positive selection, reflecting the changing immune status of the human population, and a limited repertoire of functionally viable amino acids at specific amino acid sites.

  5. Positive selection results in frequent reversible amino acid replacements in the G protein gene of human respiratory syncytial virus.

    Directory of Open Access Journals (Sweden)

    Viviane F Botosso

    2009-01-01

    Full Text Available Human respiratory syncytial virus (HRSV is the major cause of lower respiratory tract infections in children under 5 years of age and the elderly, causing annual disease outbreaks during the fall and winter. Multiple lineages of the HRSVA and HRSVB serotypes co-circulate within a single outbreak and display a strongly temporal pattern of genetic variation, with a replacement of dominant genotypes occurring during consecutive years. In the present study we utilized phylogenetic methods to detect and map sites subject to adaptive evolution in the G protein of HRSVA and HRSVB. A total of 29 and 23 amino acid sites were found to be putatively positively selected in HRSVA and HRSVB, respectively. Several of these sites defined genotypes and lineages within genotypes in both groups, and correlated well with epitopes previously described in group A. Remarkably, 18 of these positively selected tended to revert in time to a previous codon state, producing a "flip-flop" phylogenetic pattern. Such frequent evolutionary reversals in HRSV are indicative of a combination of frequent positive selection, reflecting the changing immune status of the human population, and a limited repertoire of functionally viable amino acids at specific amino acid sites.

  6. Incidence and Risk Factors for Respiratory Syncytial Virus and Human Metapneumovirus Infections among Children in the Remote Highlands of Peru

    Science.gov (United States)

    Wu, Andrew; Budge, Philip J.; Williams, John; Griffin, Marie R.; Edwards, Kathryn M.; Johnson, Monika; Zhu, Yuwei; Hartinger, Stella; Verastegui, Hector; Gil, Ana I.; Lanata, Claudio F.; Grijalva, Carlos G.

    2015-01-01

    Introduction The disease burden and risk factors for respiratory syncytial virus (RSV) and human metapneumovirus (MPV) infections among children living in remote, rural areas remain unclear. Materials and Methods We conducted a prospective, household-based cohort study of children aged factors for RSV detection included younger age (RR 1.02, 95% CI: 1.00-1.03), the presence of a smoker in the house (RR 1.63, 95% CI: 1.12-2.38), residing at higher altitudes (RR 1.93, 95% CI: 1.25-3.00 for 2nd compared to 1st quartile residents; RR 1.98, 95% CI: 1.26-3.13 for 3rd compared to 1st quartile residents). Having an unemployed household head was significantly associated with MPV risk (RR 2.11, 95% CI: 1.12-4.01). Conclusion In rural high altitude communities in Peru, childhood ARI due to RSV or MPV were common and associated with higher morbidity than ARI due to other viruses or with no viral detections. The risk factors identified in this study may be considered for interventional studies to control infections by these viruses among young children from developing countries. PMID:26107630

  7. Outcome of the Respiratory Syncytial Virus related acute lower respiratory tract infection among hospitalized newborns: a prospective multicenter study.

    Science.gov (United States)

    Alan, Serdar; Erdeve, Omer; Cakir, Ufuk; Akduman, Hasan; Zenciroglu, Aysegul; Akcakus, Mustafa; Tunc, Turan; Gokmen, Zeynel; Ates, Can; Atasay, Begum; Arsan, Saadet

    2016-01-01

    To determine the incidence and outcomes of respiratory syncytial virus (RSV)-related acute lower respiratory tract infection (ALRI) including morbidity, nosocomial infection and mortality among newborn infants who were admitted to the neonatal intensive care units (NICUs). A multicenter, prospective study was conducted in newborns who were hospitalized with community acquired or nosocomial RSV infection in 44 NICUs throughout Turkey. Newborns with ALRI were screened for RSV infection by Respi-Strip®-test. Main outcome measures were the incidence of RSV-associated admissions in the NICUs and morbidity, mortality and epidemics results related to these admissions. The incidence of RSV infection was 1.24% (n: 250) and RSV infection constituted 19.6% of all ALRI hospitalizations, 226 newborns (90.4%) had community-acquired whereas 24 (9.6%) patients had nosocomial RSV infection in the NICUs. Of the 250 newborns, 171 (68.4%) were full-term infants, 183 (73.2%) had a BW >2500 g. RSV-related mortality rate was 1.2%. Four NICUs reported seven outbreaks on different months, which could be eliminated by palivizumab prophylaxis in one NICU. RSV-associated ALRI both in preterm and term infants accounts an important percent of hospitalizations in the season, and may threat other high-risk patients in the NICU.

  8. Virus-like particle vaccine primes immune responses preventing inactivated-virus vaccine-enhanced disease against respiratory syncytial virus.

    Science.gov (United States)

    Hwang, Hye Suk; Lee, Young-Tae; Kim, Ki-Hye; Ko, Eun-Ju; Lee, Youri; Kwon, Young-Man; Kang, Sang-Moo

    2017-11-01

    Formalin inactivated respiratory syncytial virus (FI-RSV) vaccination caused vaccine-enhanced respiratory disease (ERD) upon exposure to RSV in children. Virus-like particles presenting RSV F fusion protein (F VLP) are known to increase T helper type-1 (Th1) immune responses and avoid ERD in animal models. We hypothesized that F VLP would prime immune responses preventing ERD upon subsequent exposure to ERD-prone FI-RSV. Here, we demonstrated that heterologous F VLP priming and FI-RSV boosting of mice prevented FI-RSV vaccine-enhanced lung inflammation and eosinophilia upon RSV challenge. F VLP priming redirected pulmonary T cells toward effector CD8 T cells producing Th1 cytokines and significantly suppressed pulmonary Th2 cytokines. This study suggests that RSV F VLP priming would modulate and shift immune responses to subsequent exposure to ERD-prone FI-RSV vaccine and RSV infection, suppressing Th2 immune-mediated pulmonary histopathology and eosinophilia. Copyright © 2017. Published by Elsevier Inc.

  9. Intranasal Administration of Maleic Anhydride-Modified Human Serum Albumin for Pre-Exposure Prophylaxis of Respiratory Syncytial Virus Infection

    Directory of Open Access Journals (Sweden)

    Zhiwu Sun

    2015-02-01

    Full Text Available Respiratory syncytial virus (RSV is the leading cause of pediatric viral respiratory tract infections. Neither vaccine nor effective antiviral therapy is available to prevent and treat RSV infection. Palivizumab, a humanized monoclonal antibody, is the only product approved to prevent serious RSV infection, but its high cost is prohibitive in low-income countries. Here, we aimed to identify an effective, safe, and affordable antiviral agent for pre-exposure prophylaxis (PrEP of RSV infection in children at high risk. We found that maleic anhydride (ML-modified human serum albumin (HSA, designated ML-HSA, exhibited potent antiviral activity against RSV and that the percentages of the modified lysines and arginies in ML- are correlated with such anti-RSV activity. ML-HSA inhibited RSV entry and replication by interacting with viral G protein and blocking RSV attachment to the target cells, while ML-HAS neither bound to F protein, nor inhibited F protein-mediated membrane fusion. Intranasal administration of ML-HSA before RSV infection resulted in significant decrease of the viral titers in the lungs of mice. ML-HSA shows promise for further development into an effective, safe, affordable, and easy-to-use intranasal regimen for pre-exposure prophylaxis of RSV infection in children at high risk in both low- and high-income countries.

  10. Independent lung ventilation in a newborn with asymmetric acute lung injury due to respiratory syncytial virus: a case report

    Directory of Open Access Journals (Sweden)

    Di Nardo Matteo

    2008-06-01

    Full Text Available Abstract Introduction Independent lung ventilation is a form of protective ventilation strategy used in adult asymmetric acute lung injury, where the application of conventional mechanical ventilation can produce ventilator-induced lung injury and ventilation-perfusion mismatch. Only a few experiences have been published on the use of independent lung ventilation in newborn patients. Case presentation We present a case of independent lung ventilation in a 16-day-old infant of 3.5 kg body weight who had an asymmetric lung injury due to respiratory syncytial virus bronchiolitis. We used independent lung ventilation applying conventional protective pressure controlled ventilation to the less-compromised lung, with a respiratory frequency proportional to the age of the patient, and a pressure controlled high-frequency ventilation to the atelectatic lung. This was done because a single tube conventional ventilation protective strategy would have exposed the less-compromised lung to a high mean airways pressure. The target of independent lung ventilation is to provide adequate gas exchange at a safe mean airways pressure level and to expand the atelectatic lung. Independent lung ventilation was accomplished for 24 hours. Daily chest radiograph and gas exchange were used to evaluate the efficacy of independent lung ventilation. Extubation was performed after 48 hours of conventional single-tube mechanical ventilation following independent lung ventilation. Conclusion This case report demonstrates the feasibility of independent lung ventilation with two separate tubes in neonates as a treatment of an asymmetric acute lung injury.

  11. Structural and Nonstructural Viral Proteins Are Targets of T-Helper Immune Response against Human Respiratory Syncytial Virus.

    Science.gov (United States)

    Lorente, Elena; Barriga, Alejandro; Barnea, Eilon; Mir, Carmen; Gebe, John A; Admon, Arie; López, Daniel

    2016-06-01

    Proper antiviral humoral and cellular immune responses require previous recognition of viral antigenic peptides that are bound to HLA class II molecules, which are exposed on the surface of antigen-presenting cells. The helper immune response is critical for the control and the clearance of human respiratory syncytial virus (HRSV) infection, a virus with severe health risk in infected pediatric, immunocompromised, and elderly populations. In this study, using a mass spectrometry analysis of complex HLA class II-bound peptide pools that were isolated from large amounts of HRSV-infected cells, 19 naturally processed HLA-DR ligands, most of them included in a complex nested set of peptides, were identified. Both the immunoprevalence and the immunodominance of the HLA class II response to HRSV were focused on one nonstructural (NS1) and two structural (matrix and mainly fusion) proteins of the infective virus. These findings have clear implications for analysis of the helper immune response as well as for antiviral vaccine design. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. Evidence that the respiratory syncytial virus polymerase complex associates with lipid rafts in virus-infected cells: a proteomic analysis

    International Nuclear Information System (INIS)

    McDonald, Terence P.; Pitt, Andrew R.; Brown, Gaie; Rixon, Helen W. McL.; Sugrue, Richard J.

    2004-01-01

    The interaction between the respiratory syncytial virus (RSV) polymerase complex and lipid rafts was examined in HEp2 cells. Lipid-raft membranes were prepared from virus-infected cells and their protein content was analysed by Western blotting and mass spectrometry. This analysis revealed the presence of the N, P, L, M2-1 and M proteins. However, these proteins appeared to differ from one another in their association with these structures, with the M2-1 protein showing a greater partitioning into raft membranes compared to that of the N, P or M proteins. Determination of the polymerase activity profile of the gradient fractions revealed that 95% of the detectable viral enzyme activity was associated with lipid-raft membranes. Furthermore, analysis of virus-infected cells by confocal microscopy suggested an association between these proteins and the raft-lipid, GM1. Together, these results provide evidence that the RSV polymerase complex is able to associate with lipid rafts in virus-infected cells

  13. A Preliminary Assessment of the Role of Ambient Nitric Oxide Exposure in Hospitalization with Respiratory Syncytial Virus Bronchiolitis

    Directory of Open Access Journals (Sweden)

    Nuredin I. Mohammed

    2016-06-01

    Full Text Available Some in vitro studies have indicated a possible link between respiratory syncytial virus (RSV infection and exposure to Nitric Oxide (NO. However, these studies used much higher NO concentrations than normally found in the ambient environment. This preliminary study explored whether an association was present with short-term exposure to NO in the environment. RSV-related admission data between November 2011 and February 2012 were obtained from Sheffield Children’s Hospital. The dates of admission were linked to contemporaneous ambient NO derived from sentinel air monitors. The case-crossover design was used to study the relationship between daily RSV admissions and NO, controlling for temperature and relative humidity. We found little evidence of association between daily RSV admission rates and exposure to ambient NO at different lags or average exposure across several lags. The findings should, however, be viewed with caution due to the low number of events observed during the time frame. It is possible that the apparent lack of association may be accounted for by the timing of the seasonal RSV epidemic in relation to peaks in NO concentrations. A larger study incorporating a wider range of RSV and NO peaks would determine whether said peaks enhanced the number of RSV hospitalizations in children.

  14. FACTORS DETERMINING THE HOSPITALISATION DURATION OF STAY IN CHILDREN WITH SEVERE RESPIRATORY SYNCYTIAL VIRUS (RSV INFECTION IN THE RUSSIAN FEDERATION

    Directory of Open Access Journals (Sweden)

    A.A. Baranov

    2011-01-01

    Full Text Available The epidemiologic data on RSV infection prevalence in the Russian Federation and its impact on respiratory morbidity in the pediatric population are limited. This article provides the analysis of results of a prospective, multicenter, observational cohort study. The study was conducted in 9 centers in the Russian Federation — in Moscow, St. Petersburg, and Tomsk. Children less than 2 years of age were included. It was found that during the season of high RSV morbidity RSV is found in 38 % of children hospitalized for lower respiratory tract infections; mean hospitalisation duration in children with severe RSV infection was over 1 week. Usually the duration of hospitalization was associated with disease severity and requirements for healthcare resources and oxygen supplementation. Moreover, in the Russian Federation the hospital length of stay in patients with RSV infection depended on the type of medical insurance. It was demonstrated that RSV infection caused severe respiratory failure in some infants less than 1 year of age and, therefore, was a substantial burden for the system of hospital medical care in the Russian Federation. Prophylaxis of severe RSV infection in high-risk groups of children during the might reduce the need for hospitalization. Key words: respiratory syncytial virus infection, bronchiolitis, risk factors, prophylaxis, epidemiology, children. (Pediatric pharmacology. — 2011; 8 (6: 61–66.

  15. Generation and Characterization of ALX-0171, a Potent Novel Therapeutic Nanobody for the Treatment of Respiratory Syncytial Virus Infection

    Science.gov (United States)

    Stohr, Thomas; Palomo, Concepción; Piedra, Pedro A.; Gilbert, Brian E.; Mas, Vicente; Millar, Andrena; Power, Ultan F.; Stortelers, Catelijne; Allosery, Koen; Melero, José A.; Depla, Erik

    2015-01-01

    Respiratory syncytial virus (RSV) is an important causative agent of lower respiratory tract infections in infants and elderly individuals. Its fusion (F) protein is critical for virus infection. It is targeted by several investigational antivirals and by palivizumab, a humanized monoclonal antibody used prophylactically in infants considered at high risk of severe RSV disease. ALX-0171 is a trimeric Nanobody that binds the antigenic site II of RSV F protein with subnanomolar affinity. ALX-0171 demonstrated in vitro neutralization superior to that of palivizumab against prototypic RSV subtype A and B strains. Moreover, ALX-0171 completely blocked replication to below the limit of detection for 87% of the viruses tested, whereas palivizumab did so for 18% of the viruses tested at a fixed concentration. Importantly, ALX-0171 was highly effective in reducing both nasal and lung RSV titers when delivered prophylactically or therapeutically directly to the lungs of cotton rats. ALX-0171 represents a potent novel antiviral compound with significant potential to treat RSV-mediated disease. PMID:26438495

  16. Non-specific Effect of Vaccines: Immediate Protection against Respiratory Syncytial Virus Infection by a Live Attenuated Influenza Vaccine

    Directory of Open Access Journals (Sweden)

    Young J. Lee

    2018-01-01

    Full Text Available The non-specific effects (NSEs of vaccines have been discussed for their potential long-term beneficial effects beyond direct protection against a specific pathogen. Cold-adapted, live attenuated influenza vaccine (CAIV induces local innate immune responses that provide a broad range of antiviral immunity. Herein, we examined whether X-31ca, a donor virus for CAIVs, provides non-specific cross-protection against respiratory syncytial virus (RSV. The degree of RSV replication was significantly reduced when X-31ca was administered before RSV infection without any RSV-specific antibody responses. The vaccination induced an immediate release of cytokines and infiltration of leukocytes into the respiratory tract, moderating the immune perturbation caused by RSV infection. The potency of protection against RSV challenge was significantly reduced in TLR3-/- TLR7-/- mice, confirming that the TLR3/7 signaling pathways are necessary for the observed immediate and short-term protection. The results suggest that CAIVs provide short-term, non-specific protection against genetically unrelated respiratory pathogens. The additional benefits of CAIVs in mitigating acute respiratory infections for which vaccines are not yet available need to be assessed in future studies.

  17. Surveillance van respiratoire infectieziekten in 2004/2005.

    NARCIS (Netherlands)

    Dijkstra, F.; Plas, S.M. van der; Wilbrink, B.; Jong, J.C. de; Bartelds, A.I.M.

    2005-01-01

    In order to gain more clear understanding of the epidemiology of a selection of respiratory infectious diseases in The Netherlands in the season 2004/2005, epidemiological data about a selection of respiratory syndromes and pathogens (influenza-like illnesses, other acute respiratory infections,

  18. uPAR as anti-cancer target

    DEFF Research Database (Denmark)

    Lund, Ida K; Illemann, Martin; Thurison, Tine

    2011-01-01

    , and a potential diagnostic and predictive impact of the different uPAR forms has been reported. Hence, pericellular proteolysis seems to be a suitable target for anti-cancer therapy and numerous approaches have been pursued. Targeting of this process may be achieved by preventing the binding of uPA to u...... using mouse monoclonal antibodies (mAbs) against mouse uPA or uPAR. These reagents will target uPA and uPAR in both stromal cells and cancer cells, and their therapeutic potential can now be assessed in syngenic mouse cancer models....

  19. Limnological database for Par Pond: 1959 to 1980

    International Nuclear Information System (INIS)

    Tilly, L.J.

    1981-03-01

    A limnological database for Par Pond, a cooling reservoir for hot reactor effluent water at the Savannah River Plant, is described. The data are derived from a combination of research and monitoring efforts on Par Pond since 1959. The approximately 24,000-byte database provides water quality, primary productivity, and flow data from a number of different stations, depths, and times during the 22-year history of the Par Pond impoundment. The data have been organized to permit an interpretation of the effects of twenty years of cooling system operations on the structure and function of an aquatic ecosystem

  20. Protease-activated receptor (PAR2, but not PAR1, is involved in collateral formation and anti-inflammatory monocyte polarization in a mouse hind limb ischemia model.

    Directory of Open Access Journals (Sweden)

    Lisa G van den Hengel

    Full Text Available AIMS: In collateral development (i.e. arteriogenesis, mononuclear cells are important and exist as a heterogeneous population consisting of pro-inflammatory and anti-inflammatory/repair-associated cells. Protease-activated receptor (PAR1 and PAR2 are G-protein-coupled receptors that are both expressed by mononuclear cells and are involved in pro-inflammatory reactions, while PAR2 also plays a role in repair-associated responses. Here, we investigated the physiological role of PAR1 and PAR2 in arteriogenesis in a murine hind limb ischemia model. METHODS AND RESULTS: PAR1-deficient (PAR1-/-, PAR2-deficient (PAR2-/- and wild-type (WT mice underwent femoral artery ligation. Laser Doppler measurements revealed reduced post-ischemic blood flow recovery in PAR2-/- hind limbs when compared to WT, while PAR1-/- mice were not affected. Upon ischemia, reduced numbers of smooth muscle actin (SMA-positive collaterals and CD31-positive capillaries were found in PAR2-/- mice when compared to WT mice, whereas these parameters in PAR1-/- mice did not differ from WT mice. The pool of circulating repair-associated (Ly6C-low monocytes and the number of repair-associated (CD206-positive macrophages surrounding collaterals in the hind limbs were increased in WT and PAR1-/- mice, but unaffected in PAR2-/- mice. The number of repair-associated macrophages in PAR2-/- hind limbs correlated with CD11b- and CD115-expression on the circulating monocytes in these animals, suggesting that monocyte extravasation and M-CSF-dependent differentiation into repair-associated cells are hampered. CONCLUSION: PAR2, but not PAR1, is involved in arteriogenesis and promotes the repair-associated response in ischemic tissues. Therefore, PAR2 potentially forms a new pro-arteriogenic target in coronary artery disease (CAD patients.

  1. Novel role for proteinase-activated receptor 2 (PAR2) in membrane trafficking of proteinase-activated receptor 4 (PAR4).

    Science.gov (United States)

    Cunningham, Margaret R; McIntosh, Kathryn A; Pediani, John D; Robben, Joris; Cooke, Alexandra E; Nilsson, Mary; Gould, Gwyn W; Mundell, Stuart; Milligan, Graeme; Plevin, Robin

    2012-05-11

    Proteinase-activated receptors 4 (PAR(4)) is a class A G protein-coupled receptor (GPCR) recognized through the ability of serine proteases such as thrombin and trypsin to mediate receptor activation. Due to the irreversible nature of activation, a fresh supply of receptor is required to be mobilized to the cell surface for responsiveness to agonist to be sustained. Unlike other PAR subtypes, the mechanisms regulating receptor trafficking of PAR(4) remain unknown. Here, we report novel features of the intracellular trafficking of PAR(4) to the plasma membrane. PAR(4) was poorly expressed at the plasma membrane and largely retained in the endoplasmic reticulum (ER) in a complex with the COPI protein subunit β-COP1. Analysis of the PAR(4) protein sequence identified an arginine-based (RXR) ER retention sequence located within intracellular loop-2 (R(183)AR → A(183)AA), mutation of which allowed efficient membrane delivery of PAR(4). Interestingly, co-expression with PAR(2) facilitated plasma membrane delivery of PAR(4), an effect produced through disruption of β-COP1 binding and facilitation of interaction with the chaperone protein 14-3-3ζ. Intermolecular FRET studies confirmed heterodimerization between PAR(2) and PAR(4). PAR(2) also enhanced glycosylation of PAR(4) and activation of PAR(4) signaling. Our results identify a novel regulatory role for PAR(2) in the anterograde traffic of PAR(4). PAR(2) was shown to both facilitate and abrogate protein interactions with PAR(4), impacting upon receptor localization and cell signal transduction. This work is likely to impact markedly upon the understanding of the receptor pharmacology of PAR(4) in normal physiology and disease.

  2. Positron Accumulator Ring (PAR) power supply

    International Nuclear Information System (INIS)

    Fathizadeh, M.

    1995-01-01

    The Positron Accumulator Ring (PAR) consists of 8 dipole magnets connected in series. These magnets are energized via one 12-pulse dc power supply. The power supply consists of four phase controlled half-wave wye group converters. Each of the two half-wave converters are connected through an interphase transformer to obtain a full-wave converter with 120 degrees conduction. The input voltage for these two half-wave converters are 180 degrees apart. The two full-wave converters are connected in parallel through a third interphase transformer. This type of connection of the converters not only provides the required output current, it also improves the input power factor of the power supply. The output of the wye group converters is filtered through a passive L-R-C filter to reduce the ripple content of the output current. At low current values of the power supply the current ripple is high, thus a large filter is needed, which adds to the cost of the power supply, however at high output current levels, the current ripple is less severe. The large size of the filter can be reduced by adding an anti-parallel rectifier diode(D1) to the output of the power supply. A freewheeling diode(D2) is connected before the choke to circulate the current once the power supply is turned off. In order to measure the current in the magnet a high precision, low drift, zero flux current transductor is used. This transductor senses the magnet current which provides a feedback signal to control the gating of the converter's thyristors. A true 14 bit Digital to Analog Converter (DAC) is programmed by the control computer for the required current value, providing a reference for the current regulator. Fast correction of the line transients is provided by a relatively fast voltage loop controlled by a high gain slow response current loop

  3. First-in-human uPAR PET

    DEFF Research Database (Denmark)

    Persson, Morten; Skovgaard, Dorthe; Brandt-Larsen, Malene

    2015-01-01

    A first-in-human clinical trial with Positron Emission Tomography (PET) imaging of the urokinase-type plasminogen activator receptor (uPAR) in patients with breast, prostate and bladder cancer, is described. uPAR is expressed in many types of human cancers and the expression is predictive...... for targeted molecular imaging with PET. The safety, pharmacokinetic, biodistribution profile and radiation dosimetry after a single intravenous dose of (64)Cu-DOTA-AE105 were assessed by serial PET and computed tomography (CT) in 4 prostate, 3 breast and 3 bladder cancer patients. Safety assessment...... of invasion, metastasis and indicates poor prognosis. uPAR PET imaging therefore holds promise to be a new and innovative method for improved cancer diagnosis, staging and individual risk stratification. The uPAR specific peptide AE105 was conjugated to the macrocyclic chelator DOTA and labeled with (64)Cu...

  4. Peptide-Based Optical uPAR Imaging for Surgery

    DEFF Research Database (Denmark)

    Juhl, Karina; Christensen, Anders; Persson, Morten

    2016-01-01

    Near infrared intra-operative optical imaging is an emerging technique with clear implications for improved cancer surgery by enabling a more distinct delineation of the tumor margins during resection. This modality has the potential to increase the number of patients having a curative radical...... tumor resection. In the present study, a new uPAR-targeted fluorescent probe was developed and the in vivo applicability was evaluated in a human xenograft mouse model. Most human carcinomas express high level of uPAR in the tumor-stromal interface of invasive lesions and uPAR is therefore considered...... an ideal target for intra-operative imaging. Conjugation of the flourophor indocyanine green (ICG) to the uPAR agonist (AE105) provides an optical imaging ligand with sufficiently high receptor affinity to allow for a specific receptor targeting in vivo. For in vivo testing, human glioblastoma xenograft...

  5. Contribution de la tomographie par coherence optique au diagnostic ...

    African Journals Online (AJOL)

    Contribution de la tomographie par coherence optique au diagnostic de la neuropathie optique toxique. C.O.A. Abouki, S Alamou, C.R.A. Assavedo, L Odoulami-Yehouessi, I Sounouvou, S Hounnou-Tchabi ...

  6. Analysis of ParB-centromere interactions by multiplex SPR imaging reveals specific patterns for binding ParB in six centromeres of Burkholderiales chromosomes and plasmids.

    Directory of Open Access Journals (Sweden)

    Flavien Pillet

    Full Text Available Bacterial centromeres-also called parS, are cis-acting DNA sequences which, together with the proteins ParA and ParB, are involved in the segregation of chromosomes and plasmids. The specific binding of ParB to parS nucleates the assembly of a large ParB/DNA complex from which ParA-the motor protein, segregates the sister replicons. Closely related families of partition systems, called Bsr, were identified on the chromosomes and large plasmids of the multi-chromosomal bacterium Burkholderia cenocepacia and other species from the order Burkholeriales. The centromeres of the Bsr partition families are 16 bp palindromes, displaying similar base compositions, notably a central CG dinucleotide. Despite centromeres bind the cognate ParB with a narrow specificity, weak ParB-parS non cognate interactions were nevertheless detected between few Bsr partition systems of replicons not belonging to the same genome. These observations suggested that Bsr partition systems could have a common ancestry but that evolution mostly erased the possibilities of cross-reactions between them, in particular to prevent replicon incompatibility. To detect novel similarities between Bsr partition systems, we have analyzed the binding of six Bsr parS sequences and a wide collection of modified derivatives, to their cognate ParB. The study was carried out by Surface Plasmon Resonance imaging (SPRi mulitplex analysis enabling a systematic survey of each nucleotide position within the centromere. We found that in each parS some positions could be changed while maintaining binding to ParB. Each centromere displays its own pattern of changes, but some positions are shared more or less widely. In addition from these changes we could speculate evolutionary links between these centromeres.

  7. Analysis of ParB-centromere interactions by multiplex SPR imaging reveals specific patterns for binding ParB in six centromeres of Burkholderiales chromosomes and plasmids.

    Science.gov (United States)

    Pillet, Flavien; Passot, Fanny Marie; Pasta, Franck; Anton Leberre, Véronique; Bouet, Jean-Yves

    2017-01-01

    Bacterial centromeres-also called parS, are cis-acting DNA sequences which, together with the proteins ParA and ParB, are involved in the segregation of chromosomes and plasmids. The specific binding of ParB to parS nucleates the assembly of a large ParB/DNA complex from which ParA-the motor protein, segregates the sister replicons. Closely related families of partition systems, called Bsr, were identified on the chromosomes and large plasmids of the multi-chromosomal bacterium Burkholderia cenocepacia and other species from the order Burkholeriales. The centromeres of the Bsr partition families are 16 bp palindromes, displaying similar base compositions, notably a central CG dinucleotide. Despite centromeres bind the cognate ParB with a narrow specificity, weak ParB-parS non cognate interactions were nevertheless detected between few Bsr partition systems of replicons not belonging to the same genome. These observations suggested that Bsr partition systems could have a common ancestry but that evolution mostly erased the possibilities of cross-reactions between them, in particular to prevent replicon incompatibility. To detect novel similarities between Bsr partition systems, we have analyzed the binding of six Bsr parS sequences and a wide collection of modified derivatives, to their cognate ParB. The study was carried out by Surface Plasmon Resonance imaging (SPRi) mulitplex analysis enabling a systematic survey of each nucleotide position within the centromere. We found that in each parS some positions could be changed while maintaining binding to ParB. Each centromere displays its own pattern of changes, but some positions are shared more or less widely. In addition from these changes we could speculate evolutionary links between these centromeres.

  8. Prise en charge des intoxications par envenimation chez les enfants ...

    African Journals Online (AJOL)

    Les signes cliniques étaient dominés par les douleurs (98%) suivies des hémorragies (73,80%) pour les morsures de serpent, la douleur pour les piqures de scorpion (100%) et les oedèmes pour les piqures d'abeilles (100%). Les cas de morsure de serpent ont été traités par le sérum antivenimeux polyvalent. Conclusion: ...

  9. Intoxication par la paraphényléne-diamine

    African Journals Online (AJOL)

    raoul

    9 mars 2011 ... remède contre la douleur par Averbukh [8], ou contre la constipation par Schemesh [9], mais l´utilisation à des fins autolytique reste toujours prédominante. Le tableau clinique de l´intoxication à ... une anurie ayant nécessité le recours à l´hémodialyse. Ce taux de survenue d´IRA anurique est relativement ...

  10. Croissance epitaxiale de GaAs sur substrats de Ge par epitaxie par faisceaux chimiques

    Science.gov (United States)

    Belanger, Simon

    La situation energetique et les enjeux environnementaux auxquels la societe est confrontee entrainent un interet grandissant pour la production d'electricite a partir de l'energie solaire. Parmi les technologies actuellement disponibles, la filiere du photovoltaique a concentrateur solaire (CPV pour concentrator photovoltaics) possede un rendement superieur et mi potentiel interessant a condition que ses couts de production soient competitifs. La methode d'epitaxie par faisceaux chimiques (CBE pour chemical beam epitaxy) possede plusieurs caracteristiques qui la rendent interessante pour la production a grande echelle de cellules photovoltaiques a jonctions multiples a base de semi-conducteurs III-V. Ce type de cellule possede la meilleure efficacite atteinte a ce jour et est utilise sur les satellites et les systemes photovoltaiques a concentrateur solaire (CPV) les plus efficaces. Une des principales forces de la technique CBE se trouve dans son potentiel d'efficacite d'utilisation des materiaux source qui est superieur a celui de la technique d'epitaxie qui est couramment utilisee pour la production a grande echelle de ces cellules. Ce memoire de maitrise presente les travaux effectues dans le but d'evaluer le potentiel de la technique CBE pour realiser la croissance de couches de GaAs sur des substrats de Ge. Cette croissance constitue la premiere etape de fabrication de nombreux modeles de cellules solaires a haute performance decrites plus haut. La realisation de ce projet a necessite le developpement d'un procede de preparation de surface pour les substrats de germanium, la realisation de nombreuses sceances de croissance epitaxiale et la caracterisation des materiaux obtenus par microscopie optique, microscopie a force atomique (AFM), diffraction des rayons-X a haute resolution (HRXRD), microscopie electronique a transmission (TEM), photoluminescence a basse temperature (LTPL) et spectrometrie de masse des ions secondaires (SIMS). Les experiences ont permis

  11. Evaluation of a multiplex immunoassay for bovine respiratory syncytial virus and bovine coronavirus antibodies in bulk tank milk against two indirect ELISAs using latent class analysis

    DEFF Research Database (Denmark)

    Toftaker, Ingrid; Toft, Nils; Stokstad, Maria

    2018-01-01

    Bovine respiratory syncytial virus (BRSV) and bovine coronavirus (BCV) are responsible for respiratory disease and diarrhea in cattle worldwide. The Norwegian control program against these infections is based on herd-level diagnosis using a new multiplex immunoassay. The objective of this study...... was to estimate sensitivity and specificity across different cut-off values for the MVD-Enferplex BCV/BRSV multiplex, by comparing them to a commercially available ELISA, the SVANOVIR® BCV-Ab and SVANOVIR® BRSV-Ab, respectively. We analyzed bulk tank milk samples from 360 herds in a low- and 360 herds in a high...

  12. 2'-5'-Oligoadenylate Synthetase-Like Protein Inhibits Respiratory Syncytial Virus Replication and Is Targeted by the Viral Nonstructural Protein 1.

    Science.gov (United States)

    Dhar, Jayeeta; Cuevas, Rolando A; Goswami, Ramansu; Zhu, Jianzhong; Sarkar, Saumendra N; Barik, Sailen

    2015-10-01

    2'-5'-Oligoadenylate synthetase-like protein (OASL) is an interferon-inducible antiviral protein. Here we describe differential inhibitory activities of human OASL and the two mouse OASL homologs against respiratory syncytial virus (RSV) replication. Interestingly, nonstructural protein 1 (NS1) of RSV promoted proteasome-dependent degradation of specific OASL isoforms. We conclude that OASL acts as a cellular antiviral protein and that RSV NS1 suppresses this function to evade cellular innate immunity and allow virus growth. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  13. Respiratory Syncytial Virus-Infected Mesenchymal Stem Cells Regulate Immunity via Interferon Beta and Indoleamine-2,3-Dioxygenase.

    Directory of Open Access Journals (Sweden)

    Michael B Cheung

    Full Text Available Respiratory syncytial virus (RSV has been reported to infect human mesenchymal stem cells (MSCs but the consequences are poorly understood. MSCs are present in nearly every organ including the nasal mucosa and the lung and play a role in regulating immune responses and mediating tissue repair. We sought to determine whether RSV infection of MSCs enhances their immune regulatory functions and contributes to RSV-associated lung disease. RSV was shown to replicate in human MSCs by fluorescence microscopy, plaque assay, and expression of RSV transcripts. RSV-infected MSCs showed differentially altered expression of cytokines and chemokines such as IL-1β, IL6, IL-8 and SDF-1 compared to epithelial cells. Notably, RSV-infected MSCs exhibited significantly increased expression of IFN-β (~100-fold and indoleamine-2,3-dioxygenase (IDO (~70-fold than in mock-infected MSCs. IDO was identified in cytosolic protein of infected cells by Western blots and enzymatic activity was detected by tryptophan catabolism assay. Treatment of PBMCs with culture supernatants from RSV-infected MSCs reduced their proliferation in a dose dependent manner. This effect on PBMC activation was reversed by treatment of MSCs with the IDO inhibitors 1-methyltryptophan and vitamin K3 during RSV infection, a result we confirmed by CRISPR/Cas9-mediated knockout of IDO in MSCs. Neutralizing IFN-β prevented IDO expression and activity. Treatment of MSCs with an endosomal TLR inhibitor, as well as a specific inhibitor of the TLR3/dsRNA complex, prevented IFN-β and IDO expression. Together, these results suggest that RSV infection of MSCs alters their immune regulatory function by upregulating IFN-β and IDO, affecting immune cell proliferation, which may account for the lack of protective RSV immunity and for chronicity of RSV-associated lung diseases such as asthma and COPD.

  14. Modulation of Host Immunity by Human Respiratory Syncytial Virus Virulence Factors: A Synergic Inhibition of Both Innate and Adaptive Immunity

    Directory of Open Access Journals (Sweden)

    Gisela Canedo-Marroquín

    2017-08-01

    Full Text Available The Human Respiratory Syncytial Virus (hRSV is a major cause of acute lower respiratory tract infections (ARTIs and high rates of hospitalizations in children and in the elderly worldwide. Symptoms of hRSV infection include bronchiolitis and pneumonia. The lung pathology observed during hRSV infection is due in part to an exacerbated host immune response, characterized by immune cell infiltration to the lungs. HRSV is an enveloped virus, a member of the Pneumoviridae family, with a non-segmented genome and negative polarity-single RNA that contains 10 genes encoding for 11 proteins. These include the Fusion protein (F, the Glycoprotein (G, and the Small Hydrophobic (SH protein, which are located on the virus surface. In addition, the Nucleoprotein (N, Phosphoprotein (P large polymerase protein (L part of the RNA-dependent RNA polymerase complex, the M2-1 protein as a transcription elongation factor, the M2-2 protein as a regulator of viral transcription and (M protein all of which locate inside the virion. Apart from the structural proteins, the hRSV genome encodes for the non-structural 1 and 2 proteins (NS1 and NS2. HRSV has developed different strategies to evade the host immunity by means of the function of some of these proteins that work as virulence factors to improve the infection in the lung tissue. Also, hRSV NS-1 and NS-2 proteins have been shown to inhibit the activation of the type I interferon response. Furthermore, the hRSV nucleoprotein has been shown to inhibit the immunological synapsis between the dendritic cells and T cells during infection, resulting in an inefficient T cell activation. Here, we discuss the hRSV virulence factors and the host immunological features raised during infection with this virus.

  15. Spatial patterns of Bovine Corona Virus and Bovine Respiratory Syncytial Virus in the Swedish beef cattle population

    Directory of Open Access Journals (Sweden)

    Björkman Camilla

    2010-05-01

    Full Text Available Abstract Background Both bovine coronavirus (BCV and bovine respiratory syncytial virus (BRSV infections are currently wide-spread in the Swedish dairy cattle population. Surveys of antibody levels in bulk tank milk have shown very high nationwide prevalences of both BCV and BRSV, with large variations between regions. In the Swedish beef cattle population however, no investigations have yet been performed regarding the prevalence and geographical distribution of BCV and BRSV. A cross-sectional serological survey for BCV and BRSV was carried out in Swedish beef cattle to explore any geographical patterns of these infections. Methods Blood samples were collected from 2,763 animals located in 2,137 herds and analyzed for presence of antibodies to BCV and BRSV. Moran's I was calculated to assess spatial autocorrelation, and identification of geographical cluster was performed using spatial scan statistics. Results Animals detected positive to BCV or BRSV were predominately located in the central-western and some southern parts of Sweden. Moran's I indicated global spatial autocorrelation. BCV and BRSV appeared to be spatially related: two areas in southern Sweden (Skaraborg and Skåne had a significantly higher prevalence of BCV (72.5 and 65.5% respectively; almost the same two areas were identified as being high-prevalence clusters for BRSV (69.2 and 66.8% respectively. An area in south-east Sweden (Kronoberg-Blekinge had lower prevalences for both infections than expected (23.8 and 20.7% for BCV and BRSV respectively. Another area in middle-west Sweden (Värmland-Dalarna had also a lower prevalence for BRSV (7.9%. Areas with beef herd density > 10 per 100 km2 were found to be at significantly higher risk of being part of high-prevalence clusters. Conclusion These results form a basis for further investigations of between-herds dynamics and risk factors for these infections in order to design effective control strategies.

  16. Epidemiological and molecular surveillance of influenza and respiratory syncytial viruses in children with acute respiratory infections (2004/2005 season

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    Alessandra Zappa

    2008-03-01

    Full Text Available Objective. During the 2004/2005 influenza season an active virological surveillance of influenza viruses and respiratory syncytial virus (RSV was carried out to monitor the epidemiologic trend of acute respiratory infections (ARI in the paediatric community. Materials and methods. 100 patients (51 males, 49 females; mean age: 19 months, either treated at the Emergency Unit or hospitalized in the Pediatric Unit of “San Carlo Borromeo Hospital” (Milan, reporting symptoms related to ARI were enrolled. Pharyngeal swabs were collected for virological investigation by: 1 multiplexnested- PCR for the simultaneous identification of both influenza A and B viruses and RSV; 2 multiplex-nested- PCR for the subtyping of influenza A viruses (H1 and H3. Results. 12% (12/100 subjects were infected with influenza A virus, 4% (4/100 with influenza B virus and 14 (14% with RSV. Of all the 12 influenza A positive samples 4 (33.3% belonged to subtype H1 and 8 (66.7% to subtype H3. Bronchiolitis and bronchitis episodes were significantly higher among RSV-infected subjects than among influenza- infected subjects (42.8% vs 6.2%; p<0.05 and 35.7% vs 6.2%; p<0.05, respectively. Pneumonia episodes occurred similarly both in influenza-infected children and in RSV-infected ones. Conclusions. During the 2004/2005 influenza season, influenza viruses and RSV were liable for high morbidity among paediatric subjects.The present study underlies the importance of planning an active surveillance of respiratory viral infections among paediatric cases requiring hospitalization due to ARI.A thorough analysis of target population features, of viruses antigenic properties and seasonality will be decisive in the evaluation of each clinical event.

  17. Design and characterization of epitope-scaffold immunogens that present the motavizumab epitope from respiratory syncytial virus.

    Science.gov (United States)

    McLellan, Jason S; Correia, Bruno E; Chen, Man; Yang, Yongping; Graham, Barney S; Schief, William R; Kwong, Peter D

    2011-06-24

    Respiratory syncytial virus (RSV) is a major cause of respiratory tract infections in infants, but an effective vaccine has not yet been developed. An ideal vaccine would elicit protective antibodies while avoiding virus-specific T-cell responses, which have been implicated in vaccine-enhanced disease with previous RSV vaccines. We propose that heterologous proteins designed to present RSV-neutralizing antibody epitopes and to elicit cognate antibodies have the potential to fulfill these vaccine requirements, as they can be fashioned to be free of viral T-cell epitopes. Here we present the design and characterization of three epitope-scaffolds that present the epitope of motavizumab, a potent neutralizing antibody that binds to a helix-loop-helix motif in the RSV fusion glycoprotein. Two of the epitope-scaffolds could be purified, and one epitope-scaffold based on a Staphylococcus aureus protein A domain bound motavizumab with kinetic and thermodynamic properties consistent with the free epitope-scaffold being stabilized in a conformation that closely resembled the motavizumab-bound state. This epitope-scaffold was well folded as assessed by circular dichroism and isothermal titration calorimetry, and its crystal structure (determined in complex with motavizumab to 1.9 Å resolution) was similar to the computationally designed model, with all hydrogen-bond interactions critical for binding to motavizumab preserved. Immunization of mice with this epitope-scaffold failed to elicit neutralizing antibodies but did elicit sera with F binding activity. The elicitation of F binding antibodies suggests that some of the design criteria for eliciting protective antibodies without virus-specific T-cell responses are being met, but additional optimization of these novel immunogens is required. Published by Elsevier Ltd.

  18. Profilin is required for viral morphogenesis, syncytium formation, and cell-specific stress fiber induction by respiratory syncytial virus

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    Barik Sailen

    2003-05-01

    Full Text Available Abstract Background Actin is required for the gene expression and morphogenesis of respiratory syncytial virus (RSV, a clinically important Pneumovirus of the Paramyxoviridae family. In HEp-2 cells, RSV infection also induces actin stress fibers, which may be important in the immunopathology of the RSV disease. Profilin, a major regulator of actin polymerization, stimulates viral transcription in vitro. Thus, we tested the role of profilin in RSV growth and RSV-actin interactions in cultured cells (ex vivo. Results We tested three cell lines: HEp-2 (human, A549 (human, and L2 (rat. In all three, RSV grew well and produced fused cells (syncytium, and two RSV proteins, namely, the phosphoprotein P and the nucleocapsid protein N, associated with profilin. In contrast, induction of actin stress fibers by RSV occurred in HEp-2 and L2 cells, but not in A549. Knockdown of profilin by RNA interference had a small effect on viral macromolecule synthesis but strongly inhibited maturation of progeny virions, cell fusion, and induction of stress fibers. Conclusions Profilin plays a cardinal role in RSV-mediated cell fusion and viral maturation. In contrast, interaction of profilin with the viral transcriptional proteins P and N may only nominally activate viral RNA-dependent RNA polymerase. Stress fiber formation is a cell-specific response to infection, requiring profilin and perhaps other signaling molecules that are absent in certain cell lines. Stress fibers per se play no role in RSV replication in cell culture. Clearly, the cellular architecture controls multiple steps of host-RSV interaction, some of which are regulated by profilin.

  19. Severe respiratory syncytial virus bronchiolitis in infants is associated with reduced airway interferon gamma and substance P.

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    Malcolm G Semple

    2007-10-01

    Full Text Available Severe human respiratory syncytial virus (hRSV bronchiolitis in previously well infants may be due to differences in the innate immune response to hRSV infection.to determine if factors mediating proposed mechanisms for severe bronchiolitis differ with severity of disease.197 infants admitted to hospital with hRSV bronchiolitis were recruited and grouped according to no oxygen requirement (n = 27, oxygen dependence (n = 114 or mechanical ventilation (n = 56. We collected clinical data, nasopharyngeal aspirate (NPA and if ventilated bronchoalveolar lavage (BAL. Interferon-gamma (IFN-gamma, substance P (SP, interleukin 9 (IL-9, urea and hRSV load, were measured in cell free supernatant from NPA and BAL. Multivariate analysis compared independent effects of clinical, virological and immunological variables upon disease severity. IFN-gamma and SP concentrations were lower in NPA from infants who required oxygen or mechanical ventilation. Viral load and IL-9 concentrations were high but did not vary with severity of disease. Independent predictors of severe disease (in diminishing size of effect were low weight on admission, low gestation at birth, low NPA IFN-gamma and NPA SP. Nasal airway sampling appears to be a useful surrogate for distal airway sampling since concentrations of IFN-gamma, SP, IL-9 and viral load in NPA correlate with the same in BAL.Our data support two proposed mechanisms for severe hRSV disease; reduced local IFN-gamma response and SP mediated inflammation. We found large amounts of hRSV and IL-9 in airways secretions from the upper and lower respiratory tract but could not associate these with disease severity.

  20. Analysis of biennial outbreak pattern of respiratory syncytial virus according to subtype (A and B) in the Zagreb region.

    Science.gov (United States)

    Mlinaric-Galinovic, Gordana; Tabain, Irena; Kukovec, Tamara; Vojnovic, Gordana; Bozikov, Jadranka; Bogovic-Cepin, Jasna; Ivkovic-Jurekovic, Irena; Knezovic, Ivica; Tesovic, Goran; Welliver, Robert C

    2012-06-01

    The epidemic pattern of respiratory syncytial virus (RSV) in Croatia is biennial. In order to determine if the circulation of different RSV subtypes affects the outbreak cycle, the aim of the present study was to analyze the epidemic pattern of RSV in children in Croatia (Zagreb region) over a period of 3 consecutive years. The study group consisted of 696 inpatients, aged 0-5 years, who were hospitalized with acute respiratory tract infections caused by RSV, in Zagreb, in the period 1 January 2006-31 December 2008. The virus was identified in nasopharyngeal secretions using direct immunofluorescence. The virus subtype was determined on real-time polymerase chain reaction. Of 696 RSV infections identified in children, subtype A virus caused 374 infections, and subtype B, 318. Four patients had a dual RSV infection (subtypes A and B). The period of study was characterized by four epidemic waves of RSV infections: the first, smaller, in the spring of 2006; the second, larger, in December 2006/January 2007; the third in spring 2008, followed by a fourth outbreak beginning in November of 2008. The biennial virus cycles were persistent although the predominant RSV subtype in the first two epidemic waves was subtype B, and in the second two it was subtype A. Over a 3 year period of observation, the biennial RSV cycle in Croatia cannot be explained by a difference in the predominant circulating subtype of RSV. Other unknown factors account for the biennial cycle of RSV epidemics in Croatia. © 2011 The Authors. Pediatrics International © 2011 Japan Pediatric Society.

  1. Epidemiology and Molecular Characterization of Human Respiratory Syncytial Virus in Senegal after Four Consecutive Years of Surveillance, 2012–2015

    Science.gov (United States)

    Cisse, El Hadj Abdel Kader; Kiori, Davy E.; Sarr, Fatoumata Diene; Sy, Sara; Goudiaby, Debora; Richard, Vincent; Niang, Mbayame Ndiaye

    2016-01-01

    Background The burden of respiratory syncytial virus (RSV) infection remains poorly defined in Africa. To address this, we carried out a descriptive and retrospective pilot study, with a focus on the epidemiology of RSV in Senegal after 4 years of surveillance. Methodology and Results From January 2012 to October 2015 swabs were collected from consenting ILI outpatients. Viral detection was performed using RV16 kit enabling direct subtyping of RSV-A and B. For the molecular characterization of HRSV, the second hypervariable region of the Glycoprotein (G) gene was targeted for sequencing. We enrolled 5338 patients with 2803 children younger than five years of age (52.5%). 610 (11.4%) were positive for RSV infection: 276 (45.2%) were group A infections, 334 (54.8%) were group B infections and 21 (3.4%) were A/B co-infections. RSV detection rate is significantly higher (P Senegal clustered with strains that were previously assigned NA1 and novel ON1 genotype sequences. RSV-B sequences from Senegal clustered with the BA9 genotype. At the amino acid level, RSV-A strains from Senegal show proximity with the genotype ON1 characterized by a 72 nt insertion in G, resulting in 24 extra amino acids of which 23 are duplications of aa 261–283. Conclusion Globally our results show a clear circulation pattern of RSV in the second half of each year, between June and September and possibly extending into November, with children under 5 being more susceptible. Molecular studies identified the novel strains ON1 and BA9 as the major genotypes circulating in Senegal between 2012 and 2015. PMID:27315120

  2. Epidemiology and Molecular Characterization of Human Respiratory Syncytial Virus in Senegal after Four Consecutive Years of Surveillance, 2012-2015.

    Science.gov (United States)

    Fall, Amary; Dia, Ndongo; Cisse, El Hadj Abdel Kader; Kiori, Davy E; Sarr, Fatoumata Diene; Sy, Sara; Goudiaby, Debora; Richard, Vincent; Niang, Mbayame Ndiaye

    2016-01-01

    The burden of respiratory syncytial virus (RSV) infection remains poorly defined in Africa. To address this, we carried out a descriptive and retrospective pilot study, with a focus on the epidemiology of RSV in Senegal after 4 years of surveillance. From January 2012 to October 2015 swabs were collected from consenting ILI outpatients. Viral detection was performed using RV16 kit enabling direct subtyping of RSV-A and B. For the molecular characterization of HRSV, the second hypervariable region of the Glycoprotein (G) gene was targeted for sequencing. We enrolled 5338 patients with 2803 children younger than five years of age (52.5%). 610 (11.4%) were positive for RSV infection: 276 (45.2%) were group A infections, 334 (54.8%) were group B infections and 21 (3.4%) were A/B co-infections. RSV detection rate is significantly higher (P Senegal clustered with strains that were previously assigned NA1 and novel ON1 genotype sequences. RSV-B sequences from Senegal clustered with the BA9 genotype. At the amino acid level, RSV-A strains from Senegal show proximity with the genotype ON1 characterized by a 72 nt insertion in G, resulting in 24 extra amino acids of which 23 are duplications of aa 261-283. Globally our results show a clear circulation pattern of RSV in the second half of each year, between June and September and possibly extending into November, with children under 5 being more susceptible. Molecular studies identified the novel strains ON1 and BA9 as the major genotypes circulating in Senegal between 2012 and 2015.

  3. Whole genome sequencing and evolutionary analysis of human respiratory syncytial virus A and B from Milwaukee, WI 1998-2010.

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    Cecilia Rebuffo-Scheer

    Full Text Available BACKGROUND: Respiratory Syncytial Virus (RSV is the leading cause of lower respiratory-tract infections in infants and young children worldwide. Despite this, only six complete genome sequences of original strains have been previously published, the most recent of which dates back 35 and 26 years for RSV group A and group B respectively. METHODOLOGY/PRINCIPAL FINDINGS: We present a semi-automated sequencing method allowing for the sequencing of four RSV whole genomes simultaneously. We were able to sequence the complete coding sequences of 13 RSV A and 4 RSV B strains from Milwaukee collected from 1998-2010. Another 12 RSV A and 5 RSV B strains sequenced in this study cover the majority of the genome. All RSV A and RSV B sequences were analyzed by neighbor-joining, maximum parsimony and Bayesian phylogeny methods. Genetic diversity was high among RSV A viruses in Milwaukee including the circulation of multiple genotypes (GA1, GA2, GA5, GA7 with GA2 persisting throughout the 13 years of the study. However, RSV B genomes showed little variation with all belonging to the BA genotype. For RSV A, the same evolutionary patterns and clades were seen consistently across the whole genome including all intergenic, coding, and non-coding regions sequences. CONCLUSIONS/SIGNIFICANCE: The sequencing strategy presented in this work allows for RSV A and B genomes to be sequenced simultaneously in two working days and with a low cost. We have significantly increased the amount of genomic data that is available for both RSV A and B, providing the basic molecular characteristics of RSV strains circulating in Milwaukee over the last 13 years. This information can be used for comparative analysis with strains circulating in other communities around the world which should also help with the development of new strategies for control of RSV, specifically vaccine development and improvement of RSV diagnostics.

  4. Molecular Basis for the Selective Inhibition of Respiratory Syncytial Virus RNA Polymerase by 2'-Fluoro-4'-Chloromethyl-Cytidine Triphosphate.

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    Jerome Deval

    2015-06-01

    Full Text Available Respiratory syncytial virus (RSV causes severe lower respiratory tract infections, yet no vaccines or effective therapeutics are available. ALS-8176 is a first-in-class nucleoside analog prodrug effective in RSV-infected adult volunteers, and currently under evaluation in hospitalized infants. Here, we report the mechanism of inhibition and selectivity of ALS-8176 and its parent ALS-8112. ALS-8176 inhibited RSV replication in non-human primates, while ALS-8112 inhibited all strains of RSV in vitro and was specific for paramyxoviruses and rhabdoviruses. The antiviral effect of ALS-8112 was mediated by the intracellular formation of its 5'-triphosphate metabolite (ALS-8112-TP inhibiting the viral RNA polymerase. ALS-8112 selected for resistance-associated mutations within the region of the L gene of RSV encoding the RNA polymerase. In biochemical assays, ALS-8112-TP was efficiently recognized by the recombinant RSV polymerase complex, causing chain termination of RNA synthesis. ALS-8112-TP did not inhibit polymerases from host or viruses unrelated to RSV such as hepatitis C virus (HCV, whereas structurally related molecules displayed dual RSV/HCV inhibition. The combination of molecular modeling and enzymatic analysis showed that both the 2'F and the 4'ClCH2 groups contributed to the selectivity of ALS-8112-TP. The lack of antiviral effect of ALS-8112-TP against HCV polymerase was caused by Asn291 that is well-conserved within positive-strand RNA viruses. This represents the first comparative study employing recombinant RSV and HCV polymerases to define the selectivity of clinically relevant nucleotide analogs. Understanding nucleotide selectivity towards distant viral RNA polymerases could not only be used to repurpose existing drugs against new viral infections, but also to design novel molecules.

  5. Prospective validation of a prognostic model for respiratory syncytial virus bronchiolitis in late preterm infants: a multicenter birth cohort study.

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    Maarten O Blanken

    Full Text Available This study aimed to update and validate a prediction rule for respiratory syncytial virus (RSV hospitalization in preterm infants 33-35 weeks gestational age (WGA.The RISK study consisted of 2 multicenter prospective birth cohorts in 41 hospitals. Risk factors were assessed at birth among healthy preterm infants 33-35 WGA. All hospitalizations for respiratory tract infection were screened for proven RSV infection by immunofluorescence or polymerase chain reaction. Multivariate logistic regression analysis was used to update an existing prediction model in the derivation cohort (n = 1,227. In the validation cohort (n = 1,194, predicted versus actual RSV hospitalization rates were compared to determine validity of the model.RSV hospitalization risk in both cohorts was comparable (5.7% versus 4.9%. In the derivation cohort, a prediction rule to determine probability of RSV hospitalization was developed using 4 predictors: family atopy (OR 1.9; 95%CI, 1.1-3.2, birth period (OR 2.6; 1.6-4.2, breastfeeding (OR 1.7; 1.0-2.7 and siblings or daycare attendance (OR 4.7; 1.7-13.1. The model showed good discrimination (c-statistic 0.703; 0.64-0.76, 0.702 after bootstrapping. External validation showed good discrimination and calibration (c-statistic 0.678; 0.61-0.74.Our prospectively validated prediction rule identifies infants at increased RSV hospitalization risk, who may benefit from targeted preventive interventions. This prediction rule can facilitate country-specific, cost-effective use of RSV prophylaxis in late preterm infants.

  6. Age related changes in T cell mediated immune response and effector memory to Respiratory Syncytial Virus (RSV in healthy subjects

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    Campoccia Giuseppe

    2010-10-01

    Full Text Available Abstract Respiratory syncytial virus (RSV is the major pathogen causing respiratory disease in young infants and it is an important cause of serious illness in the elderly since the infection provides limited immune protection against reinfection. In order to explain this phenomenon, we investigated whether healthy adults of different age (20-40; 41-60 and > 60 years, have differences in central and effector memory, RSV-specific CD8+ T cell memory immune response and regulatory T cell expression status. In the peripheral blood of these donors, we were unable to detect any age related difference in term of central (CD45RA-CCR7+ and effector (CD45RA-CCR7- memory T cell frequency. On the contrary, we found a significant increase in immunosuppressive regulatory (CD4+25+FoxP3+ T cells (Treg in the elderly. An immunocytofluorimetric RSV pentamer analysis performed on these donors' peripheral blood mononuclear cells (PBMCs, in vitro sensitized against RSV antigen, revealed a marked decline in long-lasting RSV specific CD8+ memory T cell precursors expressing interleukin 7 receptor α (IL-7Rα, in the elderly. This effect was paralleled by a progressive switch from a Th1 (IFN-γ and TNF-α to a Th2 (IL-10 functional phenotype. On the contrary, an increase in Treg was observed with aging. The finding of Treg over-expression status, a prominent Th2 response and an inefficient RSV-specific effector memory CD8+ T cell expansion in older donors could explain the poor protection against RSV reinfection and the increased risk to develop an RSV-related severe illness in this population. Our finding also lays the basis for new therapeutic perspectives that could limit or prevent severe RSV infection in elderly.

  7. Respiratory syncytial virus--the unrecognised cause of health and economic burden among young children in Australia.

    Science.gov (United States)

    Ranmuthugala, Geetha; Brown, Laurie; Lidbury, Brett A

    2011-06-01

    Respiratory syncytial virus (RSV) presents very similar to influenza and is the principle cause of bronchiolitis in infants and young children worldwide. Yet, there is no systematic monitoring of RSV activity in Australia. This study uses existing published data sources to estimate incidence, hospitalisation rates, and associated costs of RSV among young children in Australia. Published reports from the Laboratory Virology and Serology Reporting Scheme, a passive voluntary surveillance system, and the National Hospital Morbidity Dataset were used to estimate RSV-related age-specific hospitalisation rates in New South Wales and Australia. These estimates and national USA estimates of RSV-related hospitalisation rates were applied to Australian population data to estimate RSV incidence in Australia. Direct economic burden was estimated by applying cost estimates used to derive economic cost associated with the influenza virus. The estimated RSV-related hospitalisation rates ranged from 2.2-4.5 per 1,000 among children less than 5 years of age to 8.7-17.4 per 1,000 among infants. Incidence ranged from 110.0-226.5 per 1,000 among the under five age group to 435.0-869.0 per 1,000 among infants. The total annual direct healthcare cost was estimated to be between $24 million and $50 million. Comparison with the health burdens attributed to the influenza virus and rotavirus suggests that the disease burden caused by RSV is potentially much higher. The limitations associated with using a passive surveillance system to estimate disease burden, and the need to explore further assessments and to monitor RSV activity are discussed.

  8. Respiratory syncytial virus: a systematic scientometric analysis of the global publication output and the gender distribution of publishing authors.

    Science.gov (United States)

    Brüggmann, Dörthe; Köster, Corinna; Klingelhöfer, Doris; Bauer, Jan; Ohlendorf, Daniela; Bundschuh, Matthias; Groneberg, David A

    2017-07-26

    Worldwide, the respiratory syncytial virus (RSV) represents the predominant viral agent causing bronchiolitis and pneumonia in children. To conduct research and tackle existing healthcare disparities, RSV-related research activities around the globe need to be described. Hence, we assessed the associated scientific output (represented by research articles) by geographical, chronological and socioeconomic criteria and analysed the authors publishing in the field by gender. Also, the 15 most cited articles and the most prolific journals were identified for RSV research. Retrospective, descriptive study. The NewQIS (New Quality and Quantity Indices in Science) platform was employed to identify RSV-related articles published in the Web of Science until 2013. We performed a numerical analysis of all articles, and examined citation-based aspects (eg, citation rates); results were visualised by density equalising mapping tools. We identified 4600 RSV-related articles. The USA led the field; US-American authors published 2139 articles (46.5%% of all identified articles), which have been cited 83 000 times. When output was related to socioeconomic benchmarks such as gross domestic product or Research and Development expenditures, Guinea-Bissau, The Gambia and Chile were ranked in leading positions. A total of 614 articles on RSV (13.34% of all articles) were attributed to scientific collaborations. These were primarily established between high-income countries. The gender analysis indicated that male scientists dominated in all countries except Brazil. The majority of RSV-related research articles originated from high-income countries whereas developing nations showed only minimal publication productivity and were barely part of any collaborative networks. Hence, research capacity in these nations should be increased in order to assist in addressing inequities in resource allocation and the clinical burden of RSV in these countries. © Article author(s) (or their employer

  9. Effects of formalin-inactivated respiratory syncytial virus (FI-RSV in the perinatal lamb model of RSV.

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    Rachel J Derscheid

    Full Text Available Respiratory syncytial virus (RSV is the most frequent cause of bronchiolitis in infants and children worldwide. There are currently no licensed vaccines or effective antivirals. The lack of a vaccine is partly due to increased caution following the aftermath of a failed clinical trial of a formalin-inactivated RSV vaccine (FI-RSV conducted in the 1960's that led to enhanced disease, necessitating hospitalization of 80% of vaccine recipients and resulting in two fatalities. Perinatal lamb lungs are similar in size, structure and physiology to those of human infants and are susceptible to human strains of RSV that induce similar lesions as those observed in infected human infants. We sought to determine if perinatal lambs immunized with FI-RSV would develop key features of vaccine-enhanced disease. This was tested in colostrum-deprived lambs immunized at 3-5 days of age with FI-RSV followed two weeks later by RSV infection. The FI-RSV-vaccinated lambs exhibited several key features of RSV vaccine-enhanced disease, including reduced RSV titers in bronchoalveolar lavage fluid and lung, and increased infiltration of peribronchiolar and perivascular lymphocytes compared to lambs either undergoing an acute RSV infection or naïve controls; all features of RSV vaccine-enhanced disease. These results represent a first step proof-of-principle demonstration that the lamb can develop altered responses to RSV following FI-RSV vaccination. The lamb model may be useful for future mechanistic studies as well as the assessment of RSV vaccines designed for infants.

  10. Vaccine Induced Herd Immunity for Control of Respiratory Syncytial Virus Disease in a Low-Income Country Setting.

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    Timothy M Kinyanjui

    Full Text Available Respiratory syncytial virus (RSV is globally ubiquitous, and infection during the first six months of life is a major risk for severe disease and hospital admission; consequently RSV is the most important viral cause of respiratory morbidity and mortality in young children. Development of vaccines for young infants is complicated by the presence of maternal antibodies and immunological immaturity, but vaccines targeted at older children avoid these problems. Vaccine development for young infants has been unsuccessful, but this is not the case for older children (> 6 m. Would vaccinating older children have a significant public health impact? We developed a mathematical model to explore the benefits of a vaccine against RSV.We have used a deterministic age structured model capturing the key epidemiological characteristics of RSV and performed a statistical maximum-likelihood fit to age-specific hospitalization data from a developing country setting. To explore the effects of vaccination under different mixing assumptions, we included two versions of contact matrices: one from a social contact diary study, and the second a synthesised construction based on demographic data. Vaccination is assumed to elicit an immune response equivalent to primary infection. Our results show that immunisation of young children (5-10 m is likely to be a highly effective method of protection of infants (<6 m against hospitalisation. The majority benefit is derived from indirect protection (herd immunity. A full sensitivity and uncertainty analysis using Latin Hypercube Sampling of the parameter space shows that our results are robust to model structure and model parameters.This result suggests that vaccinating older infants and children against RSV can have a major public health benefit.

  11. Serum suPAR in patients with FSGS: trash or treasure?

    NARCIS (Netherlands)

    Maas, R.J.H.; Deegens, J.K.J.; Wetzels, J.F.M.

    2013-01-01

    The urokinase-type plasminogen activator receptor (uPAR) has important functions in cell migration. uPAR can be shed from the cell membrane resulting in soluble uPAR (suPAR). Further cleavage gives rise to shorter fragments with largely unknown functions. Recent studies have demonstrated that both

  12. Une terreur par l’image

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    Annie DULONG

    2011-09-01

    Full Text Available Si d’autres événements — Hiroshima, la découverte des camps de concentration, la chute du mur de Berlin — ont, au cours du XXe siècle, marqué suffisamment l’imaginaire pour trouver leur réponse dans des œuvres d’art, le 11 septembre 2001 pose la question de la fictionnalisation autrement : il ne s’agit plus tant de combler les manques de la représentation, liés à l’absence d’images ou au délai dans leur dévoilement, mais bien de composer avec l’omniprésence d’une représentation martelée à la télévision et sur Internet. Que cette représentation soit partielle, tronquée et qu’il lui manque la présence des corps, ces grands absents des photographies et des images tournées par les journalistes, ne change rien au fait que c’est avec le trop-plein que les artistes doivent maintenant négocier.Cet article s’intéresse aux romans qui traitent l’événement de front au lieu de l’aborder sur un mode mineur, et a pour objectif de tracer un portrait de la représentation des médias dans les romans du 11 septembre 2001. Ces romans, outre le fait qu’ils traitent des événements de New York, ont comme point commun un personnage, ou décor : les médias, représentés par la télévision, l’Internet, les photographies de presse, interviennent dans les récits d’une manière significative et témoignent de la force brute des images. À travers une étude de certains des mécanismes à l’œuvre dans The Writing on the Wall (Lynne Sharon Schwartz, Extremely Loud and Incredibly Close (Jonathan Safran Foer, Falling Man (Don DeLillo et A Disorder Peculiar to the Country (Ken Kalfus, il s’agira de proposer des réponses à ces quelques questions : quel rôle les médias jouent-ils, et comment participent-ils au récit ? Quelle pression les images exercent-elles sur les personnages ? Que révèlent les personnages enfants dans leur rapport aux médias ? Quelle critique, finalement, les romans

  13. Par Pond vegetation status Summer 1995 -- June survey descriptive summary

    International Nuclear Information System (INIS)

    Mackey, H.E. Jr.; Riley, R.S.

    1995-06-01

    The water level of Par Pond was lowered approximately 20 feet in mid-1991 in order to protect downstream residents from possible dam failure suggested by subsidence on the downstream slope of the dam and to repair the dam. This lowering exposed both emergent and nonemergent macrophyte beds to drying conditions resulting in extensive losses. A survey of the shoreline aquatic plant communities in June 1995, three months after the refilling of Par Pond to approximately 200 feet above mean sea level, indicated that much of the original plant communities and the intermediate shoreline communities present on the exposed sediments have been lost. The extensive old-field and emergent marsh communities that were present on the exposed shoreline during the drawdown have been flooded and much of the pre-drawdown Par Pond aquatic plant communities have not had sufficient time for re-establishment. The shoreline does, however, have extensive beds of maidencane which extend from the shoreline margin to areas as deep as 2 and perhaps 3 meters. Scattered individual plants of lotus and watershield are common and may indicate likely directions of future wetland development in Par Pond. In addition, within isolated coves, which apparently received ground water seepage and/or stream surface flows during the period of the Par Pond draw down, extensive beds of waterlilies and spike rush are common. Invasion of willow and red maple occurred along the lake shoreline as well. Although not absent from this survey, evidence of the extensive redevelopment of the large cattail and eel grass beds was not observed in this first survey of Par Pond. Future surveys during the growing seasons of 1995, 1996, and 1997 along with the evaluation of satellite date to map the areal extent of the macrophyte beds of Par Pond are planned

  14. Polyclonal and monoclonal antibodies specific for the six-helix bundle of the human respiratory syncytial virus fusion glycoprotein as probes of the protein post-fusion conformation

    International Nuclear Information System (INIS)

    Palomo, Concepción; Mas, Vicente; Vázquez, Mónica; Cano, Olga; Luque, Daniel; Terrón, María C.; Calder, Lesley J.; Melero, José A.

    2014-01-01

    Human respiratory syncytial virus (hRSV) has two major surface glycoproteins (G and F) anchored in the lipid envelope. Membrane fusion promoted by hRSV F occurs via refolding from a pre-fusion form to a highly stable post-fusion state involving large conformational changes of the F trimer. One of these changes results in assembly of two heptad repeat sequences (HRA and HRB) into a six-helix bundle (6HB) motif. To assist in distinguishing pre- and post-fusion conformations of hRSV F , we have prepared polyclonal (α-6HB) and monoclonal (R145) rabbit antibodies specific for the 6HB. Among other applications, these antibodies were used to explore the requirements of 6HB formation by isolated protein segments or peptides and by truncated mutants of the F protein. Site-directed mutagenesis and electron microscopy located the R145 epitope in the post-fusion hRSV F at a site distantly located from previously mapped epitopes, extending the repertoire of antibodies that can decorate the F molecule. - Highlights: • Antibodies specific for post-fusion respiratory syncytial virus fusion protein are described. • Polyclonal antibodies were obtained in rabbit inoculated with chimeric heptad repeats. • Antibody binding required assembly of a six-helix bundle in the post-fusion protein. • A monoclonal antibody with similar structural requirements is also described. • Binding of this antibody to the post-fusion protein was visualized by electron microscopy

  15. Morphogenesis of respiratory syncytial virus in human primary nasal ciliated epithelial cells occurs at surface membrane microdomains that are distinct from cilia

    International Nuclear Information System (INIS)

    Jumat, Muhammad Raihan; Yan, Yan; Ravi, Laxmi Iyer; Wong, Puisan; Huong, Tra Nguyen; Li, Chunwei; Tan, Boon Huan; Wang, De Yun; Sugrue, Richard J.

    2015-01-01

    The distribution of cilia and the respiratory syncytial virus (RSV) nucleocapsid (N) protein, fusion (F) protein, attachment (G) protein, and M2-1 protein in human ciliated nasal epithelial cells was examined at between 1 and 5 days post-infection (dpi). All virus structural proteins were localized at cell surface projections that were distinct from cilia. The F protein was also trafficked into the cilia, and while its presence increased as the infection proceeded, the N protein was not detected in the cilia at any time of infection. The presence of the F protein in the cilia correlated with cellular changes in the cilia and reduced cilia function. At 5 dpi extensive cilia loss and further reduced cilia function was noted. These data suggested that although RSV morphogenesis occurs at non-cilia locations on ciliated nasal epithelial cells, RSV infection induces changes in the cilia body that leads to extensive cilia loss. - Highlights: • Respiratory syncytial virus (RSV) infects nasal ciliated epithelial cells. • Virus morphogenesis occurs within filamentous projections distinct from cilia. • The RSV N protein was not detected in the cilia at any time during infection. • Trafficking of the F protein into the cilia occurred early in infection. • Presence of the F protein in cilia correlated with impaired cilia function

  16. Morphogenesis of respiratory syncytial virus in human primary nasal ciliated epithelial cells occurs at surface membrane microdomains that are distinct from cilia

    Energy Technology Data Exchange (ETDEWEB)

    Jumat, Muhammad Raihan [School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551 (Singapore); Yan, Yan [Department of Otolaryngology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore 119228 (Singapore); Ravi, Laxmi Iyer [School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551 (Singapore); Wong, Puisan [Detection and Diagnostics Laboratory, DSO National Laboratories, 27 Medical Drive, Singapore 117510 (Singapore); Huong, Tra Nguyen [School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551 (Singapore); Li, Chunwei [Department of Otolaryngology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore 119228 (Singapore); Tan, Boon Huan [Detection and Diagnostics Laboratory, DSO National Laboratories, 27 Medical Drive, Singapore 117510 (Singapore); Wang, De Yun [Department of Otolaryngology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore 119228 (Singapore); Sugrue, Richard J., E-mail: rjsugrue@ntu.edu.sg [School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551 (Singapore)

    2015-10-15

    The distribution of cilia and the respiratory syncytial virus (RSV) nucleocapsid (N) protein, fusion (F) protein, attachment (G) protein, and M2-1 protein in human ciliated nasal epithelial cells was examined at between 1 and 5 days post-infection (dpi). All virus structural proteins were localized at cell surface projections that were distinct from cilia. The F protein was also trafficked into the cilia, and while its presence increased as the infection proceeded, the N protein was not detected in the cilia at any time of infection. The presence of the F protein in the cilia correlated with cellular changes in the cilia and reduced cilia function. At 5 dpi extensive cilia loss and further reduced cilia function was noted. These data suggested that although RSV morphogenesis occurs at non-cilia locations on ciliated nasal epithelial cells, RSV infection induces changes in the cilia body that leads to extensive cilia loss. - Highlights: • Respiratory syncytial virus (RSV) infects nasal ciliated epithelial cells. • Virus morphogenesis occurs within filamentous projections distinct from cilia. • The RSV N protein was not detected in the cilia at any time during infection. • Trafficking of the F protein into the cilia occurred early in infection. • Presence of the F protein in cilia correlated with impaired cilia function.

  17. Polyclonal and monoclonal antibodies specific for the six-helix bundle of the human respiratory syncytial virus fusion glycoprotein as probes of the protein post-fusion conformation

    Energy Technology Data Exchange (ETDEWEB)

    Palomo, Concepción; Mas, Vicente; Vázquez, Mónica; Cano, Olga [Unidad de Biología Viral, Centro Nacional de Microbiología, Madrid (Spain); CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Majadahonda, 28220 Madrid (Spain); Luque, Daniel; Terrón, María C. [Unidad de Microscopía Electrónica y Confocal, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, 28220 Madrid (Spain); Calder, Lesley J. [National Institute for Medical Research, MRC, Mill Hill, London NW7 1AA (United Kingdom); Melero, José A., E-mail: jmelero@isciii.es [Unidad de Biología Viral, Centro Nacional de Microbiología, Madrid (Spain); CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Majadahonda, 28220 Madrid (Spain)

    2014-07-15

    Human respiratory syncytial virus (hRSV) has two major surface glycoproteins (G and F) anchored in the lipid envelope. Membrane fusion promoted by hRSV{sub F} occurs via refolding from a pre-fusion form to a highly stable post-fusion state involving large conformational changes of the F trimer. One of these changes results in assembly of two heptad repeat sequences (HRA and HRB) into a six-helix bundle (6HB) motif. To assist in distinguishing pre- and post-fusion conformations of hRSV{sub F}, we have prepared polyclonal (α-6HB) and monoclonal (R145) rabbit antibodies specific for the 6HB. Among other applications, these antibodies were used to explore the requirements of 6HB formation by isolated protein segments or peptides and by truncated mutants of the F protein. Site-directed mutagenesis and electron microscopy located the R145 epitope in the post-fusion hRSV{sub F} at a site distantly located from previously mapped epitopes, extending the repertoire of antibodies that can decorate the F molecule. - Highlights: • Antibodies specific for post-fusion respiratory syncytial virus fusion protein are described. • Polyclonal antibodies were obtained in rabbit inoculated with chimeric heptad repeats. • Antibody binding required assembly of a six-helix bundle in the post-fusion protein. • A monoclonal antibody with similar structural requirements is also described. • Binding of this antibody to the post-fusion protein was visualized by electron microscopy.

  18. Par Pond vegetation status Summer 1995 -- September survey descriptive summary

    International Nuclear Information System (INIS)

    Mackey, H.E. Jr.; Riley, R.S.

    1995-09-01

    The water level of Par Pond was lowered approximately 20 feet in mid-1991 in order to protect downstream residents from possible dam failure suggested by subsidence on the downstream slope of the dam and to repair the dam. This lowering exposed both emergent and nonemergent macrophyte beds to drying conditions resulting in extensive losses. A survey of the emergent shoreline aquatic plant communities began in June 1995, three months after the refilling of Par Pond to approximately 200 feet above mean sea level and continued with this mid-September survey. Communities similar to the pre-drawdown Par Pond aquatic plant communities are becoming re-established; especially, beds of maidencane, lotus, waterlily, and watershield are now extensive and well established. Cattail occurrence continues to increase, but large beds common to Par Pond prior to the drawdown have not formed. Future surveys during the late growing seasons of 1995, and throughout 1996 and 1997, along with the evaluation of satellite data to map the areal extent of the macrophyte beds of Par Pond, are planned

  19. Par Pond vegetation status Summer 1995 -- October survey descriptive summary

    International Nuclear Information System (INIS)

    Mackey, H.E. Jr.; Riley, R.S.

    1995-11-01

    The water level of Par Pond was lowered approximately 20 feet in mid-1991 in order to protect downstream residents from possible dam failure suggested by subsidence on the downstream slope of the dam and to repair the dam. This lowering exposed both emergent and nonemergent macrophyte beds to drying conditions resulting in extensive losses. A survey of the emergent shoreline aquatic plant communities began in June 1995, three months after the refilling of Par Pond to approximately 200 feet above mean sea level and continued with this late October survey. Communities similar to the pre-drawdown Par Pond aquatic plant communities are becoming re-established; especially, beds of maiden cane, lotus, waterlily, and watershield are now extensive and well established. Cattail occurrence continues to increase, but large beds common to Par Pond prior to the drawdown have not formed. Future surveys throughout 1996 and 1997, along with the continued evaluation of satellite data to map the areal extent of the macrophyte beds of Par Pond, are planned

  20. [Ambroise Paré, his death and his historians].

    Science.gov (United States)

    Dumaître, P

    2001-01-01

    Ambroise Paré died December the 20th., 1590. What happened after his death and what are we knowing about his life? Never forgotten, though a lack of care, we were waiting till the XIXth. century to get recollection upon a subject sustained only by accounts of his travels. After Percy, a surgeon who tried to write Paré's biography through the "Biographie universelle ancienne et moderne, de Michaud (1822)" and some second rank authors, Malgaigne is the first who inside a printing of the "Oeuvres complétes de Paré (1840-41)" has a fine look upon the question, though his work is incomplete and allows many mistakes. Doctors Chéreau and Jal, an historian, analysing civil status records, gave new information enlarged by doctors Le Paulmier, Turner and the U.S. native Janet Doe.

  1. Keratometric alterations following the 25-gauge transconjunctival sutureless pars plana vitrectomy versus the conventional pars plana vitrectomy.

    Science.gov (United States)

    Citirik, Mehmet; Batman, Cosar; Bicer, Tolga; Zilelioglu, Orhan

    2009-09-01

    To assess the alterations in keratometric astigmatism following the 25-gauge transconjunctival sutureless pars plana vitrectomy versus the conventional pars plana vitrectomy. Sixteen consecutive patients were enrolled into the study. Conventional vitrectomy was applied to eight of the cases and 25-gauge transconjunctival sutureless vitrectomy was performed in eight patients. Keratometry was performed before and after the surgery. In the 25-gauge transconjunctival sutureless pars plana vitrectomy group, statistically significant changes were not observed in the corneal curvature in any post-operative follow-up measurement (p > 0.05); whereas in the conventional pars plana vitrectomy group, statistically significant changes were observed in the first postoperative day (p = 0.01) and first postoperative month (p = 0.03). We noted that these changes returned to baseline in three months (p = 0.26). Both 25-gauge transconjunctival sutureless and conventional pars plana vitrectomy are effective surgical modalities for selected diseases of the posterior segment. Surgical procedures are critical for the visual rehabilitation of the patients. The post-operative corneal astigmatism of the vitrectomised eyes can be accurately determined at least two months post-operatively.

  2. Cyclanthaceae no estado do Pará, Brasil Cyclanthaceae in Pará State, Brazil

    Directory of Open Access Journals (Sweden)

    Eduardo da Silva Leal

    2012-12-01

    Full Text Available Cyclanthaceae apresenta distribuição exclusiva na região neotropical sendo bem diversificada nas terras baixas das florestas pluviais tropicais, ocorrendo do sul do México até a Mata Atlântica do sul do Brasil. Consistem de ervas terrestres, epífitas, hemiepífitas ou lianas. O tratamento taxonômico de Cyclanthaceae no Pará foi baseado em coleções de herbário, trabalhos de campo e consulta a bibliografia referente à família. Foram registradas 11 espécies: Asplundia altiscandens E.S. Leal, A. fanshawei (Maguire Harling, A. glandulosa (Gleason Harling, A. heteranthera Harling, A. latifrons (Drude Harling, A. schizotepala Harling, A. xiphophylla Harling, Cyclanthus bipartitus Poit. ex A. Rich., Evodianthus funifer (Poit. Lindm., Ludovia lancifolia Brongn. e Thoracocarpus bissectus (Vell. Harling. São apresentadas chave de identificação, descrições e ilustrações das espécies, além de comentários sobre distribuição geográfica, hábitat e período de floração e frutificação.Cyclanthaceae is a family with a distribution exclusively in the Neotropics and is well diversified in lowland rainforests, occurring from southern Mexico to the Atlantic Forest of southern Brazil. The family consists of terrestrial herbs, epiphytes, hemiepiphytes and lianas. This taxonomic treatment of the Cyclanthaceae from the state of Pará was based on herbarium specimens, fieldwork, and the literature. Eleven species were recorded: Asplundia altiscandens E.S. Leal, A. fanshawei (Maguire Harling, A. glandulosa (Gleason Harling, A. heteranthera Harling, A. latifrons (Drude Harling, A. schizotepala Harling, A. xiphophylla Harling, Cyclanthus bipartitus Poit. ex A. Rich., Evodianthus funifer (Poit. Lindm., Ludovia lancifolia Brongn. and Thoracocarpus bissectus (Vell. Harling. An identification key, descriptions and illustrations of species are presented. Additional information on the geographic distribution, habitat, and flowering and

  3. Canning by the diffusion caused by a heated die; Gainage par diffusion par filiere chauffante

    Energy Technology Data Exchange (ETDEWEB)

    Gauthron, M [Commissariat a l' Energie Atomique, Saclay (France).Centre d' Etudes Nucleaires

    1959-07-01

    In this process, the uranium fuel is clad with a zirconium can by passing the element through a die. The operation takes place at a temperature varying between 500 and 1000 deg. C. The heating is obtained by passing low voltage electric current through the can. This process differs from the co-extrusion process in that the uranium is not deformed. The uranium is therefore machined to the final dimensions before canning, it can also be hollow. Two types of processes can be adopted for the extrusion: a) Process in which the binding of the can to the uranium is obtained without diffusion (here the can is at high temperature - subsequently cooled - and the uranium is at a low temperature); b) Process in which uranium-zirconium diffusion is initiated. No matter which process is adopted the element is subsequently heat treated in an over at 800 deg. C in order to obtain the final diffusion. The quality of this diffusion is dependent on the initial state of the surfaces and on the degree of vacuum maintained during the operation. (author) [French] Dans ce procede, la gaine zirconium est plaquee sur le combustible uranium par passage dans une filiere. L'operation a lieu a chaud, a une temperature variant entre 500 et 1000 deg. C. Le chauffage est assure par passage d'un courant basse tension dans la gaine. A la difference du procede de cofilage, l'uranium ne subit pas de deformation durant l'operation. Il est donc prealablement usine aux cotes definitives et peut etre creux. Deux processus sont possibles pendant le passage dans la filiere: a) Obtention d'un frettage de la gaine sur l'uranium sans diffusion (avec une gaine a haute temperature et un tube d'uranium a basse temperature, eventuellement refroidi); b) Obtention d'un commencement de diffusion uranium-zirconium. Quelque soit le processus adopte, la cartouche est ensuite traitee dans un four a 800 deg. C pour obtenir la diffusion definitive. La qualite de celle-ci depend essentiellement des etats de surface initiaux

  4. La projection par plasma : une revue

    Science.gov (United States)

    Fauchais, P.; Grimaud, A.; Vardelle, A.; Vardelle, M.

    are presented in the fields of aeronautics and mechanics. La qualité d'un dépôt projete par plasma dépend de nombreux paramètres que l'on commence à mieux appréhender du fait des progrès de la modélisation et de la métrologie tant des écoulements plasmas que des transferts plasma-particules ou que des conditions d'écrasement et de refroidissement des particules lors de leur impact sur le substrat ou les couches déjà déposées. Les techniques de mesure utilisdes et leurs limitations sont d'abord rappelées tant pour les jets de plasma que pour les particules en vol et l'importance des différents phénomènes intervenant dans les transferts plasma-particules est soulignée : gradients de température et de concentration d'espèces chimiques très élevés autour des particules, effets de propagation de la chaleur, notamment pour les particules céramiques, effet d'évaporation, effet de raréfaction sensible dès la pression atmosphérique. Les problèmes de distribution de taille et de vitesse d'injection des particules sont également abordés car ils conditionnent les distributions de trajectoires et donc le traitement des particules dans le jet de plasma. La génération du plasma montre d'une part 1'influence considérable de l'injection du gaz, de sa nature, du dessin de la chambre d'arc et de la tuyère ainsi que du pompage de l'air ambiant sur la longueur des jets de plasma d'arc et d'autre part les problèmes d'injection pour éviter le couplage avec la décharge dans les jets de plasmas R.E Tout ceci est illustré avec des exemples de dépôt d'alumine, de zircone, de cermet carbure et de nickel. L'écrasement des particules est ensuite abordé avec les problèmes de réactions chimiques, de trempe ultra-rapide et donc de structure cristalline des dépôts, d'adhdsion mais aussi de containtes résiduelles et de leur contrôle via les gradients de température dans les dépôts pendant le tir. Enfin quelques applications actuelles sont pr

  5. ROLE OF PREEXISTING VIRUS-SPECIFIC IgG IN PRIMARY DISEASE AND IN REINFECTION WITH RESPIRATORY SYNCYTIAL VIRUS

    Directory of Open Access Journals (Sweden)

    V. Z. Krivitskaya

    2012-01-01

    Full Text Available Abstract. The aim of the study is evaluation of links between presence in blood of specific pre-existing IgG to respiratory-syncytial virus (RSV, clinical course of RSV infection and character specific to RSV humoral immune response in patients of different ages. The antibodies were detected by ELISA using whole RS virus or synthetic peptides corresponded to the selected determinants of the envelope RSV proteins. It was shown that RS specific maternal IgG antibodies passively transferred to babies in utero can circulate in the blood up to 10 months of life. The analysis of paired sera of 45 babies in the age of 1–10 months revealed firstly that presence of maternal IgG specific antibodies to the conservative B-cell immunogenic determinants of the F-protein (amino acids 221–232 and/or the G-protein (amino acids 152–164 and 184–198 is coupled with more high morbidity of primary RSV infection (89% versus 56%, p = 0.023, and also with more high frequency of complicated by bronchus obstruction course of the disease (81% versus 20%, р = 0.001 in compare with babies who were serologically negative to the maternal determinants specific antibodies. The correlation analysis has shown that the high presence of maternal determinant-specific IgG in the blood in babies till 10 months of life is associated in the case of primary infection with disbalance of humoral anti-viral immune response: intensive synthesis of serum RSV IgA. This is evidence of complicated course of infection with simultaneous suppression of response to RSV specific IgG. As opposed to the primary RSV infection in patients older than 3 years (n = 121 it was not detected links between anamnestic determinant-specific IgG synthesized by own immune system as the results of previous disease episodes and synthesis of anti-RSV IgG, IgM, IgE and IgA in RSV re-infections. In the contrast to babies in more older patients the feedback connection between level of pre-existing determinant

  6. Bovine respiratory syncytial virus and bovine coronavirus antibodies in bulk tank milk - risk factors and spatial analysis.

    Science.gov (United States)

    Toftaker, Ingrid; Sanchez, Javier; Stokstad, Maria; Nødtvedt, Ane

    2016-10-01

    Bovine respiratory syncytial virus (BRSV) and bovine coronavirus (BCoV) are considered widespread among cattle in Norway and worldwide. This cross-sectional study was conducted based on antibody-ELISA of bulk tank milk (BTM) from 1347 herds in two neighboring counties in western Norway. The study aims were to determine the seroprevalence at herd level, to evaluate risk factors for BRSV and BCoV seropositivity, and to assess how these factors were associated with the spatial distribution of positive herds. The overall prevalence of BRSV and BCoV positive herds in the region was 46.2% and 72.2%, respectively. Isopleth maps of the prevalence risk distribution showed large differences in prevalence risk across the study area, with the highest prevalence in the northern region. Common risk factors of importance for both viruses were herd size, geographic location, and proximity to neighbors. Seropositivity for one virus was associated with increased odds of seropositivity for the other virus. Purchase of livestock was an additional risk factor for BCoV seropositivity, included in the model as in-degree, which was defined as the number of incoming movements from individual herds, through animal purchase, over a period of five years. Local dependence and the contribution of risk factors to this effect were assessed using the residuals from two logistic regression models for each virus. One model contained only the x- and y- coordinates as predictors, the other had all significant predictors included. Spatial clusters of high values of residuals were detected using the normal model of the spatial scan statistic and visualized on maps. Adjusting for the risk factors in the final models had different impact on the spatial clusters for the two viruses: For BRSV the number of clusters was reduced from six to four, for BCoV the number of clusters remained the same, however the log-likelihood ratios changed notably. This indicates that geographical differences in proximity to

  7. Adjuvants and the vaccine response to the DS-Cav1-stabilized fusion glycoprotein of respiratory syncytial virus.

    Directory of Open Access Journals (Sweden)

    Mallika Sastry

    Full Text Available Appropriate adjuvant selection may be essential to optimize the potency and to tailor the immune response of subunit vaccines. To induce protective responses against respiratory syncytial virus (RSV-a highly prevalent childhood pathogen without a licensed vaccine-we previously engineered a pre-fusion-stabilized trimeric RSV F (pre-F "DS-Cav1" immunogen, which induced high titer RSV-neutralizing antibodies, in mice and non-human primates, when formulated with adjuvants Poly (I:C and Poly (IC:LC, respectively. To assess the impact of different adjuvants, here we formulated RSV F DS-Cav1 with multiple adjuvants and assessed immune responses. Very high RSV-neutralizing antibody responses (19,006 EC50 were observed in naïve mice immunized with 2 doses of DS-Cav1 adjuvanted with Sigma adjuvant system (SAS, an oil-in-water adjuvant, plus Carbopol; high responses (3658-7108 were observed with DS-Cav1 adjuvanted with Alum, SAS alone, Adjuplex, Poly (I:C and Poly (IC:LC; and moderate responses (1251-2129 were observed with DS-Cav1 adjuvanted with the TLR4 agonist MPLA, Alum plus MPLA or AddaVax. In contrast, DS-Cav1 without adjuvant induced low-level responses (6. A balanced IgG1 and IgG2a (Th2/Th1 immune response was elicited in most of the high to very high response groups (all but Alum and Adjuplex. We also tested the immune response induced by DS-Cav1 in elderly mice with pre-existing DS-Cav1 immunity; we observed that DS-Cav1 adjuvanted with SAS plus Carbopol boosted the response 2-3-fold, whereas DS-Cav1 adjuvanted with alum boosted the response 5-fold. Finally, we tested whether a mixture of ISA 71 VG and Carbopol would enhanced the antibody response in DS-Cav1 immunized calves. While pre-F-stabilized bovine RSV F induced very high titers in mice when adjuvanted with SAS plus Carbopol, the addition of Carbopol to ISA 71 VG did not enhance immune responses in calves. The vaccine response to pre-F-stabilized RSV F is augmented by adjuvant, but the

  8. Long-Term Shedding of Influenza Virus, Parainfluenza Virus, Respiratory Syncytial Virus and Nosocomial Epidemiology in Patients with Hematological Disorders.

    Directory of Open Access Journals (Sweden)

    Nicola Lehners

    Full Text Available Respiratory viruses are a cause of upper respiratory tract infections (URTI, but can be associated with severe lower respiratory tract infections (LRTI in immunocompromised patients. The objective of this study was to investigate the genetic variability of influenza virus, parainfluenza virus and respiratory syncytial virus (RSV and the duration of viral shedding in hematological patients. Nasopharyngeal swabs from hematological patients were screened for influenza, parainfluenza and RSV on admission as well as on development of respiratory symptoms. Consecutive swabs were collected until viral clearance. Out of 672 tested patients, a total of 111 patients (17% were infected with one of the investigated viral agents: 40 with influenza, 13 with parainfluenza and 64 with RSV; six patients had influenza/RSV or parainfluenza/RSV co-infections. The majority of infected patients (n = 75/111 underwent stem cell transplantation (42 autologous, 48 allogeneic, 15 autologous and allogeneic. LRTI was observed in 48 patients, of whom 15 patients developed severe LRTI, and 13 patients with respiratory tract infection died. Phylogenetic analysis revealed a variety of influenza A(H1N1pdm09, A(H3N2, influenza B, parainfluenza 3 and RSV A, B viruses. RSV A was detected in 54 patients, RSV B in ten patients. The newly emerging RSV A genotype ON1 predominated in the study cohort and was found in 48 (75% of 64 RSV-infected patients. Furthermore, two distinct clusters were detected for RSV A genotype ON1, identical RSV G gene sequences in these patients are consistent with nosocomial transmission. Long-term viral shedding for more than 30 days was significantly associated with prior allogeneic transplantation (p = 0.01 and was most pronounced in patients with RSV infection (n = 16 with a median duration of viral shedding for 80 days (range 35-334 days. Long-term shedding of respiratory viruses might be a catalyzer of nosocomial transmission and must be considered for

  9. Nasally administered Lactobacillus rhamnosus strains differentially modulate respiratory antiviral immune responses and induce protection against respiratory syncytial virus infection.

    Science.gov (United States)

    Tomosada, Yohsuke; Chiba, Eriko; Zelaya, Hortensia; Takahashi, Takuya; Tsukida, Kohichiro; Kitazawa, Haruki; Alvarez, Susana; Villena, Julio

    2013-08-15

    Some studies have shown that nasally administered immunobiotics had the potential to improve the outcome of influenza virus infection. However, the capacity of immunobiotics to improve protection against respiratory syncytial virus (RSV) infection was not investigated before. The aims of this study were: a) to evaluate whether the nasal administration of Lactobacillus rhamnosus CRL1505 (Lr05) and L. rhamnosus CRL1506 (Lr06) are able to improve respiratory antiviral defenses and beneficially modulate the immune response triggered by TLR3/RIG-I activation; b) to investigate whether viability of Lr05 or Lr06 is indispensable to modulate respiratory immunity and; c) to evaluate the capacity of Lr05 and Lr06 to improve the resistance of infant mice against RSV infection. Nasally administered Lr05 and Lr06 differentially modulated the TLR3/RIG-I-triggered antiviral respiratory immune response. Lr06 administration significantly modulated the production of IFN-α, IFN-β and IL-6 in the response to poly(I:C) challenge, while nasal priming with Lr05 was more effective to improve levels of IFN-γ and IL-10. Both viable Lr05 and Lr06 strains increased the resistance of infant mice to RSV infection while only heat-killed Lr05 showed a protective effect similar to those observed with viable strains. The present work demonstrated that nasal administration of immunobiotics is able to beneficially modulate the immune response triggered by TLR3/RIG-I activation in the respiratory tract and to increase the resistance of mice to the challenge with RSV. Comparative studies using two Lactobacillus rhamnosus strains of the same origin and with similar technological properties showed that each strain has an specific immunoregulatory effect in the respiratory tract and that they differentially modulate the immune response after poly(I:C) or RSV challenges, conferring different degree of protection and using distinct immune mechanisms. We also demonstrated in this work that it is possible

  10. Association of Age With Risk of Hospitalization for Respiratory Syncytial Virus in Preterm Infants With Chronic Lung Disease.

    Science.gov (United States)

    Winterstein, Almut G; Choi, Yoonyoung; Meissner, H Cody

    2018-02-01

    It is unknown whether the age threshold (≤24 months) for preterm infants with chronic lung disease (CLD) to receive immunoprophylaxis for respiratory syncytial virus (RSV) as currently recommended by American Academy of Pediatrics guidelines correctly identified infants at higher risk for hospitalization for RSV. To determine the age when the risk of hospitalization for RSV among preterm infants with CLD becomes equivalent to the risk for healthy, 1-month-old term infants who do not qualify for immunoprophylaxis. A retrospective cohort study was conducted of 1 018 593 healthy term infants and 5181 preterm infants with CLD using Medicaid billing records (Medicaid Analytic eXtract files) from January 1, 1999, to December 31, 2010, linked to Florida and Texas birth and death certificates. Age-trend discrete time logistic regression models within a survival analysis framework were developed, adjusting for covariates including the use of immunoprophylaxis, to compare the risk of hospitalization of preterm infants (CLD at 3 through 34 months of age with the risk of hospitalization of term infants (37-41 weeks' gestational age) at 1 month of age. Age at which risk of hospitalization for RSV among preterm infants with CLD equals the risk for healthy term infants at age 1 month. The study cohort included 1 018 593 healthy term infants and 5181 preterm infants with CLD; because patients could reenter the cohort for a second or third season, the total study cohort consisted of 1 880 531 healthy term infant-seasons (926 206 girls and 954 325 boys; mean [SD] age at first season entry, 12.6 [9.6] months) and 8680 CLD infant-seasons (3519 girls and 5161 boys; mean [SD] age at first season entry, 15.1 [9.1] months). Among term infants with siblings, the risk of hospitalization for RSV averaged across all covariate strata was 9.0 (95% CI, 8.4-9.6) per 1000 patient season-months at 1 month of age. The risk of hospitalization for RSV among preterm infants with CLD

  11. Parasitisme de Dacryodes edulis par le genre Tapinanthus ...

    African Journals Online (AJOL)

    SARAH

    31 août 2013 ... Parasitisme de Dacryodes edulis par le genre. Tapinanthus (Loranthaceae) et répartition de la myrmécofaune associée à Logbessou Plateau. (Douala, Cameroun). Massako F1*, Tchatat M2, Mony R3, Ladoh Yemeda CF1, Dibong SD1,4,5. 1Laboratoire de Biologie et Physiologie des Organismes ...

  12. Parasitisme des champs semenciers de cacaoyers par les ...

    African Journals Online (AJOL)

    SARAH

    30 janv. 2015 ... J. Appl. Biosci. Parasitisme des champs semenciers de cacaoyers par les loranthaceae dans la localité de Nkoemvone (sud Cameroun). 7795 to the various clones, Phragmanthera capitata was the most abundant Loranthaceae; the level of parasitism of cacao trees is more important at the cacao trees of ...

  13. Den eneste ene - hvordan etniske minoritetsunge i Danmark danner par

    DEFF Research Database (Denmark)

    Singla, Rashmi

    Rapporten handler om etniske unges måde at danne par på. Rapporten er baseret på en større empirisk undersøgelse gennemført af forfatteren i 2003 og er desuden inspireret af forfatterens egen ph.d.-afhandling: "Ungdom, etnicitet og psychosocial intervention" (2000, Københavns Universitet). Rappor...

  14. Indications and visual outcome of first hundred pars plana ...

    African Journals Online (AJOL)

    Objective: To review the indications and visual outcome of the first one hundred pars plana vitrectomies performed at the newly established surgical retina unit of Makkah Specialist Eye Hospital, Kano, Kano State, Nigeria. Materials and Methods: Aretrospective chart review was performed. Data recorded from the patient ...

  15. Epuration des effluents industriels par électroflottation Belkacem ...

    African Journals Online (AJOL)

    étudié la séparation de quelques métaux lourds tels que le fer, le nickel, ... the separation of some heavy metals such as iron, nickel, copper, zinc, lead and ... généralement basées sur l'adsorption (par ... Différents essais de concentration en.

  16. Predicting spectral and PAR light attenuation in Greenlandic coastal waters

    DEFF Research Database (Denmark)

    Murray, Ciarán; Markager, Stiig; Stedmon, Colin

    (CDOM), phytoplankton pigments and inorganic particles. These differences are due in part to hydrography and to the sources of meltwater: respectively, fjord-terminating and land-terminating glaciers. We present a model to explain the variation in spectral and PAR irradiance in terms of the variation...

  17. Priapisme induit par la chlorpromazine: A propos de deux cas

    Directory of Open Access Journals (Sweden)

    I. Marrag

    2016-06-01

    Le priapisme veineux est une urgence urologique. Il constitue un des effets secondaires des neuroleptiques parmi les quels la chlorpromazine. Cet effet iatrogène, qui est rare mais grave, doit être connu par les cliniciens afin d’être mieux prévenu pour éviter les séquelles érectiles.

  18. La lecture de Merleau-Ponty par Renaud Barbaras

    Czech Academy of Sciences Publication Activity Database

    Pechar, Jiří

    2015-01-01

    Roč. 11, č. 2 (2015), s. 1-6 ISSN 1336-6556 Institutional support: RVO:67985955 Keywords : Merleau-Ponty * Husserl * phenomenology * linguistics of Ferdinand de Saussure Subject RIV: AA - Philosophy ; Religion http://www.ostium.sk/sk/la-lecture-de-merleau-ponty-par-renaud-barbaras/

  19. Par Pond vegetation status summer 1995 - July survey descriptive summary

    International Nuclear Information System (INIS)

    Mackey, H.E. Jr.; Riley, R.S.

    1995-07-01

    A survey of the emergent shoreline aquatic plant, communities began in June 1995, three months after the refilling of Par Pond to approximately 200 feet (61 meters) above mean sea level, and continued with this July survey. Aquatic plant communities, similar to the pre-drawdown Par Pond communities, are becoming reestablished. Beds of maidencane (Panicum hemitomon), lotus (Nelumbo lutea), water lily (Nymphaea odorata), and watershield (Brasenia schreberi) are now extensive and well established. In addition, within isolated coves, extensive beds of water lilies and spike-rush (Eleocharis sp.) are common. Cattail occurrence has increased since refill, but large beds common to Par Pond prior to the drawdown have not formed. Invasion of willow (Salix sp.) and red maple (Acer rubrum) occurred along the lake shoreline during drawdown. The red maples along the present shoreline are beginning to show evidence of stress and mortality from flooding over the past four months. Some of the willows appear to be stressed as well. The loblolly pines (Pinus taeda), which were flooded in all but the shallow shoreline areas, are now dead. Future surveys are planned for the growing seasons of 1995, 1996, and 1997, along with the evaluation of satellite data for mapping the areal extent of the macrophyte beds of Par Pond

  20. fortification des farines tropicales par l'introduction de proteines ...

    African Journals Online (AJOL)

    2Université d'Abomey Calavy, Faculté des Sciences et Techniques, Bénin ... valeur recommandée par le Codex Alimentarius pour ce type de complément alimentaire destiné aux enfants. ..... neurotransmission, coagulation sanguine et.

  1. Costs of hospitalization with respiratory syncytial virus illness among children aged <5 years and the financial impact on households in Bangladesh, 2010.

    Science.gov (United States)

    Bhuiyan, Mejbah Uddin; Luby, Stephen P; Alamgir, Nadia Ishrat; Homaira, Nusrat; Sturm-Ramirez, Katharine; Gurley, Emily S; Abedin, Jaynal; Zaman, Rashid Uz; Alamgir, Asm; Rahman, Mahmudur; Ortega-Sanchez, Ismael R; Azziz-Baumgartner, Eduardo

    2017-06-01

    Respiratory syncytial virus (RSV) is the leading cause of acute respiratory illness in young children and results in significant economic burden. There is no vaccine to prevent RSV illness but a number of vaccines are in development. We conducted this study to estimate the costs of severe RSV illness requiring hospitalization among children 50% families borrowed money to meet treatment cost. We estimated that the median direct cost of RSV-associated hospitalization in children aged <5 years in Bangladesh was US$ 10 million (IQR: US$ 7-16 million), the median indirect cost was US$ 3.0 million (IQR: 2-5 million) in 2010. RSV-associated hospitalization among children aged <5 years represents a substantial economic burden in Bangladesh. Affected families frequently incurred considerable out of pocket and indirect costs for treatment that resulted in financial hardship.

  2. Comparison of Bovine coronavirus-specific and Bovine respiratory syncytial virus-specific antibodies in serum versus milk samples detected by enzyme-linked immunosorbent assay.

    Science.gov (United States)

    Ohlson, Anna; Blanco-Penedo, Isabel; Fall, Nils

    2014-01-01

    Bovine coronavirus (BCV; Betacoronavirus 1) and Bovine respiratory syncytial virus (BRSV) are significant causes of enteric and respiratory disease in beef and dairy cattle throughout the world. Indirect enzyme-linked immunosorbent assays are widely used to detect serum antibodies for herd monitoring and prevalence studies. In dairy herds, milk is more readily collected than serum. Hence, in order to investigate the test agreement between serum and milk, both serum and milk samples from 105 cows in 27 dairy herds were analyzed in parallel for presence of immunoglobulin G antibodies to BCV and BRSV. The Bland-Altman analyses of data demonstrated good agreement between serum and milk antibody titers for both viruses. The results indicate milk samples are sufficient for surveillance of antibodies to BCV and BRSV.

  3. Respiratory Syncytial Virus Infection as a Precipitant of Thyroid Storm in a Previously Undiagnosed Case of Graves' Disease in a Prepubertal Girl

    Directory of Open Access Journals (Sweden)

    Charlton RWilliam

    2011-03-01

    Full Text Available Graves' disease is less common in prepubertal than pubertal children, and initial presentation with thyroid storm is rare. We report an 11-year-old prepubertal Hispanic girl who presented with a one-day history of respiratory distress, fever, and dysphagia. She had exophthalmos, a diffuse bilateral goiter and was agitated, tachycardic, and hypertensive. Nasal swab was positive for respiratory syncytial virus (RSV. She was diagnosed with thyroid storm and admitted to the pediatric intensive care unit. While infection is a known precipitant of thyroid storm and RSV is a common pediatric infection, to the best of our knowledge, this is the first reported case of RSV infection apparently precipitating thyroid storm in a prepubertal child.

  4. The acute phase response of haptoglobin and serum amyloid A (SAA) in cattle undergoing experimental infection with bovine respiratory syncytial virus

    DEFF Research Database (Denmark)

    Heegaard, Peter M. H.; Godson, D.L.; Toussaint, M.J.M.

    2000-01-01

    respiratory syncytial virus (BRSV), analysing the induction of the two most dominant bovine acute phase proteins haptoglobin and serum amyloid A (SAA). Strong and reproducible acute phase responses were detected for both proteins, peaking at around 7-8 days after inoculation of BRSV, while no response...... was seen in mock-inoculated control animals. The serum concentrations reached for SAA and haptoglobin during the BRSV-induced acute phase response were generally the same or higher than previously reported for bacterial infections in calves. The magnitude and the duration of the haptoglobin response...... was found to correlate well with the severity of clinical signs (fever) and with the extent of lung consolidation while SAA responded most rapidly to infection....

  5. Fulminant ecchymosis as the initial manifestation of antiphospholipid syndrome (APS triggered by respiratory syncytial virus (RSV infection: A case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Jun Makino

    2017-01-01

    Full Text Available We present a unique and informative instance of respiratory syncytial virus (RSV infection associated with antiphospholipid syndrome (APS, and discuss this case in the context of the literature addressing the immunopathogenesis of APS associated with diverse infections. We describe the case of a 43-year-old man with no significant past medical history who presented with the acute onset of fever, hemoptysis, and extensive bullous, ecchymotic lesions in both lower extremities. Punch biopsy of the lesion demonstrated thrombotic vasculopathy. Further evaluation revealed serum antiphospholipid antibodies as well as a positive RSV PCR in a nasal swab specimen. Clinical manifestations, positive laboratory and pathological findings were strongly suggestive of APS associated with a recent RSV infection. When an infectious etiology is considered for APS, RSV should also be included in the differential diagnosis.

  6. Fulminant ecchymosis as the initial manifestation of antiphospholipid syndrome (APS) triggered by respiratory syncytial virus (RSV) infection: A case report and review of the literature.

    Science.gov (United States)

    Makino, Jun; Koshy, Sanjana; Bajaj, Sonal; Jeong, Young-Gwang; Perlman, David C

    2017-01-01

    We present a unique and informative instance of respiratory syncytial virus (RSV) infection associated with antiphospholipid syndrome (APS), and discuss this case in the context of the literature addressing the immunopathogenesis of APS associated with diverse infections. We describe the case of a 43-year-old man with no significant past medical history who presented with the acute onset of fever, hemoptysis, and extensive bullous, ecchymotic lesions in both lower extremities. Punch biopsy of the lesion demonstrated thrombotic vasculopathy. Further evaluation revealed serum antiphospholipid antibodies as well as a positive RSV PCR in a nasal swab specimen. Clinical manifestations, positive laboratory and pathological findings were strongly suggestive of APS associated with a recent RSV infection. When an infectious etiology is considered for APS, RSV should also be included in the differential diagnosis.

  7. Diagnosis of enzootic pneumonia in Danish cattle: reverse transcription-polymerase chain reaction assay for detection of bovine respiratory syncytial virus in naturally and experimentally infected cattle

    DEFF Research Database (Denmark)

    Larsen, Lars Erik; Tjørnehøj, Kirsten; Viuff, B.

    1999-01-01

    A reverse transcription-polymerase chain reaction (RT-PCR) assay was developed for detection of bovine respiratory syncytial virus (BRSV) in lung tissue of naturally and experimentally infected cattle. Primers were selected from the gene coding the F fusion protein, which is relatively conserved......, in addition, 10 animals that were negative with the ELISA were positive with the RT-PCR assay. These results indicates that the RT-PCR assay can be a sensitive, reliable alternative to conventional diagnostic procedures....... among BRSV isolates. The RT-PCR assay was highly specific, it yielded positive reactions only when performed on BRSV-infected cell cultures or tissues. The detection limit of the RT-PCR assay was assessed as 5 TCID50. BRSV was detected in tissues of the respiratory tract and in the tracheobroncheal...

  8. The role of pars flaccida in human middle ear sound transmission.

    Science.gov (United States)

    Aritomo, H; Goode, R L; Gonzalez, J

    1988-04-01

    The role of the pars flaccida in middle ear sound transmission was studied with the use of twelve otoscopically normal, fresh, human temporal bones. Peak-to-peak umbo displacement in response to a constant sound pressure level at the tympanic membrane was measured with a noncontacting video measuring system capable of repeatable measurements down to 0.2 micron. Measurements were made before and after pars flaccida modifications at 18 frequencies between 100 and 4000 Hz. Four pars flaccida modifications were studied: (1) acoustic insulation of the pars flaccida to the ear canal with a silicone rubber baffle, (2) stiffening the pars flaccida with cyanoacrylate cement, (3) decreasing the tension of the pars flaccida with a nonperforating incision, and (4) perforation of the pars flaccida. All of the modifications (except the perforation) had a minimal effect on umbo displacement; this seems to imply that the pars flaccida has a minor acoustic role in human beings.

  9. Absence of Association between Cord Specific Antibody Levels and Severe Respiratory Syncytial Virus (RSV) Disease in Early Infants: A Case Control Study from Coastal Kenya.

    Science.gov (United States)

    Nyiro, Joyce Uchi; Sande, Charles Jumba; Mutunga, Martin; Kiyuka, Patience Kerubo; Munywoki, Patrick Kioo; Scott, John Anthony G; Nokes, David James

    2016-01-01

    The target group for severe respiratory syncytial virus (RSV) disease prevention is infants under 6 months of age. Vaccine boosting of antibody titres in pregnant mothers could protect these young infants from severe respiratory syncytial virus (RSV) associated disease. Quantifying protective levels of RSV-specific maternal antibody at birth would inform vaccine development. A case control study nested in a birth cohort (2002-07) was conducted in Kilifi, Kenya; where 30 hospitalised cases of RSV-associated severe disease were matched to 60 controls. Participants had a cord blood and 2 subsequent 3-monthly blood samples assayed for RSV-specific neutralising antibody by the plaque reduction neutralisation test (PRNT). Two sample paired t test and conditional logistic regression were used in analyses of log2PRNT titres. The mean RSV log2PRNT titre at birth for cases and controls were not significantly different (P = 0.4) and remained so on age-stratification. Cord blood PRNT titres showed considerable overlap between cases and controls. The odds of RSV disease decreased with increase in log2PRNT cord blood titre. There was a 30% reduction in RSV disease per unit increase in log2PRNT titre (disease. Cord antibody levels show wide variation with considerable overlap between cases and controls. It is likely that, there are additional factors to specific PRNT antibody levels which determine susceptibility to severe RSV disease. In addition, higher levels of neutralizing antibody beyond the normal range may be required for protection; which it is hoped can be achieved by a maternal RSV vaccine.

  10. Up-regulation of serum periostin and squamous cell carcinoma antigen levels in infants with acute bronchitis due to respiratory syncytial virus

    Directory of Open Access Journals (Sweden)

    Hiroaki Nakamura

    2018-04-01

    Full Text Available Background: Periostin and squamous cell carcinoma antigen (SCCA are involved in the pathogenesis of asthma. Acute bronchitis due to respiratory syncytial virus (RSV infection during infancy exhibits an asthma-like pathogenesis, suggesting that it may be associated with the subsequent development of asthma. However, the mechanism by which RSV infection leads to development of asthma has not yet been fully elucidated. Methods: Infants younger than 36 months were enrolled and classified into three groups. Group I included patients hospitalized with RSV-induced bronchitis. These patients were further stratified into two sub-groups according to whether the criteria for the modified Asthma Predictive Index (mAPI had been met: Group I consisted of mAPI (+ and mAPI (− patients; Group II included patients with food allergy as a positive control group; and Group III included children with no allergy as a negative control group. Serum periostin and SCCA levels were measured in the groups. This study was registered as a clinical trial (UMIN000012339. Results: We enrolled 14 subjects in Group I mAPI (+, 22 in Group I mAPI (−, 18 in Group II, and 18 in Group III. In Group I, the serum periostin and SCCA levels were significantly higher during the acute phase compared with the recovery phase. However, no significant differences were found between Group I mAPI (+ and mAPI (−. Conclusions: The serum periostin and SCCA levels increased during acute RSV bronchitis. Both periostin and SCCA may play a role in the pathogenesis of acute bronchitis due to RSV. Keywords: Infants, Periostin, Respiratory syncytial virus, Squamous cell carcinoma antigen, T-helper 2 cell cytokines

  11. Apoplejía pituitaria con parálisis del III par craneal: Reporte de caso

    Directory of Open Access Journals (Sweden)

    Miguel Pinto Valdivia

    2011-10-01

    Full Text Available Se describe el caso de un varón de 65 años de edad, sin antecedentes patológicos de importancia, que acudió a emergencia del Hospital Nacional Cayetano Heredia por presentar cefalea intensa y ptosis palpebral izquierda. El examen físico mostró parálisis aislada del III par craneal izquierdo. Los análisis de laboratorio mostraron hiponatremia e hipopituitarismo y la resonancia magnética nuclear un adenoma pituitario con áreas de hemorragia e invasión de los senos cavernosos. El tratamiento incluyó glucocorticoides y descompresión quirúrgica transesfenoidal. La anatomía patológica confirmó el diagnóstico de infarto hemorrágico de un adenoma pituitario. El paciente fue dado de alta con terapia sustitutiva de levotiroxina y prednisona. La ptosis palpebral izquierda se recuperó en forma parcial. La apoplejía pituitaria es un síndrome clínico producido por un proceso expansivo dentro de la silla turca, secundario a hemorragia o infarto de un adenoma pituitario, que se caracteriza por cefalea, déficit visual, oftalmoplejía y alteración del nivel de conciencia. Este proceso expansivo puede comprimir los pares craneales en los senos cavernosos, produciendo diferentes grados de parálisis de los músculos oculomotores. La parálisis aislada del III par craneal es rara.(Rev Med Hered 2011;22:186-189.

  12. Épidémiologie de l'intoxication par envenimation chez les enfants ...

    African Journals Online (AJOL)

    Introduction: L'intoxication par envenimation est l'ensemble des manifestations locales et générales induites par la pénétration dans l'organisme d'une substance toxique produite par un animal venimeux. Le but de notre travail était d'étudier les signes cliniques des intoxications par envenimation chez les enfants de 0 à 15 ...

  13. An evaluation of the emerging interventions against Respiratory Syncytial Virus (RSV-associated acute lower respiratory infections in children

    Directory of Open Access Journals (Sweden)

    Simões Eric AF

    2011-04-01

    Full Text Available Abstract Background Respiratory Syncytial Virus (RSV is the leading cause of acute lower respiratory infections (ALRI in children. It is estimated to cause approximately 33.8 million new episodes of ALRI in children annually, 96% of these occurring in developing countries. It is also estimated to result in about 53,000 to 199,000 deaths annually in young children. Currently there are several vaccine and immunoprophylaxis candidates against RSV in the developmental phase targeting active and passive immunization. Methods We used a modified CHNRI methodology for setting priorities in health research investments. This was done in two stages. In Stage I, we systematically reviewed the literature related to emerging vaccines against RSV relevant to 12 criteria of interest. In Stage II, we conducted an expert opinion exercise by inviting 20 experts (leading basic scientists, international public health researchers, international policy makers and representatives of pharmaceutical companies. The policy makers and industry representatives accepted our invitation on the condition of anonymity, due to the sensitive nature of their involvement in such exercises. They answered questions from the CHNRI framework and their “collective optimism” towards each criterion was documented on a scale from 0 to 100%. Results In the case of candidate vaccines for active immunization of infants against RSV, the experts expressed very low levels of optimism for low product cost, affordability and low cost of development; moderate levels of optimism regarding the criteria of answerability, likelihood of efficacy, deliverability, sustainability and acceptance to end users for the interventions; and high levels of optimism regarding impact on equity and acceptance to health workers. While considering the candidate vaccines targeting pregnant women, the panel expressed low levels of optimism for low product cost, affordability, answerability and low development cost

  14. An evaluation of the emerging interventions against Respiratory Syncytial Virus (RSV)-associated acute lower respiratory infections in children.

    Science.gov (United States)

    Nair, Harish; Verma, Vasundhara R; Theodoratou, Evropi; Zgaga, Lina; Huda, Tanvir; Simões, Eric A F; Wright, Peter F; Rudan, Igor; Campbell, Harry

    2011-04-13

    Respiratory Syncytial Virus (RSV) is the leading cause of acute lower respiratory infections (ALRI) in children. It is estimated to cause approximately 33.8 million new episodes of ALRI in children annually, 96% of these occurring in developing countries. It is also estimated to result in about 53,000 to 199,000 deaths annually in young children. Currently there are several vaccine and immunoprophylaxis candidates against RSV in the developmental phase targeting active and passive immunization. We used a modified CHNRI methodology for setting priorities in health research investments. This was done in two stages. In Stage I, we systematically reviewed the literature related to emerging vaccines against RSV relevant to 12 criteria of interest. In Stage II, we conducted an expert opinion exercise by inviting 20 experts (leading basic scientists, international public health researchers, international policy makers and representatives of pharmaceutical companies). The policy makers and industry representatives accepted our invitation on the condition of anonymity, due to the sensitive nature of their involvement in such exercises. They answered questions from the CHNRI framework and their "collective optimism" towards each criterion was documented on a scale from 0 to 100%. In the case of candidate vaccines for active immunization of infants against RSV, the experts expressed very low levels of optimism for low product cost, affordability and low cost of development; moderate levels of optimism regarding the criteria of answerability, likelihood of efficacy, deliverability, sustainability and acceptance to end users for the interventions; and high levels of optimism regarding impact on equity and acceptance to health workers. While considering the candidate vaccines targeting pregnant women, the panel expressed low levels of optimism for low product cost, affordability, answerability and low development cost; moderate levels of optimism for likelihood of efficacy

  15. Soluble urokinase plasminogen activator receptor (suPAR) in acute care

    DEFF Research Database (Denmark)

    Rasmussen, Line Jee Hartmann; Ladelund, Steen; Haupt, Thomas Huneck

    2016-01-01

    for age, sex, Charlson score and C reactive protein. Area under the curve for receiver operating characteristics curve analysis of suPAR for 30-day mortality was 0.84 (95% CI 0.81 to 0.86). Furthermore, in the entire cohort, women had slightly higher suPAR compared with men, and suPAR was associated...

  16. Movement and equipositioning of plasmids by ParA filament disassembly

    DEFF Research Database (Denmark)

    Ringgaard, Simon; van Zon, Jeroen; Howard, Martin

    2009-01-01

    , plasmids consistently migrate behind disassembling ParA cytoskeletal structures, suggesting that ParA filaments pull plasmids by depolymerization. The perpetual cycles of ParA assembly and disassembly result in continuous relocation of plasmids, which, on time averaging, results in equidistribution...

  17. Protease-Activated Receptor 4 (PAR4): A Promising Target for Antiplatelet Therapy.

    Science.gov (United States)

    Rwibasira Rudinga, Gamariel; Khan, Ghulam Jilany; Kong, Yi

    2018-02-14

    Cardiovascular diseases (CVDs) are currently among the leading causes of death worldwide. Platelet aggregation is a key cellular component of arterial thrombi and major cause of CVDs. Protease-activated receptors (PARs), including PAR1, PAR2, PAR3 and PAR4, fall within a subfamily of seven-transmembrane G-protein-coupled receptors (GPCR). Human platelets express PAR1 and PAR4, which contribute to the signaling transduction processes. In association with CVDs, PAR4 not only contributes to platelet activation but also is a modulator of cellular responses that serve as hallmarks of inflammation. Although several antiplatelet drugs are available on the market, they have many side effects that limit their use. Emerging evidence shows that PAR4 targeting is a safer strategy for preventing thrombosis and consequently may improve the overall cardiac safety profile. Our present review summarizes the PAR4 structural characteristics, activation mechanism, role in the pathophysiology of diseases and understanding the association of PAR4 targeting for improved cardiac protection. Conclusively, this review highlights the importance of PAR4 antagonists and its potential utility in different CVDs.

  18. Protease-Activated Receptor 4 (PAR4: A Promising Target for Antiplatelet Therapy

    Directory of Open Access Journals (Sweden)

    Gamariel Rwibasira Rudinga

    2018-02-01

    Full Text Available Cardiovascular diseases (CVDs are currently among the leading causes of death worldwide. Platelet aggregation is a key cellular component of arterial thrombi and major cause of CVDs. Protease-activated receptors (PARs, including PAR1, PAR2, PAR3 and PAR4, fall within a subfamily of seven-transmembrane G-protein-coupled receptors (GPCR. Human platelets express PAR1 and PAR4, which contribute to the signaling transduction processes. In association with CVDs, PAR4 not only contributes to platelet activation but also is a modulator of cellular responses that serve as hallmarks of inflammation. Although several antiplatelet drugs are available on the market, they have many side effects that limit their use. Emerging evidence shows that PAR4 targeting is a safer strategy for preventing thrombosis and consequently may improve the overall cardiac safety profile. Our present review summarizes the PAR4 structural characteristics, activation mechanism, role in the pathophysiology of diseases and understanding the association of PAR4 targeting for improved cardiac protection. Conclusively, this review highlights the importance of PAR4 antagonists and its potential utility in different CVDs.

  19. Par3L enhances colorectal cancer cell survival by inhibiting Lkb1/AMPK signaling pathway

    International Nuclear Information System (INIS)

    Li, Taiyuan; Liu, Dongning; Lei, Xiong; Jiang, Qunguang

    2017-01-01

    Partitioning defective 3-like protein (Par3L) is a recently identified cell polarity protein that plays an important role in mammary stem cell maintenance. Previously, we showed that high expression of Par3L is associated with poor survival in malignant colorectal cancer (CRC), but the underlying mechanism remained unknown. To this end, we established a Par3L knockout colorectal cancer cell line using the CRISPR/Cas system. Interestingly, reduced proliferation, enhanced cell death and caspase-3 activation were observed in Par3L knockout (KO) cells as compared with wildtype (WT) cells. Consistent with previous studies, we showed that Par3L interacts with a tumor suppressor protein liver kinase B1 (Lkb1). Moreover, Par3L depletion resulted in abnormal activation of Lkb1/AMPK signaling cascade. Knockdown of Lkb1 in these cells could significantly reduce AMPK activity and partially rescue cell death caused by Par3L knockdown. Furthermore, we showed that Par3L KO cells were more sensitive to chemotherapies and irradiation. Together, these results suggest that Par3L is essential for colorectal cancer cell survival by inhibiting Lkb1/AMPK signaling pathway, and is a putative therapeutic target for CRC. - Highlights: • Par3L knockout using the CRISPR/Cas system induces apoptosis in colorectal cancer cells. • Par3L interacts with Lkb1 and regulates the activity of AMPK signaling cascade. • Par3L knockout cells are more sensitive to treatment of different chemotherapy drugs and irradiation.

  20. Brésil : La contamination par le mercure en Amazonie | CRDI ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    11 janv. 2011 ... En tentant de déceler la source de la contamination de l'Amazone par le ... par Jean-Rémy Davy Guimaraes de l'Université fédérale de Rio de Janeiro ... ces mattes est circonscrite par la conservation et la restauration en rive.

  1. Respiratory Syncytial Virus (RSV)

    Science.gov (United States)

    ... Careers Archives Health Topics Pregnancy Before or between pregnancies Nutrition, weight & fitness Prenatal care Is it safe? Labor & ... Report Cards Careers Archives Pregnancy Before or between pregnancies Nutrition, weight & fitness Prenatal care Is it safe? Labor & ...

  2. La syphilis congenitale revelee par une fracture spontanee

    Directory of Open Access Journals (Sweden)

    Mounia Lakhdar Idrissi

    2011-11-01

    Full Text Available Alors qu�elle est actuellement oubliee dans les pays developpes, la syphilis congenitale se voit encore chez nous faute du depistage antenatal. Ses formes cliniques sont polymorphes et orientent a tord vers d�autres pathologies surtout en periode neonatale. Le diagnostic n�est donc pas toujours facile. La revelation d�une syphilis congenitale par une fracture spontanee est exceptionnellement decrite. Nous rapportons dans ce travail le cas d�un nourrisson de 2 mois ramene en consultation pour limitation douloureuse des mouvements du bras droit. Le diagnostic est evoque sur les donnees radiologiques et confirme par la serologie syphilitique. Le traitement a repose essentiellement sur l�administration de la penicilline G avec une bonne evolution clinique.

  3. Results of Preliminary Tests of PAR Bunch Cleaning

    CERN Document Server

    Yao, Chihyuan; Grelick, Arthur; Lumpkin, Alex H; Sereno, Nicholas S

    2005-01-01

    A particle accumulator ring (PAR) is used at the Advanced Photon Source (APS) to collect multiple linac bunches and compress them into a 0.3-ns (rms) single bunch for booster injection. A 9.77-MHz fundamental rf system and a 117.3-MHz harmonic rf system are employed for initial beam capture and bunch length compression. Satellite bunches with very low charge form due to rf phase drifts or beam loading change. These satellites, when injected into the booster and then into the storage ring (SR), cause bunch impurity at three buckets from the target bucket. Storage ring and booster bunch cleaning was tried but proved to be difficult due to the top-up mode of operation in the storage ring and tune drift in the booster synchrotron. Recently we implemented a PAR bunch-cleaning system with tune-modulated harmonic rf knockout. Preliminary tests gave a measured SR bunch purity of better than 10

  4. Avis 6 sur la formation à et par la recherche

    OpenAIRE

    Centre de Coopération Internationale en Recherche Agronomique pour le Développement

    2015-01-01

    La formation à et par la recherche s’appuie sur la démarche scientifique, les savoirs, les connaissances à transmettre, tout autant que l’acquisition de compétences en gestion de projet, de capacités au travail en équipe, d’une ouverture d’esprit qui favorisera la créativité. Elle doit permettre de prendre conscience de la responsabilité endossée par la communauté scientifique vis-à-vis de la société et de l’environnement, mais aussi préparer l’avenir professionnel de celle ou de celui qu...

  5. Evaluation of the Stability After Orthodontic Treatment Using PAR Index

    Directory of Open Access Journals (Sweden)

    Chaitra Ramanathan

    2006-01-01

    Full Text Available The aim of the present study is to establish the results using the scores obtained from the methodology that was applied for assessing the stability after 2 years post orthodontic treatment and stability in a sample of 69 individuals. After applying PAR index to the collected group of patients, a series of scores were obtained, which were then needed to be evaluated further to establish the results. The scores were evaluated using the nomogram. A comparison was done between the post treatment and the 2 years post treatment PAR weighting scores to determine if the results were stable after orthodontic treatment. The majority of the orthodontic patients were treated to a good standard and that the results appeared to be stable.

  6. La parálisis cerebral en el contexto escolar /

    OpenAIRE

    González Vara, Azucena

    2012-01-01

    Se analiza el concepto de parálisis cerebral, los diferentes tipos y sus características. También las adaptaciones que se deben realizar a nivel de centro, de aula, y a nivel individual para estos alumnos, conocer los diferentes sistemas alternativos y aumentativos de comunicación y aplicar las ayudas técnicas que precisa este alumnado

  7. Tuberculose lymphonodale cervicale chez les enfants vaccines par ...

    African Journals Online (AJOL)

    La tuberculose ganglionnaire cervicale est une localisation extrapulmonaire relativement fréquente chez l'enfant. Elle pose essentiellement des difficultés de prévention. L'objectif de ce travail est d'étudier les particularités diagnostiques et thérapeutiques chez des enfants vaccinés par le BCG. Matériel et méthodes: Nôtre ...

  8. Traitement De La Peripneumonie Contagieuse Bovine Par L ...

    African Journals Online (AJOL)

    Traitement De La Peripneumonie Contagieuse Bovine Par L'oxyteTracycline Longe Action Et Transmission Experimentale de la Maladie A Partir de Bovins Traites. ... Tous les 14 animaux ont séroconverti et l'analyse post-mortem a montré la présence des lésions chroniques dont des séquestres pulmonaires chez 4 d'entre ...

  9. Adoption d'innovations agricoles par le truchement de services ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    L'agriculture est le fer de lance de nombreuses économies en développement, mais la capacité des petits agriculteurs privés de ressources à adopter des innovations agricoles est freinée par le manque d'accès à des services financiers adéquats. Des experts internationaux estiment qu'il existe un manque à gagner ...

  10. Candido: Uma Leitura Paródica de Candide

    Directory of Open Access Journals (Sweden)

    Maria Gloria Cusumano Mazzi

    2010-12-01

    Full Text Available O presente artigo estuda a leitura paródica que Leonardo Sciascia (1921-1989 faz de Voltaire (1694-1778 mediante o cotejo das obras: o hipertexto Candido ovvero Un sogno fatto in Sicilia (1977 e o hipotexto Candide ou l’optimisme (1759. Apresenta ainda outra possibilidade de leitura, ou seja, Candido como metáfora da própria intertextualidade.

  11. Solution volumes finis polynomiale par morceaux pour les ...

    African Journals Online (AJOL)

    Nous présentons dans ce papier un concept de solution volumes finis continue pour des problèmes de diffusion-convection avec des données régulières. Nous comparons dans certains cas particuliers la solution proposée avec la solution volumes finis classiques (qui est une fonction constante par morceaux) et la ...

  12. Preliminary Analysis For Wolsong Par Effects Using ISACC Calculations

    International Nuclear Information System (INIS)

    Song, Yong Mann; Kim, Dong Ha

    2012-01-01

    In the paper, hydrogen control effects using PARs only are analyzed for severe SBO station blackout (SBO) sequences beyond the design basis accidents in WS-1 which are of CANDU6 type reactor. As a computational tool, the latest version of ISAAC4.3 (Integrated Severe Accident Analysis Code for CANDU), which is a fully integrated and lumped severe accident computer code, is used to simulate hydrogen generation and transport inside the reactor building (R/B) before its failure. For the performance of hydrogen removal, the depletion rate equation of K-PAR developed in Korea is applied. In a CANDU reactor, three areas are identified as sources of hydrogen under severe accidents: fuel-coolant interactions in intact channels, suspended fuel or debris interactions in-calandria tank and debris interactions in-calandria vault. The first two origins provide source for the late ('late' terminology is used because it takes more than one day before calandria tank failure) potential hydrogen combustion before calandria tank failure and all the three origins would provide source for the very late potential hydrogen combustion occurring at or after calaria tank failure. If the hydrogen mitigation system fails, the AICC (adiabatic isochoric complete combustion) burning of highly flammable hydrogen may cause Wolsong R/B failure. So hydrogen induced failure possibility is evaluated, using preliminary ISAAC calculations, under several SBO conditions with and without PAR for both late and very late accident periods

  13. Protease activated receptors (PARS) mediation in gyroxin biological activity

    International Nuclear Information System (INIS)

    Silva, Jose Alberto Alves da

    2009-01-01

    Gyroxin is a serine protease enzyme from the South American rattlesnake (Crotalus durissus terrificus) venom; it is only partially characterized and has multiple activities. Gyroxin induces blood coagulation, blood pressure decrease and a neurotoxic behavior named barrel rotation. The mechanisms involved in this neurotoxic activity are not known. Whereas gyroxin is a member of enzymes with high potential to become a new drug with clinical applications such as thrombin, batroxobin, ancrod, tripsyn and kalicrein, it is important to find out how gyroxin works. The analysis on agarose gel electrophoresis and circular dichroism confirmed the molecules' integrity and purity. The gyroxin intravenous administration in mice proved its neurotoxicity (barrel rotation). In vivo studies employing intravital microscopy proved that gyroxin induces vasodilation with the participation of protease activated receptors (PARs), nitric oxide and Na+K+ATPase. The leukocytes' adherence and rolling counting indicated that gyroxin has no pro inflammatory activity. Gyroxin induced platelet aggregation, which was blocked by inhibitors of PAR1 and PAR4 receptors (SCH 79797 and tcY-NH 2 , respectively). Finally, it was proved that the gyroxin temporarily alter the permeability of the blood brain barrier (BBB). Our study has shown that both the protease-activated receptors and nitric oxide are mediators involved in the biological activities of gyroxin. (author)

  14. A Bipolar Spindle of Antiparallel ParM Filaments Drives Bacterial Plasmid Segregation

    DEFF Research Database (Denmark)

    Gayathri, P; Fujii, T; Møller-Jensen, Jakob

    2012-01-01

    the spindle between ParRC complexes on sister plasmids. Using a combination of structural work and total internal reflection fluorescence microscopy, we show that ParRC bound and could accelerate growth at only one end of polar ParM filaments, mechanistically resembling eukaryotic formins. The architecture...... of ParM filaments enabled two ParRC-bound filaments to associate in an antiparallel orientation, forming a bipolar spindle. The spindle elongated as a bundle of at least two antiparallel filaments, thereby pushing two plasmid clusters toward the poles....

  15. First (18)F-labeled ligand for PET imaging of uPAR

    DEFF Research Database (Denmark)

    Persson, Morten; Liu, Hongguang; Madsen, Jacob

    2013-01-01

    Urokinase-type plasminogen activator receptor (uPAR) is overexpressed in human prostate cancer and uPAR has been found to be associated with metastatic disease and poor prognosis. AE105 is a small linear peptide with high binding affinity to uPAR. We synthesized an N-terminal NOTA......-conjugated version (NOTA-AE105) for development of the first (18)F-labeled uPAR positron-emission-tomography PET ligand using the Al(18)F radiolabeling method. In this study, the potential of (18)F-AlF-NOTA-AE105 to specifically target uPAR-positive prostate tumors was investigated....

  16. Intact and cleaved uPAR forms: diagnostic and prognostic value in cancer

    DEFF Research Database (Denmark)

    Rasch, M.G.; Lund, I.K.; Hoyer-Hansen, G.

    2008-01-01

    identified in tissue and body fluids. It is well-established, that the total amount of all uPAR forms is a strong prognostic marker in different types of cancer. Using immunoassays, measuring the individual uPAR forms, has revealed that the cleaved uPAR forms are even stronger prognostic markers and have...... diagnostic utility. This review will focus on the mechanism of uPAR cleavage and the functional consequences, as well as the clinical applicability of cleaved uPAR forms Udgivelsesdato: 2008...

  17. Dynamic Filament Formation by a Divergent Bacterial Actin-Like ParM Protein.

    Directory of Open Access Journals (Sweden)

    Anthony J Brzoska

    Full Text Available Actin-like proteins (Alps are a diverse family of proteins whose genes are abundant in the chromosomes and mobile genetic elements of many bacteria. The low-copy-number staphylococcal multiresistance plasmid pSK41 encodes ParM, an Alp involved in efficient plasmid partitioning. pSK41 ParM has previously been shown to form filaments in vitro that are structurally dissimilar to those formed by other bacterial Alps. The mechanistic implications of these differences are not known. In order to gain insights into the properties and behavior of the pSK41 ParM Alp in vivo, we reconstituted the parMRC system in the ectopic rod-shaped host, E. coli, which is larger and more genetically amenable than the native host, Staphylococcus aureus. Fluorescence microscopy showed a functional fusion protein, ParM-YFP, formed straight filaments in vivo when expressed in isolation. Strikingly, however, in the presence of ParR and parC, ParM-YFP adopted a dramatically different structure, instead forming axial curved filaments. Time-lapse imaging and selective photobleaching experiments revealed that, in the presence of all components of the parMRC system, ParM-YFP filaments were dynamic in nature. Finally, molecular dissection of the parMRC operon revealed that all components of the system are essential for the generation of dynamic filaments.

  18. Proteinase-Activated Receptor 1 (PAR1 regulates leukemic stem cell functions.

    Directory of Open Access Journals (Sweden)

    Nicole Bäumer

    Full Text Available External signals that are mediated by specific receptors determine stem cell fate. The thrombin receptor PAR1 plays an important role in haemostasis, thrombosis and vascular biology, but also in tumor biology and angiogenesis. Its expression and function in hematopoietic stem cells is largely unknown. Here, we analyzed expression and function of PAR1 in primary hematopoietic cells and their leukemic counterparts. AML patients' blast cells expressed much lower levels of PAR1 mRNA and protein than CD34+ progenitor cells. Constitutive Par1-deficiency in adult mice did not affect engraftment or stem cell potential of hematopoietic cells. To model an AML with Par1-deficiency, we retrovirally introduced the oncogene MLL-AF9 in wild type and Par1-/- hematopoietic progenitor cells. Par1-deficiency did not alter initial leukemia development. However, the loss of Par1 enhanced leukemic stem cell function in vitro and in vivo. Re-expression of PAR1 in Par1-/- leukemic stem cells delayed leukemogenesis in vivo. These data indicate that Par1 contributes to leukemic stem cell maintenance.

  19. Proteinase-Activated Receptor 1 (PAR1) regulates leukemic stem cell functions.

    Science.gov (United States)

    Bäumer, Nicole; Krause, Annika; Köhler, Gabriele; Lettermann, Stephanie; Evers, Georg; Hascher, Antje; Bäumer, Sebastian; Berdel, Wolfgang E; Müller-Tidow, Carsten; Tickenbrock, Lara

    2014-01-01

    External signals that are mediated by specific receptors determine stem cell fate. The thrombin receptor PAR1 plays an important role in haemostasis, thrombosis and vascular biology, but also in tumor biology and angiogenesis. Its expression and function in hematopoietic stem cells is largely unknown. Here, we analyzed expression and function of PAR1 in primary hematopoietic cells and their leukemic counterparts. AML patients' blast cells expressed much lower levels of PAR1 mRNA and protein than CD34+ progenitor cells. Constitutive Par1-deficiency in adult mice did not affect engraftment or stem cell potential of hematopoietic cells. To model an AML with Par1-deficiency, we retrovirally introduced the oncogene MLL-AF9 in wild type and Par1-/- hematopoietic progenitor cells. Par1-deficiency did not alter initial leukemia development. However, the loss of Par1 enhanced leukemic stem cell function in vitro and in vivo. Re-expression of PAR1 in Par1-/- leukemic stem cells delayed leukemogenesis in vivo. These data indicate that Par1 contributes to leukemic stem cell maintenance.

  20. The double par locus of virulence factor pB171: DNA segregation is correlated with oscillation of ParA

    DEFF Research Database (Denmark)

    Ebersbach, G; Gerdes, K; Charbon, Gitte Ebersbach

    2001-01-01

    Prokaryotic plasmids and chromosomes encode partitioning (par) loci that segregate DNA to daughter cells before cell division. Recent database analyses showed that almost all known par loci encode an ATPase and a DNA-binding protein, and one or more cis-acting regions where the proteins act. All...

  1. ParABS Systems of the Four Replicons of Burkholderia cenocepacia: New Chromosome Centromeres Confer Partition Specificity†

    Science.gov (United States)

    Dubarry, Nelly; Pasta, Franck; Lane, David

    2006-01-01

    Most bacterial chromosomes carry an analogue of the parABS systems that govern plasmid partition, but their role in chromosome partition is ambiguous. parABS systems might be particularly important for orderly segregation of multipartite genomes, where their role may thus be easier to evaluate. We have characterized parABS systems in Burkholderia cenocepacia, whose genome comprises three chromosomes and one low-copy-number plasmid. A single parAB locus and a set of ParB-binding (parS) centromere sites are located near the origin of each replicon. ParA and ParB of the longest chromosome are phylogenetically similar to analogues in other multichromosome and monochromosome bacteria but are distinct from those of smaller chromosomes. The latter form subgroups that correspond to the taxa of their hosts, indicating evolution from plasmids. The parS sites on the smaller chromosomes and the plasmid are similar to the “universal” parS of the main chromosome but with a sequence specific to their replicon. In an Escherichia coli plasmid stabilization test, each parAB exhibits partition activity only with the parS of its own replicon. Hence, parABS function is based on the independent partition of individual chromosomes rather than on a single communal system or network of interacting systems. Stabilization by the smaller chromosome and plasmid systems was enhanced by mutation of parS sites and a promoter internal to their parAB operons, suggesting autoregulatory mechanisms. The small chromosome ParBs were found to silence transcription, a property relevant to autoregulation. PMID:16452432

  2. Serum suPAR in patients with FSGS: trash or treasure?

    Science.gov (United States)

    Maas, Rutger J H; Deegens, Jeroen K J; Wetzels, Jack F M

    2013-07-01

    The urokinase-type plasminogen activator receptor (uPAR) has important functions in cell migration. uPAR can be shed from the cell membrane resulting in soluble uPAR (suPAR). Further cleavage gives rise to shorter fragments with largely unknown functions. Recent studies have demonstrated that both overexpression of uPAR on podocytes and the administration of suPAR cause proteinuria in mice. The common pathogenic mechanism involves the activation of podocyte β3-integrin. Increased activation of β3-integrin is also observed in patients with focal and segmental glomerulosclerosis (FSGS). These observations form the basis for the hypothesis that suPAR may be the circulating factor causing FSGS. A recent study fosters this idea by demonstrating increased suPAR levels in the serum of patients with FSGS and reporting an association with recurrence after transplantation and response to plasmapheresis. However, this study was heavily biased, and subsequent studies have given conflicting results. Although the experimental work is very suggestive, at present there is no proof that any known human suPAR fragment causes FSGS in humans. We therefore suggest that the measurement of suPAR using currently available assays has absolutely no value at the present time in decision-making in routine clinical practice.

  3. PAR-2 expression in the gingival crevicular fluid reflects chronic periodontitis severity

    Directory of Open Access Journals (Sweden)

    Henrique FUKUSHIMA

    Full Text Available Abstract Recent studies investigating protease-activated receptor type 2 (PAR-2 suggest an association between the receptor and periodontal inflammation. It is known that gingipain, a bacterial protease secreted by the important periodontopathogen Porphyromonas gingivalis can activate PAR-2. Previous studies by our group found that PAR-2 is overexpressed in the gingival crevicular fluid (GCF of patients with moderate chronic periodontitis (MP. The present study aimed at evaluating whether PAR-2 expression is associated with chronic periodontitis severity. GCF samples and clinical parameters, including plaque and bleeding on probing indices, probing pocket depth and clinical attachment level, were collected from the control group (n = 19 at baseline, and from MP patients (n = 19 and severe chronic periodontitis (SP (n = 19 patients before and 6 weeks after periodontal non-surgical treatment. PAR-2 and gingipain messenger RNA (mRNA in the GCF of 4 periodontal sites per patient were evaluated by Reverse Transcription Polymerase Chain Reaction (RT-qPCR. PAR-2 and gingipain expressions were greater in periodontitis patients than in control group patients. In addition, the SP group presented increased PAR-2 and gingipain mRNA levels, compared with the MP group. Furthermore, periodontal treatment significantly reduced (p <0.05 PAR-2 expression in patients with periodontitis. In conclusion, PAR-2 is associated with chronic periodontitis severity and with gingipain levels in the periodontal pocket, thus suggesting that PAR-2 expression in the GCF reflects the severity of destruction during periodontal infection.

  4. Structures of actin-like ParM filaments show architecture of plasmid-segregating spindles.

    Science.gov (United States)

    Bharat, Tanmay A M; Murshudov, Garib N; Sachse, Carsten; Löwe, Jan

    2015-07-02

    Active segregation of Escherichia coli low-copy-number plasmid R1 involves formation of a bipolar spindle made of left-handed double-helical actin-like ParM filaments. ParR links the filaments with centromeric parC plasmid DNA, while facilitating the addition of subunits to ParM filaments. Growing ParMRC spindles push sister plasmids to the cell poles. Here, using modern electron cryomicroscopy methods, we investigate the structures and arrangements of ParM filaments in vitro and in cells, revealing at near-atomic resolution how subunits and filaments come together to produce the simplest known mitotic machinery. To understand the mechanism of dynamic instability, we determine structures of ParM filaments in different nucleotide states. The structure of filaments bound to the ATP analogue AMPPNP is determined at 4.3 Å resolution and refined. The ParM filament structure shows strong longitudinal interfaces and weaker lateral interactions. Also using electron cryomicroscopy, we reconstruct ParM doublets forming antiparallel spindles. Finally, with whole-cell electron cryotomography, we show that doublets are abundant in bacterial cells containing low-copy-number plasmids with the ParMRC locus, leading to an asynchronous model of R1 plasmid segregation.

  5. PAR-1 contributes to the innate immune response during viral infection

    Science.gov (United States)

    Antoniak, Silvio; Owens, A. Phillip; Baunacke, Martin; Williams, Julie C.; Lee, Rebecca D.; Weithäuser, Alice; Sheridan, Patricia A.; Malz, Ronny; Luyendyk, James P.; Esserman, Denise A.; Trejo, JoAnn; Kirchhofer, Daniel; Blaxall, Burns C.; Pawlinski, Rafal; Beck, Melinda A.; Rauch, Ursula; Mackman, Nigel

    2013-01-01

    Coagulation is a host defense system that limits the spread of pathogens. Coagulation proteases, such as thrombin, also activate cells by cleaving PARs. In this study, we analyzed the role of PAR-1 in coxsackievirus B3–induced (CVB3-induced) myocarditis and influenza A infection. CVB3-infected Par1–/– mice expressed reduced levels of IFN-β and CXCL10 during the early phase of infection compared with Par1+/+ mice that resulted in higher viral loads and cardiac injury at day 8 after infection. Inhibition of either tissue factor or thrombin in WT mice also significantly increased CVB3 levels in the heart and cardiac injury compared with controls. BM transplantation experiments demonstrated that PAR-1 in nonhematopoietic cells protected mice from CVB3 infection. Transgenic mice overexpressing PAR-1 in cardiomyocytes had reduced CVB3-induced myocarditis. We found that cooperative signaling between PAR-1 and TLR3 in mouse cardiac fibroblasts enhanced activation of p38 and induction of IFN-β and CXCL10 expression. Par1–/– mice also had decreased CXCL10 expression and increased viral levels in the lung after influenza A infection compared with Par1+/+ mice. Our results indicate that the tissue factor/thrombin/PAR-1 pathway enhances IFN-β expression and contributes to the innate immune response during single-stranded RNA viral infection. PMID:23391721

  6. Par-4-mediated recruitment of Amida to the actin cytoskeleton leads to the induction of apoptosis

    International Nuclear Information System (INIS)

    Boosen, Meike; Vetterkind, Susanne; Koplin, Ansgar; Illenberger, Susanne; Preuss, Ute

    2005-01-01

    Par-4 (prostate apoptosis response-4) sensitizes cells to apoptotic stimuli, but the exact mechanisms are still poorly understood. Using Par-4 as bait in a yeast two-hybrid screen, we identified Amida as a novel interaction partner, a ubiquitously expressed protein which has been suggested to be involved in apoptotic processes. Complex formation of Par-4 and Amida occurs in vitro and in vivo and is mediated via the C-termini of both proteins, involving the leucine zipper of Par-4. Amida resides mainly in the nucleus but displays nucleo-cytoplasmic shuttling in heterokaryons. Upon coexpression with Par-4 in REF52.2 cells, Amida translocates to the cytoplasm and is recruited to actin filaments by Par-4, resulting in enhanced induction of apoptosis. The synergistic effect of Amida/Par-4 complexes on the induction of apoptosis is abrogated when either Amida/Par-4 complex formation or association of these complexes with the actin cytoskeleton is impaired, indicating that the Par-4-mediated relocation of Amida to the actin cytoskeleton is crucial for the pro-apoptotic function of Par-4/Amida complexes in REF52.2 cells. The latter results in enhanced phosphorylation of the regulatory light chain of myosin II (MLC) as has previously been shown for Par-4-mediated recruitment of DAP-like kinase (Dlk), suggesting that the recruitment of nuclear proteins involved in the regulation of apoptotic processes to the actin filament system by Par-4 represents a potent mechanism how Par-4 can trigger apoptosis

  7. A Respiratory Syncytial Virus Vaccine Vectored by a Stable Chimeric and Replication-Deficient Sendai Virus Protects Mice without Inducing Enhanced Disease.

    Science.gov (United States)

    Wiegand, Marian Alexander; Gori-Savellini, Gianni; Gandolfo, Claudia; Papa, Guido; Kaufmann, Christine; Felder, Eva; Ginori, Alessandro; Disanto, Maria Giulia; Spina, Donatella; Cusi, Maria Grazia

    2017-05-15

    Respiratory syncytial virus (RSV) is a major cause of severe respiratory infections in children and elderly people, and no marketed vaccine exists. In this study, we generated and analyzed a subunit vaccine against RSV based on a novel genome replication-deficient Sendai virus (SeV) vector. We inserted the RSV F protein, known to be a genetically stable antigen, into our vector in a specific way to optimize the vaccine features. By exchanging the ectodomain of the SeV F protein for its counterpart from RSV, we created a chimeric vectored vaccine that contains the RSV F protein as an essential structural component. In this way, the antigen is actively expressed on the surfaces of vaccine particles in its prefusion conformation, and as recently reported for other vectored vaccines, the occurrence of silencing mutations of the transgene in the vaccine genome can be prevented. In addition, its active gene expression contributes to further stimulation of the immune response. In order to understand the best route of immunization, we compared vaccine efficacies after intranasal (i.n.) or intramuscular (i.m.) immunization of BALB/c mice. Via both routes, substantial RSV-specific immune responses were induced, consisting of serum IgG and neutralizing antibodies, as well as cytotoxic T cells. Moreover, i.n. immunization was also able to stimulate specific mucosal IgA in the upper and lower respiratory tract. In virus challenge experiments, animals were protected against RSV infection after both i.n. and i.m. immunization without inducing vaccine-enhanced disease. Above all, the replication-deficient SeV appeared to be safe and well tolerated. IMPORTANCE Respiratory syncytial virus (RSV) is a major cause of respiratory diseases in young children and elderly people worldwide. There is a great demand for a licensed vaccine. Promising existing vaccine approaches based on live-attenuated vaccines or viral vectors have suffered from unforeseen drawbacks related to immunogenicity

  8. Bacterial mitosis: Partitioning protein ParA oscillates in spiral-shaped structures and positions plasmids at mid-cell

    DEFF Research Database (Denmark)

    Ebersbach, G.; Gerdes, Kenn

    2004-01-01

    The par2 locus of Escherichia coli plasmid pB171 encodes oscillating ATPase ParA, DNA binding protein ParB and two cis-acting DNA regions to which ParB binds (parC1 and parC2). Three independent techniques were used to investigate the subcellular localization of plasmids carrying par2. In cells......A-GFP oscillated in spiral-shaped structures. Amino acid substitutions in ParA simultaneously abolished ParA spiral formation, oscillation and either plasmid localization or plasmid separation at mid-cell. Therefore, our results suggest that ParA spirals position plasmids at the middle of the bacterial nucleoid...

  9. Envenimation mortelle par morsure de serpent chez une femme ...

    African Journals Online (AJOL)

    Les auteurs rapportent un cas de morsure de serpent au niveau de la face chez une femme enceinte, dont l'évolution a été marquée par l'installation d'un oedème cervico-facial nécessitant une trachéotomie en urgence, et une mort foetale in utero avec troubles de l'hémostase responsable du décès maternel dans un ...

  10. Analysis of clinical features and visual outcomes of pars planitis.

    Science.gov (United States)

    Berker, Nilufer; Sen, Emine; Elgin, Ufuk; Atilgan, Cemile Ucgul; Dursun, Erdem; Yilmazbas, Pelin

    2018-04-01

    To evaluate the demographic characteristics, clinical features, treatment and outcomes of patients with pars planitis in a tertiary referral center in Turkey. Medical records of patients with pars planitis were retrospectively reviewed. The data including demographic and ocular features and treatment outcomes were recorded. The distribution of clinical findings and complications were evaluated according to age and gender groups. The changes in final BCVA compared to the initial BCVA were noted. Statistical analysis was performed using SPSS software (Version 18.0, SPSS Inc., Chicago, USA). Twenty-seven patients (54 eyes) were included in this study. 16 patients were male (59.3%), and 11 were female (40.7%). Mean age at diagnosis was 12.84 ± 8.26 (range 4-36) years. Mean follow-up period was 61.3 ± 52.15 (range 9-172) months. Mean BCVA was 0.58 ± 0.36 (range 0.03-1.00) (0.40 ± 0.45 logMAR) at presentation, and 0.81 ± 0.28 (range 0.10-1.00) (0.14 ± 0.27 logMAR) at final visit (P = 0.001). Vitreous inflammation (100%), vitreous haze (92.6%), snowballs (74.1%), snowbanks (66.7%), anterior chamber cells (66.7%) and peripheral retinal vascular sheathing (48.1%) were the most common presentations. Ocular complications included vitreous condensation (51.9%), cystoid macular edema (22.2%), cataract (18.5%), inferior peripheral retinal detachment (11.1%), glaucoma (5.6%) and vitreous hemorrhage (3.7%). Treatments included topical, periocular, intravitreal and systemic corticosteroids, immunosuppressives, peripheral laser photocoagulation and pars plana vitrectomy when needed. Pars planitis is an idiopathic chronic intermediate uveitis mostly affecting children and adolescents. In spite of its chronic nature with high potential of causing ocular complications, adequate treatment and close follow-up lead to favorable visual outcomes.

  11. Cartographie par carroyage et précision spatiale

    Directory of Open Access Journals (Sweden)

    Patrice LANGLOIS

    1998-03-01

    Full Text Available Dans le cadre d'une cartographie par carroyage, on étudie la désagrégation de variables zonales, en revenant sur l'hypothèse de l'équirépartition spatiale des populations. L'objectif est d'approcher des règles différenciées de désagrégation des variables en fusionnant des plans d'information de nature morphologique, topologique et environnementale.

  12. PET imaging of urokinase-type plasminogen activator receptor (uPAR) in prostate cancer

    DEFF Research Database (Denmark)

    Skovgaard, Dorthe; Persson, Morten; Kjaer, Andreas

    2016-01-01

    Overexpression of urokinase-type plasminogen activator receptors (uPAR) represents an important biomarker for aggressiveness in most common malignant diseases, including prostate cancer (PC). Accordingly, uPAR expression either assessed directly in malignant PC tissue or assessed directly in plasma...... and prognostic imaging method. In this review, we will focus on the recent development of uPAR PET and the relevance within prostate cancer imaging. Novel antibody and small-molecule radiotracers-targeting uPAR, including a series of uPAR-targeting PET ligands, based on the high affinity peptide ligand AE105......, have been synthesized and tested in vitro and in vivo in preclinical murine xenograft models and, recently, in a first-ever clinical uPAR PET study in cancer patients, including patients with PC. In this phase I study, a high and specific uptake of the tracer 64Cu-DOTA-AE105 was found in both primary...

  13. Paracrine Apoptotic Effect of p53 Mediated by Tumor Suppressor Par-4

    Directory of Open Access Journals (Sweden)

    Ravshan Burikhanov

    2014-01-01

    Full Text Available The guardian of the genome, p53, is often mutated in cancer and may contribute to therapeutic resistance. Given that p53 is intact and functional in normal tissues, we harnessed its potential to inhibit the growth of p53-deficient cancer cells. Specific activation of p53 in normal fibroblasts selectively induced apoptosis in p53-deficient cancer cells. This paracrine effect was mediated by p53-dependent secretion of the tumor suppressor Par-4. Accordingly, the activation of p53 in normal mice, but not p53−/− or Par-4−/− mice, caused systemic elevation of Par-4, which induced apoptosis of p53-deficient tumor cells. Mechanistically, p53 induced Par-4 secretion by suppressing the expression of its binding partner, UACA, which sequesters Par-4. Thus, normal cells can be empowered by p53 activation to induce Par-4 secretion for the inhibition of therapy-resistant tumors.

  14. Four cases of endophthalmitis after 25-gauge pars plana vitrectomy

    Directory of Open Access Journals (Sweden)

    Mutoh T

    2012-08-01

    Full Text Available Tetsuya Mutoh, Koji Kadoya, Makoto ChikudaDepartment of Ophthalmology, Dokkyo Medical University Koshigaya Hospital, Koshigaya, Saitama, JapanAbstract: We report our recent experience with four cases of endophthalmitis (one male, three females after 25-gauge pars plana vitrectomy (PPV. One was a case of persistent cystoid macular edema caused by branch retinal vein occlusion, whereas the remaining three were cases of epiretinal membrane. Preoperative antibiotics before the first PPV procedure were not administered in three of the four cases. Endophthalmitis occurred 2–4 days after the first procedure in all cases, for which ceftazidime 2.0 mg/0.1 mL and vancomycin 1.0 mg/0.1 mL were injected into the vitreous cavity. This was followed by emergent 20-gauge PPV and intraocular lens removal using an infusion fluid containing ceftazidime and vancomycin. After the second PPV procedure, progress was good in three cases while retinal detachment occurred in the remaining case one month after surgery; this case required a third PPV procedure. Final best-corrected visual acuity ranged from 20/100 to 20/25 for the four cases. Bacterial cultures were negative after the second PPV procedure in all cases. In conclusion, postoperative endophthalmitis occurred in four of 502 cases (0.80% that underwent 25-gauge PPV at our hospital. It is important to minimize the incidence of endophthalmitis after 25-gauge PPV.Keywords: 25-gauge pars plana vitrectomy, endophthalmitis, incidence

  15. Stress reactions involving the pars interarticularis in young athletes

    Energy Technology Data Exchange (ETDEWEB)

    Jackson, D.W.; Wiltse, L.L.; Dingeman, R.D.; Hayes, M.

    A stress reaction involving the pars interarticularis of the lumbar spine was confirmed in seven young athletes with a positive technetium pyrophosphate bone scan. No pars defects were detectable on their lumbosacral roentgenograms, which included oblique views. The return to normal levels of radioactive uptake on repeat bone scans correlated closely with their clinical course. If the bony reaction is recognized early, it may heal at a subroentgenographic level and prevent the development of lumbar spondylolysis. These early lesions usually show unilateral increased uptake at one lumbar level on the bone scan and, initially, the athlete localizes the pain to the corresponding unilateral lumbar paraspinous area. The ''one-legged hyperextension test'' is positive on the ipsilateral side and aggravates the pain. Treatment consists of avoiding the aggravating activities and resting. The average time for return to pain-free competition was 7.3 months. These developing defects may be the source of considerable prolonged disability in the young athlete, particularly if undiagnosed and untreated.

  16. Stress reactions involving the pars interarticularis in young athletes

    International Nuclear Information System (INIS)

    Jackson, D.W.; Wiltse, L.L.; Dingeman, R.D.; Hayes, M.

    1981-01-01

    A stress reaction involving the pars interarticularis of the lumbar spine was confirmed in seven young athletes with a positive technetium pyrophosphate bone scan. No pars defects were detectable on their lumbosacral roentgenograms, which included oblique views. The return to normal levels of radioactive uptake on repeat bone scans correlated closely with their clinical course. If the bony reaction is recognized early, it may heal at a subroentgenographic level and prevent the development of lumbar spondylolysis. These early lesions usually show unilateral increased uptake at one lumbar level on the bone scan and, initially, the athlete localizes the pain to the corresponding unilateral lumbar paraspinous area. The ''one-legged hyperextension test'' is positive on the ipsilateral side and aggravates the pain. Treatment consists of avoiding the aggravating activities and resting. The average time for return to pain-free competition was 7.3 months. These developing defects may be the source of considerable prolonged disability in the young athlete, particularly if undiagnosed and untreated

  17. Réduction du risque d'infection par le VIH au Botswana - essais ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Au Botswana, ce sont les jeunes femmes qui sont le plus touchées par les nouvelles infections par le VIH. Le présent projet a pour but de réduire le nombre de nouveaux cas d'infection par le VIH, en particulier chez les femmes de 15 à 29 ans. Bien que l'on recense des cas de VIH/sida dans la plupart des régions du ...

  18. Combined virus-like particle and fusion protein-encoding DNA vaccination of cotton rats induces protection against respiratory syncytial virus without causing vaccine-enhanced disease

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Hye Suk; Lee, Young-Tae; Kim, Ki-Hye; Park, Soojin; Kwon, Young-Man; Lee, Youri; Ko, Eun-Ju; Jung, Yu-Jin [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States); Lee, Jong Seok [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States); National Institute of Biological Resources, Incheon (Korea, Republic of); Kim, Yu-Jin [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States); Lee, Yu-Na; Kim, Min-Chul [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States); Animal and Plant Quarantine Agency, Gyeonggi-do, Gimcheon, Gyeongsangbukdo (Korea, Republic of); Cho, Minkyoung [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States); Kang, Sang-Moo, E-mail: skang24@gsu.edu [Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences and Department of Biology, Georgia State University, Atlanta, GA (United States)

    2016-07-15

    A safe and effective vaccine against respiratory syncytial virus (RSV) should confer protection without causing vaccine-enhanced disease. Here, using a cotton rat model, we investigated the protective efficacy and safety of an RSV combination vaccine composed of F-encoding plasmid DNA and virus-like particles containing RSV fusion (F) and attachment (G) glycoproteins (FFG-VLP). Cotton rats with FFG-VLP vaccination controlled lung viral replication below the detection limit, and effectively induced neutralizing activity and antibody-secreting cell responses. In comparison with formalin inactivated RSV (FI-RSV) causing severe RSV disease after challenge, FFG-VLP vaccination did not cause weight loss, airway hyper-responsiveness, IL-4 cytokines, histopathology, and infiltrates of proinflammatory cells such as eosinophils. FFG-VLP was even more effective in preventing RSV-induced pulmonary inflammation than live RSV infections. This study provides evidence that FFG-VLP can be developed into a safe and effective RSV vaccine candidate. - Highlights: • Combined RSV FFG VLP vaccine is effective in inducing F specific responses. • FFG VLP vaccine confers RSV neutralizing activity and viral control in cotton rats. • Cotton rats with RSV FFG VLP vaccination do not show vaccine-enhanced disease. • Cotton rats with FFG VLP vaccine induce F specific antibody secreting cell responses. • Cotton rats with FFG VLP do not induce lung cellular infiltrates and Th2 cytokine.

  19. Association between the level of antibodies in bulk tank milk and bovine respiratory syncytial virus exposure in the herd.

    Science.gov (United States)

    Klem, T B; Tollersrud, T; Osterås, O; Stokstad, M

    2014-07-12

    Antibody levels in bulk tank milk (BTM) against bovine respiratory syncytial virus (BRSV) are used to classify BRSV status of herds. The aim of this study was to investigate how these levels correspond with the time at which the herds were infected. Bulk tank milk, individual milk and serum samples from cows and young stock were investigated using an indirect ELISA. Screenings of BTM from 89 dairy herds during two winter seasons revealed a prevalence of positive herds from 82 per cent to 85 per cent. Eleven herds showed a marked increase in antibody levels between two screenings, indicating new infection. However, two of these herds had been free from BRSV for the last five to seven years. Two newly infected herds were monitored for four years and did not appear to get reinfected. Surprisingly, the BTM antibody levels in these herds remained high throughout the study period, but fluctuated significantly. This shows that the levels of antibodies in BTM can remain high for several years, even in herds where reinfection does not occur. BTM serology is a useful tool in the monitoring of infectious diseases in dairy herds, but has limitations as a diagnostic tool for BRSV infections. British Veterinary Association.

  20. Differences in viral load among human respiratory syncytial virus genotypes in hospitalized children with severe acute respiratory infections in the Philippines.

    Science.gov (United States)

    Kadji, Francois Marie Ngako; Okamoto, Michiko; Furuse, Yuki; Tamaki, Raita; Suzuki, Akira; Lirio, Irene; Dapat, Clyde; Malasao, Rungnapa; Saito, Mariko; Pedrera-Rico, Gay Anne Granada; Tallo, Veronica; Lupisan, Socorro; Saito, Mayuko; Oshitani, Hitoshi

    2016-06-27

    Human respiratory syncytial virus (HRSV) is a leading viral etiologic agent of pediatric lower respiratory infections, including bronchiolitis and pneumonia. Two antigenic subgroups, HRSV-A and B, each contain several genotypes. While viral load may vary among HRSV genotypes and affect the clinical course of disease, data are scarce regarding the actual differences among genotypes. Therefore, this study estimated and compared viral load among NA1 and ON1 genotypes of HRSV-A and BA9 of HRSV-B. ON1 is a newly emerged genotype with a 72-nucleotide duplication in the G gene as observed previously with BA genotypes in HRSV-B. Children <5 years of age with an initial diagnosis of severe or very severe pneumonia at a hospital in the Philippines from September 2012 to December 2013 were enrolled. HRSV genotypes were determined and the viral load measured from nasopharyngeal swabs (NPS). The viral load of HRSV genotype NA1 were significantly higher than those of ON1 and BA9. Regression analysis showed that both genotype NA1 and younger age were significantly associated with high HRSV viral load. The viral load of NA1 was higher than that of ON1 and BA9 in NPS samples. HRSV genotypes may be associated with HRSV viral load. The reasons and clinical impacts of these differences in viral load among HRSV genotypes require further evaluation.

  1. Proteomic analysis of mitochondria in respiratory epithelial cells infected with human respiratory syncytial virus and functional implications for virus and cell biology.

    Science.gov (United States)

    Munday, Diane C; Howell, Gareth; Barr, John N; Hiscox, Julian A

    2015-03-01

    The aim of this study was to quantitatively characterise the mitochondrial proteome of airway epithelial cells infected with human respiratory syncytial virus (HRSV), a major cause of paediatric illness. Quantitative proteomics, underpinned by stable isotope labelling with amino acids in cell culture, coupled to LC-MS/MS, was applied to mitochondrial fractions prepared from HRSV-infected and mock-infected cells 12 and 24 h post-infection. Datasets were analysed using ingenuity pathway analysis, and the results were validated and characterised using bioimaging, targeted inhibition and gene depletion. The data quantitatively indicated that antiviral signalling proteins converged on mitochondria during HRSV infection. The mitochondrial receptor protein Tom70 was found to act in an antiviral manner, while its chaperone, Hsp90, was confirmed to be a positive viral factor. Proteins associated with different organelles were also co-enriched in the mitochondrial fractions from HRSV-infected cells, suggesting that alterations in organelle dynamics and membrane associations occur during virus infection. Protein and pathway-specific alterations occur to the mitochondrial proteome in a spatial and temporal manner during HRSV infection, suggesting that this organelle may have altered functions. These could be targeted as part of potential therapeutic strategies to disrupt virus biology. © 2014 Royal Pharmaceutical Society.

  2. Respiratory syncytial virus infection induces higher Toll-like receptor-3 expression and TNF-α production than human metapneumovirus infection.

    Directory of Open Access Journals (Sweden)

    Ying Dou

    Full Text Available Respiratory syncytial virus (RSV and human metapneumovirus (hMPV are common causes of respiratory infections in children. Diseases caused by hMPV are generally considered to be less severe than those caused by RSV; the underlying mechanisms, however, remain unknown. In the present study, the expressions of TLRs in airway epithelial cells and lungs of BALB/c mice infected by hMPV or RSV were measured in an attempt to explore the differences in the airway inflammation caused by the two viruses. Our results demonstrate that both hMPV and RSV infection upregulated the expressions of TLRs and inflammatory cytokines. Specifically, the TLR3 expression was revealed to be elevated in vitro and in mouse lungs. IFN-α produced by A549 cells after RSV or hMPV infection remained undistinguishable, whereas production of TNF-α was significantly higher after RSV infection than hMPV infection either in the presence or absence of Poly I:C. This study provides a clue that more severe clinical syndrome of RSV infection may be due to the greater magnitude of induction of airway inflammation by RSV involving TLR3 activation and production of TNF-α.

  3. Structural characterization of respiratory syncytial virus fusion inhibitor escape mutants: homology model of the F protein and a syncytium formation assay

    International Nuclear Information System (INIS)

    Morton, Craig J.; Cameron, Rachel; Lawrence, Lynne J.; Lin Bo; Lowe, Melinda; Luttick, Angela; Mason, Anthony; McKimm-Breschkin, Jenny; Parker, Michael W.; Ryan, Jane; Smout, Michael; Sullivan, Jayne; Tucker, Simon P.; Young, Paul R.

    2003-01-01

    Respiratory syncytial virus (RSV) is a ubiquitous human pathogen and the leading cause of lower respiratory tract infections in infants. Infection of cells and subsequent formation of syncytia occur through membrane fusion mediated by the RSV fusion protein (RSV-F). A novel in vitro assay of recombinant RSV-F function has been devised and used to characterize a number of escape mutants for three known inhibitors of RSV-F that have been isolated. Homology modeling of the RSV-F structure has been carried out on the basis of a chimera derived from the crystal structures of the RSV-F core and a fragment from the orthologous fusion protein from Newcastle disease virus (NDV). The structure correlates well with the appearance of RSV-F in electron micrographs, and the residues identified as contributing to specific binding sites for several monoclonal antibodies are arranged in appropriate solvent-accessible clusters. The positions of the characterized resistance mutants in the model structure identify two promising regions for the design of fusion inhibitors

  4. Genetic variability in G2 and F2 region between biological clones of human respiratory syncytial virus with or without host immune selection pressure

    Directory of Open Access Journals (Sweden)

    Claudia Trigo Pedroso Moraes

    2015-02-01

    Full Text Available Human respiratory syncytial virus (HRSV is an important respiratory pathogens among children between zero-five years old. Host immunity and viral genetic variability are important factors that can make vaccine production difficult. In this work, differences between biological clones of HRSV were detected in clinical samples in the absence and presence of serum collected from children in the convalescent phase of the illness and from their biological mothers. Viral clones were selected by plaque assay in the absence and presence of serum and nucleotide sequences of the G2 and F2 genes of HRSV biological clones were compared. One non-synonymous mutation was found in the F gene (Ile5Asn in one clone of an HRSV-B sample and one non-synonymous mutation was found in the G gene (Ser291Pro in four clones of the same HRSV-B sample. Only one of these clones was obtained after treatment with the child's serum. In addition, some synonymous mutations were determined in two clones of the HRSV-A samples. In conclusion, it is possible that minor sequences could be selected by host antibodies contributing to the HRSV evolutionary process, hampering the development of an effective vaccine, since we verify the same codon alteration in absence and presence of human sera in individual clones of BR-85 sample.

  5. Genetic variability in G2 and F2 region between biological clones of human respiratory syncytial virus with or without host immune selection pressure.

    Science.gov (United States)

    Moraes, Claudia Trigo Pedroso; Oliveira, Danielle Bruna Leal; Campos, Angelica Cristine Almeida; Bosso, Patricia Alves; Lima, Hildener Nogueira; Stewien, Klaus Eberhard; Gilio, Alfredo Elias; Vieira, Sandra Elisabete; Botosso, Viviane Fongaro; Durigon, Edison Luiz

    2015-02-01

    Human respiratory syncytial virus (HRSV) is an important respiratory pathogens among children between zero-five years old. Host immunity and viral genetic variability are important factors that can make vaccine production difficult. In this work, differences between biological clones of HRSV were detected in clinical samples in the absence and presence of serum collected from children in the convalescent phase of the illness and from their biological mothers. Viral clones were selected by plaque assay in the absence and presence of serum and nucleotide sequences of the G2 and F2 genes of HRSV biological clones were compared. One non-synonymous mutation was found in the F gene (Ile5Asn) in one clone of an HRSV-B sample and one non-synonymous mutation was found in the G gene (Ser291Pro) in four clones of the same HRSV-B sample. Only one of these clones was obtained after treatment with the child's serum. In addition, some synonymous mutations were determined in two clones of the HRSV-A samples. In conclusion, it is possible that minor sequences could be selected by host antibodies contributing to the HRSV evolutionary process, hampering the development of an effective vaccine, since we verify the same codon alteration in absence and presence of human sera in individual clones of BR-85 sample.

  6. Neuraminidase treatment of respiratory syncytial virus-infected cells or virions, but not target cells, enhances cell-cell fusion and infection

    International Nuclear Information System (INIS)

    Barretto, Naina; Hallak, Louay K.; Peeples, Mark E.

    2003-01-01

    Respiratory syncytial virus (RSV) infection of HeLa cells induces fusion, but transient expression of the three viral glycoproteins induces fusion poorly, if at all. We found that neuraminidase treatment of RSV-infected cells to remove sialic acid (SA) increases fusion dramatically and that the same treatment of transiently transfected cells expressing the three viral glycoproteins, or even cells expressing the fusion (F) protein alone, results in easily detectable fusion. Neuraminidase treatment of the effector cells, expressing the viral glycoproteins, enhanced fusion while treatment of the target cells did not. Likewise, infectivity was increased by treating virions with neuraminidase, but not by treating target cells. Reduction of charge repulsion by removal of the negatively charged SA is unlikely to explain this effect, since removal of negative charges from either membrane would reduce charge repulsion. Infection with neuraminidase-treated virus remained heparan-sulfate-dependent, indicating that a novel attachment mechanism is not revealed by SA removal. Interestingly, neuraminidase enhancement of RSV infectivity was less pronounced in a virus expressing both the G and the F glycoproteins, compared to virus expressing only the F glycoprotein, possibly suggesting that the G protein sterically hinders access of the neuraminidase to its fusion-enhancing target

  7. Duration of secretory IgM and IgA antibodies to respiratory syncytial virus in a community study in Guinea-Bissau

    DEFF Research Database (Denmark)

    Stensballe, L G; Kofoed, P E; Nante, E J

    2000-01-01

    Respiratory syncytial virus (RSV) is probably the single major cause of lower respiratory infection (LRI) among infants worldwide. Its relative importance may be underestimated, as the diagnosis is based on antigen detection and antigen may only be detectable in the early phase of infection. We...... phase of infection. A secondary response may be more likely in children with low IgM responses in the acute phase (RR = 2.08 (95% confidence interval (CI) 0.92-4.70)). The IgA response was highest on days 28 and 42 after antigen detection, 72% having a detectable IgA response within the first 1.5 mo...... have therefore assessed the duration of secretory IgM and IgA antibody responses and whether assays for these antibodies can be used to improve the diagnosing of RSV-associated infections. During two RSV epidemics in Guinea-Bissau, 32 RSV antigen-positive children with LRI were followed with sequential...

  8. Respiratory syncytial virus infection in infants with acute leukemia: a retrospective survey of the Japanese Pediatric Leukemia/Lymphoma Study Group.

    Science.gov (United States)

    Hatanaka, Michiki; Miyamura, Takako; Koh, Katsuyoshi; Taga, Takashi; Tawa, Akio; Hasegawa, Daisuke; Kajihara, Ryosuke; Adachi, Souichi; Ishii, Eiichi; Tomizawa, Daisuke

    2015-12-01

    Respiratory syncytial virus (RSV) can cause life-threatening complications of lower respiratory tract infection (LRTI) in young children with malignancies, but reports remain limited. We performed a retrospective nationwide survey to clarify the current status of RSV disease among infants with hematological malignancies. Clinical course, treatment, and outcome of patients with hematological malignancies who suffered from RSV infections at the age of acute leukemia were identified as having experienced RSV disease. The primary diseases were acute myeloid leukemia (n = 8) and acute lymphoblastic leukemia (n = 4). RSV infection occurred pre- or during induction therapy (n = 8) and during consolidation therapy (n = 4). Eight patients developed LRTI, four of whom had severe pneumonia or acute respiratory distress syndrome; these four patients died despite receiving intensive care. In our survey, the prognosis of RSV disease in pediatric hematological malignancies was poor, and progression of LRTI in particular was associated with high mortality. In the absence of RSV-specific therapy, effective prevention and treatment strategies for severe RSV disease must be investigated.

  9. Epidemiology of respiratory syncytial virus-associated acute lower respiratory tract infection hospitalizations among HIV-infected and HIV-uninfected South African children, 2010-2011.

    Science.gov (United States)

    Moyes, Jocelyn; Cohen, Cheryl; Pretorius, Marthi; Groome, Michelle; von Gottberg, Anne; Wolter, Nicole; Walaza, Sibongile; Haffejee, Sumayya; Chhagan, Meera; Naby, Fathima; Cohen, Adam L; Tempia, Stefano; Kahn, Kathleen; Dawood, Halima; Venter, Marietjie; Madhi, Shabir A

    2013-12-15

    There are limited data on respiratory syncytial virus (RSV) infection among children in settings with a high prevalence of human immunodeficiency virus (HIV). We studied the epidemiology of RSV-associated acute lower respiratory tract infection (ALRTI) hospitalizations among HIV-infected and HIV-uninfected children in South Africa. Children aged infection among HIV-infected and uninfected children were examined. The relative risk of hospitalization in HIV-infected and HIV-uninfected children was calculated in 1 site with population denominators. Of 4489 participants, 4293 (96%) were tested for RSV, of whom 1157 (27%) tested positive. With adjustment for age, HIV-infected children had a 3-5-fold increased risk of hospitalization with RSV-associated ALRTI (2010 relative risk, 5.6; [95% confidence interval (CI), 4.5-6.4]; 2011 relative risk, 3.1 [95% CI, 2.6-3.6]). On multivariable analysis, HIV-infected children with RSV-associated ALRTI had higher odds of death (adjusted odds ratio. 31.1; 95% CI, 5.4-179.8) and hospitalization for >5 days (adjusted odds ratio, 4.0; 95% CI, 1.5-10.6) than HIV-uninfected children. HIV-infected children have a higher risk of hospitalization with RSV-associated ALRTI and a poorer outcome than HIV-uninfected children. These children should be targeted for interventions aimed at preventing severe RSV disease.

  10. The Central Conserved Region (CCR) of Respiratory Syncytial Virus (RSV) G Protein Modulates Host miRNA Expression and Alters the Cellular Response to Infection.

    Science.gov (United States)

    Bakre, Abhijeet A; Harcourt, Jennifer L; Haynes, Lia M; Anderson, Larry J; Tripp, Ralph A

    2017-07-03

    Respiratory Syncytial Virus (RSV) infects respiratory epithelial cells and deregulates host gene expression by many mechanisms including expression of RSV G protein (RSV G). RSV G protein encodes a central conserved region (CCR) containing a CX3C motif that functions as a fractalkine mimic. Disruption of the CX3C motif (a.a. 182-186) located in the CCR of the G protein has been shown to affect G protein function in vitro and the severity of RSV disease pathogenesis in vivo. We show that infection of polarized Calu3 respiratory cells with recombinant RSV having point mutations in Cys173 and 176 (C173/176S) (rA2-GC12), or Cys186 (C186S) (rA2-GC4) is associated with a decline in the integrity of polarized Calu-3 cultures and decreased virus production. This is accompanied with downregulation of miRNAs let-7f and miR-24 and upregulation of interferon lambda (IFNλ), a primary antiviral cytokine for RSV in rA2-GC12/rA2-GC4 infected cells. These results suggest that residues in the cysteine noose region of RSV G protein can modulate IFN λ expression accompanied by downregulation of miRNAs, and are important for RSV G protein function and targeting.

  11. A cost-benefit analysis of the immunisation of children against respiratory syncytial virus (RSV) using the English Hospital Episode Statistics (HES) data set.

    Science.gov (United States)

    Thomas, Gareth

    2018-03-01

    Respiratory syncytial virus (RSV) is a common cause of respiratory infection that is highly prevalent in infants, particularly those with underlying medical conditions. Severe cases of RSV require hospitalisation as well as admission to intensive care and may even result in death. The objective of the study was to measure the net benefits that could arise from an immunisation programme of infants that may well eradicate RSV to a high degree and save the direct and indirect medical care costs from hospitalisation, morbidity and the gain from potential life-time earnings by reducing the probability of mortality. In this context, the majority of existing empirical investigations are based on data from clinical trials, and where relevant facts are not available, a series of strong assumptions is derived from the published literature, whereas in this study, for the first time, the hospital episode statistics database is used to calculate the cost-benefit ratios. The methodology of the analysis adopts a cost-benefit approach to assess the impact of the immunisation and whether it is beneficial to society. The underlying assumptions of the basic model are assessed by adopting a sensitivity analysis. The results show that a number of categories are cost-effective with the use of the passive drug, which means benefits by raising the life expectancy and quality as well as reducing the resource burden on society.

  12. Combined virus-like particle and fusion protein-encoding DNA vaccination of cotton rats induces protection against respiratory syncytial virus without causing vaccine-enhanced disease

    International Nuclear Information System (INIS)

    Hwang, Hye Suk; Lee, Young-Tae; Kim, Ki-Hye; Park, Soojin; Kwon, Young-Man; Lee, Youri; Ko, Eun-Ju; Jung, Yu-Jin; Lee, Jong Seok; Kim, Yu-Jin; Lee, Yu-Na; Kim, Min-Chul; Cho, Minkyoung; Kang, Sang-Moo

    2016-01-01

    A safe and effective vaccine against respiratory syncytial virus (RSV) should confer protection without causing vaccine-enhanced disease. Here, using a cotton rat model, we investigated the protective efficacy and safety of an RSV combination vaccine composed of F-encoding plasmid DNA and virus-like particles containing RSV fusion (F) and attachment (G) glycoproteins (FFG-VLP). Cotton rats with FFG-VLP vaccination controlled lung viral replication below the detection limit, and effectively induced neutralizing activity and antibody-secreting cell responses. In comparison with formalin inactivated RSV (FI-RSV) causing severe RSV disease after challenge, FFG-VLP vaccination did not cause weight loss, airway hyper-responsiveness, IL-4 cytokines, histopathology, and infiltrates of proinflammatory cells such as eosinophils. FFG-VLP was even more effective in preventing RSV-induced pulmonary inflammation than live RSV infections. This study provides evidence that FFG-VLP can be developed into a safe and effective RSV vaccine candidate. - Highlights: • Combined RSV FFG VLP vaccine is effective in inducing F specific responses. • FFG VLP vaccine confers RSV neutralizing activity and viral control in cotton rats. • Cotton rats with RSV FFG VLP vaccination do not show vaccine-enhanced disease. • Cotton rats with FFG VLP vaccine induce F specific antibody secreting cell responses. • Cotton rats with FFG VLP do not induce lung cellular infiltrates and Th2 cytokine.

  13. Characterization of the CD8+ T cell responses directed against respiratory syncytial virus during primary and secondary infection in C57BL/6 mice

    International Nuclear Information System (INIS)

    Lukens, Michael V.; Claassen, Erwin A.W.; Graaff, Patricia M.A. de; Dijk, Mariska E.A. van; Hoogerhout, Peter; Toebes, Mireille; Schumacher, Ton N.; Most, Robbert G. van der; Kimpen, Jan L.L.; Bleek, Grada M. van

    2006-01-01

    The BALB/c mouse model for human respiratory syncytial virus infection has contributed significantly to our understanding of the relative role for CD4 + and CD8 + T cells to immune protection and pathogenic immune responses. To enable comparison of RSV-specific T cell responses in different mouse strains and allow dissection of immune mechanisms by using transgenic and knockout mice that are mostly available on a C57BL/6 background, we characterized the specificity, level and functional capabilities of CD8 + T cells during primary and secondary responses in lung parenchyma, airways and spleens of C57BL/6 mice. During the primary response, epitopes were recognized originating from the matrix, fusion, nucleo- and attachment proteins, whereas the secondary response focused predominantly on the matrix epitope. C57BL/6 mice are less permissive for hRSV infection than BALB/c mice, yet we found CD8 + T cell responses in the lungs and bronchoalveolar lavage, comparable to the responses described for BALB/c mice

  14. Clinical and epidemiological aspects related to the detection of adenovirus or respiratory syncytial virus in infants hospitalized for acute lower respiratory tract infection

    Directory of Open Access Journals (Sweden)

    Eduardo A. Ferone

    2014-01-01

    Full Text Available OBJECTIVE: To characterize and compare clinical, epidemiological, and laboratory aspects ofinfants with acute lower respiratory infection (ALRI associated with the detection of adenovirus(ADV or respiratory syncytial virus (RSV. METHODS: A preliminary respiratory infection surveillance study collected samples of nasopharyngeal aspirate (NPA for viral research, linked to the completion of a standard protocol, from children younger than two years admitted to a university hospital with ALRI, between March of 2008 and August of 2011. Polymerase chain reaction (PCR was used for eight viruses: ADV, RSV, metapneumovirus, Parainfluenza 1, 2, and 3, and Influenza A and B. Cases with NPA collectedduring the first 24 hours of admission, negative results of blood culture, and exclusive detection of ADV (Gadv group or RSV (Grsv group were selected for comparisons. RESULTS: The preliminary study included collection of 1,121 samples of NPA, 813 collected in thefirst 24 hours of admission, of which 50.3% were positive for at least one virus; RSV was identifiedin 27.3% of cases surveyed, and ADV was identified in 15.8%. Among the aspects analyzed inthe Gadv (n = 58 and Grsv (n = 134 groups, the following are noteworthy: the higher meanage, more frequent prescription of antibiotics, and the highest median of total white blood cellcount and C-reactive protein values in Gadv. CONCLUSIONS: PCR can detect persistent/latent forms of ADV, an aspect to be considered wheninterpreting results. Additional studies with quantitative diagnostic techniques could elucidatethe importance of the high frequency observed.

  15. PAR-2 expression in the gingival crevicular fluid reflects chronic periodontitis severity.

    Science.gov (United States)

    Fukushima, Henrique; Alves, Vanessa Tubero Euzebio; Carvalho, Verônica Franco de; Ambrósio, Lucas Macedo Batitucci; Eichler, Rosangela Aparecida Dos Santos; Carvalho, Maria Helena Catelli de; Saraiva, Luciana; Holzhausen, Marinella

    2017-01-26

    Recent studies investigating protease-activated receptor type 2 (PAR-2) suggest an association between the receptor and periodontal inflammation. It is known that gingipain, a bacterial protease secreted by the important periodontopathogen Porphyromonas gingivalis can activate PAR-2. Previous studies by our group found that PAR-2 is overexpressed in the gingival crevicular fluid (GCF) of patients with moderate chronic periodontitis (MP). The present study aimed at evaluating whether PAR-2 expression is associated with chronic periodontitis severity. GCF samples and clinical parameters, including plaque and bleeding on probing indices, probing pocket depth and clinical attachment level, were collected from the control group (n = 19) at baseline, and from MP patients (n = 19) and severe chronic periodontitis (SP) (n = 19) patients before and 6 weeks after periodontal non-surgical treatment. PAR-2 and gingipain messenger RNA (mRNA) in the GCF of 4 periodontal sites per patient were evaluated by Reverse Transcription Polymerase Chain Reaction (RT-qPCR). PAR-2 and gingipain expressions were greater in periodontitis patients than in control group patients. In addition, the SP group presented increased PAR-2 and gingipain mRNA levels, compared with the MP group. Furthermore, periodontal treatment significantly reduced (p periodontitis. In conclusion, PAR-2 is associated with chronic periodontitis severity and with gingipain levels in the periodontal pocket, thus suggesting that PAR-2 expression in the GCF reflects the severity of destruction during periodontal infection.

  16. Un « gouvernement des journalistes par le Pouvoir politique » par défaut ?

    Directory of Open Access Journals (Sweden)

    Matthieu Lardeau

    2013-12-01

    Full Text Available Cet article présente les interactions de deux mouvements concomitants apparusprincipalement dans les décennies 1950 à 1970 dans le champ de la presse française : d’un côté les initiatives – consécutives à la démarche pionnière, en 1951, de création de la première Société des journalistes (SDJ au sein du Monde – menées par les journalistes de rédactions de quotidiens pour créer des SDJ dont la destination peut aller jusqu’à gouverner les journaux; de l’autre côté, les « réponses » apportées par les Pouvoirs politique et public pour contenir ces initiatives visant à étendre le pouvoir des journalistes dans la gestion et la gouvernance de leurs journaux. Cette étude exploratoire repose principalement sur l’analyse de deux types de littérature, souvent déconsidérés ou négligés par le champ académique, en dépit de leur grande richesse : (1 la littérature professionnelle, ayant pour principaux auteurs les journalistes et managers de presse (Périer Daville, Boegner, Pigasse, etc., florissante depuis 1944 et singulièrement durant les décennies 1960 et 1970 ; (2 la littérature grise constituée notamment par des rapports publics rédigés par des institutions comme les services du Premier ministre (commissions Lindon de 1970 et Serisé de 1972, le Conseil économique et social, etc. Nos principaux résultats montrent que les propositions ou actions menées par les journalistes (1 restent le plus souvent inexploitées in concreto par les journalistes eux-mêmes; (2 entrent le plus souvent en opposition avec les politiques de nouveaux actionnaires ou directions de journaux et avec les projets des autorités politiques et publiques qui cherchent à encadrer l’autonomie de la profession journalistique pour mieux gouverner celle-ci ; (3 combien in fine les représentants des différents acteurs impliqués s’accordent pour contenir l’émergence d’un « gouvernement des journalistes » par les

  17. The polarity protein Par6 is coupled to the microtubule network during molluscan early embryogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Homma, Taihei [Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Shimizu, Miho [Kuroda Chiromorphology Team, ERATO-SORST, JST, Komaba, Meguro-ku, Tokyo 153-8902 (Japan); Kuroda, Reiko, E-mail: ckuroda@mail.ecc.u-tokyo.ac.jp [Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Kuroda Chiromorphology Team, ERATO-SORST, JST, Komaba, Meguro-ku, Tokyo 153-8902 (Japan); Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Komaba, Meguro-ku, Tokyo 153-8902 (Japan)

    2011-01-07

    Research highlights: {yields} The cDNAs encoding Par6 and aPKC homologues were cloned from the snail Lymnaea stagnalis. {yields} L. stagnalis Par6 directly interacts with tubulin and microtubules and localizes to the microtubule cytoskeleton during the early embryogenesis. {yields} Identical sequence and localization of LsPar6 for the dextral and the sinistral snails exclude the possibility of the gene being the primary determinant of body handedness. -- Abstract: Cell polarity, which directs the orientation of asymmetric cell division and segregation of fate determinants, is a fundamental feature of development and differentiation. Regulators of polarity have been extensively studied, and the critical importance of the Par (partitioning-defective) complex as the polarity machinery is now recognized in a wide range of eukaryotic systems. The Par polarity module is evolutionarily conserved, but its mechanism and cooperating factors vary among different systems. Here we describe the cloning and characterization of a pond snail Lymnaea stagnalis homologue of partitioning-defective 6 (Lspar6). The protein product LsPar6 shows high affinity for microtubules and localizes to the mitotic apparatus during embryonic cell division. In vitro assays revealed direct binding of LsPar6 to tubulin and microtubules, which is the first evidence of the direct interaction between the two proteins. The interaction is mediated by two distinct regions of LsPar6 both located in the N-terminal half. Atypical PKC, a functional partner of Par6, was also found to localize to the mitotic spindle. These results suggest that the L. stagnalis Par complex employs the microtubule network in cell polarity processes during the early embryogenesis. Identical sequence and localization of LsPar6 for the dextral and the sinistral snails exclude the possibility of the gene being the primary determinant of handedness.

  18. The polarity protein Par6 is coupled to the microtubule network during molluscan early embryogenesis

    International Nuclear Information System (INIS)

    Homma, Taihei; Shimizu, Miho; Kuroda, Reiko

    2011-01-01

    Research highlights: → The cDNAs encoding Par6 and aPKC homologues were cloned from the snail Lymnaea stagnalis. → L. stagnalis Par6 directly interacts with tubulin and microtubules and localizes to the microtubule cytoskeleton during the early embryogenesis. → Identical sequence and localization of LsPar6 for the dextral and the sinistral snails exclude the possibility of the gene being the primary determinant of body handedness. -- Abstract: Cell polarity, which directs the orientation of asymmetric cell division and segregation of fate determinants, is a fundamental feature of development and differentiation. Regulators of polarity have been extensively studied, and the critical importance of the Par (partitioning-defective) complex as the polarity machinery is now recognized in a wide range of eukaryotic systems. The Par polarity module is evolutionarily conserved, but its mechanism and cooperating factors vary among different systems. Here we describe the cloning and characterization of a pond snail Lymnaea stagnalis homologue of partitioning-defective 6 (Lspar6). The protein product LsPar6 shows high affinity for microtubules and localizes to the mitotic apparatus during embryonic cell division. In vitro assays revealed direct binding of LsPar6 to tubulin and microtubules, which is the first evidence of the direct interaction between the two proteins. The interaction is mediated by two distinct regions of LsPar6 both located in the N-terminal half. Atypical PKC, a functional partner of Par6, was also found to localize to the mitotic spindle. These results suggest that the L. stagnalis Par complex employs the microtubule network in cell polarity processes during the early embryogenesis. Identical sequence and localization of LsPar6 for the dextral and the sinistral snails exclude the possibility of the gene being the primary determinant of handedness.

  19. Paternal age related schizophrenia (PARS): Latent subgroups detected by k-means clustering analysis.

    Science.gov (United States)

    Lee, Hyejoo; Malaspina, Dolores; Ahn, Hongshik; Perrin, Mary; Opler, Mark G; Kleinhaus, Karine; Harlap, Susan; Goetz, Raymond; Antonius, Daniel

    2011-05-01

    Paternal age related schizophrenia (PARS) has been proposed as a subgroup of schizophrenia with distinct etiology, pathophysiology and symptoms. This study uses a k-means clustering analysis approach to generate hypotheses about differences between PARS and other cases of schizophrenia. We studied PARS (operationally defined as not having any family history of schizophrenia among first and second-degree relatives and fathers' age at birth ≥ 35 years) in a series of schizophrenia cases recruited from a research unit. Data were available on demographic variables, symptoms (Positive and Negative Syndrome Scale; PANSS), cognitive tests (Wechsler Adult Intelligence Scale-Revised; WAIS-R) and olfaction (University of Pennsylvania Smell Identification Test; UPSIT). We conducted a series of k-means clustering analyses to identify clusters of cases containing high concentrations of PARS. Two analyses generated clusters with high concentrations of PARS cases. The first analysis (N=136; PARS=34) revealed a cluster containing 83% PARS cases, in which the patients showed a significant discrepancy between verbal and performance intelligence. The mean paternal and maternal ages were 41 and 33, respectively. The second analysis (N=123; PARS=30) revealed a cluster containing 71% PARS cases, of which 93% were females; the mean age of onset of psychosis, at 17.2, was significantly early. These results strengthen the evidence that PARS cases differ from other patients with schizophrenia. Hypothesis-generating findings suggest that features of PARS may include a discrepancy between verbal and performance intelligence, and in females, an early age of onset. These findings provide a rationale for separating these phenotypes from others in future clinical, genetic and pathophysiologic studies of schizophrenia and in considering responses to treatment. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. Electron microscope study of vacancy clusters produced by quenching in magnesium; Etude par microscopie electronique des amas de lacunes crees par trempe dans le magnesium

    Energy Technology Data Exchange (ETDEWEB)

    Levy, V; Espinasse, J; Mairy, C; Hillairet, J [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1969-07-01

    Vacancy clustering in quenched magnesium has been studied by transmission electron microscopy. The nature of the vacancy loops observed, seems to depend essentially on the impurity content of the metal; this effect can be attributed to a variation of the stacking fault energy of magnesium due to impurities. (authors) [French] On a etudie par microscopie electronique en transmission les defauts crees par trempe dans le magnesium. Un effet considerable des impuretes du metal sur la nature des boucles obtenues par condensation de lacunes a ete mis en evidence; cet effet semble s'expliquer de facon satisfaisante par un abaissement de l'energie de faute d'empilement du magnesium du aux impuretes. (auteur)

  1. Neutrons detection by scintillation; Detection de neutrons par scintillations

    Energy Technology Data Exchange (ETDEWEB)

    Giraudon, J [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1955-01-15

    The absence of charge of neutrons and their elevated penetration power make difficult their detection. Techniques vary otherwise with the energy of the particle. The author proposes the realization of a scintillation detector with a big volume of liquid scintillator and containing boron for the detection of slowing-down neutrons in the domain of intermediate energies from 1 to 10{sup 5} eV about. (M.B.) [French] L'absence de charge du neutron et son pouvoir de penetration eleve rendent difficile sa detection. Les techniques par ailleurs varient avec l'energie de cette particule. L'auteur propose la realisation d'un detecteur a scintillations comprenant un grand volume de scintillateur liquide et contenant du bore pour la detection des neutrons en ralentissement dans le domaine des energies intermediaires de 1 a 10{sup 5} eV environ. (M.B.)

  2. Cancro em mogno africano no estado do Pará

    Directory of Open Access Journals (Sweden)

    Célia Regina Tremacoldi

    2013-06-01

    Full Text Available Sintomas de cancro foram observados em plantios de mogno africano, no município de Dom Eliseu, Pará. Os fungos associados aos tecidos sintomáticos foram identificados como Lasiodiplodia theobromae e Fusarium subglutinans. Culturas puras desses fungos foram testadas quanto à patogenicidade em mudas de mogno africano sadias. Apenas L. theobromae produziu cancro, por meio de inoculação por ferimento e alta umidade. A confirmação de L. theobromae como agente causal do cancro ocorreu após o reisolamento do fungo a partir das plantas inoculadas em casa de vegetação, concluindo a primeira verificação do postulado de Koch para esse patossistema.

  3. IMPROVEMENT OF PRODUCTION PLANNING IN COMPANY PARS KOMPONENTY

    Directory of Open Access Journals (Sweden)

    René Klega

    2014-03-01

    Full Text Available The article analyzes the current status of production planning in company Pars Komponenty s.r.o., proposes a new method of planning based on application of the principle of MRP. It is a discrete type of production with high complexity of BOM and MTO (Make-to-Order and ETO (Engineering-to-Order from the point of decoupling point. The original planning system plans according to production capacity backward without collisions, but for a given type of production does not work in practice. Planning system was analyzed and the main problems were identified, which were high work in progress and material stocks. This article target is to propose a new planining system based on the inclusion of time reserves of purchased material items. New planning system was tested in practise with benefit in reducing both the material inventory and work in progress.

  4. Pierre Vilar Frontinhan 1906 - París 2003

    Directory of Open Access Journals (Sweden)

    Pablo Rodríguez

    2003-01-01

    Full Text Available En el pasado mes de agosto falleció en París el historiador y maestro de tantas generaciones Pierre Vilar. Aunque había mantenido una intensa actividad de reflexión sobre los sucesos contemporáneos, ésta se vio afectada en 1991 luego que una grave enfermedad le negó la visión. Fue entonces cuando decidió con la ayuda de Rosa Congost escribir sus reflexiones y recuerdos, especie de memoria de juventud. Pensar Históricamente (Barcelona: Editorial Crítica, 1997, el libro que reúne estos ejercicios, es una obra de sumo interés para conocer la infancia, adolescencia y juventud de este connotado historiador.

  5. Neutrons detection by scintillation; Detection de neutrons par scintillations

    Energy Technology Data Exchange (ETDEWEB)

    Giraudon, J. [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1955-01-15

    The absence of charge of neutrons and their elevated penetration power make difficult their detection. Techniques vary otherwise with the energy of the particle. The author proposes the realization of a scintillation detector with a big volume of liquid scintillator and containing boron for the detection of slowing-down neutrons in the domain of intermediate energies from 1 to 10{sup 5} eV about. (M.B.) [French] L'absence de charge du neutron et son pouvoir de penetration eleve rendent difficile sa detection. Les techniques par ailleurs varient avec l'energie de cette particule. L'auteur propose la realisation d'un detecteur a scintillations comprenant un grand volume de scintillateur liquide et contenant du bore pour la detection des neutrons en ralentissement dans le domaine des energies intermediaires de 1 a 10{sup 5} eV environ. (M.B.)

  6. Determination of tritium by counting; Dosage du tritium par comptage

    Energy Technology Data Exchange (ETDEWEB)

    Schott, R; Froment, G; Pinson, J; Genty, C [Commissariat a l' Energie Atomique, Bruyeres-le-Chatel (France). Centre d' Etudes

    1968-07-01

    Ionisation chamber assay of tritium in any gaseous mixture is a simple, fast and accurate method. We used the method of relative determination by comparison to a standard rather than the method of absolute assay in which case the constants are known with too little accuracy. The efficiency of the chamber was studied in connection to the pressure inside the chamber and its total volume. The calibration is linear in the range we are taking into account (1 to 80 millicuries). The reproducibility of the method is good: 13 runs gave a coefficient of variation of 1.6 per cent. The relative accuracy was found equal to {+-} 1.3 per cent. To end the paper, we describe in detail the apparatus and the ways of proceedings. (authors) [French] Le comptage du tritium par chambre d'ionisation est une methode simple, rapide et precise pour determiner la teneur en tritium d'un melange gazeux quelconque. Nous avons prefere utiliser la methode de determination relative par rapport a un etalon car, dans le cas d'une determination absolue, les constantes sont connues avec une trop grande incertitude. L'efficacite de la chambre a ete etudiee en fonction de la variation de la pression d'argon a l'interieur de la chambre et du volume total, de cette derniere. L'etalonnage s'est revele lineaire dans le domaine de mesures qui nous interessaient (1 a 80 millicuries). La reproductibillte de la methode est tres bonne, le coefficient de variation pour une serie de 13 essais etant de 1,6 pour cent, quant a la precision relative, elle a ete evaluee a {+-} 1,3 pour cent. Pour terminer, nous donnons une description detaillee de l'appareillage utilise et du mode operatoire suivi. (auteurs)

  7. Clinical outcomes of pars plicata anterior vitrectomy: 2-year results

    Directory of Open Access Journals (Sweden)

    Priya Narang

    2015-01-01

    Full Text Available Purpose: To demonstrate the safety and outcome of a surgical approach that uses pars plicata site for anterior vitrectomy during phacoemulsification procedure complicated by posterior capsule rupture and residual cortical matter. Design: Single center, retrospective, interventional, noncomparative study. Materials and Methods: Medical records of a consecutive series of 35 eyes of 35 patients who underwent pars plicata anterior vitrectomy (PPAV were reviewed. The main outcome measures were corrected and uncorrected distance visual acuity (CDVA, UDVA, early and late postoperative complications and intraocular pressure (IOP. Ultrasound biomicroscopic (UBM evaluation of sclerotomy site and spectral domain optical coherence tomography analysis for central macular thickness (CMT was performed. The final visual outcome at 2 years was evaluated. Results: At 2 years follow-up, the mean postoperative UDVA (logarithm of the minimum angle of resolution [logMAR] and CDVA (logMAR was 0.49 ± 0.26 and 0.19 ± 0.14, respectively. There was no significant change in the IOP (P = 0.061 and the mean CMT at 2 years was 192.5 ± 5.54 mm. The postoperative UBM image of the sclerotomy site at 8 weeks demonstrated a clear wound without any vitreous adhesion or incarceration. Intraoperative hyphema was seen in 1 (2.8% case and postoperative uveitis was seen in 2 (5.7% cases, which resolved with medications. No case of an iatrogenic retinal break or retinal detachment was reported. Conclusions: PPAV enables a closed chamber approach, allows thorough cleanup of vitreous in the pupillary plane and anterior chamber and affords better access to the subincisional and retropupillary cortical remnant with a significant visual outcome and an acceptable complication rate.

  8. Urokinase-type plasminogen activator receptor (uPAR) as a promising new imaging target

    DEFF Research Database (Denmark)

    Persson, Morten; Kjaer, Andreas

    2013-01-01

    modalities such as optical imaging, magnetic resonance imaging, single photon emission computer tomography (SPECT) and positron emission topography (PET). In this review, we will discuss recent advances in the development of uPAR-targeted imaging ligands according to imaging modality. In addition, we...... will discuss the potential future clinical application for uPAR imaging as a new imaging biomarker....

  9. Pars plana vitrectomy for disturbing primary vitreous floaters: clinical outcome and patient satisfaction

    NARCIS (Netherlands)

    Nie, K.F. de; Crama, N.; Tilanus, M.A.D.; Klevering, B.J.; Boon, C.J.F.

    2013-01-01

    BACKGROUND: Primary vitreous floaters can be highly bothersome in some patients. In the case of persistently bothersome floaters, pars plana vitrectomy may be the most effective treatment. The aim of this study is to evaluate the incidence of complications, and patient satisfaction, after pars plana

  10. Solar PAR and UVR modify the community composition and photosynthetic activity of sea ice algae.

    Science.gov (United States)

    Enberg, Sara; Piiparinen, Jonna; Majaneva, Markus; Vähätalo, Anssi V; Autio, Riitta; Rintala, Janne-Markus

    2015-10-01

    The effects of increased photosynthetically active radiation (PAR) and ultraviolet radiation (UVR) on species diversity, biomass and photosynthetic activity were studied in fast ice algal communities. The experimental set-up consisted of nine 1.44 m(2) squares with three treatments: untreated with natural snow cover (UNT), snow-free (PAR + UVR) and snow-free ice covered with a UV screen (PAR). The total algal biomass, dominated by diatoms and dinoflagellates, increased in all treatments during the experiment. However, the smaller biomass growth in the top 10-cm layer of the PAR + UVR treatment compared with the PAR treatment indicated the negative effect of UVR. Scrippsiella complex (mainly Scrippsiella hangoei, Biecheleria baltica and Gymnodinium corollarium) showed UV sensitivity in the top 5-cm layer, whereas Heterocapsa arctica ssp. frigida and green algae showed sensitivity to both PAR and UVR. The photosynthetic activity was highest in the top 5-cm layer of the PAR treatment, where the biomass of the pennate diatom Nitzschia frigida increased, indicating the UV sensitivity of this species. This study shows that UVR is one of the controlling factors of algal communities in Baltic Sea ice, and that increased availability of PAR together with UVR exclusion can cause changes in algal biomass, photosynthetic activity and community composition. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  11. Spectral variations of UV-A and PAR solar radiation in estuarine waters of Goa

    Digital Repository Service at National Institute of Oceanography (India)

    Talaulikar, M.; Suresh, T.; Silveira, N.; Desa, E.; Matondkar, S; Lotlikar, A

    radiation (400 to 700 nm), PAR and ultraviolet radiation in the range 350-400 nm (UV-A) are presented here. The mean PAR values at the surface were 327 W/m sup(2) and reduced to 84 W/m sup(2) at first optical depth, Z sub(90) (m) in water. The first optical...

  12. Narrative Identities and the Plebiscite in Pará: An Analysis of the Front Pages for O Liberal and Diário do Pará

    Directory of Open Access Journals (Sweden)

    Alda Cristina Silva da Costa

    2017-05-01

    Full Text Available On December 11, 2011, a plebiscite was held in Pará proposing to create two separatist states, Carajás and Tapajós, out of the state of Pará. The public voted against both projects. This article analyzes the narrative identities found on the front pages of O Liberal and Diário do Pará newspapers about the plebiscite in Pará. Depth Hermeneutics (DH, as proposed by Thompson (2011, was used as the methodological reference. DH emphasizes the object of analysis as a meaningful symbolic construction requiring interpretation. Narrative analysis, as proposed by Motta (2007, was the main research technique used to highlight the movement of construction of journalistic (discursive characters. The narrative identities built by the two newspapers showed that both were against the creation of the new states, but for very different reasons. The flag of Pará was the main object used to induce the idea of unity. Em 11 de dezembro de 2011, o plebiscito no Pará propôs a criação dos estados de Carajás e de Tapajós a partir da divisão do estado do Pará. O resultado da consulta pública foi negativo aos dois projetos. O artigo analisa as identidades narrativas constituídas pelas primeiras páginas dos jornais O Liberal e Diário do Pará sobre o plebiscito no Pará. Utilizou-se como referencial metodológico a Hermenêutica em Profundidade (HP, proposta por Thompson (2011. A HP evidencia o fato de que o objeto de análise é uma construção simbólica significativa, que exige uma interpretação. Como principal técnica de pesquisa, a análise narrativa, proposta por Motta (2007, com ênfase no movimento de construção de personagens jornalísticas (discursivas. As identidades narrativas construídas pelos dois jornais indicaram que ambos eram contrários à criação dos novos estados, porém por motivos divergentes. A bandeira do Pará foi o principal elemento utilizado para evocar a ideia de unidade. En 11 de diciembre de 2011, el plebiscito en

  13. Comparison of the Simplexa™ Flu A/B & RSV kit (nucleic acid extraction-dependent assay) and the Prodessa ProFlu+™ assay for detecting influenza and respiratory syncytial viruses.

    Science.gov (United States)

    Selvaraju, Suresh B; Bambach, Adrienne V; Leber, Amy L; Patru, Maria-Magdalena; Patel, Anami; Menegus, Marilyn A

    2014-09-01

    The relative performance of 2 widely used reverse transcription polymerase chain reaction (RT-PCR) assays, the Focus diagnostics Simplexa™ Flu A/B & RSV kit (nucleic acid extraction-dependent assay) and the Prodessa Proflu+™ assay, was evaluated using 735 prospectively and retrospectively collected nasopharyngeal swab specimens. Overall, the assays showed positive and negative agreements of 100% and 99.7% for influenza A, 98.1% and 99.9% for influenza B, and 99.3% and 99.5% for respiratory syncytial virus. The relative analytical sensitivity of the 2 assays was also similar. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Use of palivizumab and infection control measures to control an outbreak of respiratory syncytial virus in a neonatal intensive care unit confirmed by real-time polymerase chain reaction.

    LENUS (Irish Health Repository)

    O'Connell, K

    2011-04-01

    Respiratory syncytial virus (RSV) is a potentially life-threatening infection in premature infants. We report an outbreak involving four infants in the neonatal intensive care unit (NICU) of our hospital that occurred in February 2010. RSV A infection was confirmed by real-time polymerase chain reaction. Palivizumab was administered to all infants in the NICU. There were no additional symptomatic cases and repeat RSV surveillance confirmed that there was no further cross-transmission within the unit. The outbreak highlighted the infection control challenge of very high bed occupancy in the unit and the usefulness of molecular methods in facilitating detection and management.

  15. The urokinase receptor (uPAR) and the uPAR-associated protein (uPARAP/Endo180)

    DEFF Research Database (Denmark)

    Behrendt, Niels

    2004-01-01

    The breakdown of the barriers formed by extracellular matrix proteins is a pre-requisite for all processes of tissue remodeling. Matrix degradation reactions take part in specific physiological events in the healthy organism but also represent a crucial step in cancer invasion. These degradation...... on the surface of various cell types that serves to bind the urokinase plasminogen activator and localize the activation reactions in the proteolytic cascade system of plasminogen activation. uPARAP is an integral membrane protein with a pronounced role in the internalization of collagen for intracellular...... degradation. Both receptors have additional functions that are currently being unraveled. The present discussion of uPAR and uPARAP is centered on their protein structure and molecular and cellular function....

  16. Effect of simvastatin and ezetimibe on suPAR levels and outcomes

    DEFF Research Database (Denmark)

    Hodges, Gethin W; Bang, Casper N; Forman, Julie L

    2018-01-01

    -lowering therapy also lowers suPAR levels is unknown. METHODS: We investigated whether treatment with Simvastatin 40 mg and Ezetimibe 10 mg lowered plasma suPAR levels in 1838 patients with mild-moderate, asymptomatic aortic stenosis, included in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study, using...... and Ezetimibe treatment impeded the progression of the time-related increase in plasma suPAR levels. Year-1 suPAR was associated with all-cause mortality, MCE, and AVE irrespective of baseline levels (SEAS study: NCT00092677)....... cardiovascular events (MCE) composed of ischemic cardiovascular events (ICE) and aortic valve related events (AVE). RESULTS: After 4.3 years of follow-up, suPAR levels had increased by 9.2% (95% confidence interval [CI]: 7.0%-11.5%) in the placebo group, but only by 4.1% (1.9%-6.2%) in the group with lipid...

  17. Brulure par Plaque de Bistouri Electrique: a Propos de Quatre Cas

    Science.gov (United States)

    Khales, A.; Achbouk, A.; Belmir, R.; Cherkab, L.; Ennouhi, M.A.; Ababou, K.; Ihrai, H.

    2010-01-01

    Summary La brûlure par plaque de bistouri électrique est un accident rare mais grave par la profondeur de la lésion et par sa localisation, surtout quand qu’elle survient dans un contexte chirurgical dont le vécu reste difficile de la part du malade et du chirurgien. Cette brûlure bien que imprévisible reste grave par la profondeur et la localisation de la brûlure et par sa survenue dans un contexte opératoire, chez des patients malades. La prise en charge de la brûlure doit se faire en milieu spécialisé. La prévention reste le seul moyen d’éviter ce type d’accident. PMID:21991216

  18. par genes in Mycobacterium bovis and Mycobacterium smegmatis are arranged in an operon transcribed from "SigGC" promoters

    Directory of Open Access Journals (Sweden)

    Casart Yveth

    2008-03-01

    Full Text Available Abstract Background The ParA/Soj and ParB/Spo0J proteins, and the cis-acting parS site, participate actively in chromosome segregation and cell cycle progression. Genes homologous to parA and parB, and two putative parS copies, have been identified in the Mycobacterium bovis BCG and Mycobacterium smegmatis chromosomes. As in Mycobacterium tuberculosis, the parA and parB genes in these two non-pathogenic mycobacteria are located near the chromosomal origin of replication. The present work focused on the determination of the transcriptional organisation of the ~6 Kb orf60K-parB region of M. bovis BCG and M. smegmatis by primer extension, transcriptional fusions to the green fluorescence protein (GFP and quantitative RT-PCR. Results The parAB genes were arranged in an operon. However, we also found promoters upstream of each one of these genes. Seven putative promoter sequences were identified in the orf60K-parB region of M. bovis BCG, whilst four were identified in the homologous region of M. smegmatis, one upstream of each open reading frame (ORF. Real-time PCR assays showed that in M. smegmatis, mRNA-parA and mRNA-parB levels decreased between the exponential and stationary phases. In M. bovis BCG, mRNA-parA levels also decreased between the exponential and stationary phases. However, parB expression was higher than parA expression and remained almost unchanged along the growth curve. Conclusion The majority of the proposed promoter regions had features characteristic of Mycobacterium promoters previously denoted as Group D. The -10 hexamer of a strong E. coli σ70-like promoter, located upstream of gidB of M. bovis BCG, overlapped with a putative parS sequence, suggesting that the transcription from this promoter might be regulated by the binding of ParB to parS.

  19. MODIS-derived daily PAR simulation from cloud-free images and its validation

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Liangfu; Gu, Xingfa; Tian, Guoliang [State Key Laboratory of Remote Sensing Science, Jointly Sponsored by Institute of Remote Sensing Applications of Chinese Academy of Sciences and Beijing Normal University, Beijing 100101 (China); The Center for National Spaceborne Demonstration, Beijing 100101 (China); Gao, Yanhua [State Key Laboratory of Remote Sensing Science, Jointly Sponsored by Institute of Remote Sensing Applications of Chinese Academy of Sciences and Beijing Normal University, Beijing 100101 (China); Institute of Geographic Sciences and Natural Resources Research, Chinese Academy of Sciences, Beijing 100101 (China); Yang, Lei [State Key Laboratory of Remote Sensing Science, Jointly Sponsored by Institute of Remote Sensing Applications of Chinese Academy of Sciences and Beijing Normal University, Beijing 100101 (China); Jilin University, Changchun 130026 (China); Liu, Qinhuo [State Key Laboratory of Remote Sensing Science, Jointly Sponsored by Institute of Remote Sensing Applications of Chinese Academy of Sciences and Beijing Normal University, Beijing 100101 (China)

    2008-06-15

    In this paper, a MODIS-derived daily PAR (photosynthetically active radiation) simulation model from cloud-free image over land surface has been developed based on Bird and Riordan's model. In this model, the total downwelling spectral surface irradiance is divided into two parts: one is beam irradiance, and another is diffuse irradiance. The attenuation of solar beam irradiance comprises scattering by the gas mixture, absorption by ozone, the gas mixture and water vapor, and scattering and absorption by aerosols. The diffuse irradiance is scattered out of the direct beam and towards the surface. The multiple ground-air interactions have been taken into account in the diffuse irradiance model. The parameters needed in this model are atmospheric water vapor content, aerosol optical thickness and spectral albedo ranging from 400 nm to 700 nm. They are all retrieved from MODIS data. Then, the instantaneous photosynthetically available radiation (IPAR) is integrated by using a weighted sum at each of the visible MODIS wavebands. Finally, a daily PAR is derived by integration of IPAR. In order to validate the MODIS-derived PAR model, we compared the field PAR measurements in 2003 and 2004 against the simulated PAR. The measurements were made at the Qianyanzhou ecological experimental station, Chinese Ecosystem Research Network. A total of 54 days of cloud-free MODIS L1B level images were used for the PAR simulation. Our results show that the simulated PAR is consistent with field measurements, where the correlation coefficient of linear regression between calculated PAR and measured PAR is 0.93396. However, there were some uncertainties in the comparison of 1 km pixel PAR with the tower flux stand measurement. (author)

  20. 2126-IJBCS- Article-Berroukche

    African Journals Online (AJOL)

    hp

    la diminution de mémoire de commande. RESULTATS. Il est à noter une évolution antagoniste des taux de NOx et Suies en fonction de la température de culasse .... l'augmentation des fumées ou suies. Les particules émises par le moteur. Diesel sont responsables de pathologies respiratoires (allergies, asthme et cancer.

  1. A single intranasal administration of virus-like particle vaccine induces an efficient protection for mice against human respiratory syncytial virus.

    Science.gov (United States)

    Jiao, Yue-Ying; Fu, Yuan-Hui; Yan, Yi-Fei; Hua, Ying; Ma, Yao; Zhang, Xiu-Juan; Song, Jing-Dong; Peng, Xiang-Lei; Huang, Jiaqiang; Hong, Tao; He, Jin-Sheng

    2017-08-01

    Human respiratory syncytial virus (RSV) is an important pediatric pathogen causing acute viral respiratory disease in infants and young children. However, no licensed vaccines are currently available. Virus-like particles (VLPs) may bring new hope to producing RSV VLP vaccine with high immunogenicity and safety. Here, we constructed the recombinants of matrix protein (M) and fusion glycoprotein (F) of RSV, respectively into a replication-deficient first-generation adenoviral vector (FGAd), which were used to co-infect Vero cells to assemble RSV VLPs successfully. The resulting VLPs showed similar immunoreactivity and function to RSV virion in vitro. Moreover, Th1 polarized response, and effective mucosal virus-neutralizing antibody and CD8 + T-cell responses were induced by a single intranasal (i.n.) administration of RSV VLPs rather than intramuscular (i.m.) inoculation, although the comparable RSV F-specific serum IgG and long-lasting RSV-specific neutralizing antibody were detected in the mice immunized by both routes. Upon RSV challenge, VLP-immunized mice showed increased viral clearance but decreased signs of enhanced lung pathology and fewer eosinophils compared to mice immunized with formalin-inactivated RSV (FI-RSV). In addition, a single i.n. RSV VLP vaccine has the capability to induce RSV-specific long-lasting neutralizing antibody responses observable up to 15 months. Our results demonstrate that the long-term and memory immune responses in mice against RSV were induced by a single i.n. administration of RSV VLP vaccine, suggesting a successful approach of RSV VLPs as an effective and safe mucosal vaccine against RSV infection, and an applicable and qualified platform of FGAd-infected Vero cells for VLP production. Copyright © 2017. Published by Elsevier B.V.

  2. The relationship between antibody status to bovine corona virus and bovine respiratory syncytial virus and disease incidence, reproduction and herd characteristics in dairy herds

    Directory of Open Access Journals (Sweden)

    Tråvén Madeleine

    2010-06-01

    Full Text Available Abstract Background Bovine respiratory syncytial virus (BRSV and bovine corona virus (BCV affects cattle worldwide. Our objective was to evaluate the effects of these infections on general health and reproduction parameters measurable on herd level and to explore the association between antibody status and some herd characteristics. Methods We collected a pooled milk sample from five primiparous cows from 79 Swedish dairy herds in September 2006. The samples were analysed for immunoglobulin G antibodies to BCV and BRSV with indirect enzyme-linked immunosorbent assays. Herd level data from 1 September 2005 to 30 August 2006 were accessed retrospectively. The location of the herds was mapped using a geographical information system. Results Ten herds were antibody negative to both viruses and were compared with 69 herds positive to BCV or BRSV or both. Positive herds had a higher (P = 0.001 bulk tank milk somatic cell count (BMSCC compared with negative herds. The medians for all other analyzed health and reproductive parameters were consistently in favour of the herds negative to both viruses although the differences were not statistically significant. A higher proportion (P = 0.01 of herds used professional technicians for artificial insemination, rather than farm personnel, amongst the 33 herds negative to BCV compared with the 46 positive herds. Conclusions Our result shows that herds that were antibody positive to BCV and/or BRSV had a higher BMSCC compared with herds negative to BCV and BRSV. There was also tendency that negative herds had a better general herd health compared with positive. A higher proportion amongst the BCV negative herds used external technicians for AI instead of farm personnel, indicating that it is possible to avoid infection although having regular visits. Negative herds were located in close proximity to positive herds, indicating that local spread and airborne transmission between herds might not be of great

  3. Virucidal activities of medium- and long-chain fatty alcohols and lipids against respiratory syncytial virus and parainfluenza virus type 2: comparison at different pH levels.

    Science.gov (United States)

    Hilmarsson, H; Traustason, B S; Kristmundsdóttir, T; Thormar, H

    2007-01-01

    Recent studies have shown that some lipids and fatty alcohols have microbicidal activities against a broad variety of pathogens. In this study, virucidal activities of fatty acids, monoglycerides and fatty alcohols were tested against respiratory syncytial virus (RSV) and human parainfluenza virus type 2 (HPIV2) at different concentrations, times and pH levels. The most active compounds were mixed with milk products and fruit juices and the mixtures tested for virucidal effects. The aim was to determine which compounds are the most active against these respiratory viruses and could possibly be used in pharmaceutical formulations or as additives to milk products or juice. Several compounds caused a significant inactivation of virus, and there was generally a good agreement between the activities against RSV and parainfluenza virus. By changing the pH from 7 to 4.2, the virucidal activities of some of the compounds were greatly increased, i.e., they inactivated virus in a shorter time and at lower concentrations. The most active compound tested was 1-monoglyceride of capric acid, monocaprin, which also showed activity against influenza A virus and significant virucidal activities after addition to milk products and fruit juices, even at a concentration as low as 0.06-0.12%. The significant virucidal activities of fatty alcohols and lipids on RSV and parainfluenza virus demonstrated in this in vitro study raise the question of the feasibility of using such compounds as ingredients in pharmaceutical dosage forms against respiratory infections caused by these viruses, and possibly other paramyxo- and myxoviruses.

  4. Phosphorylation of the human respiratory syncytial virus P protein mediates M2-2 regulation of viral RNA synthesis, a process that involves two P proteins.

    Science.gov (United States)

    Asenjo, Ana; Villanueva, Nieves

    2016-01-04

    The M2-2 protein regulates the balance between human respiratory syncytial virus (HRSV) transcription and replication. Here it is shown that M2-2 mediated transcriptional inhibition is managed through P protein phosphorylation. Transcription inhibition by M2-2 of the HRSV based minigenome pRSVluc, required P protein phosphorylation at serines (S) in positions 116, 117, 119 and increased inhibition is observed if S232 or S237 is also phosphorylated. Phosphorylation of these residues is required for viral particle egression from infected cells. Viral RNA synthesis complementation assays between P protein variants, suggest that two types of P proteins participate in the process as components of RNA dependent RNA polymerase (RdRp). Type I is only functional when, as a homotetramer, it is bound to N and L proteins through residues 203-241. Type II is functionally independent of these interactions and binds to N protein at a region outside residues 232-241. P protein type I phosphorylation at S116, S117 and S119, did not affect the activity of RdRp but this phosphorylation in type II avoids its interaction with N protein and impairs RdRp functionality for transcription and replication. Structural changes in the RdRp, mediated by phosphorylation turnover at the indicated residues, in the two types of P proteins, may result in a fine adjustment, late in the infectious cycle, of transcription, replication and progression in the morphogenetic process that ends in egression of the viral particles from infected cells. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Multiple Functional Domains and Complexes of the Two Nonstructural Proteins of Human Respiratory Syncytial Virus Contribute to Interferon Suppression and Cellular Location▿

    Science.gov (United States)

    Swedan, Samer; Andrews, Joel; Majumdar, Tanmay; Musiyenko, Alla; Barik, Sailen

    2011-01-01

    Human respiratory syncytial virus (RSV), a major cause of severe respiratory diseases, efficiently suppresses cellular innate immunity, represented by type I interferon (IFN), using its two unique nonstructural proteins, NS1 and NS2. In a search for their mechanism, NS1 was previously shown to decrease levels of TRAF3 and IKKε, whereas NS2 interacted with RIG-I and decreased TRAF3 and STAT2. Here, we report on the interaction, cellular localization, and functional domains of these two proteins. We show that recombinant NS1 and NS2, expressed in lung epithelial A549 cells, can form homo- as well as heteromers. Interestingly, when expressed alone, substantial amounts of NS1 and NS2 localized to the nuclei and to the mitochondria, respectively. However, when coexpressed with NS2, as in RSV infection, NS1 could be detected in the mitochondria as well, suggesting that the NS1-NS2 heteromer localizes to the mitochondria. The C-terminal tetrapeptide sequence, DLNP, common to both NS1 and NS2, was required for some functions, but not all, whereas only the NS1 N-terminal region was important for IKKε reduction. Finally, NS1 and NS2 both interacted specifically with host microtubule-associated protein 1B (MAP1B). The contribution of MAP1B in NS1 function was not tested, but in NS2 it was essential for STAT2 destruction, suggesting a role of the novel DLNP motif in protein-protein interaction and IFN suppression. PMID:21795342

  6. Activation of cytokines and NF-kappa B in corneal epithelial cells infected by respiratory syncytial virus: potential relevance in ocular inflammation and respiratory infection

    Directory of Open Access Journals (Sweden)

    Oakes John E

    2004-07-01

    Full Text Available Abstract Background Respiratory syncytial virus (RSV is a major cause of lower respiratory tract infection, claiming millions of lives annually. The virus infects various cells of the respiratory tract as well as resident inflammatory cells such as macrophages. Infection activates a variety of cellular factors such as cytokines and the pro-inflammatory transcription factor, NF-kappa B, all of which are important players in the respiratory disease. However, the exact natural route of RSV infection and its etiology remain relatively unknown. In this paper, we test the hypothesis that human corneal epithelial cells, which constitute the outermost layer of the cornea, can be infected with RSV, and that the infection leads to the activation of proinflammatory macromolecules. Results Corneal swabs obtained from pediatric patients with acute respiratory disease were found to contain RSV at a high frequency (43 positive out of 72 samples, i.e., 60%. Primary corneal epithelial cells in tissue culture supported robust infection and productive growth of RSV. Infection resulted in the activation of TNF-α, IL-6 and sixteen chemokines as well as NF-κB. Three proinflammatory CXC chemokines (MIG, I-TAC, IP-10 underwent the greatest activation. Conclusions The ocular epithelium is readily infected by RSV. The pro-inflammatory cytokines are likely to play critical roles in the etiology of inflammation and conjunctivitis commonly seen in pediatric patients with respiratory infections. RSV-eye interactions have important implications in RSV transmission, immunopathology of RSV disease, and in the management of conjunctivitis.

  7. Seasonality of Influenza and Respiratory Syncytial Viruses and the Effect of Climate Factors in Subtropical-Tropical Asia Using Influenza-Like Illness Surveillance Data, 2010 -2012.

    Science.gov (United States)

    Kamigaki, Taro; Chaw, Liling; Tan, Alvin G; Tamaki, Raita; Alday, Portia P; Javier, Jenaline B; Olveda, Remigio M; Oshitani, Hitoshi; Tallo, Veronica L

    2016-01-01

    The seasonality of influenza and respiratory syncytial virus (RSV) is well known, and many analyses have been conducted in temperate countries; however, this is still not well understood in tropical countries. Previous studies suggest that climate factors are involved in the seasonality of these viruses. However, the extent of the effect of each climate variable is yet to be defined. We investigated the pattern of seasonality and the effect of climate variables on influenza and RSV at three sites of different latitudes: the Eastern Visayas region and Baguio City in the Philippines, and Okinawa Prefecture in Japan. Wavelet analysis and the dynamic linear regression model were applied. Climate variables used in the analysis included mean temperature, relative and specific humidity, precipitation, and number of rainy days. The Akaike Information Criterion estimated in each model was used to test the improvement of fit in comparison with the baseline model. At all three study sites, annual seasonal peaks were observed in influenza A and RSV; peaks were unclear for influenza B. Ranges of climate variables at the two Philippine sites were narrower and mean variables were significantly different among the three sites. Whereas all climate variables except the number of rainy days improved model fit to the local trend model, their contributions were modest. Mean temperature and specific humidity were positively associated with influenza and RSV at the Philippine sites and negatively associated with influenza A in Okinawa. Precipitation also improved model fit for influenza and RSV at both Philippine sites, except for the influenza A model in the Eastern Visayas. Annual seasonal peaks were observed for influenza A and RSV but were less clear for influenza B at all three study sites. Including additional data from subsequent more years would help to ascertain these findings. Annual amplitude and variation in climate variables are more important than their absolute values for

  8. A single intranasal immunization with a subunit vaccine formulation induces higher mucosal IgA production than live respiratory syncytial virus

    International Nuclear Information System (INIS)

    Garg, Ravendra; Theaker, Michael; Martinez, Elisa C.; Drunen Littel-van den Hurk, Sylvia van

    2016-01-01

    Respiratory syncytial virus (RSV) causes serious respiratory illness in infants and elderly. RSV infection induces short-lived immunity, which leaves people prone to re-infection. In contrast, the RSV fusion (F) protein formulated with a novel adjuvant (∆F/TriAdj) elicits long term protective immunity. A comparison of RSV-immunized mice to mice vaccinated with a single dose of ∆F/TriAdj showed no difference in IgG1 and IgG2a production; however, local IgA secreting memory B cell development and B cell IgA production were significantly lower in RSV vaccinated mice than in ∆F/TriAdj-immunized mice. This indicates a potential reason as to why long-term immunity is not induced by RSV infection. The comparison also revealed that germinal center lymphocyte populations were higher in ∆F/TriAdj-vaccinated mice. Furthermore, ∆F/TriAdj induced higher gene expression of activation-induced cytidine deaminase (AID), as well as IL-6, IL-21, TGF-β cytokines, which are key players in IgA class switch recombination, ultimately leading to a sustained long-term memory response. - Highlights: •Immune responses to adjuvanted RSV F protein, ∆F/TriAdj, and RSV were compared. •∆F/TriAdj stimulates more local IgA production than RSV. •∆F/TriAdj induces more local IgA secreting memory B cells than RSV. •Germinal center lymphocyte populations are higher in ∆F/TriAdj-vaccinated mice. •∆F/TriAdj induces higher gene expression of AID, IL-6, IL-21, and TGF-β than RSV.

  9. Delta inulin-derived adjuvants that elicit Th1 phenotype following vaccination reduces respiratory syncytial virus lung titers without a reduction in lung immunopathology.

    Science.gov (United States)

    Wong, Terianne M; Petrovsky, Nikolai; Bissel, Stephanie J; Wiley, Clayton A; Ross, Ted M

    2016-08-02

    Respiratory syncytial virus (RSV) is a significant cause of lower respiratory tract infections resulting in bronchiolitis and even mortality in the elderly and young children/infants. Despite the impact of this virus on human health, no licensed vaccine exists. Unlike many other viral infections, RSV infection or vaccination does not induce durable protective antibodies in humans. In order to elicit high titer, neutralizing antibodies against RSV, we investigated the use of the adjuvant Advax™, a novel polysaccharide adjuvant based on delta inulin microparticles, to enhance antibody titers following vaccination. BALB/c mice were vaccinated intramuscularly with live RSV as a vaccine antigen in combination with one of two formulations of Advax™. Advax-1 was comprised of the standard delta inulin adjuvant and Advax-2 was formulated delta inulin plus CpG oligodendronucleotides (ODNs). An additional group of mice were either mock vaccinated, immunized with vaccine only, or administered vaccine plus Imject Alum. Following 3 vaccinations, mice had neutralizing antibody titers that correlated with reduction in viral titers in the lungs. Advax-1 significantly enhanced serum RSV-specific IgG1 levels at week 6 indicative of a Th2 response, similar to titers in mice administered vaccine plus Imject Alum. In contrast, mice vaccinated with vaccine plus Advax-2 had predominately IgG2a titers indicative of a Th1 response that was maintained during the entire study. Interestingly, regardless of which Advax TM adjuvant was used, the neutralizing titers were similar between groups, but the viral lung titers were significantly lower (∼10E+3pfu/g) in mice administered vaccine with either Advax TM adjuvant compared to mice administered adjuvants only. The lung pathology in vaccinated mice with Advax TM was similar to Imject Alum. Overall, RSV vaccine formulated with Advax TM had high neutralizing antibody titers with low lung viral titers, but exacerbated lung pathology compared

  10. [Prevalence of respiratory syncytial virus infection in hospitalized children at a children's hospital and effects of climate change on the prevalence in Suzhou, China].

    Science.gov (United States)

    Geng, Jia; Guo, Wan-Liang; Zhang, Xue-Lan

    2015-05-01

    To investigate the prevalence of respiratory syncytial virus (RSV) infection in hospitalized children and the relationship between the prevalence and the climate change in Suzhou, China. A total of 42 664 nasopharyngeal secretions from hospitalized children with acute respiratory infection at the Suzhou Children's Hospital were screened for RSV antigens using direct immunofluorescence. Monthly meteorological data (mean monthly air temperature, monthly relative humidity, monthly rainfall, total monthly sunshine duration, and mean monthly wind velocity) in Suzhou between 2001 and 2011 were collected. The correlations between RSV detection rate and climatic factors were evaluated using correlation and stepwise regression analysis. The annual RSV infection rate in hospitalized children with respiratory infection in the Suzhou Children's Hospital varied between 11.85% and 27.30% from 2001 to 2011. In the 9 epidemic seasons, each spanning from November to April of the next year, from 2001 to 2010, the RSV detection rates were 40.75%, 22.72%, 39.93%, 27.37%, 42.71%, 21.28%, 38.57%, 19.86%, and 29.73%, respectively; there were significant differences in the detection rate between the epidemic seasons. The monthly RSV detection rate was negatively correlated with mean monthly air temperature, total monthly sunshine duration, monthly rainfall, monthly relative humidity, and mean monthly wind velocity (P<0.05). Stepwise regression analysis showed that mean monthly air temperature fitted into a linear model (R(2)=0.64, P<0.01). From 2001 to 2011, RSV infection in Suzhou was predominantly prevalent between November and April of the next year. As a whole, the infection rate of RSV reached a peak every other year. Air temperature played an important role in the epidemics of RSV infection in Suzhou.

  11. A prime-boost vaccination strategy using attenuated Salmonella typhimurium and a replication-deficient recombinant adenovirus vector elicits protective immunity against human respiratory syncytial virus.

    Science.gov (United States)

    Fu, Yuan-Hui; He, Jin-Sheng; Wang, Xiao-Bo; Zheng, Xian-Xian; Wu, Qiang; Xie, Can; Zhang, Mei; Wei, Wei; Tang, Qian; Song, Jing-Dong; Qu, Jian-Guo; Hong, Tao

    2010-04-23

    Human respiratory syncytial virus (RSV), for which no clinically approved vaccine is available yet, is globally a serious pediatric pathogen of the lower respiratory tract. Several approaches have been used to develop vaccines against RSV, but none of these have been approved for use in humans. An efficient vaccine-enhancing strategy for RSV is still urgently needed. We found previously that oral SL7207/pcDNA3.1/F and intranasal FGAd/F were able to induce an effective protective immune response against RSV. The heterologous prime-boost immunization regime has been reported recently to be an efficient vaccine-enhancing strategy. Therefore, we investigated the ability of an oral SL7207/pcDNA3.1/F prime and intranasal (i.n.) FGAd/F boost regimen to generate immune responses to RSV. The SL7207/pcDNA3.1/F prime-FGAd/F boost regimen generated stronger RSV-specific humoral and mucosal immune responses in BALB/c mice than the oral SL7207/pcDNA3.1/F regimen alone, and stronger specific cellular immune responses than the i.n. FGAd/F regimen alone. Histopathological analysis showed an increased efficacy against RSV challenge by the heterologous prime-boost regimen. These results suggest that such a heterologous prime-boost strategy can enhance the efficacy of either the SL7207 or the FGAd vector regimen in generating immune responses in BALB/c mice. 2010 Elsevier Inc. All rights reserved.

  12. Water extract of Pueraria lobata Ohwi has anti-viral activity against human respiratory syncytial virus in human respiratory tract cell lines

    Directory of Open Access Journals (Sweden)

    Tzeng-Jih Lin

    2013-12-01

    Full Text Available Human respiratory syncytial virus (HRSV infects all age groups and causes bronchiolitis, pneumonia, and acute respiratory distress syndrome with a significant mortality rate. To date, only ribavirin has been used to manage HRSV infection. However, ribavirin is expensive with an only modest effect. Furthermore, ribavirin has several side effects, which means it has limited clinical benefit. Pueraria lobata Ohwi (P. lobata is a common ingredient of Ge-Gen-Tang (Kakkon-to and Sheng-Ma-Ge-Gen-Tang (Shoma-kakkon-to, which are prescriptions of Chinese traditional medicine proven to have antiviral activity against HRSV. Therefore, it was hypothesized that P. lobata might be effective against HRSV. To find a cost-effective therapeutic modality, both human upper (HEp-2 and lower (A549 respiratory tract cell lines were used to test the hypothesis that P. lobata could inhibit HRSV-induced plaque formation. Results showed that the water extract of P. lobata was effective (p < 0.0001 against HRSV-induced plaque formation. P. lobata was more effective when given prior to viral inoculation (p < 0.0001 by inhibiting viral attachment (p < 0.0001 and penetration (p < 0.0001. However, supplementation with P. lobata could not stimulate interferon secretion after HRSV infection. In conclusion, P. lobata has antiviral activity against HRSV-induced plaque formation in airway mucosa mainly by inhibiting viral attachment and internalization. Further identification of effective constituents could contribute to the prevention of HRSV infection.

  13. A single intranasal immunization with a subunit vaccine formulation induces higher mucosal IgA production than live respiratory syncytial virus

    Energy Technology Data Exchange (ETDEWEB)

    Garg, Ravendra [VIDO-InterVac, University of Saskatchewan, Saskatoon, SK S7N 5E3 (Canada); Theaker, Michael [Microbiology & Immunology, University of Saskatchewan, Saskatoon, SK S7N 5E3 (Canada); Martinez, Elisa C. [VIDO-InterVac, University of Saskatchewan, Saskatoon, SK S7N 5E3 (Canada); Microbiology & Immunology, University of Saskatchewan, Saskatoon, Canada SK S7N 5E3 (Canada); Drunen Littel-van den Hurk, Sylvia van, E-mail: sylvia.vandenhurk@usask.ca [VIDO-InterVac, University of Saskatchewan, Saskatoon, SK S7N 5E3 (Canada); Microbiology & Immunology, University of Saskatchewan, Saskatoon, SK S7N 5E3 (Canada)

    2016-12-15

    Respiratory syncytial virus (RSV) causes serious respiratory illness in infants and elderly. RSV infection induces short-lived immunity, which leaves people prone to re-infection. In contrast, the RSV fusion (F) protein formulated with a novel adjuvant (∆F/TriAdj) elicits long term protective immunity. A comparison of RSV-immunized mice to mice vaccinated with a single dose of ∆F/TriAdj showed no difference in IgG1 and IgG2a production; however, local IgA secreting memory B cell development and B cell IgA production were significantly lower in RSV vaccinated mice than in ∆F/TriAdj-immunized mice. This indicates a potential reason as to why long-term immunity is not induced by RSV infection. The comparison also revealed that germinal center lymphocyte populations were higher in ∆F/TriAdj-vaccinated mice. Furthermore, ∆F/TriAdj induced higher gene expression of activation-induced cytidine deaminase (AID), as well as IL-6, IL-21, TGF-β cytokines, which are key players in IgA class switch recombination, ultimately leading to a sustained long-term memory response. - Highlights: •Immune responses to adjuvanted RSV F protein, ∆F/TriAdj, and RSV were compared. •∆F/TriAdj stimulates more local IgA production than RSV. •∆F/TriAdj induces more local IgA secreting memory B cells than RSV. •Germinal center lymphocyte populations are higher in ∆F/TriAdj-vaccinated mice. •∆F/TriAdj induces higher gene expression of AID, IL-6, IL-21, and TGF-β than RSV.

  14. Humane metapneumovirus (HMPV) associated pulmonary infections in immunocompromised adults—Initial CT findings, disease course and comparison to respiratory-syncytial-virus (RSV) induced pulmonary infections

    International Nuclear Information System (INIS)

    Syha, R.; Beck, R.; Hetzel, J.; Ketelsen, D.; Grosse, U.; Springer, F.; Horger, M.

    2012-01-01

    Aim: To describe computed tomography (CT)-imaging findings in human metapneumovirus (HMPV)-related pulmonary infection as well as their temporal course and to analyze resemblances/differences to pulmonary infection induced by the closely related respiratory-syncytial-virus (RSV) in immunocompromised patients. Materials and methods: Chest-CT-scans of 10 HMPV PCR-positive patients experiencing pulmonary symptoms were evaluated retrospectively with respect to imaging findings and their distribution and results were then compared with data acquired in 13 patients with RSV pulmonary infection. Subsequently, we analyzed the course of chest-findings in HMPV patients. Results: In HMPV, 8/10 patients showed asymmetric pulmonary findings, whereas 13/13 patients with RSV-pneumonia presented more symmetrical bilateral pulmonary infiltrates. Image analysis yielded in HMPV patients following results: ground-glass-opacity (GGO) (n = 6), parenchymal airspace consolidations (n = 5), ill-defined nodular-like centrilobular opacities (n = 9), bronchial wall thickening (n = 8). In comparison, results in RSV patients were: GGO (n = 10), parenchymal airspace consolidations (n = 9), ill-defined nodular-like centrilobular opacities (n = 10), bronchial wall thickening (n = 4). In the course of the disease, signs of acute HMPV interstitial pneumonia regressed transforming temporarily in part into findings compatible with bronchitis/bronchiolitis. Conclusions: Early chest-CT findings in patients with HMPV-related pulmonary symptoms are compatible with asymmetric acute interstitial pneumonia accompanied by signs of bronchitis; the former transforming with time into bronchitis and bronchiolitis before they resolve. On the contrary, RSV-induced pulmonary infection exhibits mainly symmetric acute interstitial pneumonia.

  15. Risk factors of respiratory syncytial virus infection among pediatric influenza-like illness and severe acute respiratory infections in Suzhou, China.

    Science.gov (United States)

    Huang, Yukai; Hua, Jun; Wang, Dan; Chen, Liling; Zhang, Jun; Zhu, Hong; Tian, Jianmei; Zhang, Tao; Zhao, Genming

    2018-03-01

    The characteristics and risk factors of respiratory syncytial virus (RSV) infection among children has not yet been fully understood. To address the characteristics of RSV-associated illness and risk factors of RSV infection among children under 5 years of age in Suzhou, China. From April 2011 to March 2014, we conducted a prospective surveillance among children in Suzhou, China. Nasal or throat swabs were collected from outpatients with influenza-like illness (ILI) and inpatients with severe acute respiratory infections (SARI). RSV was detected by reverse-transcriptase polymerase chain reaction and direct fluorescent antibody assay for children with ILI and SARI, respectively. Multivariable logistic-regression models were constructed to explore risk factors and symptoms of RSV infection. Of 3267 ILI and 1838 SARI children enrolled in the study, 192 (5.9%) and 287 (15.6%) tested positive for RSV, respectively. Among ILI patients, children with RSV infections visited clinics more often (P = 0.005) and had longer duration of fever (P = 0.032) than those without RSV infection. All RSV-positive children had an increased risk of having cough (OR = 2.9), rhinorrhea (OR = 1.6), breathing difficulty (OR = 3.4), wheezing (OR = 3.3), and irritability (OR = 2.7). Children aged respiratory infections (OR = 1.3) were more likely to get infected by RSV. Children with SARI had higher positive rate of RSV than those with ILI. Cough, rhinorrhea, and wheezing were the most common symptoms in RSV infection. Children aged respiratory infections were the potential risk factors for RSV infection. © 2017 Wiley Periodicals, Inc.

  16. Humane metapneumovirus (HMPV) associated pulmonary infections in immunocompromised adults—Initial CT findings, disease course and comparison to respiratory-syncytial-virus (RSV) induced pulmonary infections

    Energy Technology Data Exchange (ETDEWEB)

    Syha, R., E-mail: roland.syha@med.uni-tuebingen.de [Department of Diagnostic Radiology, Eberhard-Karls-University, Hoppe-Seyler-Str.3, 72076 Tübingen (Germany); Beck, R. [Institute of Medical Virology, Eberhard-Karls-University, Elfriede-Authorn-Str. 6, 72076 Tübingen (Germany); Hetzel, J. [Department of Medical Oncology and Hematology, Eberhard-Karls-University, Otfried-Müller-Str. 10, 72070 Tübingen (Germany); Ketelsen, D.; Grosse, U.; Springer, F.; Horger, M. [Department of Diagnostic Radiology, Eberhard-Karls-University, Hoppe-Seyler-Str.3, 72076 Tübingen (Germany)

    2012-12-15

    Aim: To describe computed tomography (CT)-imaging findings in human metapneumovirus (HMPV)-related pulmonary infection as well as their temporal course and to analyze resemblances/differences to pulmonary infection induced by the closely related respiratory-syncytial-virus (RSV) in immunocompromised patients. Materials and methods: Chest-CT-scans of 10 HMPV PCR-positive patients experiencing pulmonary symptoms were evaluated retrospectively with respect to imaging findings and their distribution and results were then compared with data acquired in 13 patients with RSV pulmonary infection. Subsequently, we analyzed the course of chest-findings in HMPV patients. Results: In HMPV, 8/10 patients showed asymmetric pulmonary findings, whereas 13/13 patients with RSV-pneumonia presented more symmetrical bilateral pulmonary infiltrates. Image analysis yielded in HMPV patients following results: ground-glass-opacity (GGO) (n = 6), parenchymal airspace consolidations (n = 5), ill-defined nodular-like centrilobular opacities (n = 9), bronchial wall thickening (n = 8). In comparison, results in RSV patients were: GGO (n = 10), parenchymal airspace consolidations (n = 9), ill-defined nodular-like centrilobular opacities (n = 10), bronchial wall thickening (n = 4). In the course of the disease, signs of acute HMPV interstitial pneumonia regressed transforming temporarily in part into findings compatible with bronchitis/bronchiolitis. Conclusions: Early chest-CT findings in patients with HMPV-related pulmonary symptoms are compatible with asymmetric acute interstitial pneumonia accompanied by signs of bronchitis; the former transforming with time into bronchitis and bronchiolitis before they resolve. On the contrary, RSV-induced pulmonary infection exhibits mainly symmetric acute interstitial pneumonia.

  17. Epidemiology, clinical characteristics, laboratory findings and severity of respiratory syncytial virus acute lower respiratory infection in Malaysian children, 2008-2013.

    Science.gov (United States)

    Ng, Khuen F; Tan, Kah K; Sam, Zhi H; Ting, Grace Ss; Gan, Wan Y

    2017-04-01

    The aim of this study is to describe epidemiology, clinical features, laboratory data and severity of respiratory syncytial virus (RSV) acute lower respiratory infection (ALRI) in Malaysian children and to determine risk factors associated with prolonged hospital stay, paediatric intensive care unit (PICU) admission and mortality. Retrospective data on demographics, clinical presentation, outcomes and laboratory findings of 450 children admitted into Tuanku Jaafar Hospital in Seremban, Malaysia from 2008 to 2013 with documented diagnosis of RSV ALRI were collected and analysed. Most admissions were children below 2 years old (85.8%; 386/450). Commonest symptoms were fever (84.2%; 379/450), cough (97.8%; 440/450) and rhinorrhea (83.6%; 376/450). The median age among febrile patients (n = 379) was 9.0 months with interquartile range (IQR) of 4.0-19.0 months whereas the median age among those who were apyrexial (n = 71) was 2 months with IQR of 1-6 months (P-value <0.001). 15.3% (69/450) needed intensive care and 1.6% (7/450) died. Young age, history of prematurity, chronic comorbidity and thrombocytosis were significantly associated with prolonged hospital stay, PICU admission and mortality. Infants less than 6 months old with RSV ALRI tend to be afebrile at presentation. Younger age, history of prematurity, chronic comorbidity and thrombocytosis are predictors of severe RSV ALRI among Malaysian children. Case fatality rate for Malaysian children below 5 years of age with RSV ALRI in our centre is higher than what is seen in developed countries, suggesting that there is room for improvement. © 2016 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).

  18. Clinical characteristics and viral load of respiratory syncytial virus and human metapneumovirus in children hospitaled for acute lower respiratory tract infection.

    Science.gov (United States)

    Yan, Xiao-Li; Li, Yu-Ning; Tang, Yi-Jie; Xie, Zhi-Ping; Gao, Han-Chun; Yang, Xue-Mei; Li, Yu-Mei; Liu, Li-Jun; Duan, Zhao-Jun

    2017-04-01

    Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) are two common viral pathogens in acute lower respiratory tract infections (ALRTI). However, the association of viral load with clinical characteristics is not well-defined in ALRTI. To explore the correlation between viral load and clinical characteristics of RSV and HMPV in children hospitalized for ALRTI in Lanzhou, China. Three hundred and eighty-seven children hospitalized for ALRTI were enrolled. Nasopharyngeal aspirates (NPAs) were sampled from each children. Real-time PCR was used to screen RSV, HMPV, and twelve additional respiratory viruses. Bronchiolitis was the leading diagnoses both in RSV and HMPV positive patients. A significantly greater frequency of wheezing (52% vs. 33.52%, P = 0.000) was noted in RSV positive and negative patients. The RSV viral load was significant higher in children aged infections (P = 0.000). No difference was found in the clinical features of HMPV positive and negative patients. The HMPV viral load had no correlation with any clinical characteristics. The incidences of severe disease were similar between single infection and coinfection for the two viruses (RSV, P = 0.221; HMPV, P = 0.764) and there has no statistical significance between severity and viral load (P = 0.166 and P = 0.721). Bronchiolitis is the most common disease caused by RSV and HMPV. High viral load or co-infection may be associated with some symptoms but neither has a significant impact on disease severity for the two viruses. J. Med. Virol. 89:589-597, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  19. A prospective, open-label, non-comparative study of palivizumab prophylaxis in children at high risk of serious respiratory syncytial virus disease in the Russian Federation

    Directory of Open Access Journals (Sweden)

    Turti Tatyana V

    2012-09-01

    Full Text Available Abstract Background Respiratory syncytial virus (RSV is a leading cause of lower respiratory tract infections (LRTIs in children globally. Predisposing conditions for the development of serious RSV disease include preterm infants and those with cardiopulmonary illness, including congenital heart disease (CHD and bronchopulmonary dysplasia (BPD. No vaccine is currently approved for the prevention of RSV infection. It is recommended that children at high risk be prophylactically administered palivizumab, a monoclonal antibody that has been shown in a number of clinical studies to reduce hospitalization rates due to serious RSV infection. The objective of the current study was to determine the safety and effectiveness of palivizumab in preventing serious RSV disease in high-risk children in the Russian Federation. Children at high risk of serious RSV disease (ie, born at ≤35 wk gestational age and ≤6 mo of age, and/or aged ≤24 mo with BPD or hemodynamically significant CHD were enrolled. Subjects were to receive 3 to 5 monthly injections of palivizumab 15 mg/kg (depending on the month of the initial injection over the RSV season. The primary endpoint was RSV-related hospitalizations. Adverse events (AEs were reported through 100 days following the final injection. Results One hundred subjects received ≥1 injection of palivizumab; 94 completed their dosing schedule. There were no RSV hospitalizations or deaths. Six of 7 subjects hospitalized for respiratory/cardiac conditions had an RSV test, which was negative in all cases. Three non-serious AEs (acute intermittent rhinitis and rhinitis, 1 subject; atopic dermatitis, 1 subject were considered possibly related to palivizumab. All other AEs were mild or moderate and considered not related/probably not related to palivizumab. Conclusion Palivizumab was generally well tolerated and effectively prevented serious RSV infection in a mixed population of high-risk children in the Russian

  20. Seasonality of Influenza and Respiratory Syncytial Viruses and the Effect of Climate Factors in Subtropical-Tropical Asia Using Influenza-Like Illness Surveillance Data, 2010 -2012.

    Directory of Open Access Journals (Sweden)

    Taro Kamigaki

    Full Text Available The seasonality of influenza and respiratory syncytial virus (RSV is well known, and many analyses have been conducted in temperate countries; however, this is still not well understood in tropical countries. Previous studies suggest that climate factors are involved in the seasonality of these viruses. However, the extent of the effect of each climate variable is yet to be defined.We investigated the pattern of seasonality and the effect of climate variables on influenza and RSV at three sites of different latitudes: the Eastern Visayas region and Baguio City in the Philippines, and Okinawa Prefecture in Japan. Wavelet analysis and the dynamic linear regression model were applied. Climate variables used in the analysis included mean temperature, relative and specific humidity, precipitation, and number of rainy days. The Akaike Information Criterion estimated in each model was used to test the improvement of fit in comparison with the baseline model.At all three study sites, annual seasonal peaks were observed in influenza A and RSV; peaks were unclear for influenza B. Ranges of climate variables at the two Philippine sites were narrower and mean variables were significantly different among the three sites. Whereas all climate variables except the number of rainy days improved model fit to the local trend model, their contributions were modest. Mean temperature and specific humidity were positively associated with influenza and RSV at the Philippine sites and negatively associated with influenza A in Okinawa. Precipitation also improved model fit for influenza and RSV at both Philippine sites, except for the influenza A model in the Eastern Visayas.Annual seasonal peaks were observed for influenza A and RSV but were less clear for influenza B at all three study sites. Including additional data from subsequent more years would help to ascertain these findings. Annual amplitude and variation in climate variables are more important than their

  1. Structure and functional analysis of the RNA- and viral phosphoprotein-binding domain of respiratory syncytial virus M2-1 protein.

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    Marie-Lise Blondot

    Full Text Available Respiratory syncytial virus (RSV protein M2-1 functions as an essential transcriptional cofactor of the viral RNA-dependent RNA polymerase (RdRp complex by increasing polymerase processivity. M2-1 is a modular RNA binding protein that also interacts with the viral phosphoprotein P, another component of the RdRp complex. These binding properties are related to the core region of M2-1 encompassing residues S58 to K177. Here we report the NMR structure of the RSV M2-1(58-177 core domain, which is structurally homologous to the C-terminal domain of Ebola virus VP30, a transcription co-factor sharing functional similarity with M2-1. The partial overlap of RNA and P interaction surfaces on M2-1(58-177, as determined by NMR, rationalizes the previously observed competitive behavior of RNA versus P. Using site-directed mutagenesis, we identified eight residues located on these surfaces that are critical for an efficient transcription activity of the RdRp complex. Single mutations of these residues disrupted specifically either P or RNA binding to M2-1 in vitro. M2-1 recruitment to cytoplasmic inclusion bodies, which are regarded as sites of viral RNA synthesis, was impaired by mutations affecting only binding to P, but not to RNA, suggesting that M2-1 is associated to the holonucleocapsid by interacting with P. These results reveal that RNA and P binding to M2-1 can be uncoupled and that both are critical for the transcriptional antitermination function of M2-1.

  2. Genetic variability of human respiratory syncytial virus A strains circulating in Ontario: a novel genotype with a 72 nucleotide G gene duplication.

    Directory of Open Access Journals (Sweden)

    Alireza Eshaghi

    Full Text Available Human respiratory syncytial virus (HRSV is the main cause of acute lower respiratory infections in children under 2 years of age and causes repeated infections throughout life. We investigated the genetic variability of RSV-A circulating in Ontario during 2010-2011 winter season by sequencing and phylogenetic analysis of the G glycoprotein gene.Among the 201 consecutive RSV isolates studied, RSV-A (55.7% was more commonly observed than RSV-B (42.3%. 59.8% and 90.1% of RSV-A infections were among children ≤12 months and ≤5 years old, respectively. On phylogenetic analysis of the second hypervariable region of the 112 RSV-A strains, 110 (98.2% clustered within or adjacent to the NA1 genotype; two isolates were GA5 genotype. Eleven (10% NA1-related isolates clustered together phylogenetically as a novel RSV-A genotype, named ON1, containing a 72 nucleotide duplication in the C-terminal region of the attachment (G glycoprotein. The predicted polypeptide is lengthened by 24 amino acids and includes a23 amino acid duplication. Using RNA secondary structural software, a possible mechanism of duplication occurrence was derived. The 23 amino acid ON1 G gene duplication results in a repeat of 7 potential O-glycosylation sites including three O-linked sugar acceptors at residues 270, 275, and 283. Using Phylogenetic Analysis by Maximum Likelihood analysis, a total of 19 positively selected sites were observed among Ontario NA1 isolates; six were found to be codons which reverted to the previous state observed in the prototype RSV-A2 strain. The tendency of codon regression in the G-ectodomain may infer a decreased avidity of antibody to the current circulating strains. Further work is needed to document and further understand the emergence, virulence, pathogenicity and transmissibility of this novel RSV-A genotype with a72 nucleotide G gene duplication.

  3. Burden of Respiratory Syncytial Virus Infection in South African Human Immunodeficiency Virus (HIV)-Infected and HIV-Uninfected Pregnant and Postpartum Women: A Longitudinal Cohort Study.

    Science.gov (United States)

    Madhi, Shabir A; Cutland, Clare L; Downs, Sarah; Jones, Stephanie; van Niekerk, Nadia; Simoes, Eric A F; Nunes, Marta C

    2018-05-17

    Limited data exist on the burden of respiratory syncytial virus (RSV) illness among pregnant women, to determine their potential benefit from RSV vaccination. We evaluated the incidence of RSV illness from midpregnancy until 24 weeks postpartum in human immunodeficiency virus (HIV)-uninfected and HIV-infected women and their infants. Mother-infant dyads were enrolled in maternal influenza vaccine efficacy trials. These included 1060 and 1056 HIV-uninfected pregnant women in 2011 and 2012, respectively, 194 HIV-infected pregnant women in 2011, and their infants. Upper respiratory tract samples obtained at illness visits were tested for RSV. The incidence (per 1000 person-months) of RSV illness (n = 43 overall) among HIV-uninfected women was lower in 2011 (1.2; 95% confidence interval [CI], .6-2.2) than in 2012 (4.0; 95% CI, 2.8-5.6). The incidence of RSV illness (n = 5) in HIV-infected women was 3.4 (95% CI, 1.4-8.1). Maternal RSV infection was associated with respiratory symptoms including cough (72.1%), rhinorrhea (39.5%), sore throat (37.2%), and headache (42%), but fever was absent. RSV infection during pregnancy was not associated with adverse pregnancy outcomes. Postpartum, RSV infection in mothers (n = 27) was associated with concurrent infection among 51.9% of their infants and, conversely, 29.8% of mothers investigated within 7 days of their infants having an RSV illness also tested positive for RSV. RSV infection is associated with respiratory illness during pregnancy and postpartum. Vaccination of pregnant women against RSV could benefit the mother, albeit primarily against nonfebrile illness, and her infant. NCT01306669 and NCT01306682.

  4. Molecular characterization of circulating respiratory syncytial virus (RSV genotypes in Gilgit Baltistan Province of Pakistan during 2011-2012 winter season.

    Directory of Open Access Journals (Sweden)

    Uzma Bashir

    Full Text Available Respiratory syncytial virus (RSV is the major cause of acute lower respiratory tract infections in young children, but very little is known about its epidemiology and circulating genotypes in Pakistan. This study analyzed the epidemiological and molecular characteristics of RSV genotypes detected in Pakistani children less than 2 years of age with acute respiratory tract infections (ARIs in a tertiary care hospital in Gilgit Baltistan (GB province during 2011-12 winter season. RSV was detected in 75 out of 105 children presenting with acute respiratory infection. Male infants between 2-6 months age made up the highest percentage of RSV positive cases. Epidemiological factors such as pre-maturity, mean weight, clinical features and diagnosis when compared between RSV positive and negative groups were found to be statistically insignificant. Phylogenetic analysis classified all 75 of the RSV strains into 71 strains of subgroups A and 4 strains of subgroup B, respectively. Strains belonging to subgroups A and B were further subdivided into NA1/GA2 and BA, respectively. The nucleotide and deduced amino acid sequence identities were relatively high among these strains (>90%. Both RSV-A and RSV-B isolates had two potential N-glycosylation sites in HVR2 of G protein and with heavy O-glycosylation of serine and threonine residues (G scores of 0.5-0.7. This report highlights the significance of RSV as a dominant viral etiologic agent of pediatric ARIs, and need for continued molecular epidemiological surveys for early detection of prevalent strains and newly emerging genotypes to understand epidemiology of RSV infections in various regions of Pakistan.

  5. Recombinant Human Respiratory Syncytial Virus (RSV) Monoclonal Antibody Fab is Effective Therapeutically when Introduced Directly into the Lungs of RSV-Infected Mice

    Science.gov (United States)

    Crowe, James E., Jr.; Murphy, Brian R.; Chanock, Robert M.; Williamson, R. Anthony; Barbas, Carlos F., III; Burton, Dennis R.

    1994-02-01

    Previously, recombinant human respiratory syncytial virus (RSV) monoclonal antibody Fabs were generated by antigen selection from random combinatorial libraries displayed at the tip of filamentous phage. Two such Fabs, which exhibited high binding affinity for RSV F glycoprotein (a major protective antigen), were evaluated for therapeutic efficacy in infected mice just before or at the time of peak virus replication in the lungs. Fab 19, which neutralized RSV infectivity with high efficiency in tissue culture, was effective therapeutically when delivered directly into the lungs by intranasal instillation under anesthesia. In contrast, RSV Fab 126, which failed to neutralize virus in cell culture, did not exhibit a therapeutic effect under these conditions. The amount of Fab 19 required to effect a 5000- to 12,000-fold reduction in titer of RSV in the lungs within 24 hr was rather small. In four separate experiments, a single instillation of 12.9-50 μg of RSV Fab 19 was sufficient to achieve such a reduction in pulmonary virus in a 25g mouse. The use of Fabs instead of the whole immunoglobulin molecules from which they are derived reduced the protein content of a therapeutic dose. This is important because the protein load that can be delivered effectively into the lungs is limited. The therapeutic effect of a single treatment with Fab 19 was not sustained, so that a rebound in pulmonary virus titer occurred on the 2nd day after treatment. This rebound in pulmonary RSV titer could be prevented by treating infected mice with a single dose of Fab 19 daily for 3 days. These observations suggest that human monoclonal Fabs grown in Escherichia coli may prove useful in the treatment of serious RSV disease as well as diseases caused by other viruses where replication in vivo is limited primarily to the lumenal lining of the respiratory tract.

  6. Urine suPAR levels compared with plasma suPAR levels as predictors of post-consultation mortality risk among individuals assumed to be TB-negative: a prospective cohort study

    DEFF Research Database (Denmark)

    Rabna, Paulo; Andersen, Andreas; Wejse, Christian

    2010-01-01

    -suPAR was measured using a commercial ELISA (suPARnostic®). We found that U-suPAR carried significant prognostic information on mortality for HIV-infected subjects with an area under the ROC curve of 0.75. For HIV-negative individuals, little or no prognostic effect was observed. However, in both HIV positives...... and negatives, the predictive effect of U-suPAR was found to be inferior to that of P-suPAR....

  7. Proteinase-Activated Receptor-1 and Immunomodulatory Effects of a PAR1-Activating Peptide in a Mouse Model of Prostatitis

    Science.gov (United States)

    Stanton, M. Mark; Nelson, Lisa K.; Benediktsson, Hallgrimur; Hollenberg, Morley D.; Buret, Andre G.; Ceri, Howard

    2013-01-01

    Background. Nonbacterial prostatitis has no established etiology. We hypothesized that proteinase-activated receptor-1 (PAR1) can play a role in prostatitis. We therefore investigated the effects of PAR1 stimulation in the context of a new model of murine nonbacterial prostatitis. Methods. Using a hapten (ethanol-dinitrobenzene sulfonic acid- (DNBS-)) induced prostatitis model with both wild-type and PAR1-null mice, we examined (1) the location of PAR1 in the mouse prostate and (2) the impact of a PAR1-activating peptide (TFLLR-NH2: PAR1-TF) on ethanol-DNBS-induced inflammation. Results. Ethanol-DNBS-induced inflammation was maximal at 2 days. In the tissue, PAR1 was expressed predominantly along the apical acini of prostatic epithelium. Although PAR1-TF on its own did not cause inflammation, its coadministration with ethanol-DNBS reduced all indices of acute prostatitis. Further, PAR1-TF administration doubled the prostatic production of interleukin-10 (IL-10) compared with ethanol-DNBS treatment alone. This enhanced IL-10 was not observed in PAR1-null mice and was not caused by the reverse-sequence receptor-inactive peptide, RLLFT-NH2. Surprisingly, PAR1-TF, also diminished ethanol-DNBS-induced inflammation in PAR1-null mice. Conclusions. PAR1 is expressed in the mouse prostate and its activation by PAR1-TF elicits immunomodulatory effects during ethanol-DNBS-induced prostatitis. However, PAR1-TF also diminishes ethanol-DNBS-induced inflammation via a non-PAR1 mechanism by activating an as-yet unknown receptor. PMID:24459330

  8. Profiling gene expression induced by protease-activated receptor 2 (PAR2 activation in human kidney cells.

    Directory of Open Access Journals (Sweden)

    Jacky Y Suen

    Full Text Available Protease-Activated Receptor-2 (PAR2 has been implicated through genetic knockout mice with cytokine regulation and arthritis development. Many studies have associated PAR2 with inflammatory conditions (arthritis, airways inflammation, IBD and key events in tumor progression (angiogenesis, metastasis, but they have relied heavily on the use of single agonists to identify physiological roles for PAR2. However such probes are now known not to be highly selective for PAR2, and thus precisely what PAR2 does and what mechanisms of downstream regulation are truly affected remain obscure. Effects of PAR2 activation on gene expression in Human Embryonic Kidney cells (HEK293, a commonly studied cell line in PAR2 research, were investigated here by comparing 19,000 human genes for intersecting up- or down-regulation by both trypsin (an endogenous protease that activates PAR2 and a PAR2 activating hexapeptide (2f-LIGRLO-NH(2. Among 2,500 human genes regulated similarly by both agonists, there were clear associations between PAR2 activation and cellular metabolism (1,000 genes, the cell cycle, the MAPK pathway, HDAC and sirtuin enzymes, inflammatory cytokines, and anti-complement function. PAR-2 activation up-regulated four genes more than 5 fold (DUSP6, WWOX, AREG, SERPINB2 and down-regulated another six genes more than 3 fold (TXNIP, RARG, ITGB4, CTSD, MSC and TM4SF15. Both PAR2 and PAR1 activation resulted in up-regulated expression of several genes (CD44, FOSL1, TNFRSF12A, RAB3A, COPEB, CORO1C, THBS1, SDC4 known to be important in cancer. This is the first widespread profiling of specific activation of PAR2 and provides a valuable platform for better understanding key mechanistic roles of PAR2 in human physiology. Results clearly support the development of both antagonists and agonists of human PAR2 as potential disease modifying therapeutic agents.

  9. Comparaison du Pangola (Digitaria decumbens) et du Stargrass (Cynodon nlemfluensis) exploités par des ovins

    OpenAIRE

    Boval, Maryline

    1989-01-01

    A la Martinique l'utilisation comparée de Digitaria decumbens (Dd) et de Cynodon nlemfuensis (Cn) par des brebis allaitantes a été étudiée pendant une période d'observation de 6 mois. Le cheptel est à un taux élevé de 1 600 kg de poids vif par hectare et par an, obtenu par une fertilisation de 450 kg/ha/an en azote.

  10. Improved Satellite-based Photosysnthetically Active Radiation (PAR) for Air Quality Studies

    Science.gov (United States)

    Pour Biazar, A.; McNider, R. T.; Cohan, D. S.; White, A.; Zhang, R.; Dornblaser, B.; Doty, K.; Wu, Y.; Estes, M. J.

    2015-12-01

    One of the challenges in understanding the air quality over forested regions has been the uncertainties in estimating the biogenic hydrocarbon emissions. Biogenic volatile organic compounds, BVOCs, play a critical role in atmospheric chemistry, particularly in ozone and particulate matter (PM) formation. In southeastern United States, BVOCs (mostly as isoprene) are the dominant summertime source of reactive hydrocarbon. Despite significant efforts in improving BVOC estimates, the errors in emission inventories remain a concern. Since BVOC emissions are particularly sensitive to the available photosynthetically active radiation (PAR), model errors in PAR result in large errors in emission estimates. Thus, utilization of satellite observations to estimate PAR can help in reducing emission uncertainties. Satellite-based PAR estimates rely on the technique used to derive insolation from satellite visible brightness measurements. In this study we evaluate several insolation products against surface pyranometer observations and offer a bias correction to generate a more accurate PAR product. The improved PAR product is then used in biogenic emission estimates. The improved biogenic emission estimates are compared to the emission inventories over Texas and used in air quality simulation over the period of August-September 2013 (NASA's Discover-AQ field campaign). A series of sensitivity simulations will be performed and evaluated against Discover-AQ observations to test the impact of satellite-derived PAR on air quality simulations.

  11. Pars plana Ahmed valve and vitrectomy in patients with glaucoma associated with posterior segment disease.

    Science.gov (United States)

    Wallsh, Josh O; Gallemore, Ron P; Taban, Mehran; Hu, Charles; Sharareh, Behnam

    2013-01-01

    To assess the safety and efficacy of a modified technique for pars plana placement of the Ahmed valve in combination with pars plana vitrectomy in the treatment of glaucoma associated with posterior segment disease. Thirty-nine eyes with glaucoma associated with posterior segment disease underwent pars plana vitrectomy combined with Ahmed valve placement. All valves were placed in the pars plana using a modified technique, without the pars plana clip, and using a scleral patch graft. The 24 eyes diagnosed with neovascular glaucoma had an improvement in intraocular pressure from 37.6 mmHg to 13.8 mmHg and best-corrected visual acuity from 2.13 logarithm of minimum angle of resolution to 1.40 logarithm of minimum angle of resolution. Fifteen eyes diagnosed with steroid-induced glaucoma had an improvement in intraocular pressure from 27.9 mmHg to 14.1 mmHg and best-corrected visual acuity from 1.38 logarithm of minimum angle of resolution to 1.13 logarithm of minimum angle of resolution. Complications included four cases of cystic bleb formation and one case of choroidal detachment and explantation for hypotony. Ahmed valve placement through the pars plana during vitrectomy is an effective option for managing complex cases of glaucoma without the use of the pars plana clip.

  12. Effects of solar PAR and UV radiation on tropical biofouling communities

    KAUST Repository

    Dobretsov, SV

    2010-03-08

    We investigated the effect of solar ultraviolet radiation (UVR) and photosynthetically active radiation (PAR) on the development of tropical micro- and macrofouling communities for 30 d. The experimental design involved 3 treatments: full spectrum (PAR+UVR), PAR only, and minimal light (reduced PAR and UVR). Terminal restriction fragment length polymorphism analysis demonstrated that different light conditions resulted in the formation of highly different microbial communities. The lowest densities of bacteria were found under the full spectrum treatment, while the lowest densities of diatoms were found in the minimal light treatment. Macrofouling communities consisted of 13 species and differed among light treatments. In the presence of UVR, communities had low species diversity, evenness, and richness, while in minimal light and PAR treatments, communities had high species diversity, evenness, and richness. Similarity percentage (SIMPER) analysis revealed that the tubeworm Hydroides elegans, the alga Ulva (Enteromorpha) sp., and the bivalve Perna viridis were the species responsible for most of the dissimilarities in macrofouling communities among treatments. While densities of H. elegans were similar in the PAR and minimal light treatments, this polychaete had higher growth rates under minimal light conditions. We conclude that UVR and PAR directly control the development of shallow micro- and macrofouling communities by inhibiting the recruitment and growth of sensitive species and promoting the growth of resistant species, but also that these forms of solar radiation influence the surface cues available to competent larvae by altering the development of the microbial community.

  13. The pars intermedia: an anatomic basis for a coordinated vascular response to female genital arousal.

    Science.gov (United States)

    Shih, Cheryl; Cold, Christopher J; Yang, Claire C

    2013-06-01

    The pars intermedia is an area of the vulva that has been inconsistently described in the literature. We conducted anatomic studies to better describe the tissues and vascular structures of the pars intermedia and proposed a functional rationale of the pars intermedia in the female sexual response. Nine cadaveric vulvectomy specimens were used. Each was serially sectioned and stained with hematoxylin and eosin and Masson's trichrome. Histologic ultrastructural description of the pars intermedia. The pars intermedia contains veins traveling longitudinally in the angle of the clitoris, supported by collagen-rich stromal tissues. These veins drain the different vascular compartments of the vulva, including the clitoris, the bulbs, and labia minora; also, the interconnecting veins link the different vascular compartments. The pars intermedia is not composed of erectile tissue, distinguishing it from the erectile tissues of the corpora cavernosa of the clitoris as well as the corpus spongiosum of the clitoral (vestibular) bulbs. The venous communications of the pars intermedia, linking the erectile tissues with the other vascular compartments of the vulva, appear to provide the anatomic basis for a coordinated vascular response during female sexual arousal. © 2012 International Society for Sexual Medicine.

  14. Hunger amidst plenty along the coast of Pará

    Directory of Open Access Journals (Sweden)

    Ivete Nascimento

    2006-08-01

    Full Text Available In this work one analyzes some referring questions to the new significações of the temporality constructed socially enters the artisan fishing of the coast, in the city of Maracanã, using as boundary-maker the concepts the concepts of abundance and famitura the one that they send themselves to the speech in way of life of the past and the gift. It will see as the typical way of life of the rescued past of the memory of old and the meaning of the abundance in the time of the fishing-farmer, the counterpoint with the concept of famitura of the fishing-exclusive of the gift, where the loss surpasses the scope of the strict survival reaching the proper way of life with the weakness of solidarity. This analysis will be given mecanicamente in the conceptual field of the time measured for the tasks and of the time chronometered for the clock. The intensive field work ocurred on Fortaleza of the Mocooca community incorporating data gotten a long the author's experience in the fish artisan thematic of the Pará coast.

  15. Le Web pour enseigner par projets et favoriser la collaboration

    Directory of Open Access Journals (Sweden)

    Sylvie Ratté

    2004-01-01

    Full Text Available L’utilisation du Web présentée dans cet article vient appuyer une démarche pédagogique fondée sur le partage des savoirs. Dans le contexte d’une simulation industrielle, les étudiants d’un cours de programmation avancée doivent apprendre à partager leur expertise, à communiquer clairement leurs questions, à décrire des problèmes et à faire face à des retournements inattendus. Le Web devient un espace de collaboration pour diffuser les requêtes d’un client fictif, les directives, les travaux préliminaires et les ententes. Les résultats obtenus tendent à suggérer que cette approche globale force l’étudiant à mieux planifier, l’invite à mieux formuler et décrire les problèmes, augmente le niveau de collaboration et facilite la production d’analogies. Un système facilitant la logistique entourant la revue par les pairs (récupération des travaux, construction d’une grille d’évaluation et diffusion des résultats est également présenté.

  16. Design of 118 MHz twelfth harmonic cavity of APS PAR

    International Nuclear Information System (INIS)

    Kang, Y.W.; Kustom, R.L.; Bridges, J.F.

    1992-01-01

    Two radio frequency (RF) cavities are needed in the Positron Accumulator Ring (PAR) of the Advanced Photon Source. One is for the first harmonic frequency at 9.8 MHz, and the other is for the twelfth harmonic frequency at 118 MHz. This note reports on the design of the 118 MHz RF cavity. Computer models are used to find the mode frequencies, impedances, Q-factors, and field distributions in the cavity. The computer codes MAFIA, URMEL, and URMEL-T are useful tools which model and simulate the resonance characteristics of a cavity. These codes employ the finite difference method to solve Maxwell's equations. MAFIA is a three-dimensional problem solver and uses square patches to approximate the inner surface of a cavity. URMEL and URMEL-T are two-dimensional problem solvers and use rectangular and triangular meshes, respectively. URMEL-T and MAFIA can handle problems with arbitrary dielectric materials located inside the boundary. The cavity employs a circularly cylindrical ceramic window to limit the vacuum to the beam pipe. The ceramic window used in the modeling will have a wall thickness of 0.9 cm. This wall thickness is not negligible in determining the resonant frequencies of the cavity. In the following, results of two- and three-dimensional modeling of the cavities using the URMEL-T and MAFIA codes are reported

  17. Characterization of ParTI Phoswiches Using Charged Pion Beams

    Science.gov (United States)

    Churchman, Emily; Zarrella, Andrew; Youngs, Michael; Yennello, Sherry

    2017-09-01

    The Partial Truncated Icosahedron (ParTI) detector array consists of 15 phoswiches. Each phoswich is made of two scintillating components - a thallium-doped cesium iodide (CsI(Tl)) crystal and an EJ-212 scintillating plastic - coupled to a photomultiplier tube. Both materials have different scintillation times and are sensitive to both charged and neutral particles. The type of particle and amount of energy deposited determine the shape of the scintillation pulse as a function of time. By integrating the fast and slow signals of the scintillation pulses, a ``Fast vs. Slow Integration'' plot can be created that produces particle identification lines based on the energy deposited in the scintillating materials. Four of these phoswiches were taken to the Paul Scherrer Institute (PSI) in Switzerland where π + , π-, and proton beams were scattered onto the phoswiches to demonstrate their particle identification (PID) capabilities. Using digitizers to record the detector response waveforms, pions can also be identified by the characteristic decay pulse of the muon daughters.

  18. Monitoreo de parásitos en efluentes domiciliarios

    Directory of Open Access Journals (Sweden)

    Semenas Liliana

    1999-01-01

    Full Text Available OBJETIVO: Evaluar la presencia de parásitos en efluentes semisólidos y líquidos en distintas localidades de la Patagonia argentina considerando que ésta es una de las restricciones para su uso. MÉTODOS: Las muestras tomadas en 4 Plantas de Tratamiento de Efluentes Domiciliarios se analizaron siguiendo las normativas de Environmental Protection Agency, Organización Mundial de la Salud, Standard Methods for Examination of Water and Wastewater y de algunas clasificaciones. RESULTADOS: Solamente 2 de las 6 muestras de semisólidos analizadas tenían huevos de Ascaris lumbricoides no viables. De las 10 muestras líquidas, solamente 2 no tenían huevos mientras las restantes tenían patógenos de las categorías I (Giardia sp., Hymenolepis diminuta y Enterobius vermicularis y III (Ascaris lumbricoides, Ancylostoma duodenale y Trichuris trichiura. CONCLUSIONES: Todas las muestras de semisólidos analizadas fueron aptas para su uso como fertilizantes porque no se registró en ninguna de ellas la presencia de huevos viables de Ascaris lumbricoides y solamente 6 de las muestras líquidas fueron aptas para riego por carecer de huevos o por ser su concentración igual o inferior a 1 huevo por litro.

  19. MMP-1/PAR-1 signal transduction axis and its prognostic impact in esophageal squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Hong-hua Peng

    2012-01-01

    Full Text Available The matrix metalloprotease-1 (MMP-1/protease-activated receptor-1 (PAR-1 signal transduction axis plays an important role in tumorigenesis. To explore the expression and prognostic value of MMP-1 and PAR-1 in esophageal squamous cell carcinoma (ESCC, we evaluated the expression of two proteins in resected specimens from 85 patients with ESCC by immunohistochemistry. Sixty-two (72.9% and 58 (68.2% tumors were MMP-1- and PAR-1-positive, respectively, while no significant staining was observed in normal esophageal squamous epithelium. MMP-1 and PAR-1 overexpression was significantly associated with tumor node metastasis (TNM stage and regional lymph node involvement. Patients with MMP-1- and PAR-1-positive tumors, respectively, had poorer disease-free survival (DFS than those with negative ESCC (P = 0.002 and 0.003, respectively. Univariate analysis showed a significant relationship between TNM stage [hazard ratio (HR = 2.836, 95% confidence interval (CI = 1.866-4.308], regional lymph node involvement (HR = 2.955, 95%CI = 1.713-5.068, MMP-1 expression (HR = 2.669, 95%CI = 1.229-6.127, and PAR-1 expression (HR = 1.762, 95%CI = 1.156-2.883 and DFS. Multivariate analysis including the above four parameters identified TNM stage (HR = 2.035, 95%CI = 1.167-3.681, MMP-1 expression (HR = 2.109, 95%CI = 1.293-3.279, and PAR-1 expression (HR = 1.967, 95%CI = 1.256-2.881 as independent and significant prognostic factors for DFS. Our data suggest for the first time that MMP-1 and PAR-1 were both overexpressed in ESCC and are novel predictors of poor patient prognosis after curative resection. The MMP-1/PAR-1 signal transduction axis might be a new therapeutic target for future therapies tailored against ESCC.

  20. MMP-1/PAR-1 signal transduction axis and its prognostic impact in esophageal squamous cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Peng, Hong-hua; Zhang, Xi; Cao, Pei-guo [Department of Oncology, the Third Xiangya Hospital, Central South University, Changsha, Hunan Province (China)

    2011-11-18

    The matrix metalloprotease-1 (MMP-1)/protease-activated receptor-1 (PAR-1) signal transduction axis plays an important role in tumorigenesis. To explore the expression and prognostic value of MMP-1 and PAR-1 in esophageal squamous cell carcinoma (ESCC), we evaluated the expression of two proteins in resected specimens from 85 patients with ESCC by immunohistochemistry. Sixty-two (72.9%) and 58 (68.2%) tumors were MMP-1- and PAR-1-positive, respectively, while no significant staining was observed in normal esophageal squamous epithelium. MMP-1 and PAR-1 overexpression was significantly associated with tumor node metastasis (TNM) stage and regional lymph node involvement. Patients with MMP-1- and PAR-1-positive tumors, respectively, had poorer disease-free survival (DFS) than those with negative ESCC (P = 0.002 and 0.003, respectively). Univariate analysis showed a significant relationship between TNM stage [hazard ratio (HR) = 2.836, 95% confidence interval (CI) = 1.866-4.308], regional lymph node involvement (HR = 2.955, 95%CI = 1.713-5.068), MMP-1 expression (HR = 2.669, 95%CI = 1.229-6.127), and PAR-1 expression (HR = 1.762, 95%CI = 1.156-2.883) and DFS. Multivariate analysis including the above four parameters identified TNM stage (HR = 2.035, 95%CI = 1.167-3.681), MMP-1 expression (HR = 2.109, 95%CI = 1.293-3.279), and PAR-1 expression (HR = 1.967, 95%CI = 1.256-2.881) as independent and significant prognostic factors for DFS. Our data suggest for the first time that MMP-1 and PAR-1 were both overexpressed in ESCC and are novel predictors of poor patient prognosis after curative resection. The MMP-1/PAR-1 signal transduction axis might be a new therapeutic target for future therapies tailored against ESCC.

  1. Prognostic value of suPAR and hs-CRP on cardiovascular disease

    DEFF Research Database (Denmark)

    Diederichsen, Marie Zöga; Diederichsen, Søren Zöga; Mickley, Hans

    2018-01-01

    Background and aims: Studies have shown that soluble urokinase Plasminogen Activator Receptor (suPAR) and CRP (both inflammatory markers) and coronary artery calcification (CAC) are independent risk predictors for cardiovascular (CV) disease. The aim of this study is to assess whether suPAR and CRP...... have an increased predictive prognostic value beyond the traditional CV risk factors and the CAC score. Methods: A population sample of 1179 subjects, free of CV disease was included. The subjects underwent traditional CV risk evaluation, CAC assessment and blood sampling for suPAR and CRP. CV events...

  2. Profils des enfants infectes par le vih en debut du traitement ...

    African Journals Online (AJOL)

    But : Décrire les profils des enfants infectés par le VIH au début du traitement antirétroviral. Matériels et méthode: Les dossiers des enfants infectés par le VIH dans la région maritime ont été analysés de mai 2008 à février 2010 par le comité thérapeutique. Résultats: Parmi les 96 dossiers analysés, 66,67% venaient du ...

  3. Les dispensées par fantaisie en éducation physique et sportive ...

    African Journals Online (AJOL)

    Cette étude vise à comprendre les raisons avancées par les élèves dispensés par fantaisie des cours d'EPS, pour justifier leur attitude et principalement leur forfait. Une enquête par questionnaire écrit a été menée dans 13 établissements publics de la ville de Porto-Novo au Bénin. Au total, 203 élèves parmi les 771 élèves ...

  4. MODELISATION DE LA CINETIQUE CHIMIQUE DANS LA REDUCTION DES OXYDES D4AZOTE PAR DECHARGE COURONNE.

    OpenAIRE

    MEDJAHDI, Sarah ines

    2015-01-01

    CE TRAVAIL DE recherche rentre dans le cadre général de modélisation de la réduction des oxydes d'azote . l'utilisation des réacteurs a plasma froid non-thermique généré par des décharges couronnes est actuellement l'une des techniques les puis promettre .ses pour la destruction des oxydes d'azote .en effet , le traitement des gaz pollués par les décharges couronnes est notamment rendu possible par la multiplication des décharges Électriques .

  5. Thrombin induces rapid PAR1-mediated non-classical FGF1 release

    International Nuclear Information System (INIS)

    Duarte, Maria; Kolev, Vihren; Soldi, Raffaella; Kirov, Alexander; Graziani, Irene; Oliveira, Silvia Marta; Kacer, Doreen; Friesel, Robert; Maciag, Thomas; Prudovsky, Igor

    2006-01-01

    Thrombin induces cell proliferation and migration during vascular injury. We report that thrombin rapidly stimulated expression and release of the pro-angiogenic polypeptide fibroblast growth factor 1 (FGF1). Thrombin failed to induce FGF1 release from protease-activated receptor 1 (PAR1) null fibroblasts, indicating that this effect was dependent on PAR1. Similarly to thrombin, FGF1 expression and release were induced by TRAP, a specific oligopeptide agonist of PAR1. These results identify a novel aspect of the crosstalk between FGF and thrombin signaling pathways which both play important roles in tissue repair and angiogenesis

  6. Complexation de l'aluminium par des hétéropolyanions lacunaires ...

    African Journals Online (AJOL)

    L'objectif visé par cette étude est la dépollution des eaux à partir de la complexation d'un métal toxique, l'aluminium en solution, par des hétéropolyanions lacunaires (HPA) de type Dawson. Les complexes formés sont récupérés par membrane liquide émulsionnée (MEL).Les résultats de la complex1ation de l'aluminium ...

  7. Influence of P-Reactor operation on the aquatic ecology of Par Pond: a literature review

    International Nuclear Information System (INIS)

    Wilde, E.W.; Tilly, L.J.

    1985-02-01

    Par Pond is a 1012 hectare reservoir that was constructed in 1958 to provide cooling water for Savannah River nuclear reactors. The purpose of this report is to summarize all known studies on the Par Pond system and point out demonstrable or probable effects that can be correlated with reactor operations. Reactor operation effects the Par Pond ecosystem through: (1) pumping, (2) thermal alteration, and (3) the addition of Savannah River makeup water. The influence of each of these factors is discussed. 108 references, 24 figures, 34 tables. (MF)

  8. Monoradiculopathy and secondary segmental instability caused by postoperative pars interarticularis fracture: a case report.

    Science.gov (United States)

    Kaner, Tuncay; Tutkan, Ibrahim

    2009-04-01

    Instability can develop after lumbar spinal surgery. What is also known as secondary segmental instability is one of the important causes of failed back syndrome. In this paper, we described a 45-year-old female patient who was diagnosed with secondary segmental instability caused by left L3 pars interarticularis fracture after a high lumbar disc surgery and was subsequently treated with re-operation. We evaluated the clinical course, diagnosis, and treatment methods for secondary segmental instability caused by postoperative pars interarticularis fracture. Furthermore, we emphasized the importance of preserving the pars interarticularis during upper lumbar disc surgeries in order to avoid a potential stress fracture.

  9. Influencia de los parámetros de proceso, en el comportamiento del parámetro vibración absoluta en turbinas de vapor.

    Directory of Open Access Journals (Sweden)

    F. de la Torre Silva

    2008-01-01

    Full Text Available Este trabajo muestra el estudio realizado en turbinas de vapor de pequeña capacidad de generación de las centrales termoeléctricas cubanas, relacionadas con la influencia estadística entre parámetros de proceso de la turbina, respecto al parámetro vibración absoluta, medidos en las chumaceras de la turbina. Se utilizan las bases de datos de los sistemas de monitoreado on-line de la turbina. Se exponen las relaciones existentes entre los principales parámetros seleccionados para este estudio.This work show the study in small steam turbine capacity of generation in cubans thermoelectric power station to relative with statistical influence between steam process parameters regarding absolute vibration parameter, in the steam housing measurements. Themselves use database as steam on-line monitoring systems. Expose the existing relation between the principal selection parameters for this study.

  10. Efficacy and safety of the pars plana clip in the Ahmed valve device inserted via the pars plana in patients with refractory glaucoma

    Directory of Open Access Journals (Sweden)

    Manuel Diaz-Llopis

    2010-05-01

    Full Text Available Manuel Diaz-Llopis1,2,3, David Salom1,3, Salvador García-Delpech1,2,3, Patricia Udaondo1,3, Jose Maria Millan3,5, J Fernando Arevalo61Department of Ophthalmology, La Fe University Hospital of Valencia, Valencia, Spain; 2Department of Ophthalmology of the Valencia University, Valencia, Spain; 3Biomedical Network Research Centre on Rare Diseases (CIBERER, Valencia, Spain; 4Catholic University San Vicente Martir, Valencia, Spain; 5Department of Genetics, La Fe University Hospital of Valencia, Valencia, Spain; 6Clinica Oftalmologica Centro Caracas, Retina and VItreous Service, Caracas, DC, VenezuelaPurpose: To evaluate the efficacy and safety of the pars plana clip (PPC in the Ahmed valve tube inserted via the pars plana in patients with secondary refractory glaucomas.Methods: Prospective and interventional case series that included 10 patients with secondary refractory glaucoma. The pars plana vitrectomy and the implant of the modified tube were performed during the same surgery. Control of intraocular pressure (IOP and the development of intra- and postoperative complications were evaluated during the follow-up.Results: Follow-up time was twelve months in all the patients. Control of IOP was achieved in 90% of patients, and 70% needed no antiglaucoma treatment. The complications that occurred were transient hypotony in three cases, choroidal detachment in two cases, and one case of intraocular hemorrhage. No case of tube extrusion or tube kink was observed.Conclusions: Our data suggests that implantation of the Ahmed tube modified with the PPC via the pars plana is safe and effective in patients with secondary refractory glaucomas. Keywords: pars plana clip, Ahmed valve, refractory glaucoma, pars plana vitrectomy

  11. A mechanism for ParB-dependent waves of ParA, a protein related to DNA segregation during cell division in prokaryotes

    DEFF Research Database (Denmark)

    Hunding, Axel; Gerdes, Kenn; Charbon, Gitte Ebersbach

    2003-01-01

    in an autocatalytic process. We discuss this mechanism in relation to recent models for MinDE oscillations in E.coli and to microtubule degradation in mitosis. The study points to an ancestral role for the presented pattern types in generating bipolarity in prokaryotes and eukaryotes.......Prokaryotic plasmids encode partitioning (par) loci involved in segregation of DNA to daughter cells at cell division. A functional fusion protein consisting of Walker-type ParA ATPase and green fluorescent protein (Gfp) oscillates back and forth within nucleoid regions with a wave period of about...

  12. Outcome of early pars plana vitrectomy in exogenous endophthalmitis

    International Nuclear Information System (INIS)

    Dar, A.J.; Islam, Q.U.; Hanif, M.K.

    2013-01-01

    Objective: To evaluate the role of early pars plana vitrectomy (PPV) in cases of exogenous endophthalmitis in terms of final visual outcome and to determine association between various study variables and final visual outcome. Study Design: Quasi experimental study. Place and Duration of Study: Armed Forces Institute of Ophthalmology (AFIO) Rawalpindi, from Aug 2010 to May 2012. Patients and Methods: Eleven cases of exogenous endophthalmitis (post surgical/post traumatic) were managed surgically through 20 G or 23/25 G complete and early PPV. Vitreous aspirate/explanted intraocular lens (IOL) were sent for culture and sensitivity in all cases. Intra and post operative complications were recorded and best corrected visual acuity (BCVA) at 3 months post operative interval was taken as final visual acuity. Results: Median age of study population was 55 years with male preponderance (64%). Approximately 2/3 rd of study population developed endophthalmitis within 6 weeks of surgery/trauma and 55% of patients were operated within 2 weeks of presentation. Positive culture from vitreous aspirate/IOL explant was obtained in 27% of cases. All the patients had initial BCVA in the range of counting finger (CF) at 2 meter to perception of light (PL+). However, 18% of the patients achieved final BCVA of 6/12 or better and 64% achieved final BCVA of 6/36 or better. Maculopathy (macular scar, macular pucker), corneal decompensation, corneal opacity and raised intraocular pressure were the major complications associated with compromised visual outcome. Conclusion: With the advancement in vitreoretinal surgical techniques and availability of more sophisticated viewing and illumination systems, early and complete vitrectomy for post operative or post traumatic endophthalmitis results in favorable visual outcome and early rehabilitation. (author)

  13. Intrinsic and integrative properties of substantia nigra pars reticulata neurons

    Science.gov (United States)

    Zhou, Fu-Ming; Lee, Christian R.

    2011-01-01

    The GABA projection neurons of the substantia nigra pars reticulata (SNr) are output neurons for the basal ganglia and thus critical for movement control. Their most striking neurophysiological feature is sustained, spontaneous high frequency spike firing. A fundamental question is: what are the key ion channels supporting the remarkable firing capability in these neurons? Recent studies indicate that these neurons express tonically active TRPC3 channels that conduct a Na-dependent inward current even at hyperpolarized membrane potentials. When the membrane potential reaches −60 mV, a voltage-gated persistent sodium current (INaP) starts to activate, further depolarizing the membrane potential. At or slightly below −50 mV, the large transient voltage-activated sodium current (INaT) starts to activate and eventually triggers the rapid rising phase of action potentials. SNr GABA neurons have a higher density of (INaT), contributing to the faster rise and larger amplitude of action potentials, compared with the slow-spiking dopamine neurons. INaT also recovers from inactivation more quickly in SNr GABA neurons than in nigral dopamine neurons. In SNr GABA neurons, the rising phase of the action potential triggers the activation of high-threshold, inactivation-resistant Kv3-like channels that can rapidly repolarize the membrane. These intrinsic ion channels provide SNr GABA neurons with the ability to fire spontaneous and sustained high frequency spikes. Additionally, robust GABA inputs from direct pathway medium spiny neurons in the striatum and GABA neurons in the globus pallidus may inhibit and silence SNr GABA neurons, whereas glutamate synaptic input from the subthalamic nucleus may induce burst firing in SNr GABA neurons. Thus, afferent GABA and glutamate synaptic inputs sculpt the tonic high frequency firing of SNr GABA neurons and the consequent inhibition of their targets into an integrated motor control signal that is further fine-tuned by neuromodulators

  14. Oncolytic targeting of androgen-sensitive prostate tumor by the respiratory syncytial virus (RSV): consequences of deficient interferon-dependent antiviral defense

    International Nuclear Information System (INIS)

    Echchgadda, Ibtissam; Chang, Te-Hung; Sabbah, Ahmed; Bakri, Imad; Ikeno, Yuji; Hubbard, Gene B; Chatterjee, Bandana; Bose, Santanu

    2011-01-01

    Oncolytic virotherapy for cancer treatment utilizes viruses for selective infection and death of cancer cells without any adverse effect on normal cells. We previously reported that the human respiratory syncytial virus (RSV) is a novel oncolytic virus against androgen-independent PC-3 human prostate cancer cells. The present study extends the result to androgen-dependent prostate cancer, and explores the underlying mechanism that triggers RSV-induced oncolysis of prostate cancer cells. The oncolytic effect of RSV on androgen-sensitive LNCaP human prostate cancer cells and on androgen-independent RM1 murine prostate cancer cells was studied in vitro in culture and in vivo in a xenograft or allograft tumor model. In vitro, cell viability, infectivity and apoptosis were monitored by MTT assay, viral plaque assay and annexin V staining, respectively. In vivo studies involved virus administration to prostate tumors grown in immune compromised nude mice and in syngeneic immune competent C57BL/6J mice. Anti-tumorogenic oncolytic activity was monitored by measuring tumor volume, imaging bioluminescent tumors in live animals and performing histopathological analysis and TUNEL assay with tumors We show that RSV imposes a potent oncolytic effect on LNCaP prostate cancer cells. RSV infectivity was markedly higher in LNCaP cells compared to the non-tumorigenic RWPE-1 human prostate cells. The enhanced viral burden led to LNCaP cell apoptosis and growth inhibition of LNCaP xenograft tumors in nude mice. A functional host immune response did not interfere with RSV-induced oncolysis, since growth of xenograft tumors in syngeneic C57BL/6J mice from murine RM1 cells was inhibited upon RSV administration. LNCaP cells failed to activate the type-I interferon (IFNα/β)-induced transcription factor STAT-1, which is required for antiviral gene expression, although these cells could produce IFN in response to RSV infection. The essential role of IFN in restricting infection was further

  15. Risk factors for respiratory syncytial virus associated with acute lower respiratory infection in children under five years: Systematic review and meta–analysis

    Directory of Open Access Journals (Sweden)

    Ting Shi

    2015-12-01

    Full Text Available Respiratory syncytial virus (RSV is the most common pathogen identified in young children with acute lower respiratory infection (ALRI as well as an important cause of hospital admission. The high incidence of RSV infection and its potential severe outcome make it important to identify and prioritise children who are at higher risk of developing RSV–associated ALRI. We aimed to identify risk factors for RSV–associated ALRI in young children. We carried out a systematic literature review across 4 databases and obtained unpublished studies from RSV Global Epidemiology Network (RSV GEN collaborators. Quality of all eligible studies was assessed according to modified GRADE criteria. We conducted meta–analyses to estimate odds ratios with 95% confidence intervals (CI for individual risk factors. We identified 20 studies (3 were unpublished data with “good quality” that investigated 18 risk factors for RSV–associated ALRI in children younger than five years old. Among them, 8 risk factors were significantly associated with RSV–associated ALRI. The meta–estimates of their odds ratio (ORs with corresponding 95% confidence intervals (CI are prematurity 1.96 (95% CI 1.44–2.67, low birth weight 1.91 (95% CI 1.45–2.53, being male 1.23 (95% CI 1.13–1.33, having siblings 1.60 (95% CI 1.32–1.95, maternal smoking 1.36 (95% CI 1.24–1.50, history of atopy 1.47 (95% CI 1.16–1.87, no breastfeeding 2.24 (95% CI 1.56–3.20 and crowding 1.94 (95% CI 1.29–2.93. Although there were insufficient studies available to generate a meta–estimate for HIV, all articles (irrespective of quality scores reported significant associations between HIV and RSV–associated ALRI. This study presents a comprehensive report of the strength of association between various socio–demographic risk factors and RSV–associated ALRI in young children. Some of these amenable risk factors are similar to those that have been identified for (all cause ALRI and

  16. Respiratory syncytial virus and TNFalpha induction of chemokine gene expression involves differential activation of Rel A and NF-kappaB1

    Directory of Open Access Journals (Sweden)

    Roebuck Kenneth A

    2002-03-01

    Full Text Available Abstract Background Respiratory syncytial virus (RSV infection of airway epithelial cells stimulates the expression and secretion of a variety of cytokines including the chemotactic cytokines interleukin-8 (IL-8, monocyte chemoattractant protein-1 (MCP-1, and RANTES (regulated upon activation, normal T cell expressed and secreted. Chemokines are important chemoattractants for the recruitment of distinct sets of leukocytes to airway sites of inflammation. Results We have shown previously that chemokine expression is regulated in airway epithelial cells (A549 in a stimulus-specific manner in part through the redox-responsive transcription factors AP-1 and NF-κB. In this study, we examined the NF-κB-mediated effects of RSV and the proinflammatory cytokine TNFα on the induction of IL-8, MCP-1 and RANTES chemokine gene expression in A549 epithelial cells. The results demonstrate that RSV induces chemokine expression with distinct kinetics that is associated with a specific pattern of NF-κB binding activity. This distinction was further demonstrated by the differential effects of the NF-κB inhibitors dexamethasone (DEX and N-acetyl-L-cysteine (NAC. NAC preferentially inhibited RSV induced chemokine expression, whereas DEX preferentially inhibited TNFα induced chemokine expression. DNA binding studies using NF-κB subunit specific binding ELISA demonstrated that RSV and TNFα induced different NF-κB binding complexes containing Rel A (p65 and NF-κB1 (p50. Both TNFα and RSV strongly induced Rel A the activation subunit of NF-κB, whereas only TNFα was able to substantially induce the p50 subunit. Consistent with the expression studies, RSV but not TNFα induction of Rel A and p50 were markedly inhibited by NAC, providing a mechanism by which TNFα and RSV can differentially activate chemokine gene expression via NF-κB. Conclusions These data suggest that RSV induction of chemokine gene expression, in contrast to TNFα, involves redox

  17. Bovine respiratory syncytial virus outbreak reduced bulls' weight gain and feed conversion for eight months in a Norwegian beef herd.

    Science.gov (United States)

    Klem, Thea Blystad; Kjæstad, Hans Petter; Kummen, Eiliv; Holen, Hallstein; Stokstad, Maria

    2016-01-25

    Cost-benefit evaluation of measures against respiratory disease in cattle requires accounting with the associated production losses. Investigations of naturally occurring respiratory infections in a herd setting are an opportunity for accurate estimates of the consequences. This article presents estimates based on individual monitoring of weight and concentrate intake of several hundred bulls previous to, during and after a respiratory infection outbreak with bovine respiratory syncytial virus (BRSV) as the main pathogen. The aim of the study was to analyse the association between exposure to BRSV, weight gain and feed conversion rate, quantify any change in these parameters, and estimate the duration of the change in production. A comparison of growth curves for the bulls that were present during the outbreak revealed that bulls with severe clinical signs had a clear and consistent trend of poorer growth rate than those with milder or no signs. The weight/age-ratio was 0.04-0.10 lower in the severely affected bulls, and evident throughout the study period of 8 months. A comparison of growth rates between apparently healthy bulls being present during the outbreak and a comparable group of bulls exactly 1 year later (n = 377) showed a reduced growth rate of 111 g/day in the first group. The difference amounted to 23 extra days needed to reach the reference weight. Feed conversion was also reduced by 79 g weight gain/kilogram concentrate consumed in the outbreak year. This study indicates significant negative effects on performance of animals that develop severe clinical signs in the acute stage, and that the growth and production is negatively affected many months after apparent recovery. In addition, the performance of apparently healthy animals that are exposed during an outbreak are severely negatively affected. The duration of this decrease in production in animals after recovery, or animals that have not shown disease at all, has not previously been

  18. Characteristics and Their Clinical Relevance of Respiratory Syncytial Virus Types and Genotypes Circulating in Northern Italy in Five Consecutive Winter Seasons.

    Directory of Open Access Journals (Sweden)

    Susanna Esposito

    Full Text Available In order to investigate the genetic diversity and patterns of the co-circulating genotypes of respiratory syncytial virus (RSV and their possible relationships with the severity of RSV infection, we studied all of the RSV-positive nasopharyngeal samples collected from children during five consecutive winters (2009-2010, 2010-2011, 2011-2012, 2012-2013 and 2013-2014. The RSVs were detected using the respiratory virus panel fast assay and single-tube RT-PCR, their nucleotides were sequenced, and they were tested for positive selection. Of the 165 positive samples, 131 (79.4% carried RSV-A and 34 (20.6% RSV-B; both groups co-circulated in all of the study periods, with RSV-A predominating in all the seasons except for winter 2010-2011, which had a predominance of RSV-B. Phylogenetic analysis of the RSV-A sequences identified genotypes NA1 and ON1, the second replacing the first during the last two years of the study period. The RSV-B belonged to genotypes BA9 and BA10. BA9 was detected in all the years of the study whereas BA only desultorily. Comparison of the subjects infected by RSV-A and RSV-B types did not reveal any significant differences, but the children infected by genotype A/NA1 more frequently had lower respiratory tract infections (p<0.0001 and required hospitalisation (p = 0.007 more often than those infected by genotype A/ON1. These findings show that RSV has complex patterns of circulation characterised by the periodical replacement of the predominant genotypes, and indicate that the circulation and pathogenic role of the different RSV strains should be investigated as each may have a different impact on the host. A knowledge of the correlations between types, genotypes and disease severity may also be important in order to be able to include the more virulent strains in future vaccines.

  19. Burden of paediatric respiratory syncytial virus disease and potential effect of different immunisation strategies: a modelling and cost-effectiveness analysis for England.

    Science.gov (United States)

    Cromer, Deborah; van Hoek, Albert Jan; Newall, Anthony T; Pollard, Andrew J; Jit, Mark

    2017-08-01

    Vaccines and prophylactic antibodies against respiratory syncytial virus (RSV) are in development and likely to be available in the next 5-10 years. The most efficient way to use these products when they become available is an important consideration for public health decision makers. We performed a multivariate regression analysis to estimate the burden of RSV in children younger than 5 years in England (UK), a representative high-income temperate country, and used these results to assess the potential effect of different RSV immunisation strategies (targeting vaccination for infants, or pregnant women, or prophylactic antibodies for neonates). We did a cost-effectiveness analysis for these strategies, implemented either separately or concurrently, and assessed the effect of restricting vaccination to certain months of the year. We estimated that RSV is responsible for 12 primary care consultations (95% CI 11·9-12·1) and 0·9 admissions to hospital annually per 100 children younger than 5 years (95% CI 0·89-0·90), with the major burden occurring in infants younger than 6 months. The most cost-effective strategy was to selectively immunise all children born before the start of the RSV season (maximum price of £220 [95% uncertainty interval (UI) 208-232] per vaccine, for an incremental cost-effectiveness ratio of £20 000 per quality-adjusted life-year). The maximum price per fully protected person that should be paid for the infant, newborn, and maternal strategies without seasonal restrictions was £192 (95% UI 168-219), £81 (76-86), and £54 (51-57), respectively. Nearly double the number of primary care consultations, and nearly five times the number of admissions to hospital occurred with RSV compared with influenza. RSV vaccine and antibody strategies are likely to be cost-effective if they can be priced below around £200 per fully protected person. A seasonal vaccination strategy is likely to provide the most direct benefits. Herd effects might

  20. The burden of respiratory syncytial virus (RSV) associated acute lower respiratory infections in children with Down syndrome: A systematic review and meta-analysis.

    Science.gov (United States)

    Chan, Markus; Park, John J; Shi, Ting; Martinón-Torres, Federico; Bont, Louis; Nair, Harish

    2017-12-01

    Acute lower respiratory tract infections (ALRIs) caused by respiratory syncytial virus (RSV) are a leading cause of hospitalization in infants. Numerous risk factors have been identified in the aetiology of severe RSV-associated ALRI necessitating hospitalisation, including prematurity and congenital heart disease. Down syndrome (DS), a common genetic disorder associated with congenital and dysmorphic features, has recently been identified as an independent risk factor for RSV-associated ALRI requiring hospitalisation; however, the disease burden of RSV-associated ALRI in this population has not yet been established. Similarly, the impact of DS as an independent risk factor has not yet been quantified. We aimed therefore to estimate the incidence of admissions in children with DS, and by comparing this with unaffected children, to quantify the risk of DS independent of other risk factors. A systematic review of the existing literature published between 1995 and March 1, 2017 was performed to quantify the incidence of hospitalisation due to RSV-associated ALRI in children with DS. Meta-analyses were performed on extracted data using STATA statistical software, and hospitalisation rates for children with and without DS under the age of 2 were calculated. 5 articles were ultimately deemed eligible for analyses. Analyses were limited to children under the age of 2 years. We calculated the hospitalisation rate for children with DS in this age group to be 117.6 per 1000 child-years (95% CI 67.4-205.2), vs a rate of 15.2 per 1000 child-years (95% CI 8.3-27.6) in unaffected children. This indicates DS contributes to a 6.8 (95% CI 5.5-8.4) fold increase in the relative risk of hospitalisation for RSV-associated ALRI. Though limited by a small number of articles, this review found sufficient evidence to conclude DS was a significant independent risk factor for the development of severe RSV-associated ALRI requiring hospitalisation. Further studies are needed to define the